Obstetric hemorrhages during first term of pregnancy. Ectopic pregnancy. Obstetric hemorrhages during second part of pregnancy, labor and postpartum period. Intensive therapy and reanimation at obstetric hemorrhages. Pregnancy and labor at extragenital diseases. Emergency in obstetrics.
Prepared by Kuziv I.
Obstetric hemorrhages during first term of pregnancy. Ectopic pregnancy. Obstetric hemorrhages during second part of pregnancy, labor and postpartum period.
An estimated 5 % of women describe bleeding of some extent during pregnancy. At times, the amount of bleeding is hardly more than "spotting," whereas at other times profuse hemorrhage can lead to maternal death in a very short time. In most cases, antepartum bleeding is minimal spotting, often following sexual intercourse, and is thought to be related to trauma to the friable ectocervix.
The main causes of bleeding in the second half of pregnancy are:
Tears or lacerations
Tears or lacerations
Glandular tissue (normal)
A previous Pap test and examination of the lower genital tract should eliminate the likelihood of lower genital tract neoplasms in most cases. At times, patients may mistake bleeding from hemorrhoids or even hematuria for vaginal bleeding, but the difference is easily distinguished by examination.
The two causes of hemorrhage in the second half of pregnancy that require greatest attention, because of the associated maternal and fetal morbidity and mortality rates, are placenta previa and abruptio placentae. Various characteristics of these entities are compared in Table.
Differential characteristics between placenta previa and abruptio placentae
Magnitude of blood loss
Often ceases within 1-2 hours
Can be severe
Fetal heart rate pattern
on electronic monitoring
Tachycardia, then bradycardia; loss of
variability; decelerations frequently
present; intrauterine demise not rare
Associated, but infrequent; DIG often
severe when present Cocaine use
multiple gestation; polyhydramnios
Placenta previa refers to an abnormal localisation of the placenta over, or in close proximity to the internal cervical os. Placenta previa can be categorized as:
1. complete or total - if the entire cervical os is covered (Fig. 1);
2. partial - if the margin of the placenta extends across part but not all of the internal os (Fig. 2);
3. marginal , if the edge of the placenta lies adjacent to the internal os;
4. low lying - if the placenta is located near but not directly adjacent to the internal os.
Fig. 1 Total placenta previa
Fig. 2 Partial placental previa
The etiology of placenta previa is not understood, but abnormal vascularization has long been proposed as a mechanism for this abnormal placement of the placenta. In some cases, such as in twin pregnancy or if it is hydropic, the placenta may extend to the region of the internal cervical os because of its size alone. Increasing maternal age, increasing parity, and previous cesarean delivery are factors commonly associated with placenta previa, although recent evidence suggests that age alone is not an important factor.
The incidence of placenta previa varies with gestational age, usually reported overall as approximately 1 in 250 pregnancies. There is great variation in incidence, however, with parity. The incidence in nulliparas is only 1 in 1000 to 1500, whereas that in grandmultiparas is as high as 1 in 20. Women with the highest risk for placenta previa are grandmultiparas, those who have had a previous placenta previa (4% to 8%), and those who have had four or more cesarean sections. With common use of ultrasonography examinations, it has been shown repeatedly that the placenta may cover the internal cervical os in approximately 5% of pregnancies when examined at midpregnancy, a finding seen even more frequently earlier in gestation. Because of subsequent growth of both the upper and lower uterine segments, the placenta appears to "migrate" away from the internal os in the majority of cases. The likelihood of this apparent movement diminishes as the gestational age at first detection increases.
Clinical findings and Diagnosis. The average gestational age at the time of the first bleeding episode is 29 to 30 weeks. Although the bleeding may be substantial, it almost always ceases spontaneously, unless digital examination or other trauma occurs. The bleeding is caused by separation of part of the placenta from the lower uterine segment and cervix, possibly in response to mild uterine contractions. The blood that is lost is usually maternal in origin. The patient often describes a sudden onset of bleeding without any apparent antecedent signs. There is no pain associated with placenta previa in most cases, unless coincident with labor or with an abruptio placenta (approximately 5% to 10% of cases).
Frequently, bleeding from placenta previa has its onset without warning, presenting without pain in a woman who has had an uneventful prenatal course. Fortunately, the initial bleeding is rarely so profuse as to prove fatal. Usually it ceases spontaneously, only to recur. In some cases, particularly those with a placenta implanted near but not over the cervical os, bleeding does not appear until the onset of labor, when it may vary from slight to profuse hemorrhage and may clinically mimic placental abruption.
The cause of hemorrhage is reemphasized. When the placenta is located over the internal os, the formation of the lower uterine segment and the dilatation of the internal os result inevitably in tearing of placental attachments. The bleeding is augmented by the inability of the myometrial fibers of the lower uterine segment to contract and thereby constrict the torn vessels.
Hemorrhage from the placental implantation site in the lower uterine segment may continue after delivery of the placenta, because the lower uterine segment is more prone to contract poorly than is the uterine body. Bleeding may also result from lacerations in the friable cervix and lower uterine segment, especially following manual removal of a somewhat adherent placenta.
In women with uterine bleeding during the latter half of pregnancy, placenta previa or abruptio placentae should always be suspected. The possibility of placenta previa should not be dismissed until appropriate evaluation, including sonography, has clearly proved its absence. The diagnosis of placenta previa can seldom be established firmly by clinical examination unless a finger is passed through the cervix and the placenta is palpated. Such examination of the cervix is never permissible unless the woman is in an operating room with all the preparations for immediate cesarean section, because even the gentlest examination of this sort can cause torrential hemorrhage. Furthermore, such an examination should not be made unless delivery is planned, for it may cause bleeding of such a degree that immediate delivery becomes necessary even though the fetus is immature. Today, however, such a “double set-up” examination is rarely necessary, as placental location can almost always be obtained by careful sonography.
Ultrasonography has been of enormous benefit in localizing the placenta, especially when the placenta is anterior or lateral. If the placenta lies in the posterior portion of the lower uterine segment, its exact relation with the internal os may be more difficult to ascertain. In most cases, though, ultrasonography examination can accurately diagnose placenta previa or, by illustrating the placenta location away from the cervix and lower uterine segment, exclude it as a cause for bleeding. In some instances, transvaginal ultrasonography may be a useful adjunct to the transabdominal approach, especially in the case of posterior placenta.
Double setup examination can confirm the diagnosis of placenta previa. It involves careful evaluation of the cervix in the operating room with full preparations for rapid cesarean delivery.
Includes initial hospitalization with hemodynamic stabilization, followed by expectant management until fetal maturity has occurred. Ideal expectant management would be continuous hospitalization with enforced bed rest and immediate access to emergency care.
In the complete placenta previa – cesarean section in full term pregnancy. In the case of low lying, marginal and partial placenta previa and full term pregnancy, when blood loss is less than 250 ml – amniotomy with the following prescription of contractile drugs. If blood loss is more than 250 ml – cesarean section.
The number of bleeding episodes is unrelated to the degree of placenta previa or to the prognosis for fetal survival. Such expectant management combined with appropriate use of blood transfusion and cesarean birth have resulted in the lowering of the maternal mortality rate from !25%-30% to < 1% and the perinatal mortality rate from 60%-70% to < 10%. If the fetus is thought to be mature by gestational criteria or by amniocentesis for fetal lung maturity testing, there is little benefit to be gained by a delay in delivery. The further from term that bleeding from placenta previa occurs, the more important it is to delay delivery to allow for further fetal growth and maturation. The degree of bleeding and the maturity of the fetus must be constantly weighed in managing these patients. Fetal maturity is usually assessed at approximately 36 weeks, with cesarean delivery performed once the fetus is deemed mature.
In some cases, when the location of the placenta cannot be accurately determined by ultrasound and delivery is required, the route of delivery is determined by a double setup examination. This procedure involves careful evaluation of the cervix in the operating room with full preparations for rapid cesarean delivery.
Localization by Sonography. The simplest, most precise, and safest method of placental localization is provided by transabdominal sonography, which is used to locate the placenta with considerable accuracy (Figs. 3, and 4 ).
Fig. 3 Partial anterior placenta previa at 36 weeks’ gestation. Placenta (P) extends anteriorly and downward toward cervix (Cx). Fetus (F), amnionic fluid (AF), and bladder (B) are seen. (Courtesy of Dr. R. Santos.)
Fig. 4 Total placenta previa at 34 weeks’ gestation. Placenta (P) completely overlies cervix (Cx). Bladder (B) and amnionic fluid (AF) are also visualized clearly. (Courtesy of Dr. R. Santos.)
The average accuracy is about 95 percent, and rates as high as 98 percent have been obtained. False-positive results are often a result of bladder distention. Therefore, ultrasonic scans in apparently positive cases should be repeated after emptying the bladder. Another source of error has been identification of abundant placenta implanted in the uterine fundus but failure to appreciate that the placenta was large and extended downward all the way to the internal os of the cervix. This, however is uncommon.
Farine and associates (1988) reported that the use of transvaginal ultrasonography has substantively improved diagnostic accuracy of placenta previa. They were able to visualize the internal cervical os in all cases with the transvaginal technique, in contrast to only 70 percent using transabdominal equipment. An example is shown in Figure 5.
Fig. 5 Transvaginal ultrasonic scan at 34 weeks’ gestation. Cervical canal is clearly visible (CX) and distance from internal os to placental edge, measured between calipers (X) is 0.75 cm. The patient was delivered by cesarean section 4 weeks later because of vaginal bleeding. (P = placenta; B = bladder.) (Reproduced, with permission, from Oppenheimer LW, Farine D, Ritchie JWK, Lewinsky RM, Telford J, Fairbanks LA. What is a low-lying placenta? Am J Obstet Gynecol. 165:1035, 1991.)
Likewise, Leerentveld and colleagues (1990) studied 100 women suspected of having placenta previa. They reported a 93 percent positive predictive value and 98 percent negative predictive value for transvaginal ultrasonography. Hertzberg and associates (1992) demonstrated that transperineal sonography allowed visualization of the internal os in all 164 cases examined because transabdominal sonography disclosed a previa or was inconclusive. Placenta previa was correctly excluded in 154 women, and in 10 in whom it was diagnosed sonographically, nine had a previa confirmed at delivery.
Magnetic Resonance Imaging.
Preliminary investigation using magnetic resonance imaging to visualize placental abnormalities, including placenta previa, have been reported by several groups. Kay and Spritzer (1991) discussed the many positive attributes of such technology (Fig. 6). It is unlikely that this will replace ultrasonic scanning for routine evaluation in the near future.
Fig. 6 A sagittal T2-weighted (2000/80 ms) image of a patient with a posterior marginal placenta previa. The arrowhead points to the placental edge and the arrow indicates the internal os. (F = fetal head; P = placenta; B = maternal bladder.) (From Kay HH, Spritzer CE. Preliminary experience with magnetic resonance imaging in patients with third-trimester bleeding. Obstet Gynecol. 78:424, 1991. Reprinted with permission from the American College of Obstetricians and Gynecologists.)
Since the report by King (1973), the apparent peripatetic nature of the placenta has been well established. McClure and Dornal (1990) found a low-lying placenta in 25 percent of 1490 ultrasonic scans done at 18 weeks; however, at delivery, only 7 of these 385 low-lying placentas persisted. Sanderson and Milton (1991) found that only 12 percent of placentas were low lying in 4300 women surveyed ultrasonically at 18 to 20 weeks. Of those not covering the internal os, previa did not persist and hemorrhage was not encountered. Conversely, of those covering the os at midpregnancy, about 40 percent persisted as a previa. Therefore, placentas that lie close to the internal cervical os, but not over it, during the second trimester, or even early in the third trimester, are very unlikely to persist as previas by term.
The low frequency with which placenta previa persists when it has been identified sonographically before 30 weeks is shown in Table 32–4. It is apparent from these data that in the absence of any other abnormality, sonography need not be frequently repeated simply to follow placental position, and restriction of activity need not be practiced unless the previa persists beyond 30 weeks, or becomes clinically apparent before that time.
The mechanism of apparent placental movement is not completely understood. The term migration is clearly a misnomer, however, as invasion of chorionic villi into the decidua on either side of the cervical os will persist. The apparent movement of the low-lying placenta relative to the internal os probably results from inability to precisely define this relationship in a three-dimensional manner using two-dimensional sonography in early pregnancy. This difficulty is coupled with differential growth of lower and upper myometrial segments as pregnancy progresses. Thus those placentas that “migrate” most likely never had actual circumferential villus invasion that reached the internal cervical os in the first place.
If placental tissue is seen or palpated at the internal cervical os, prompt cesarean delivery is performed. If the placental margin is away from the internal os, artificial rupture of the membranes and oxytocin induction of labor may be performed in anticipation of vaginal delivery. Before the widespread use of ultrasound, this procedure was done more frequently than it is in modern obstetrics; nonetheless, it is still an important tool in selected cases.
An attempt at vaginal delivery of a patient with placenta previa may be indicated if the delivery can be accomplished with minimal blood loss and if the fetus is dead, has major fetal malformations, or is clearly previable. If making such an attempt is appropriate, ceasing the process and moving to cesarean delivery for a maternal indication must always be considered. Placenta previa is associated with a nearly doubling of the rate of congenital malformations, the most serious including major anomalies of the central nervous system, gastrointestinal tract, cardiovascular system, and respiratory tract. At the time of diagnosis of placenta previa, a detailed fetal survey should be performed for anomalies.
Abnormal placental location can be further complicated by abnormal growth of the placental mass into the substance of the uterus, a condition termed placenta previa accreta. In placenta previa accreta, the poorly formed decidua of the lower uterine segment offers little resistance to trophoblastic invasion. The incidence of this severe complication is variously reported as 5% to 10% of placenta previas, although the incidence is much higher in patients with multiple previous cesarean sections. At the time of delivery, sustained and significant bleeding may ensue, often requiring hysterectomy.
Whereas placenta previa refers to the abnormal location of the placenta, abruptio placentae, often called placental abruption, refers to the premature separation of the normally implanted placenta from the uterine wall.
Etiology. Placental abruption occurs when there is hemorrhage into the decidua basalis, leading to premature placental separation and further bleeding. The cause for this bleeding is not known.
Placental abruption is associated with maternal hypertension and sudden decompression of the uterus in cases of rupture of membranes in a patient with excessive amniotic fluid (hydramnios) or after delivery of the first of multiple fetuses. A more recent and serious association involves cocaine use by the mother, which leads to intense vasoconstriction and, in some cases, sudden separation of the placenta from the uterine wall. Placental abruption can also occur following trauma, even when the extent of injury is not considered serious. For example, pregnant women involved in motor vehicle accidents can sustain placental abruption even though lap belts and shoulder strap restraints are used. Moreover, direct trauma to the abdomen is not required, because sudden force applied elsewhere to the body can result in coup and countercoup injury.
Fig. 7. Types of placental abruption
Clinical findings and Diagnosis
The signs and symptoms can vary considerable. External bleeding can be profuse or there may be no external bleeding (concealed hemorrhage) but the placenta is completely sheared off and the fetus dead. Besides, common findings are uterine tenderness, back pain, fetal distress, uterine hypertonus or high-frequently contractions, idiopathic preterm labor, and a dead fetus.
Because the separation of the placenta from the uterus interferes with oxygénation of the fetus, a nonreassuring fetal status is quite common in cases of significant placental abruption. Thus, in any patient in whom placental abruption is suspected, electronic fetal monitoring should be included in the initial management.
Placental abruption may be total and partial.
Fig. 8 Total placental abruption
Coagulation abnormalities may also be found, thereby compounding the patient's already compromised status. Placental abruption is the most common cause of consumptive coagulopathy in pregnancy and is manifested by hypofibrinogenemia as well as by increased levels of fibrin degradation products. The platelet count can also be decreased, and prothrombin time and partial thromboplastin time can be increased as well. Such coagulopathy is a result of intravascular and retroplacental coagulation. The intravascular fibrinogen is converted to fibrin by way of the extrinsic clotting cascade. Thus not only is serum fibrinogen decreased but platelets and other clotting factors are thereby also depleted.
Ultrasound is of little benefit in diagnosing placental abruption, except to exclude placenta previa as a cause for the hemorrhage. Relatively large retroplacental clots may be detected on ultrasound examination, but the absence of ultrasonographically identified retroplacental clots does not rule out the possibility of placental abruption, and conversely, a retroplacental echogenic area can be seen in patients without placental abruption. The diagnosis rests on the classic clinical presentation of vaginal bleeding, a tender uterus, and frequent uterine contractions with some evidence of fetal distress. The extravasation of blood into the uterine muscle causes contractions such that the resting intrauterine pressure, when measured with an intrauterine pressure catheter, is often elevated; this sign can be helpful in making the diagnosis. The entire uterus has a purplish or bluish appearance, owing to such extravasation of blood (Couvelaire uterus) – Fig. 9.
Fig. 9 Couvelaire uterus
Management of a patient with placental abruption when the fetus is mature is hemodynamic stabilization and delivery. Appropriate facilities and staff for cesarean section must be continuously available whenever placental abruption is suspected Careful attention to blood component therapy is critical, and the coagulation status must be followed closely. Unless there is evidence of fetal distress or hemodynamic instability, vaginal delivery by oxytocin induction of labor is preferable to a cesarean delivery, although the maternal or fetal status may require that abdominal delivery be performed. When the fetus is not mature and the placental abruption is limited and not associated with premature labor or fetal or maternal distress, observation with close monitoring of both fetal and maternal well-being may be considered while awaiting fetal maturity. In the case of Couvelaire uterus total hysterectomy is performed because of danger of uterine hypotony and disseminated intravascular clotting syndrome.
AMNIOTOMY. Rupture of the membranes as early as possible has long been championed in the management of placental abruption. The rationale for amniotomy is that the escape of amnionic fluid might both decrease bleeding from the implantation site and reduce the entry into the maternal circulation of thromboplastin and perhaps activated coagulation factors from the retroplacental clot. There is no evidence, however, that either is accomplished by amniotomy. If the fetus is reasonably mature, rupture of the membranes may hasten delivery. If the fetus is immature, the intact sac may be more efficient in promoting cervical dilatation than will a small fetal part poorly applied to the cervix.
LABOR. With slight degrees of placental separation, uterine contractions are usually of normal frequency, duration, and intensity. With extensive placental abruption, the uterus will likely be persistently hypertonic. The baseline intra-amnionic pressure may be 25 to 50 mm Hg or higher, with rhythmic increases up to 75 to 100 mm Hg. Because of persistent hypertonus, it may be difficult at times to determine by palpation if the uterus is contracting and relaxing to any degree (Fig. 32–9 ).
OXYTOCIN. Although hypertonicity characterizes myometrial function in most cases of severe placental abruption, if no rhythmic uterine contractions are superimposed, then oxytocin is given in standard doses. Uterine stimulation to effect vaginal delivery provides benefits that override the risks. The use of oxytocin has been challenged on the basis that it might enhance the escape of thromboplastin into the maternal circulation and thereby initiate or enhance consumptive coagulopathy or amnionic fluid embolism syndrome. There is no evidence to support this fear (Clark and colleagues, 1995; Pritchard and Brekken, 1967).
Although rarely encountered, vasa previa presents significant risk to the fetus. In vasa previa (Fig. 10), the umbilical cord inserts into the membranes of the placenta (rather than into the central mass of the placental tissue), and one such vessel lies below the presenting fetal part in the vicinity of the internal os. If this vessel ruptures, fetal bleeding occurs. Because of the low blood volume of the fetus, seemingly insignificant amounts of blood may place the fetus in jeopardy. A small amount of vaginal bleeding associated with fetal tachycardia may be the clinical presentation. A test to distinguish fetal blood from maternal blood, such as the Kleihauer-Betke or the Apt test, can be of value when such a condition is suspected. These tests distinguish between maternal and fetal blood on the basis of the marked resistance to pH changes in fetal red cells compared with the friable nature of adult red cells in the presence of strong bases. Immediate cesarean section is the only way to save the fetus in vasa previa.
Fig. 10 Sonogram showing placenta (P), succenturiate lobe (S), and leading fetal vessels in vasa previa (arrow). (From Gianopoulas J, Carver T, Tomich PG, Karlman R, Gadwood K. Diagnosis of vasa previa with ultrasonography. Obstet Gynecol. 69:488, 1987).
APPROACH TO A PATIENT WITH VAGINAL BLEEDING IN THE SECOND HALF OF GESTATION
In any woman with vaginal bleeding during the second half of pregnancy, fetal and maternal status should be evaluated promptly. At the same time that a search is undertaken for the cause of the bleeding, attention must be directed toward stabilization of the maternal hemodynamic state. The approach is not unlike that for any hemorrhaging patient and includes ready access for fluid replacement through one or more large-bore intravenous catheters, serial complete blood counts, type and cross-match of ample amounts of blood, and if the condition is unstable, intracardiac monitoring. Attention to urinary output is a simple and important reflection of the volume status of a patient. Because normal antepartum blood volume expansion is substantial, pregnant women may lose considerable amounts of blood before vital sign changes are apparent. In more than half of the cases of significant vaginal bleeding in pregnancy, no specific cause can be discovered despite careful evaluation. In general, patients with significant bleeding should remain hospitalized until delivery, although in some cases minimal bleeding ceases, and the patient appears normal in every way. Caution is advised, however, because patients with bleeding of undetermined etiology can be at greater risk for preterm delivery, intrauterine growth restriction, and fetal distress than patients with bleeding of known cause.
HEMORRHAGE IN THE THIRD STAGE OF LABOR AND EARLY PUERPERAL PERIOD
Postpartum hemorrhage is defined as blood loss in excess of 400 mL at the time of vaginal delivery.
Postpartum hemorrhage before delivery of the placenta is called third-stage hemorrhage.
Postpartum hemorrhage after delivery of placenta during the first two hours is called as hemorrhage in early puerperal stage.
Hemorrhage after placental separation is stopped thanks to:
1. uterine contractions – caliberes of ruptured vessels decreases during uterine contractions;
2. formation of thrombs, especially in the region of placental site;
3. torsion of thin septs in which vessels are situated.
Causes of Postpartum Hemorrhage:
1. uterine atony,
2. genital tract trauma,
3. bleeding from the placental site (retained placental tissue, low placental implantation, placental adherence, uterine inversion)
4. coagulation disorders.
The main causes of third-stage bleeding are genital tract trauma and bleeding from placental site.
The main causes of hemorrhage in early puerperal stage are all of the above causes of Postpartum hemorrhage.
Predisposing factors and causes of immediate postpartum hemorrhage:
1. Overdistended uterus – multiple fetuses, Hydramnios, distention with clots.
2. Anesthesia or analgesia – halogenated agents, conducted analgesia with hypertension.
3. Exhausted myometrium – rapid labor, prolonged labor, oxytocin or prostaglandin stimulation.
4. Previous uterine atony.
Genital tract trauma:
1. Complicated vaginal delivery.
2. Cesarean section or hysterectomy, forceps or vacuum.
3. Uterine rupture; risk increased by: previously scarred uterus, high parity, hyperstimulation, obstructed labor, intrauterine manipulation.
4. Large episiotomy, including extensions.
5. Lacerations of the perineum, vagina or cervix.
Bleeding form placental implantation cite:
1. Retained placental tissue – avulsed cotyledon, succentuariate lobe
2.Abnormally adherent – accreta, increta, percreta.
Coagulation defects – intensifies other causes:
1. Placental abruption.
2. Prolonged retention of dead fetus.
3. Amnionic fluid embolism.
4. Saline-induced abortion.
5. Sepsis with endotoxemia.
6. Severe intravescular hemolysis.
7. Massive transfusions.
8. Severe preeclampsia or eclampsia.
9. Congenital coagulopathies.
Clinical findings and diagnosis
The two most common causes of immediate hemorrhage are hypotonic myometrium (uterine atony) and lacerations of the vagina and cervix. Retention of part or all of the placenta, a less common cause, may produce either immediate or delayed hemorrhage (or both).
Uterine atony is called as total absence of uterine contractions into the external irritation. Uterine hypotony is called as presence of inadequate uterine contractions on the external irritation. In the pauses between uterine contractions a uterus is soft. But blood form clots in the case of uterine hypo- or atony. These clots are stored in the uterine cavity that’s why a uterus is enlarged in sizes.
The differentiation between bleeding from uterine atony and from lacerations is tentatively based on the condition of the uterus. If bleeding persists despite a firm, well-contracted uterus, the cause of the hemorrhage most probably lacerations. Bright red blood also suggests lacerations. To ascertain the role of lacerations as a cause of bleeding, careful inspection of the vagina, cervix, and uterus is essential.
Placental accreta is any implantation of the placenta in which there is abnormally firm adherence to the uterine wall. As a consequence of partial or total absence of the decidua basalis and imperfect development of the fibrinoid layer (Nitabush’s membrane):
1. the placental villi are attached into the basal layer - placenta adhaerens;
2. the placental villi are attached to the myometrium - placenta accreta (Fig. 11);
3. extensive growth of placental tissue into the uterine muscle itself – placenta increta;
4. complete invasion through the sickness of the uterine muscle to the serosa or beyond – placenta percreta (Fig. 12, 13 ).
Fig. 11 A fatal case of inverted uterus associated with placenta accreta following delivery at home.
Fig. 12 Placenta percreta in a woman at term with a known placenta previa. The placenta had grown into the entire lower uterine segment. (Photograph courtesy of Dr. Tom Dowd.)
Fig. 13 Placenta percreta. On the left, the placenta is fungating through the fundus above the old classical cesarean section scar. In the opened specimen on the right, the variable penetration of the fundus by the placenta is evident. (From Morison, 1978.)
Complete or total placenta accreta will not cause bleeding because the placenta remains attached, but partial ( the abnormal adherence involves a few to several cotyledons) or focal ( the abnormal adherence involves a single cotyledon) type may cause profuse bleeding, as the normal part of the placenta separates and the myometrium cannot contract sufficiently to occlude the placental site vessels.
The abnormal placental adherence is diagnosed by:
1. Absence of the signs of placental separation during 30 minutes.
Signs of placental separation:
1. the uterus rises in the abdomen;
2. the shape of the uterus changes from discoid to globular
3. the umbilical cord lengthens.
2. External bleeding – in the case of partial adherence, absence of the bleeding – in the case of total placenta accreta.
3. Manual removal of the placenta confirms the diagnosis of different types of abnormal placental adherence. In the case of partial placental adhaerence it stops bleeding, but in the case of placenta accreta, increta and percrata it increases bleeding. Attempts at manual removal are futile. That’s why in these cases manual removal of the placenta should be stopped immediately and hysterectomy should be performed.
Coagulation disorders are recognized thanks to coagulation studies and inspection for clot formation.
MANAGEMENT OF THE PATIENTS IN THE THIRD-STAGE BLEEDING
1. Catheterization of the urinary bladder.
2. Cold on the lower abdomen.
3. Manual massage of the uterine corpus: one hand gently massages the uterus from the abdomen while the other is inserted so that the cervix is cradled in the fingers and thumb to allow maximal compression and massage.
4. Prescription of the uterine contracting drugs: oxytocin – 5 units, methylergonovine (Methergine) – 1mL intramuscularly or in intravenous infusion. If the uterus remains atonic and the placental site bleeding continuos during the oxytocin infusion, a rapid continuos intravenous infusion of dilute oxytocin (20 units in 1L of normal saline) should be given to increase uterine tone. Analogues of prostaglandin F2 alpha (Hemabate) in a dose 5 mg given intramuscularly or intravenously are quite effective in controlling postpartum hemorrhage caused by uterine atony. Large-bore intravenous catheters – 1 or 2 well functioning lines. Mifipristone – 800 mkg per rectum, enzaprost – 5 mg into anterior abdominal wall.
5. Manual exploration of the uterine cavity under the general anesthesia, bimanual uterine compression. (fig. 14)
6. A tampon with ether is inserted into the posterior fornix.
7. Clemmas on the parametrium or into the cervix of the uterus are putted on.
8. Aorta compression to the spinal column.
In a case if blood loss increase 800 mL and bleeding continuos - surgery management should be perform:
1.Uterine artery ligation;
2. Hypogastric artery ligation;
Fig.14 Bimanual compression of the uterus and massage with the abdominal hand usually will effectively control hemorrhage from uterine atony.
GENITAL TRACT TRAUMA – ligation and suturing of all ruptures of the vagina, cervix and perineum. In the case of uterine rupture – hysterectomy should be performed.
BLEEDING FROM PLACENTAL IMPLANTATION CITE
1) placental separation signs are absent – manual separation and removal of the placenta and exploration of the uterine cavity, uterine massage, uterine contracting drugs are prescribed;
2) complete and partial placenta adhaerens - manual separation and removal of the placenta (Fig. 15);
3) placenta accreta, increta and percreta – hysterectomy. With more extensive involvement, however, hemorrhage becomes profuse as manual removal of the placenta is attempted.
Fig. 15 Technique of manual removal of the placenta
Technique of Manual Removal. Adequate analgesia or anesthesia is mandatory. Aseptic surgical technique should be employed. After grasping the fundus through the abdominal wall with one hand, the other hand is introduced into the vagina and passed into the uterus, along the umbilical cord. As soon as the placenta is reached, its margin is located and the ulnar border of the hand insinuated between it and the uterine wall. Then with the back of the hand in contact with the uterus, the placenta is peeled off its uterine attachment by a motion similar to that employed in separating the leaves of a book. After its complete separation, the placenta should be grasped with the entire hand, which is then gradually withdrawn. Membranes are removed at the same time by carefully teasing them from the decidua, using ring forceps to grasp them as necessary. Some prefer to wipe out the uterine cavity with a sponge. If this is done, it is imperative that a sponge not be left in the uterus or vagina.
Placenta Accreta, Increta, and Percreta
In most instances, the placenta separates spontaneously from its implantation site during the first few minutes after delivery of the infant. The precise reason for delay in detachment beyond this time is not obvious always, but quite often it seems to be due to inadequate uterine contraction. Very infrequently, the placenta is unusually adherent to the implantation site, with scanty or absent decidua, so that the physiological line of cleavage through the decidual spongy layer is lacking. As a consequence, one or more cotyledons are firmly bound to the defective decidua basalis or even to the myometrium. When the placenta is densely anchored in this fashion, the condition is called placenta accreta.
The term placenta accreta is used to describe any placental implantation in which there is abnormally firm adherence to the uterine wall. As the consequence of partial or total absence of the decidua basalis and imperfect development of the fibrinoid layer (Nitabuch layer), placental villi are attached to the myometrium in placenta accreta, actually invade the myometrium in placenta increta, or penetrate through the myometrium in placenta percreta. The abnormal adherence may involve all of the cotyledons (total placenta accreta), a few to several cotyledons (partial placenta accreta), or a single cotyledon (focal placenta accreta).
An abnormally adherent placenta, although an uncommon condition, assumes considerable significance clinically because of morbidity and, at times, mortality from severe hemorrhage, uterine perforation, and infection. The true frequencies of placenta accreta, increta, and percreta are unknown. Breen and associates (1977) reviewed reports published since 1891. The incidence varied from 1 in 540 deliveries to 1 in 70,000 deliveries, with an average incidence of about 1 in 7000. Read and co-workers (1980) reported an incidence of about 1 per 2500 deliveries and concluded that today there is a higher reported incidence, lower parity, and greater incidence of associated placenta previa, as well as decreasing maternal and perinatal mortality.
Abnormal placental adherence is found most often in circumstances where decidual formation was likely to have been defective. Associated conditions include implantation in the lower uterine segment, over a previous cesarean section scar or other previous uterine incisions, or after uterine curettage. In his review of 622 reported cases of placenta accreta collected between 1945 and 1969, Fox (1972) noted the following characteristics: (1) placenta previa was identified in a third of affected pregnancies, (2) one fourth of the women had been previously delivered by cesarean section, (3) nearly one fourth had previously undergone curettage, and (4) one fourth were gravida 6 or more. Read and co-workers (1980) reported similar findings for women studied in the 1970s; however, the overall incidence and parity had decreased. In a preliminary investigation, Hardardottir and colleagues (1996) found that almost half of placentas in women with a prior cesarean section had adherent myometrial fibers detected microscopically.
Antepartum hemorrhage is common, but in the great majority of cases, bleeding before delivery is the consequence of coexisting placenta previa. Myometrial invasion by placental villi at the site of a previous cesarean section scar may lead to uterine rupture during labor or even before (Berchuck and Sokol, 1983). Archer and Furlong (1987) described a woman who presented with an acute abdomen from massive hemoperitoneum caused by placenta percreta at 21 weeks’ gestation. In women whose pregnancies go to term, however, labor will most likely be normal in the absence of an associated placenta previa or an involved uterine scar.
The problems associated with delivery of the placenta and subsequent developments vary appreciably, depending upon the site of implantation, depth of myometrial penetration, and number of cotyledons involved. It is very likely that focal placenta accreta with implantation in the upper uterine segment develops much more often than is recognized. The involved cotyledon is either pulled off the myometrium with perhaps somewhat excessive bleeding, or the cotyledon is torn from the placenta and adheres to the implantation site with increased bleeding, immediately or later.
With more extensive involvement, hemorrhage becomes profuse as delivery of the placenta is attempted. Successful treatment depends upon immediate blood replacement therapy, and nearly always prompt hysterectomy.
With total placenta accreta, there may be very little or no bleeding, at least until manual placental removal is attempted. At times, traction on the umbilical cord will invert the uterus, as will be described in the next section. Moreover, usual attempts at manual removal will not succeed, because a cleavage plane between the maternal placental surface and the uterine wall cannot be developed. The safest treatment in this circumstance is prompt hysterectomy.
In the 622 cases reviewed by Fox (1972), the most common form of “conservative” management was manual removal of as much placenta as possible and then packing of the uterus. One fourth of the women died, which was four times as many as when treatment consisted of immediate hysterectomy. So-called “conservative” treatment in at least four instances was followed by an apparently normal pregnancy.
The possibility exists that placenta increta might be diagnosed antepartum. Cox and associates (1988) described a case of placenta previa in which they also were able to identify placenta increta ultrasonically from the lack of the usual subplacental sonolucent space. They hypothesize that the presence of this normal subplacental sonolucent area represents the decidual basalis and the underlying myometrial tissue. The absence of this sonolucent area is consistent with the presence of a placenta increta. Pasto and associates (1983) confirmed that the absence of a subplacental sonolucent or “hypoechoic retroplacental zone” is consistent with placenta increta.
Inversion of the Uterus
Complete uterine inversion after delivery of the infant is almost always the consequence of strong traction on an umbilical cord attached to a placenta implanted in the fundus (Fig. 16).
Most likely site of placental implantation in cases of uterine inversion. With traction on the cord and the placenta still attached, the likelihood of inversion is obvious.
Fig. 16 Contributing to uterine inversion is a tough cord that does not readily break away from the placenta, combined with fundal pressure and a relaxed uterus, including the lower segment and cervix.
Placenta accreta may be implicated although uterine inversion can occur without the placenta being so firmly adherent. At times, the inversion may be incomplete (Fig. 11).
Shah-Hosseini and Evrard (1989) reported an incidence of about 1 in 6400 deliveries at the Women and Infants Hospital of Rhode Island. Of the 11 inversions identified, most were in primiparous women and immediate vaginal replacement of the inverted uterus was successful in nine instances. Platt and Druzin (1981) reported 28 cases in over 60,000 deliveries, for an incidence of about 1 in 2100. These same investigators suggested that parenteral magnesium sulfate, which was administered to women with pregnancy-induced hypertension, might have played a role in the etiology of this complication.
Uterine inversion is most often associated with immediate life-threatening hemorrhage, and without prompt treatment it may be fatal (Fig. 11).
In the past it was stated that shock tends to be disproportionate to blood loss. Careful evaluation of the effects from transfusion of large volumes of blood in such cases does not support this concept, but instead makes it very apparent that blood loss in such circumstances was often massive but greatly underestimated (Watson and associates, 1980).
Delay in treatments increases the mortality rate appreciably. It is imperative that a number of steps be taken immediately and simultaneously:
1. Assistance, including an anesthesiologist, is summoned immediately.
2. The freshly inverted uterus with placenta already separated from it may often be replaced simply by immediately pushing up on the fundus with the palm of the hand and fingers in the direction of the long axis of the vagina.
3. Preferably two intravenous infusion systems are made operational, and lactated Ringer solution and whole blood are given to reverse hypovolemia.
4. If attached, the placenta is not removed until the infusion systems are operational, fluids are being given, and anesthesia, preferably halothane or enflurane, has been administered. Tocolytic drugs have also been used successfully for this purpose. Terbutaline, ritodrine, or magnesium sulfate have been used for uterine relaxation and repositioning (Catanzarite and associates, 1986; Kovacs and DeVore, 1984; Thiery and Delbeke, 1985). To remove the placenta before this time increases hemorrhage. In the meantime, the inverted uterus, if prolapsed beyond the vagina, is replaced within the vagina.
5. After removing the placenta, the palm of the hand is placed on the center of the fundus with the fingers extended to identify the margins of the cervix. Pressure is then applied with the hand so as to push the fundus upward through the cervix.
6. Oxytocin is not given until after the uterus is restored to its normal configuration.
As soon as the uterus is restored to its normal configuration, the agent used to provide relaxation is stopped and simultaneously oxytocin is started to contract the uterus while the operator maintains the fundus in normal relationship. Initially, bimanual compression will aid in the control of further hemorrhage until uterine tone is recovered.
Fig.17 Uterine replacement
After the uterus is well contracted, the operator continues to monitor the uterus transvaginally for any evidence of subsequent inversion.
Surgical Intervention. Most often, the inverted uterus can be restored to its normal position by the techniques described. If the uterus cannot be reinverted by vaginal manipulation because of a dense constriction ring (Fig. 18), laparotomy is imperative.
Fig. 18 Completely inverted uterus viewed from above.
The fundus then may be simultaneously pushed upward from below and pulled from above. A traction suture well placed in the inverted fundus may be of aid. If the constriction ring still prohibits reposition, it is carefully incised posteriorly to expose the fundus. A graphic outline of this surgical technique was described by Van Vugt and associates (1981). After replacement of the fundus, the anesthetic agent used to relax the myometrium is stopped, oxytocin infusion is begun, and the uterine incision repaired. Following restoration of the uterus, the adjacent viscera are carefully examined for trauma.
Attention ! Irrespective of the apparent cause, whenever there is any suggestion at the delivery or postpartum of excessive blood loss from the genital tract, immediate steps must be taken to identify the presence of uterine atony, retained placental fragments, and trauma.
1. At least one or, in the presence of frank hemorrhage, two intravenous infusion systems of large caliber must be established right away to permit rapid administration of aqueous electrolyte solutions and blood as nedded
2. An operating room and a surgical team, including an anesthesiologist, must be immediate available.
The treatment of coagulation defects is aimed at correcting the coagulation defects and include infusion of:
1. platelet concentrate – increases platelet count by about 20 000 to 25 000;
1. cryoprecipitate – supplies fibrinogen, factor VIII, and factor XIII (3 to 10 times more concentrated than the equivalent volume of fresh plasma);
2. fresh-frozen plasma – supplies all factors except platelets (1 g of fibrinogen);
3. packed red blood cells – raises hematocrit 3 % to 4 %.
Intensive therapy and reanimation at obstetric hemorrhages.
(OBSTETRIC SHOCK. TERMINAL STATES IN OBSTETRICS)
Shock encompasses various pathophysiological aberrations that lead to inadequate tissue perfusion and impaired cellular metabolism. Although hypotension often is the most obvious clinical sign in shock of any cause, such blood pressure changes are the final common manifestation of a number of distinct pathologic processes. The successful clinical management of patients in shock depends on the proper definition of the underlying pathophysiology as well as an under of the unique effects of pregnancy on such conditions.
Uterine bleeding (hemorrhage) during labor and early puerperal stage play an important role among different kinds of severe obstetrics pathology, such as hemorrhagic shock, disseminated intravascular coagulopathy, sepsis and other. Uterine bleeding is the leading cause of maternal death.
Uterine bleeding frequency is 8,0 – 11, 0 %.
The main causes of uterine bleeding are:
During pregnancy: placenta praevia, placenta abruptio.
During labor: placenta praevia, placenta abruptio, uterine rupture, traumatization of the soft birth canal tissues.
In the third period of labor and early puerperal stage: uterine hypo- and atony; uterine rupture and traumatization of the soft birth canal tissues; placenta accreta, increta, and percreta; retention of some parts of afterbirth in the uterine cavity; thrombohemorrhagic bleeding.
Methods of blood loss determination
1. Libov’s method.
After surgical intervention the napkins, which are filling by blood, should be weighted.
Blood loss volume = Weight x 15 % ( if blood loss is < 1000 ml);
Blood loss volume = Weight x 30 % ( if blood loss is > 1000 ml).
2. By hematocrit
Blood loss volume, ml
44 – 40
38 – 32
30 – 22
1. Algover’s index
Shock’ index = Heart rate
Systolic arterial blood pressure
In normal Algover’s index is < 1.
Blood loss volume, % out of circulating blood volume
0,8 and <
0,9 – 1,2
1,3 – 1,4
1,5 and >
HEMORRHAGIC (HYPOVOLEMIC) SHOCK
Hemorrhagic shock is a very serious complication in the case of pathological hemorrhage.
Physiological blood loss during labor is 0, 5 % out of puerperant’ weight. Physiological blood loss is 350, 0 – 400, 0 ml.in the puerperant with 70-75 kg of weight. If blood loss predominate physiological one, hemorrhagic shock have been occurred.
There are 4 stages of hemorrhagic shock according to Baker classification. Evaluation of hemorrhagic shock stage severity is presented in the table.
Evaluation of hemorrhagic shock stage severity
Circulating blood volume deficiency
% from body weight
1,0 – 1,5 %
Ps – 90-100 beats per min;
Arterial blood pressure (BP) - >100 mm Hg;
Central Venous pressure (CVP) – 80-100 mm Hg;
Diuresis – N.
Ps – 120 beats per min;
BP - <100 mm Hg;
CVP – < 60 mm Hg;
Diuresis – < 50 ml per hour (oligouria)
Ps – 140 beats per min;
BP - < 70 mm Hg;
CVP – < 40 mm Hg;
Diuresis – < 30 ml per hour (anuria)
40% and >
2000,0 and >
Ps – 140 beats per min;
BP – < 50 mm Hg;
CVP – 0;
The main principles of obstetrics hemorrhage and hemorrhagic shock treatment:
1. Hemorrhage stopping.
2. Determination of blood loss stage.
3. Restoration of the circulating blood volume.
4. Normalization of vascular tone.
5. Blood reology, its structural, biochemical, and electrolytes compounds correction.
6. Detoxication therapy.
7. Desensibilizing therapy.
8. Correction of clotting, antyclotting, fibrinolitic systems functions.
9. Regulation of the main human organs functions.
10. Prevention of infectious complications.
INTERM restoration of the circulating blood volume – is the main step in the treatment of acute blood loss. Human organism should be survived in the case of 2/3-erythrocytes volume loss, but it doesn’t survive in the case of 1/3 plasma volume loss. That’s why it should be remembered that in considerable blood loss the first step is the transfusion not only blood, but also кровозамінники, which eliminate hypovolemia very quickly.
Transfusion therapy in obstetrics hemorrhages
Volume of infusion
10 ml /kg
10 ml /kg
10 ml /kg
5 - 10 ml /kg
5 ml /kg
10 - 15 ml /kg
10 - 20 ml /kg
> 2000 ml
> 6000 ml
10 ml /kg
15 - 20 ml /kg
30 ml /kg
The volume of infusion therapy in hemorrhagic shock should be predominated in 1,5-2,5 times its real blood loss.
Glucose transfusion doesn’t administrated in blood loss, because it very quickly enter intracellular space and doesn’t increase circulating blood volume, it caused metabolic acidosis.
Attention! Erythrocyte transfusion has value only after hemodynamics and peripheral blood circulation normalization. Only in these conditions erythrocytes should be taken oxygen.
Attention ! In all stages of hemorrhagic shock 2-4 veins should be catheterized in one moment (one or two of them are central, such as v. subclavia).
Infusion speed depends on blood loss volume and patient state. In the case of hemorrhagic shock and low arterial blood pressure it should be reach 200 ml per minute. The infusion speed gradually decreased to 150-100-50 ml-per minute in the case of increasing arterial blood pressure to 80-90 mm Hg.
The main prescription of infusion therapy in the case of acute blood lose is the stabilization of central hemodynamics which lead to cerebral and coronary blood circulation stabilization.
Vascular tone normalization.
In the first stage of hemorrhagic shock because of vascular spasm presence spasmolitics drugs are used, such as Nospani, Papaverini hydrochloridi. On the II-III-IV stages because of vascular dilation glucocorticoids are prescribed. They are: Prednisoloni, Hydrocortisone – in the dose 1,5-2 g/ daily, Dexametazoni.
If intravenous insertion 800-1000 ml any solution with the speed of 50-100 ml/per minute doesn’t change (increase) arterial blood pressure – vasopressors agents should be prescribed, such as Remestip – in the dose 0,2-1,0 mg; Dopamine – 5mkg/kg/minute or glucocrticoids.
In considerable infusion therapy after circulating blood volume normalization diuresis stimulation is recommended. For this purpose Euphillini in the dose 3 mh per kg, lazix – 2-4 mg/kg or furosemidi in the dose 6-8 mg/kg have been used.
Structural, biochemical, electrolytes compounds correction of blood, detoxycation, desensibilizing therapy and normalization of clotting, antyclotting, fibrinolytic systems functions and functions of the main human organs is obligatory in the treatment of hemorrhagic shock.
Introduction of cardiologic drugs is possible only after blood loss restoration. For this purpose such agents have been used as Corgliconi –0, 6 % - 0,5 –1 ml; Cocarboxylase – 50 mg twice a day.
Prevention of infectious complications by prescription of wide spectrum antibiotics (cefalosporines, aminoglycozides) in the daily dose is recommended also.
Main steps of urgent medical care in the obstetrics bleeding during pregnancy, labor, and puerperal stage
1. Blood loss is 0, 8 – 1, 0 % of body weight
1. To determine the cause of hemorrhage
Placenta praevia, placenta abruptio, uterine rupture
Uterine cervix rupture, deep vagival ruptures, traumatization of the soft birth canal tissues.
Uterine hypo- and atony; uterine rupture and traumatization of the soft birth canal tissues; placenta accreta, increta, and percreta; retention of some parts of afterbirth in the uterine cavity
Urgent cesarean section
Manual uterine revision
2. To start intravenous infusion: crystalloids (0,9 % NaCl + 10 Units of oxytocin), colloids – Refortan, Stabisol, Poliglucin.
2. Blood loss is 1, 0 %– 1, 5 % of body weight.
1. Injection of 250 – 1000 mkg Prostin F2a intramuscularly or 0,4 mg Remestip + 10 ml 0,9 % NaCl into uterine cervix.
2. Catheterization of two veins (one of them is v. subclavia), intravenous transfusion of autoblood, plasma, erythrocyte massa, Refortan, Stabisol.
Attention! Surgical intervention should be performed in continuing bleeding! (if blood loss is more than 1, 0 % - 800 ml of body weight ).
3. Blood loss is > 1, 5 % of body weight.
1. Laparotomy. Total hysterectomy without adnexa (adnexa are removed if inflammatory, degenerative changes are presented).
2. Restoration of the blood circulating volume: autoblood, donor’s blood – 100 % from blood loss, cryoprecipitate, albumin.
DISSEMINATED INTRAVASCULAR COAGULOPATHY (DIC)
DIC is not a distinct clinical entity; rather, it represents a manifestation of various disease processes that have in common activation of intravascular clotting and fibrinolysis, resulting in excess consumption of solutable coagulation components. In obstetrics, secondary fibrinogenolysis commonly dominates the clotting aberration and results in the circulation of fibrin and fibrinolytic split products, which further accentuates the clinical presentation of henorrhage. In addition, sometimes a dilutional coagulopathy is encountered in pregnancy. This condition obtains when massive hemorrhage is teplaced only by red blood cells and crystalloids solution, resulting in a dilutional depletion of platelets and soluble clotting factors.. In practice, the hemorrhage associated with dilutional coagulopathy often results in hypotension and shock. The tissue hypoxia that accompanies shock of any cause is well known to potentially activate the coagulation-fibrinolysis cycle associated with DIC.
DIC is the pathological complex, which is characterized by blood clotting that has been leading to microcirculation blockade by fibrin in the main human organs (lungs, kidneys, liver). Dysfunction of these organs is the result of their damage. In the end of this process thrombohemorrhagic disorders have been developed.
The main causes of DIC in the obstetrics are:
1. All kinds of shock (hemorrhagic, septic, anaphylactic);
2. Placenta abruption;
3. Embolic fluid embolism;
4. OPH – hestosis;
5. Hypotonic bleeding;
6. Uterine ruptures;
7. Excessive labor induction;
8. Cesarean section;
9. Extragenital pathology;
10. Septic abortion;
11. Puerperal endometritis;
12. Intensive uterine massage;
13. dead fetus syndrome
Classification of thrombohemorrhagic syndrome
1. By clinical duration:
2. By stages:
I stage – hypercoagulation;
II stage – hypocoagulation without generalizing fibrinolysis activation;
III stage – hypocoagulation with generalizing fibrinolysis activation;
IV stage – total fibronolysis.
Clinical manifestation of DIC is connected with ischemic and hemorrhagic changes in human organs and tissues. They are:
1. Hemorrhages into skin and mucous membranes;
2. Hemorrhages from the places of injections, incisions, uterus.
3. Necrosis of some areas of skin and mucous membranes;
4. Central nervous system impairment;
5. Acute renal, liver, lung insufficiency.
Laboratory diagnosis of DIC
The main laboratory data
Blood clotting time, minutes
Spontaneous thrombus lisis
Throm-bocytes number, ×109/l
< 5 (N)
II.Hypocoagulation without generalizing fibrinolysis
III Hypocoagu-lation with generalizing fibrinolysis
IV. Total fibrinolysis
Thrombus doesn’t formed
General principles of DIC treatment are:
1. Heparin, fibrinogen are contraindicated in all stages of thrombohemorrhagic syndrome.
2. Proteolytic enzymes inhibitors in the dose of 10 mg/kg/hour have been used for inhibit excessive fibrinolysis and prevention of intracellular clotting.
3. Early and quick introduction of fresh frozen donor’s plasma. The main aim of its usage is the restoration of haemostatic potential of blood (it contains all soluble clotting factors, similar to whole blood). It has been used in all stages of thrombohemorrhagic syndrome. Initially the dose of intravenous introduction is 6-12 ml/kg. After it dose is 300-400 ml each 6-8 hours.
4. Stimulation of vascular-thrombocytes link of hemostasis (dicinone, etamsilat).
5. Transamacha acid usage – in the dose 500-750 mg on 0,9 % NaCl. This medicine inhibits plasmine activity, stabilizes coagulate factors and fibrin, decreases vascular permeability and gives permanent hemostatic action, which have been prevented fibrinogen degradation.
Treatment of thrombhemorrhagic syndrome in obstetric hemorrhagic shock in different stages
For normalization blood reology: Trental – 100mg on 100 ml 0,9 % NaCl, Curantill – 0,5 – 2, %
II.Hypocoagulation without generalizing fibrinolysis
Procoagulants: fresh frozen plasma 500,0, blood of 3-5 days of conservation. Transamacha – antyplasmin drug – 500-750 mg on 0, 9 % NaCl.
Fibrinolysis inhibitors: Contrical in the dose 10-20.000 units/ daily dose 100-200.000 units; Trasilol – 40.000 units or Gordox – 100-200.000 units. Cortycosteroids – Prednisolone – 10mg/kg/hour or Hydrocortisone – 100 mg/kg.
III Hypocoagulation with generalizing fibrinolysis
Proteolytic enzymes inhibitors: Contrycal 40.000 units (daily dose 500.000 units)
Procoagulants – fresh frozen plasma, blood, albumin. Cortycosteroids. Cryoprecipitate – 200-400,0, Transamcha – 500-700 mg.
IV. Total fibrinolysis
The treatment should be started from the large doses of proteolytic enzymes inhibitors – Contrical 100.000 units to 500.000 units. Blood, albumin, plasma, cryoprecipitate, cortycosteroids.
AMNIOTIC FLUID EMBOLISM (AFE)
Amniotic fluid embolism is a rare, sudden, and often fatal obstetric complication caused by entry of amniotic fluid into the maternal venous circulation.
The initial physiological disturbances involve profound alterations in hemodynamics and oxygenation, often followed by the development of a consumptive coagulopathy.
The main pathogenetical factors that have been predisposing to amniotic fluid embolism are predomination of amniotic pressure over venous and traumatization of venous uterine vessels.
Predomination of amniotic pressure over venous is presented in excessive labor contractions, breach presentation, postdate pregnancy, multiple pregnancy, uterine cervix dystocia, hypovolemia of different etiology.
Traumatization of venous uterine vessels is presented in placenta abruption, cesarean section, manual removal of placenta, puerperal hypotonic hemorrhage.
The condition results in severe cardiorespiratory collapse and usually a coagulopathy.
Cardiorespiratory collapse is the result of entry large amount of amniotic fluid into the maternal circulation and characterized by severe pain in the chest, cough, feeling of the death. The most common presentation is that of sudden dyspnea and hypotension commonly followed within minutes by cardiorespiratory arrest. Heart fibrillation and sudden death are the results of this disorder. In 10 % to 20 % of cases, these initial events accompanied by seizure activity. In 70 % of cases, a chest radiography reveals some degree of pulmonary edema. One half of the patients with AFE die within 1 hour after the onset of symptoms; in survivors, neurologic damage or brain death secondary to the initial severe hypoxia is not uncommon..
In the case of entering of small number of amniotic fluid into the maternal circulation disseminated intravascular coagulopathy is common.
The definitive diagnosis of AFE has classically been made at autopsy with the demonstration of fetal squamosus cells, mucin, hair, or vernix in the pulmonary artery vasculature.
Treatment is directed toward total support of the cardiovascular and coagulation systems and include:
I. 1. Assisted pulmonary ventilation, oxygen therapy, closed chest massage. Intravenous 10 % 10,0 ml Calcii chloridi and intracardiac 0.1 % - 0,5 ml adrenalin hydrochloridi are indicated.
2. Sedative drugs: Droperidol – 4-5 ml intravenous, 20 % - 20, 0 ml Natrii oxybuturate, 2, 0 ml Diazepame.
3. Spasmolytic agents are prescribed: Euphyllini – 2,4 % 10, 0 ml intravenous, Nospani – 2 % - 4 ml, Papaverini hydrochloridi – 2 % - 4 ml.
4. Cardiovascular drugs: Corglyconi 0, 06 % - 0,5 ml or Strophantini – 0,05 % - 0, 5 ml intravenous on 20 ml 10 % glucose.
5. Drugs that have been increasing arterial pressure and vascular tone: hydrocortizone 250 mg, dopamine infusion.
6. Elimination of acute hypovolemia and metabolic acidosis, initial optimization of cardiac preload: polyglucin 400 ml, Natrii hydrocarbonatis 200 ml intravenous.
7. Disseminated intravascular coagulopathy treatment.
II. Immediate delivery: by cesarean section or by forceps.
Septic shock is the result of entering of infective agents into the maternal circulation in different obstetrics and gynecologic conditions. It is a serious complication that requires aggressive management. Pregnancy is classically thought to be a factor that predisposes a patient to septic shock. In obstetrics, septic abortion, chorionamnionitis, pyelonephritis, and endometritis are the most common conditions associated with septic shock.
Pathogenesis. Septic shock in obstetrics most commonly is associated with infection caused by endotoxin-releasing gram-negative aerobic coliform organisms. Endotoxin, a complex cell wall-associated lipopolysaccharide, is released into the circulation at the time of bacterial death, resulting in multiple hemodynamic effects.
Early septic shock is a classic example of distributive shock, related to a systemic maldistribution of relatively normal or even increased output. Clinical findings include hypotension, fever, and chills. Initial hemodynamic findings include decreased systemic vascular resistance and high normal or elevated cardiac output The continued maldistribution of cardiac output leads to local tissue hypoxia and the development of lactic acidosis and end-organ dysfunction. This decrease in systemic vascular resistance is caused by the release of vasoactive substances as well as by vascular endothelial cell injury, which promotes capillary plugging secondary to complement induced leukocyte aggregation. These factors lead to increased arteriovenous shunting.
These patients are acutely ill, with fevers of up to 39,5 0 C, general weakness, tachycardia, severe pelvic and abdominal pain, and nausea and vomiting.
On physical examination patients may exhibit muscular guarding, and or rebound tenderness. A purulent cervical discharge is often seen and uterus or adnexa are usually moderately to exquisitely tender.
Such phases of septic shock have been distinguished as:
1. hyperdynamic or “warm” phase (systolic arterial blood pressure is decreased to 80-90 mm. Hg durinh 1-2 hours);
2. hypodynamic or “cold” phase (continuous decreasing of arterial blood pressure; shock’ index is more than 1,5; chest, abdominal, back pain; oliguria, consciousness impairment, dyspnea; mulberry rash; skin necrosis);
3. irreversible shock (anuria, respiratory and heart insufficiency, coma).
The treatment of septic shock in this early phase involves optimizing preload by restoring relative intravascular volume with crystalloid infusion as well as aggressive treating the underlying infection. If the offending organism is known, single-agent antibiotic therapy may be used. More commonly in obstetrics, the infection is polymicrobial, and broad-spectrum coverage for gram-negative and gram-positive aerobic and anaerobic organisms is most appropriate.. If an abscess is involved, prompt surgical drainage after initial resuscitation is mandatory.
If the process should continue, the patient may enter a second hemodynamic phase of septic shock. Of primary importance in this late phase is the development and progression of myocardial dysfunction leading to ventricular failure.
Patients who recover from the initial hemodynamic instability of septic shock may suffer prolonged morbidity secondary to endotoxin-mediated pulmonary capillary injury and noncardiogenic pulmonary capillary edema. Such lung failure is a major cause of death in patients with septic shock. Similarly, pregnant patients whose hypotension was prolonged may experience acute tubular necrosis. Endotoxin-mediated endothelial cell injury and associated tyhromboplastin-like activity as well as prolonged shock from any cause may also lead to activation of the coagulation cascade and a clinical picture of disseminated intravascular coagulation. Although the use of high-dose corticosteroids has been advocated in the acute management of septic shock, reports have failed to demonstrate a benefit from such therapy.
Aggressive therapy for patients with septic shock should be tailored the site of infection and the individual patient. Hospitalized patients require high dose intravenous antibiotic therapy with an antimicrobial spectrum that covers aerobic and anaerobic organisms (Tienam – 1000 mg 4 times a day intravenous each 6 hours. Its daily dose is 4 gram. Cyprinol – intravenous administration 400 mg twice a day). Surgical intervention - hysterectomy should be performed immediately. Pulmonary ventilation, disseminated intravascular coagulopathy elimination, normalization of vascular tone, immunocorrection, detoxycation therapy have been prescribed.
Anaphylactic shock is a allergic reaction of human organism as result of bounding of different origin antigens with antibodies which are fixed on the cell membranes. It is leading to cell’ membranes destruction and excessive entering into the blood such substances as histamine, serotonin, acetylcholine, and some substances of anaphylaxia. The last ones effect into the vessels and provoke arterial blood pressure decreasing and , as result, development of hypovolemia and tissual hypoxia. Human reaction should be general and local. Local reaction is characterized by edema in the site of drug’ injection, its chills, and hyperemia (allergic manifestation after drug’s administration). General reaction is manifested by respiratory, cardiovascular disorders.
Such forms of anaphylactic shock have been distinguished as typical, hemodynamics, asphyxial, cerebral, and abdominal.
The management of the patients with anaphylactic shock consists of medicines that have been eliminated cardiovascular, respiratory, epileptic disorders, antyallergic drugs.
The urgent care in the case of anaphylactic shock include:
1. Intravenous administration of adrenalini hydrochloridu 0.1 % - 1, 0. In cardiac arrest – this drug is injected intracardiac.
2. Injection in the place of allergen’ entering adrenalini hydrtochloridi also.
3. The place above the allergic drug injection should be pressed obligatory.
3. For elimination respiratory disorders (asphyxia) intravenous (or intramuscular) administration of Cordiamine 4 ml, Coffeini benzoate Natrii – 10 % - 10. 0 ml, Euphylline – 2,4 % - 10, 0 ml have been prescribed.
4. Cortycosteroids are very effective for allergic manifestations elimination. Prednizolone in the dose 0,005 g/kg intravenous, Dexamatazone – 0,02 g intravenous, Hydrocortizone – 0,5 g into 0,9 % Nacl have been prescribed.
4. Antyhistaminic drugs are indicated also – Diphynylhydramine hydrochloride – 1, 0 % - 5 ml, Suprastin – 2-6 ml 2 % intravenous or intramuscular.
5. Epileptic state is eliminated by intravenous administration of Aminazine – 2,5 % - 2 ml or Sibazone – 0,5 % - 2-4 ml.
Introduction of detoxycative, hypoallergenic, dehydrative drugs and glucocorticoids is prescribed during 8-10 days after anaphylactic reaction.
Pregnancy and labor at extragenital diseases. Emergency in obstetrics.
Heart Disease in Pregnancy
Heart disease complicates about 1 percent of pregnancies. Rheumatic heart disease formerly accounted for the majority of cases, and more than 90 percent of women with heart disease cared for at the Boston Lying-in Hospital from 1921 to 1938 had rheumatic lesions (Hamilton and Thomson, 1941). This incidence has changed remarkably as rheumatic fever has almost disappeared in this country. Meyer and colleagues (1994) described 74 pregnancies complicated by cardiac disease over 10 years and only a few were caused by rheumatic fever. Better medical management, together with a number of newer surgical techniques, has enabled more girls with congenital heart disease to reach childbearing age. Congenital heart lesions now constitute at least half of all cases of heart disease encountered during pregnancy (Bitsch and colleagues, 1989; McFaul and associates, 1988). Hypertensive heart disease contributes a few cases of organic heart disease in pregnancy, whereas other varieties are even less common. These include coronary, thyroid, syphilitic, and kyphoscoliotic cardiac disease, as well as idiopathic cardiomyopathy, cor pulmonale, constrictive pericarditis, various forms of heart block, and isolated myocarditis.
Sachs and associates (1988) reported that maternal mortality from cardiac disease fell from 5.6 to 0.3 per 100,000 live births in Massachusetts from 1954 through 1985. Unfortunately, heart disease still significantly contributes to maternal mortality, both in the United States and throughout the world. Berg and colleagues (1996) found that cardiomyopathy was responsible for 5.6 percent of 1453 pregnancy-related deaths in the United States from 1987 to 1990. Dorfman (1990) reported that 8 percent of maternal deaths in New York City from 1981 through 1983 were caused by cardiac disease. Similar statistics were reported from Turkey by Ayhan and co-workers (1994), who reported cardiac disease as causative in 8.5 percent of maternal deaths between 1968 and 1992.
The marked hemodynamic changes stimulated by pregnancy have a profound effect on underlying heart disease in the pregnant woman. These physiological changes are detailed in Chapter 8. The most important consideration is that during pregnancy cardiac output is increased by as much as 30 to 50 percent. Capeless and Clapp (1989) have shown that almost half of the total increase has occurred by 8 weeks, and it is maximized by midpregnancy. The early increase can be attributed to augmented stroke volume that apparently results from decreased vascular resistance and is accompanied by diminished blood pressure. Later in pregnancy, there is also an increased resting pulse, and stroke volume is even more increased, presumably related to increased diastolic filling from the augmented blood volume. These changes and their study designs were recently reviewed by van Oppen and colleagues (1996).
Because significant hemodynamic alterations are apparent early in pregnancy, the woman with clinically significant cardiac dysfunction may experience worsening of heart failure before midpregnancy. Additional hemodynamic burdens are placed upon the heart in the immediate peripartum period when the physiological capability for rapid changes in cardiac output may be overwhelmed in the presence of structural cardiac disease. Of 542 women whose pregnancies were complicated by heart disease, 8 of 10 maternal deaths were during the puerperium (Etheridge and Pepperell, 1977).
The likelihood of a favorable outcome for the mother with heart disease depends upon the (1) functional cardiac capacity, (2) other complications that further increase cardiac load, and (3) quality of medical care provided. Psychological and socioeconomical factors may also assume great importance, because for some women, bed rest may be required throughout pregnancy.
Diagnosis of Heart Disease
Many of the physiological changes of normal pregnancy tend to make the diagnosis of heart disease more difficult. For example, in normal pregnancy, functional systolic heart murmurs are quite common. Respiratory effort in normal pregnancy is accentuated, at times suggesting dyspnea. Edema is generally present in the lower extremities during the latter half of pregnancy. Importantly, the physician must be careful not to diagnose heart disease during pregnancy when none exists, and at the same time not fail to detect and appropriately treat heart disease when it does exist. Pregnant women who have none of these findings rarely have serious heart disease.
As the diaphragm is elevated in advancing pregnancy, there is an average 15-degree left-axis deviation in the electrocardiogram, and mild ST changes may be seen in the inferior leads. Atrial and ventricular premature contractions are relatively frequent (Carruth and colleagues, 1981). Pregnancy does not alter voltage findings.
Echocardiography. The widespread use of echocardiography has allowed accurate diagnosis of most heart diseases during pregnancy. It has also provided data on normal pregnancy-induced hemodynamic and cardiovascular changes. These tests are expensive, they may be anxiety-provoking, and their results may be misinterpreted in light of pregnancy-induced changes. For example, during normal pregnancy, there is a high prevalence of tricuspid regurgitation (Limacher and co-workers, 1985), and left-atrial size and left-ventricular outflow cross-sectional area are increased significantly.
There is no clinically applicable test for accurately measuring functional cardiac capacity. A helpful clinical classification was first published in 1928 by the New York Heart Association, and was revised for the eighth time in 1979. One important change was the addition of an assessment of cardiac status after all data have been reviewed. Thus, the classification is no longer based only on clinical symptoms. The following is based on past and present disability and is uninfluenced by physical signs.
· Class I. Uncompromised: Patients with cardiac disease and no limitation of physical activity. They do not have symptoms of cardiac insufficiency, nor do they experience anginal pain.
· Class II. Slightly compromised: Patients with cardiac disease and slight limitation of physical activity. These women are comfortable at rest, but if ordinary physical activity is undertaken, discomfort results in the form of excessive fatigue, palpitation, dyspnea, or anginal pain.
· Class III. Markedly compromised: Patients with cardiac disease and marked limitation of physical activity. They are comfortable at rest, but less than ordinary activity causes discomfort by excessive fatigue, palpitation, dyspnea, or anginal pain.
· Class IV. Severely compromised: Patients with cardiac disease and inability to perform any physical activity without discomfort. Symptoms of cardiac insufficiency or angina may develop even at rest, and if any physical activity is undertaken, discomfort is increased.
Although a number of generalizations regarding management may be drawn, in clinical practice few women actually fit any “classic” pattern of structural cardiac disease. For this reason, individualization is essential in assuring optimal outcome. In most instances, management is with a team approach, involving the cardiologist, the obstetrician, and other specialties such as anesthesiology. Cardiovascular changes likely to be poorly tolerated by an individual woman are identified, and a plan is formulated to minimize such changes.
Four concepts that affect management are emphasized by the American College of Obstetricians and Gynecologists (1992a): (1) the 50 percent increase in blood volume and cardiac output by the early third trimester; (2) further fluctuations in volume and cardiac output in the peripartum period; (3) a decline in systemic vascular resistance, reaching a nadir in the second trimester, and then rising to peak at 20 percent below normal by late pregnancy; and (4) hypercoagulability, of special importance in women requiring anticoagulation in the nonpregnant state with coumarin derivatives. Within this framework, both prognosis and management are influenced by the nature and severity of the specific lesion, in addition to the functional classification.
Management of Classes I and II
With rare exceptions, women in class I and most in class II go through pregnancy without morbidity. Throughout pregnancy and the puerperium, however, special attention should be directed toward both prevention and early recognition of heart failure. As emphasized by Sugrue and associates (1981), a more favorable functional classification at the outset should not engender any relaxation in vigilance. Almost 40 percent of their class I patients developed overt cardiac failure. According to Sullivan and Ramanathan (1985), maternal mortality is 0.4 percent in classes I and II, but McFaul and co-workers (1988) encountered no maternal deaths in 445 such women.
Infection has proved to be an important factor in precipitating cardiac failure. Each woman should receive instructions to avoid contact with persons who have respiratory infections, including the common cold, and to report at once any evidence for infection. Pneumococcal and influenza vaccines are recommended.
Cigarette smoking is prohibited, both because of its cardiac effects as well as the propensity to cause upper respiratory infections. Illicit drug use may be particularly harmful, as with the cardiovascular effects of cocaine or amphetamines, as well as the propensity for intravenous use of any illegal substance to cause infective endocarditis.
The onset of congestive heart failure is generally gradual. The first warning sign is likely to be persistent basilar rales, frequently accompanied by a cough. A sudden diminution in ability to carry out usual duties, increasing dyspnea on exertion, or attacks of smothering with cough are symptoms of serious heart failure. Clinical findings may include hemoptysis, progressive edema, and tachycardia.
Labor and Delivery
In general, delivery should be accomplished vaginally unless there are obstetrical indications for cesarean delivery. In spite of the physical effort inherent in labor and vaginal delivery, less morbidity and mortality are associated with this route. In some women with severe heart disease, pulmonary artery catheterization may be indicated for continuous hemodynamic monitoring (American College of Obstetricians and Gynecologists, 1992b). This may be performed electively when labor begins or planned cesarean delivery is performed. Such monitoring is rarely indicated in patients who have remained in functional class I or II throughout pregnancy.
Relief from pain and apprehension without undue depression is especially important. For many multiparous women, intravenous analgesics provide satisfactory pain relief. For others, especially nulliparas, continuous epidural analgesia often proves valuable. The major danger of conduction analgesia is maternal hypotension. This is especially dangerous in women with intracardiac shunts, in whom flow may be reversed with blood passing from the right-to-left within the heart or aorta, thereby bypassing the lungs. Hypotension is also hazardous with pulmonary hypertension or aortic stenosis because ventricular output is dependent upon adequate preload. In women with these conditions, narcotic conduction analgesia or general anesthesia is usually given if needed.
During labor, the mother should be kept in a semirecumbent position with lateral tilt. Vital signs should be taken frequently between contractions. Increases in pulse rate much above 100 per minute or in the respiratory rate above 24, particularly when associated with dyspnea, may suggest impending ventricular failure. With any evidence of cardiac decompensation, intensive medical management must be instituted immediately. It is essential to remember that delivery itself will not necessarily improve the maternal condition; operative delivery may be particularly hazardous. Clearly, both maternal and fetal conditions must be considered in the decision to hasten delivery under these circumstances.
For vaginal delivery in women with only mild cardiovascular compromise, pudendal analgesia given along with intravenous sedation often suffices. However, when low- or mid-forceps use is contemplated, or in women with cardiac conditions who are unable to accommodate the marked changes in cardiac output often seen during labor and delivery, epidural analgesia is preferable. This has been shown to minimize intrapartum cardiac output fluctuations. Subarachnoid blockade—spinal analgesia or saddle block—is not generally recommended in women with significant heart disease. For cesarean delivery, epidural blockade provides excellent surgical anesthesia; however, if unavailable or inadvisable, endotracheal anesthesia with thiopental, succinylcholine, nitrous oxide, and at least 30 percent oxygen has also proved satisfactory .
Intrapartum Heart Failure
Cardiovascular decompensation during labor may manifest as pulmonary edema and hypoxia, hypotension, or both. The proper therapeutic approach will depend upon the specific hemodynamic status and the underlying cardiac lesion. For example, decompensated mitral stenosis with pulmonary edema due to absolute or relative fluid overload is often best approached with aggressive diuresis, or if precipitated by tachycardia, by heart rate control with beta-blocking agents. On the other hand, the same treatment in a woman suffering decompensation and hypotension due to aortic stenosis could prove fatal. Unless the underlying pathophysiology is understood and the cause of the decompensation clear, empirical therapy is hazardous. Pulmonary artery catheterization may assist the clinician in a therapeutic approach appropriate to the individual condition.
Women who have shown little or no evidence of cardiac distress during pregnancy, labor, or delivery may still decompensate after delivery. Therefore, it is important that meticulous care be continued into the puerperium. Postpartum hemorrhage, anemia, infection, and thromboembolism are much more serious complications with heart disease. Indeed, these factors frequently act in concert to precipitate postpartum heart failure in women with underlying disease (Cunningham and associates, 1986).
If tubal sterilization is to be performed and epidural anesthesia is not in place, or if the women is not hemodynamically stable, it may be best to delay the procedure for several days until it is obvious that the mother is afebrile, not anemic, and has demonstrated that she can ambulate without evidence of distress. Women who do not undergo tubal sterilization should be given detailed contraceptive advice.
Management of Classes III and IV
Maternal mortality for classes III and IV has been reported to be 4 to 7 percent (McFaul and colleagues, 1988; Sullivan and Ramanathan, 1985). The important question is whether pregnancy should be undertaken or continued. If women choose to become pregnant, they must understand the risks and cooperate fully with planned care. If seen early enough, women with some types of severe cardiac disease should consider pregnancy interruption. If the pregnancy is continued, prolonged hospitalization or bed rest will often be necessary.
As with women in classes I and II, the preferred method of delivery in most cases is vaginal, and cesarean section is limited to obstetrical indications. The decision for cesarean section must take into account the specific cardiac lesion, overall maternal condition, availability and experience of anesthetic support, as well as physical facilities. Such very sick women often tolerate major surgical procedures poorly, and should if possible be delivered in a facility with extensive experience with complicated cardiac disease.
Surgically Corrected Heart Disease
To improve cardiac function, several kinds of procedures have been performed on the heart and large vessels, with many cases requiring open heart surgery and bypass. Morris and Menashe (1991) reviewed mortality statistics for over 2700 children having corrective cardiac surgery in Oregon from 1958 through 1989. At 25 years, more than 75 percent were still alive. With successful repair, many women now are likely to attempt pregnancy. In some instances, surgical corrections have been performed during pregnancy.
A number of reproductive-age women have had a cardiac valvar prosthesis implanted to replace a severely damaged mitral or aortic valve. Reports of subsequent pregnancy outcomes are now quite numerous, and indeed, successful pregnancies have followed prosthetic replacement of even three heart valves (Nagorney and Field, 1981).
Effect on Pregnancy
Severe complications can arise during pregnancy when the mother has a prosthetic valve. Other than thromboembolism and hemorrhage from anticoagulation, there may be deterioration in cardiac function. Spontaneous abortions, stillborns, low-birthweight infants, and malformed fetuses are more common. Pregnancy is to be undertaken in these women only after serious consideration.
Women with a mechanical valve prosthesis must be maintained on anticoagulant therapy; when not pregnant, warfarin is recommended. There are reports that describe a higher incidence of thromboembolic complications with prostheses during pregnancy. Sareli and co-workers (1989) summarized 442 reported cases and identified 12 with thrombotic obstruction of the prosthesis and 14 with systemic embolization despite anticoagulation. In another series, Ismail and colleagues (1986) reported four maternal deaths in 50 women during 76 pregnancies. The critical issue in anticoagulation for these women is a suggestion that heparin may be less effective than warfarin in preventing systemic embolic events, coupled with the known adverse fetal effects of warfarin (Greenspoon, 1991).
Iturbe-Alessio and colleagues (1986) provide an estimate of risk for both mother and fetus. They studied prospectively 72 women with cardiac valve prostheses. In some women, warfarin derivatives were given throughout pregnancy, while in others 5000 U of heparin was administered subcutaneously twice daily and substituted for warfarin from the 6th through 12th weeks, after which warfarin again was given. Three of 35 women taking low-dose heparin suffered a massive thrombosis of a Björk–Shiley mitral prosthesis, and two of them died. On the other hand, while the women taking warfarin had no thromboses, there was evidence for embryopathy in 28 percent of their fetuses.
Porcine tissue valves are much safer for pregnant women, primarily because anticoagulation is not required. Deviri and colleagues (1985) reported no thrombi in 22 pregnancies in 11 unanticoagulated women with porcine xenografts. Lee and associates (1994) described generally good outcomes in 95 pregnancies in 57 women with a porcine graft. Four of these developed valve dysfunction. Unfortunately, although less thrombogenic, such bioprostheses are not as durable as mechanical prostheses. Their use necessitates the acceptance of additional open-heart surgery at a future date.
Full anticoagulation is recommended with either warfarin or heparin after the woman is counseled regarding respective risks. We recommend full heparinization during pregnancy. Heparin is given to prolong the partial thromboplastin time by 1.5 to 2.5 times baseline values. Just before delivery, heparin is stopped. If delivery supervenes while the anticoagulant is still effective, and extensive bleeding is encountered, protamine sulfate is given. Anticoagulant therapy with warfarin or heparin may be restarted 6 hours following vaginal delivery, usually with no problems. Following cesarean delivery, however, full anticoagulation should be withheld for at least 24 hours.
Rheumatic fever is uncommon in the United States because of less crowded living conditions, availability of penicillin, and evolution of nonrheumatogenic streptococcal strains. Still, it remains the chief cause of serious valvar disease in adults. During epidemics of streptococcal pharyngitis, as many as 3 percent of untreated young adults may develop rheumatic fever. In 1986, the estimated prevalence of rheumatic fever and heart disease was 1.7 million persons, or 7 per 1000. Thus, as many as 0.5 to 1 percent of childbearing-age women may have rheumatic valvar disease.
Rheumatic endocarditis is the most common cause of mitral stenosis. Mitral valve stenosis impedes blood flow from the left atrium to the ventricle. With tight mitral stenosis, the left atrium is dilated, as shown in Figure 47–2. Thus, left atrial pressure is chronically elevated and may result in significant passive pulmonary hypertension if not surgically corrected. The increased preload of normal pregnancy, as well as other factors that require increased cardiac output, may cause ventricular failure with pulmonary edema in these women with relatively fixed cardiac output. Indeed, 25 percent of women with mitral stenosis have cardiac failure for the first time during pregnancy (Sullivan and Ramanathan, 1985). This may be confused with idiopathic peripartum cardiomyopathy (Cunningham and colleagues, 1986).
The normal mitral valve surface area is 4.0 cm2. When stenosis narrows this to less than 2.5 cm2, symptoms usually develop. The most prominent complaint is dyspnea due to pulmonary venous hypertension and pulmonary edema. Other common symptoms are fatigue, palpitations, and hemoptysis. Occasionally, symptoms of heart failure appear suddenly.
In patients with significant mitral stenosis, tachycardia of any etiology shortens ventricular diastolic filling time and increases the mitral gradient, which raises left atrial and pulmonary venous and capillary pressures and may result in pulmonary edema. Thus, sinus tachycardia is often treated prophylactically with beta-blocking agents. Atrial tachyarrhythmias, including fibrillation, are common in mitral stenosis and are treated aggressively with cardioversion if necessary. Atrial fibrillation also predisposes to mural thrombus formation and aortic embolization which may lead to a thrombotic cerebrovascular accident.
Limited physical activity is generally recommended. If symptoms of pulmonary congestion develop, activity is restricted even more, dietary sodium is restricted, and a diuretic is administered. A b-blocker drug is often given to slow heart rate response to activity and anxiety. Al Kasab and associates (1990) treated 25 pregnant women with mitral stenosis with either propanolol or atenolol. Their mean heart rate was decreased from 86 to 78 beats/min, and 92 percent had significant symptomatic improvement as measured by reassignment to a lower New York Heart Association classification. If new-onset atrial fibrillation develops, intravenous verapamil, 5 to 10 mg, is given, or electrocardioversion is performed.
Labor and delivery are particularly stressful for women with tight mitral stenosis. Pain, work, and anxiety cause tachycardia, with increasing chances of rate-related heart failure. Epidural analgesia for labor, with strict attention to avoid intravenous fluid overload, is ideal. As shown in Figure 47–3 , pulmonary capillary wedge pressures usually increase even more immediately postpartum. Clark and colleagues (1985) hypothesize that this is likely due to loss of the low-resistance placental circulation as well as “autotransfusion” from the lower extremities and pelvic veins and the now-empty uterus. Abrupt increases in preload may lead to increased pulmonary capillary wedge pressure and pulmonary edema. Thus, care must be taken to avoid fluid overload.
Vaginal delivery is preferable, and some recommend elective induction so that labor and delivery can be monitored and attended by the most knowledgeable team. In cases of severe stenosis with chronic heart failure, insertion of a pulmonary-artery catheter may help guide management decisions. Intrapartum endocarditis prophylaxis is required.
Mitral regurgitation develops when there is improper coaptation of mitral valve leaflets during systole, and this is eventually followed by left-ventricular dilatation and hypertrophy. Chronic mitral regurgitation may be due to a number of causes, including rheumatic fever, mitral valve prolapse, or left-ventricular dilatation of any etiology—for example, dilated cardiomyopathy. Less common causes include a calcified mitral annulus, connective-tissue diseases, and in older women, ischemic heart disease. Acute mitral insufficiency is caused by rupture of a chordae tendineae, infarction of papillary muscle, or by leaflet perforation from infective endocarditis.
In nonpregnant patients, symptoms from mitral valve incompetence are rare, and valve replacement is seldom indicated, except for infective endocarditis. Likewise, mitral regurgitation is well tolerated during pregnancy, probably due to decreased systemic vascular resistance, which actually results in less regurgitation. Heart failure only rarely develops during pregnancy, and occasionally tachyarrhythmias need to be treated. Prophylaxis against bacterial endocarditis is given intrapartum.
In a woman less than 30 years old, aortic stenosis is most likely due to a congenital lesion. This is the result of the decline in incidence of rheumatic diseases. The most common stenotic lesion is a bicuspid valve. Stenosis reduces the normal 2 to 3 cm2 aortic orifice and creates resistance to ejection. A systolic pressure gradient develops between the left ventricle and the systemic arterial outflow tract. Concentric left-ventricular hypertrophy follows, and if severe, end-diastolic pressures become elevated, ejection fraction declines, and cardiac output is reduced. Characteristic clinical manifestations develop late and include chest pain, syncope, heart failure, and sudden death from arrhythmias. Life expectancy after exertional chest pain develops averages only 5 years, and valve replacement is indicated for symptomatic patients.
Clinically significant aortic stenosis is uncommonly encountered during pregnancy. Mild to moderate degrees of stenosis are well tolerated, but severe disease is life threatening. The principal underlying hemodynamic problem is the fixed cardiac output associated with severe stenosis. During pregnancy, a number of factors may be encountered that commonly decrease preload further and thus aggravate the fixed cardiac output. Some examples include blood loss, regional analgesia, and vena caval occlusion. Importantly, all of these decrease cardiac, cerebral, and uterine perfusion. Because of these considerations, severe aortic stenosis may be extremely dangerous during pregnancy. Reports after 1975 describe a collective mortality of 7 percent (Lao and colleagues, 1993b). Patients with valve gradients exceeding 100 mm Hg appear to be at greatest risk.
Management in Pregnancy
For the asymptomatic pregnant woman, no treatment except close observation is required. Management of the symptomatic woman includes strict limitation of activity and prompt treatment of infections. If symptoms persist despite bed rest, valve replacement or valvotomy using cardiopulmonary bypass must be considered. Angel and colleagues (1988), as well as Lao and associates (1993a), described percutaneous balloon valvoplasty at midpregnancy for women with severe symptomatic aortic stenosis. Anesthesia and cardiopulmonary bypass were obviated, and fetal radiation exposure was acceptable.
For women with critical aortic stenosis, intensive monitoring during labor is important. Pulmonary-artery catheterization may be helpful because of the narrow margin separating fluid overload from hypovolemia. During labor, narcotic epidural analgesia seems ideal, thus avoiding potentially hazardous hypotension, which may be seen with standard conduction anesthetic techniques. Easterling and colleagues (1988) used standard epidural analgesia for five women with severe stenosis without morbidity. They demonstrated the immediate and profound effects of decreased filling pressures associated with its use. Lao and associates (1993b) also offered this routinely to 20 such women. Forceps or vacuum delivery are used for standard obstetrical indications in hemodynamically stable women (Clark and colleagues, 1991).
Patients with aortic stenosis are dependent upon adequate end-diastolic ventricular filling pressures to maintain cardiac output and systemic perfusion. Abrupt decreases in end-diastolic volume may result in hypotension, syncope, myocardial infarction, and sudden death. Thus the key to the management of these women is the avoidance of decreased ventricular preload and maintenance of cardiac output. During labor and delivery, such women should be managed on the “wet” side, maintaining a margin of safety in intravascular volume in anticipation of unexpected hemorrhage. In women with a competent mitral valve, pulmonary edema is rare, even with moderate volume overload. Bacterial endocarditis prophylaxis is given at delivery.
Aortic regurgitation is the diastolic flow of blood from the aorta into the left ventricle. Because the prevalence of rheumatic fever has declined, major causes of aortic valvar incompetence are connective-tissue abnormalities and congenitally acquired lesions. For example, with Marfan syndrome, the aortic root may dilate, resulting in aortic insufficiency. Acute insufficiency may develop with bacterial endocarditis or aortic dissection. With chronic disease, left-ventricular hypertrophy and dilatation develop. This is followed by delayed symptoms of fatigue, dyspnea, and edema, although rapid deterioration usually follows.
Generally, aortic insufficiency is well tolerated during pregnancy, and like mitral valve incompetence, diminished peripheral vascular resistance is thought to improve the lesion (McAnulty and associates, 1988; Mendelson and Lang, 1995). Development of symptoms necessitates therapy for heart failure including bed rest, sodium restriction, and diuretics. Epidural analgesia is used for labor pain and vaginal or cesarean delivery. Intrapartum bacterial endocarditis prophylaxis is given.
Congenital Heart Disease
Mendelson and Lang (1995) divide congenital heart lesions that complicate pregnancy into three groups: (1) volume overload or left-to-right shunts, examples of which include atrial or ventricular septal defects; (2) pressure overload, such as aortic and pulmonary stenosis, aortic coarctation, and hypertrophic subaortic stenosis; and (3) cyanotic lesions or right-to-left shunts that include Fallot tetralogy and Eisenmenger syndrome.
Atrial septal defect is the second most common cardiac abnormality in adults after bicuspid aortic valve. Many of these lesions are asymptomatic. The secundum type defect accounts for 70 percent of all cases, and associated mitral valve myxomatous abnormalities with prolapse are common. Unless the lesion is large, findings of right atrial and ventricular dilatation are clinically inconsequential. Pregnancy is well tolerated unless pulmonary hypertension has developed, but this is rare because pulmonary artery pressures are low with an atrial septal defect. If congestive heart failure or an arrhythmia develops, treatment is given. Bacterial endocarditis prophylaxis is controversial, unless the defect was repaired with a patch.
Ventricular septal defect is the most common cardiac anomaly found at birth . In adults it follows bicuspid aortic valve, atrial septal defect, and pulmonic stenosis in frequency. Almost 75 percent of defects are paramembraneous, and physiological derangements are related to their size. Most defects are small and close spontaneously by 10 years; however, in children when the effective size of the defect is greater than the aortic valve orifice, symptoms rapidly develop. Many of these children undergo surgical repair before pulmonary hypertension develops, and they do well. Jackson and colleagues (1993) described two women who had severe pulmonary hypertension despite early repair of septal defects in childhood. One pregnancy was aborted and the second woman died 5 days following preterm delivery. Those with unrepaired defects of longer duration develop pulmonary hypertension, and they also have a high incidence of bacterial endocarditis. In general, if the defect is less than 1.25 cm2, pulmonary hypertension and heart failure do not develop.
Pregnancy is well tolerated with small to moderate left-to-right shunts. When pulmonary arterial pressures reach systemic levels, however, there is reversal or bidirectional flow or Eisenmenger syndrome. When this develops, maternal mortality is 30 to 50 percent. Thus, pregnancy is contraindicated, and therapeutic abortion is advised if contraception fails. Bacterial endocarditis is common with unrepaired defects, and antibiotic prophylaxis is recommended.
Cyanotic Heart Disease
When congenital heart lesions are associated with right-to-left shunting of blood past the pulmonary capillary bed, then cyanosis develops. The classical and most commonly encountered lesion in pregnancy is the Fallot tetralogy. This is characterized by a large ventricular septal defect, right ventricular hypertrophy, and an overriding aorta. The magnitude of the shunt varies inversely with systemic vascular resistance. Hence, during pregnancy, when peripheral resistance decreases, the shunt increases and cyanosis worsens. Women who have undergone repair, and in whom cyanosis did not reappear, do well in pregnancy.
Some women with Ebstein anomaly of the tricuspid valve may reach reproductive age. Right-ventricular failure from volume overload and appearance or worsening of cyanosis are common during pregnancy. If there is no cyanosis, these women usually tolerate pregnancy well.
Effect on Pregnancy
Women with cyanotic heart disease do poorly during pregnancy. With uncorrected Fallot tetralogy, for example, maternal mortality approaches 10 percent. Any disease complicated by severe maternal hypoxemia is likely to lead to abortion, preterm labor and delivery, or fetal death. There is a relationship between chronic hypoxemia and the polycythemia it causes with the outcome of pregnancy. Whittemore and colleagues (1982) reported fetal wastage of 35 percent in women with cyanotic congenital heart disease. When hypoxemia is intense enough to stimulate a rise in hematocrit above 65 percent, pregnancy wastage is virtually 100 percent. Shime and associates (1987) reported that 13 of 23 women with cyanotic heart disease developed functional deterioration during pregnancy, and seven had cardiac failure. Three of these 23 infants (13 percent) died, and low birthweight was common. Patton and colleagues (1990) described six such pregnancies; all were complicated by fetal growth retardation and were eventually terminated for fetal indications, rather than maternal deterioration.
With satisfactory surgical correction prior to pregnancy, maternal risks are decreased dramatically, and fetal environment is improved. Singh and associates (1982), on the basis of 40 pregnancies in 27 women with surgically corrected Fallot tetralogy, concluded that in women with no major residual defects after surgery, that pregnancy is usually well tolerated. Lao (1994), Megerian (1994), Lynch-Salamon (1993), and their colleagues described a total of 14 pregnancies in 10 women following successful Mustard repair for transposition of the great vessels. Two women developed cardiac failure during pregnancy, one was terminated during early pregnancy and the other became symptomatic at 32 weeks. Two women developed worrisome arrhythmias that required treatment. There was late-onset fetal growth restriction in two women, and two others were delivered preterm following spontaneous membrane rupture.
Vaginal delivery of a woman with cyanotic heart disease is preferred unless there is an obstetrical indication for cesarean delivery. Pulmonary artery catheter monitoring has limitations because of the sometimes bizarre anatomical abnormalities. Care must be taken to avoid sudden blood pressure decreases, and most approach the use of epidural analgesia with caution (Patton and colleagues, 1990).
Eisenmenger syndrome develops with any cardiac lesion in which pulmonary vascular resistance becomes greater than systemic vascular resistance and in whom at least some right-to-left shunting occurs at rest or with exercise. These women may survive for decades with relatively few symptoms (Nugent and colleagues, 1990).
The prognosis for pregnancy complicated by these lesions is poor, as it is whenever there is pulmonary hypertension from any cause. Gleicher and associates (1979) reported that both maternal and perinatal mortality rates for Eisenmenger syndrome were about 50 percent. Shime and colleagues (1987) described 19 pregnancies in nine such women; half were terminated by spontaneous or therapeutic abortion, and there were only four term births. Three women developed heart failure and one died. These women tolerate hypotension poorly, and the cause of death usually is right-ventricular failure with cardiogenic shock (see the discussion of pulmonary hypertension in the next section).
Other Cardiovascular Conditions
Pulmonary hypertension is generally secondary to cardiac or pulmonary disease, and common causes are persistent and prolonged left-to-right shunting as discussed. Other causes are recurrent pulmonary emboli and drug abuse. Primary pulmonary hypertension, characterized by medial hypertrophy and plexiform lesions, is usually idiopathic, but some previously unexplained cases may be due to antiphospholipid antibodies .
Effects on Pregnancy
Maternal mortality is appreciable, whether pulmonary hypertension is primary or secondary. Kiss and colleagues (1995) reviewed literature since 1956 and reported a maternal mortality rate of 7 of 11 (65 percent) with primary pulmonary hypertension. Torres and associates (1994) documented diminished pulmonary vascular resistance during pregnancy in a woman with primary disease. Thus, with severe disease, pregnancy is contraindicated, but milder degrees of secondary pulmonary hypertension probably go unnoticed. For example, with the more common use of pulmonary artery catheterization in women with heart disease, we have identified women with mild to moderate pulmonary hypertension who tolerated pregnancy, labor, and delivery quite well. Boggess and colleagues (1995) described nine women with interstitial and restrictive lung disease who ostensibly had varying degrees of pulmonary hypertension. Three women had severe disease, and all nine tolerated pregnancy reasonably well.
Treatment of symptomatic pregnant women includes limitation of activity and avoidance of the supine position in late pregnancy. Management of labor and delivery is particularly problematic. These women are at greatest risk when there is diminished venous return and right ventricular filling; this is associated with most maternal deaths. Careful attention is given to blood loss at delivery and avoidance of standard (nonnarcotic) epidural analgesia. Pollack and colleagues (1990), as well as others, have reported successful labor analgesia without significant cardiovascular effects from morphine administered intrathecally. Thornhill and Camann (1994) argue against the use of pulmonary artery catheterization for a number of technical and safety issues, not the least of which is that data are usually not clinically useful.
Mitral Valve Prolapse
Mitral valve prolapse implies the presence of a pathological connective-tissue disorder—often termed myxomatous degeneration—which may involve the valve leaflets themselves, the annulus, or the chordae tendinae. This condition has been reported in as many as 15 percent of otherwise normal young women. Mitral valve prolapse appears to be inherited, and it is commonly associated with a wide variety of other cardiac disorders, including atrial septal defect, Marfan syndrome, Epstein anomaly, and hypertrophic cardiomyopathy. The etiology of isolated myxomatous degeneration is unknown.
Most women with mitral valve prolapse are asymptomatic and are diagnosed by routine physical examination or as an incidental finding at echocardiography. The small percentage of women with symptoms have anxiety, palpitations, dyspnea, atypical chest pain, and syncope. Nishimura and colleagues (1985) identified only those patients with redundant mitral valve leaflets to be at increased risk of sudden death, infective endocarditis, or cerebral embolism. Artal and colleagues (1988) described such a woman who developed transient cerebral ischemia during pregnancy.
Diagnosis. Mitral valve prolapse implies the presence of a pathological condition and should be diagnosed with great caution and precision. As emphasized by Perloff and co-workers (1986), simple displacement of the mitral leaflets away from the plane of the annulus is common, and simply represents a normal variant . Reliance upon strict diagnostic criteria is urged prior to assigning a pathological diagnosis or administration of endocarditis prophylaxis.
Effects on Pregnancy
Pregnant women with mitral valve prolapse rarely have cardiac complications. In fact, pregnancy-induced hypervolemia may improve alignment of the mitral valve (Rayburn and colleagues, 1987). For women who are symptomatic, b-blocking drugs are given to decrease sympathetic tone, relieve chest pain and palpitations, and reduce the risk of life-threatening arrhythmias. In general, mitral valve prolapse has not been deleterious to pregnancy. We manage these women as if not pregnant and prescribe b-blocker drugs for symptoms. Mitral valve prolapse with regurgitation is considered to be a significant risk factor for development of bacterial endocarditis. Women should be given antibiotic prophylaxis if there is regurgitation, valvular damage, or any of the risk factors discussed (Degani and associates, 1989). Patients without evidence of pathological myxomatous change may in general expect excellent pregnancy outcome (Chia and associates, 1994).
A common time for women to develop heart failure is during labor or shortly after delivery. The term peripartum cardiomyopathy is now used widely to describe women with peripartum heart failure with no readily apparent etiology; however, it is doubtful that there is a cardiomyopathy unique to pregnancy. Among 28 women with peripartum heart failure of obscure etiology who were initially thought to have idiopathic cardiomyopathy, heart failure in 21 was ultimately attributed to chronic hypertension, unrecognized mitral stenosis, obesity, or viral myocarditis (Cunningham and associates, 1986). Similarly, Mabie and colleagues (1993) prospectively studied 45 women with peripartum heart failure over a 6-year period. In most cases, they were able to find an etiology of heart failure using echocardiography. Chronic underlying hypertension (40 percent) and preeclampsia (50 percent) were other common complications.
Underlying hypertension, especially with superimposed preeclampsia, is a common finding in otherwise inexplicable peripartum heart failure (Fig. 47–5 ). Obesity is a common co-factor. Although it commonly co-exists with chronic hypertension, obesity alone was correlated with increased left-ventricular mass in the Framingham Heart Study (Lauer and colleagues, 1991).
Regardless of the underlying condition that causes cardiac dysfunction, women who develop peripartum heart failure often have superimposed preeclampsia, and they usually have other obstetrical complications that either contribute to or precipitate heart failure. Factors commonly associated with heart failure include anemia and infection. Anemia likely magnifies the physiological effects of compromised ventricular function. Similarly, infection and accompanying fever increase cardiac output and oxygen utilization.
Infective endocarditis involves cardiac endothelium and produces vegetations that usually deposit on a valve. Although the incidence of rheumatic fever has diminished, that of bacterial endocarditis has become more common. This is most often because children and adults who survive corrective surgery for congenital heart disease are at greatest risk. Indeed, except for acute bacterial endocarditis associated with illicit drug use, about 75 percent of adult patients have a known preexisting heart lesion.
Subacute bacterial endocarditis usually is due to a low-virulence bacterial infection superimposed on an underlying lesion. Organisms that cause subacute, indolent bacterial endocarditis are most commonly streptococci, including a-hemolytic or viridans group or those from group D including Enterococcus species. Group B streptococcal endocarditis can be subacute or acute. Gallagher and Watanakunakorn (1986) observed that almost 10 percent of such cases reported since 1962 were in pregnant women.
Acute endocarditis is usually caused by coagulase-positive staphylococci, and the predominant organism in intravenous drug abusers is Staphylococcus aureus. This organism, along with Streptococcus pneumoniae and Neisseria gonorrheae, causes acute, fulminating disease. Bataskov and colleagues (1991) described fatal gonococcal endocarditis complicating pregnancy. Deger and Ludmir (1992) reported endocarditis caused by Neisseria sicca, and we have had a maternal death due to endocarditis from Neisseria mucosa.
Symptoms of endocarditis are variable and often develop insidiously. Fever, chills, and night sweats typically accompany anorexia, fatigue, and weakness. Constitutional symptoms are common, and the illness is frequently described as “flu-like.” Other findings are manifestations of embolic lesions, including focal neurological manifestations, chest or abdominal pain, and ischemia in an extremity. In some cases, heart failure may develop. In the usual case, symptoms usually persist for 4 to 8 weeks before the diagnosis is made (Durack, 1990). Thus, a high index of suspicion is necessary to consider endocarditis. Diagnosis is confirmed by excluding other causes of febrile illnesses and recovering positive blood cultures for typical organisms. Echocardiography and two-dimensional sector scanning are useful, but lesions only 3 to 4 mm in size or those on the tricuspid valve may be missed. A negative echocardiographic study does not exclude endocarditis.
Treatment is primarily medical with appropriate timing of surgical intervention if this becomes necessary. Knowledge of the infecting organism is imperative for sensible antimicrobial selection. Most viridans streptococci are sensitive to penicillin G given intravenously along with gentamicin for 2 weeks (Durack, 1990). Women with complicated infections are treated longer, and those allergic to penicillin are either desensitized or given intravenous ceftriaxone or vancomycin for 4 weeks. Staphylococci, enterococci, and other organisms are treated according to microbial sensitivity for 4 to 6 weeks or longer. Carefully timed surgical intervention may be necessary to eradicate infection or to reverse heart failure. Persistent native valve infection may require replacement, and this is even more commonly indicated with an infected prosthetic valve.
During pregnancy, there are a number of important adaptations of the respiratory system and changes in pulmonary function. Physiologically these changes are necessary so that the increased oxygen demands of the hyperdynamic circulation and the fetus can be satisfied. There is no evidence that pulmonary function is impaired because of pregnancy, but inferential data suggest that advanced pregnancy may worsen the pathophysiological effects of many acute and chronic lung diseases. An example for acute disease is the disparate number of adult deaths in pregnant women that were observed during the influenza pandemics of 1918 to 1919 and 1957 to 1958. An example for chronic disease is the poor tolerance to pregnancy of women with severe chronic lung disease and especially cor pulmonale.
From 1 to 4 percent of pregnancies are complicated by asthma. During winter months, both viral as well as bacterial pneumonitis are frequent in young adults. Tuberculosis is more frequent now than it has been in many years, and more worrisome, mycobacterial infections are becoming resistant to contemporaneous tuberculostatic medications. Finally, a number of chronic pulmonary disorders—albeit uncommon—may precede pregnancy and present special management problems.
Because of their importance to the clinical approach of lung disease complicating pregnancy, some of these are now reiterated. There are four lung volumes and four lung capacities that are used commonly to describe pulmonary physiology. Except for residual volume and lung capacities derived therefrom, these can be measured using direct spirometric techniques. The physiological changes induced by pregnancy have been summarized by de Swiet (1991):
1. Vital capacity may be increased by 100 to 200 mL.
2. Inspiratory capacity increases by about 300 mL by late pregnancy.
3. Expiratory reserve volume decreases from a total of 1300 mL to about 1100 mL.
4. Residual volume decreases from a total of 1500 mL to about 1200 mL.
5. Functional residual capacity, the sum of expiratory reserve and residual volumes, is reduced considerably, by about 500 mL.
6. Tidal volume increases considerably from about 500 to 700 mL.
7. Minute ventilation increases 40 percent, from 7.5 L to a total of 10.5 L/min; this is primarily due to increased tidal volume because the respiratory rate is unchanged.
The sum of these changes is substantively increased ventilation due to deeper but not more frequent breathing. Presumably these changes are induced to help supply increased basal oxygen consumption, which increases incrementally by 20 to 40 mL/min in the second half of pregnancy. As a result, arterial PO2 falls very slightly, PCO2 averages 28 mm Hg, plasma pH is slightly alkalotic at 7.45, and bicarbonate decreases to about 20 mEq/L.
Dyspnea During Pregnancy
Pregnant women are frequently aware of the need to breathe. The common complaint of “shortness of breath” is not associated with exercise, and frequently is worse when the woman is sitting down. Milne and associates (1978) reported that about half of women notice dyspnea at rest by midpregnancy, and three fourths complained of this by 31 weeks. Although its exact mechanisms are unclear, dyspnea has been attributed to alveolar hyperventilation and a response to substantively decreased PCO2, as well as a consequence of normal anatomical changes in the thorax.
Community-acquired pneumonia is a common and potentially serious illness. In the United States in nonpregnant persons, it is the sixth leading case of death and the number one cause of death from infectious diseases (American Thoracic Society, 1993). For those treated as outpatients, mortality is 1 to 5 percent, but it is 25 percent if hospitalization is required. In young and healthy women these figures will be substantively lower, but maternal deaths from pneumonia still occur.
Pneumonia is inflammation affecting the lung parenchyma distal to the larger airways and involving the respiratory bronchioles and alveolar units. Bronchopneumonia refers to patchy and diffuse areas of involvement, and at least implies a less severe form of pneumonitis because there is no consolidation seen radiographically. Pneumonitis causing an appreciable loss of ventilatory capacity is tolerated less well by women during pregnancy. This generalization seems to hold true regardless of the etiology of the pneumonia. Moreover, hypoxemia and acidosis are poorly tolerated by the fetus, and they frequently lead to preterm labor after midpregnancy. Because many cases of pneumonia follow common viral upper respiratory illnesses, worsening or persistence of symptoms should prompt consideration for the diagnosis of pulmonary parenchymal infection. Any pregnant woman suspected of having pneumonia should undergo anteroposterior and lateral chest radiography.
Bacteria usually reach the lung by inhalation or by aspiration of nasopharyngeal secretions. Some bacterial organisms that cause community-acquired pneumonia, such as Streptococcus pneumoniae, are part of the normal resident flora. Viruses usually are not present in normal flora. There are a number of factors that can upset the symbiotic relationship between colonizing bacteria and the mucosal and phagocytic defenses of the nasopharynx and bronchial tree. For example, there may be acquisition of a new virulent and invasive strain, or infection may follow a viral infection. Importantly, cigarette smoking and chronic bronchitis favor colonization with S pneumoniae, H influenzae, and Legionella. Whitty and colleagues (1996) recently described binge drinking and cigarette smoking as risk factors for pneumonia in pregnant women.
Causes of Pneumonia. According to Bartlett and Mundy (1995), the attack rate for all adults is 12 per 1000. It is much lower for young healthy women, and over the 4-year period from 1989 to 1993, the incidence of pneumonia complicating nearly 60,000 pregnancies at Parkland Hospital was 1 in 850 (Richey and associates, 1994). At least two thirds of adult pneumonias are bacterial, and S pneumoniae causes two thirds of these. The Research Committee of the British Thoracic Society (1987) prospectively studied the clinical courses of 453 adults of all age groups admitted to 25 hospitals for pneumonia. In two thirds of cases, a microbial etiology was determined; S pneumoniae was found in 34 percent, Mycoplasma pneumoniae in 18 percent, and influenza A virus in 7 percent. In most of the unclassified third, there was indirect evidence that there was pneumococcal infection.
The TWAR organism, now termed Chlamydia pneumoniae, has been shown to be responsible for 5 to 10 percent of adults hospitalized with pneumonias (Bartlett, 1995). It seems logical that this organism is a significant cause of pneumonia during pregnancy. Legionella pneumophilia occasionally causes outbreaks or sporadic cases of Legionnaire disease in young adults. Gherman and associates (1995) recently described a 32-week pregnant woman in whom Chlamydia psittaci caused pneumonia and fetal-placental infection.
Diagnosis and Management
Typical symptoms of pneumonia include productive cough, fever, chest pain, and dyspnea. Mild upper respiratory symptoms and malaise usually precede these symptoms. There usually is mild leukocytosis. The chest x-ray is essential for diagnosis, although its appearance does not accurately predict the etiology .
As discussed, the responsible pathogen is identified in perhaps only half of cases. Although some recommend examination of Gram-stained sputum to search for pneumococci or possibly staphylococci, the American Thoracic Society (1993) stresses that its sensitivity and specificity vary widely. Likewise, although routine sputum cultures often demonstrate pathogenic organisms, they too have poor sensitivity and specificity. Bartlett and Mundy (1995) reported that half of sputum samples show likely pathogens. Invasive techniques such as transtracheal aspiration are seldom indicated. Serological testing and cold agglutinin measurements are not routinely recommended with community-acquired pneumonia. Finally, there are no currently available tests for bacterial antigens that are useful in evaluation of most of these patients. Research is being conducted to evaluate methods using monoclonal antibodies, DNA probes, and polymerase chain reaction amplification.
According to the American Thoracic Society (1993), the decision for hospitalization is perhaps the single most important decision for management of community-acquired pneumonia. Although it is the policy at Parkland Hospital to hospitalize all pregnant women with radiographically confirmed pneumonia, this is probably not necessary with appropriate home health care. At the least, the presence of risk factors—especially if multiple—that are shown in Table 48–1 should prompt consideration for hospitalization. Initial hospitalization does not have to be a long-term commitment, but can serve to allow close observation for the first day or so to be sure that infection is responsive to therapy and not worsening.
Because of factors cited, initial treatment must be empirical. Given that the majority of adult pneumonias are caused by pneumococci or mycoplasmas, erythromycin therapy is the logical choice in the uncomplicated case (American Thoracic Society, 1993). The usual dose is 500 to 1000 mg every 6 hours, and this can be given intravenously, at least initially. Clairthromycin or azithromycin are acceptable alternatives. In women who appear more ill, or in those in whom staphylococcal or Haemophilus pneumonia is suspected, then cefotaxime, ceftizoxime, or cefuroxime is given instead. A b-lactam antimicrobial with a b-lactamase inhibitor is also suitable. Erythromycin added to either of these latter two regimens is recommended by some. Of concern is the recent emergence of pneumococcal resistance to penicillin, erythromycin, and the cephalosporins (Hofmann and colleagues, 1995). In a study of 590 bacteremic patients, Plouffe and associates (1996) reported 14 percent penicillin resistance, 12 percent resistance to ceftazidime, and 24 percent to trimethoprim-sulfamethoxazole.
Clinical improvement is usually evident by 48 to 72 hours. Fever typically lasts 2 to 4 days. If fever persists, follow-up radiography should be considered. It is common for radiographic findings to worsen initially, and there may be progression of infiltrates or development of a pleural effusion. For example, 20 percent of cases of pneumococcal pneumonia have associated effusions. In the case of mild clinical disease with improvement, such radiographic progression is inconsequential. Conversely, radiographic deterioration in the setting of severe community-acquired pneumonia is a poor prognostic feature and highly predictive of mortality.
PREVENTION. Pneumococcal vaccine has been shown to be 60 to 70 percent protective against vaccine-related serotypes. Its use may help decrease the emergence of drug-resistant pneumococci (Jernigan and colleagues, 1996). It is recommended by the Advisory Committee on Immunization Practices (1988) for immunocompromised adults including those with human immunodeficiency virus infection. It is also given to those who have underlying diabetes, cardiac, pulmonary, or renal disease. Another example is the pregnant woman with sickle-cell disease who is especially susceptible to these infections. It is not recommended for otherwise healthy pregnant women.
Effect of Pneumonia on Pregnancy
There is no doubt that maternal mortality from pneumonia was considerable during the pre-antibiotic era. In 1939, Finland and Dublin reported a 32 percent maternal mortality rate in 212 women. In more recent reports, an overall downward trend in maternal and fetal morbidity and mortality has been emphasized. Berkowitz and LaSala (1990) described their experiences with 26 cases of antepartum pneumonia complicating nearly 10,000 deliveries at Sloane Hospital for Women. S pneumoniae was most commonly isolated, and there was a high incidence of cocaine abuse and human immunodeficiency virus infection. Perinatal outcome was good despite severe infection, including two women with asthma who required tracheal intubation.
Madinger and colleagues (1989) reported frequent maternal and fetal complications in their review of 25 cases of pneumonia among more than 32,000 deliveries at Cedars-Sinai Medical Center. Of these, 20 percent required tracheal intubation and mechanical ventilation, and 15 percent had empyema, pneumothorax, or pericardial tamponade. Underlying disease was associated with increased maternal complications, and the one maternal death was a woman with cystic fibrosis and Pseudomonas pneumonia. Preterm labor developed in 45 percent and there were three perinatal deaths.
Richey and colleagues (1994) described outcomes in 71 pregnant women cared for at Parkland Hospital over a 4-year period. Pneumonia appeared to be more common in women with underlying diseases, especially asthma. Although these underlying disorders were not associated with more complications, there were two maternal–fetal deaths and three other fetal deaths in these 72 pregnancies. Briggs and associates (1996) described 34 women with antepartum pneumonia; seven required mechanical ventilation and two died. These outcomes underscore the severity of pneumonia and also serve to emphasize the need for prompt diagnosis, close observation, and effective treatment.
Asthma affects about 3 to 4 percent of the general population. According to the Centers for Disease Control (1990a), the prevalence of asthma increased during the years 1980 to 1987. Asthma causes nearly 4000 deaths annually in the United States, and the mortality rate ranges from 1 to 3 percent. The National Asthma Education Program (1993) estimates that 1 to 4 percent of pregnancies are complicated by asthma. Status asthmaticus complicates about 0.2 percent of pregnancies (Mabie and associates, 1992).
Clinically, asthma represents a broad spectrum of illness ranging from mild wheezing to severe bronchoconstriction capable of causing respiratory failure, severe hypoxemia, and death. The functional result of acute bronchospasm is airway obstruction and decreased air flow. The work of breathing progressively increases and patients present with chest tightness, wheezing, or breathlessness. Subsequent alterations in oxygenation primarily reflect ventilation–perfusion mismatching as the distribution of airway narrowing is uneven.
With mild disease, hypoxia initially is well compensated by hyperventilation, as reflected by a normal arterial oxygen tension and decreased carbon dioxide tension with resultant respiratory alkalosis. As airway narrowing worsens, ventilation–perfusion defects increase and arterial hypoxemia ensues. With severe obstruction, ventilation becomes impaired sufficiently because of respiratory muscle fatigue to result in early CO2 retention. Because of hyperventilation, this may only be seen initially as an arterial CO2 tension returning to the normal range. Finally, with critical obstruction, respiratory failure follows, characterized by hypercapnia and acidemia.
Although these changes in pulmonary function are generally reversible and well tolerated in the healthy nonpregnant individual, even the early stages of asthma may pose grave risk to the pregnant woman and her fetus. The smaller functional residual capacity and the increased effective shunt render her more susceptible to develop hypoxia and hypoxemia.
Effects of Pregnancy on Asthma
There is no evidence that pregnancy has a predictable effect on underlying asthma. Schatz and colleagues (1988) studied prospectively both symptoms and spirometry measurements throughout pregnancy and the puerperium in 366 asthmatic women. They reported that 28 percent of these women improved, 33 percent remained unchanged, 35 percent clearly worsened, while 4 percent had equivocal changes. In another prospective study of 198 pregnancies by Stenius-Aarniala and associates (1988), almost 40 percent of women required more intensive therapy for their asthma at some time during the pregnancy. Thus, about one third of asthmatic women can expect worsening of disease at some time during pregnancy.
Women beginning pregnancy with severe asthma are more likely to experience worsening disease than are those with mild disease. In about 60 percent of women, asthma behaves similarly with successive pregnancies. About 10 percent will have an exacerbation during labor and delivery (Schatz and colleagues, 1988). Importantly, Mabie and associates (1992) reported an 18-fold increased risk of exacerbation following cesarean delivery compared with vaginal delivery.
Effects of Asthma on Pregnancy
Asthma, especially when severe, can affect pregnancy outcome substantively. According to Clark and colleagues (1993), two large epidemiological investigations clearly defined these potential adverse effects. They included increased incidences of preterm labor, low-birthweight infants, perinatal mortality, and preeclampsia. Lehrer and associates (1993) reported that asthmatic women had a 2.5-fold increased incidence of pregnancy-induced hypertension. Schatz and associates (1990) showed a small but significant correlation between measurements of maternal pulmonary function and birthweight. Among 277 women with asthma from the Collaborative Study of Cerebral Palsy, perinatal mortality was twice that of control women (Gordon and co-workers, 1970). Fetal complications, including death, are increased with severe disease.
Maternal deaths may be associated with status asthmaticus. Among the 16 women with severe asthma from the Collaborative Perinatal Project, four women died (Gordon and associates, 1970). Life-threatening complications include pneumothorax, pneumomediastinum, acute cor pulmonale, cardiac arrhythmias, and muscle fatigue with respiratory arrest. Mortality rates exceed 40 percent when asthma requires mechanical ventilation.
Both animal and human studies are suggestive that maternal alkalosis may cause fetal hypoxemia well before maternal oxygenation is compromised (Rolston and associates, 1974). Fetal compromise is hypothesized to result from a combination of factors to include decreased uterine blood flow, decreased maternal venous return, and an alkaline-induced leftward shift of the oxyhemoglobin dissociation curve. Once the mother can no longer maintain normal oxygen tension and hypoxemia develops, the fetus responds with decreased umbilical blood flow, increased systemic and pulmonary vascular resistance, and finally decreased cardiac output. Realization that the fetus may be seriously compromised before maternal disease is severe underscores the need for aggressive management of all pregnant women with acute asthma. Monitoring the fetal response, in effect, becomes an indicator of maternal compromise.
The subjective impression by the patient of the severity of asthma frequently does not correlate with objective measures of airway function or ventilation. Clinical examination also is inaccurate to predict severity, but helpful signs include labored breathing, tachycardia, pulsus paradoxus, prolonged expiration, and use of accessory respiratory muscles. Signs of a potentially fatal attack include central cyanosis and altered level of consciousness.
Arterial blood gas analysis provides objective assessment of maternal oxygenation, ventilation, and acid–base status. With this information, the severity of an acute attack can be assessed . In a prospective evaluation, however, Wendel and associates (1996) did not find routine blood gas analysis to help direct care in most women. In addition, care must be taken to interpret the results in relation to normal values for pregnancy. For example, a PCO2 greater than 35 mm Hg with a pH less than 7.35 is consistent with hyperventilation and CO2 retention in a pregnant woman.
Pulmonary function testing has become routine in the management of chronic and acute asthma. Sequential measurements of the forced expiratory volume in one second (FEV1) from maximum expiration is the single best measure to reflect severity of disease. The peak expiratory flow rate (PEFR) correlates well with the FEV1, and it can be measured reliably with inexpensive portable peak flow meters. These are the most useful tests to monitor airway obstruction. An FEV1 less than 1 L or less than 20 percent of predicted correlates with severe disease as manifest by hypoxia, poor response to therapy, and a high relapse rate (Noble and colleagues, 1988).
Management of Chronic Asthma
According to Clark and associates (1993), effective management of asthma during pregnancy includes (1) objective assessment of pulmonary function and fetal well-being, (2) avoidance or control of environmental precipitating factors, (3) pharmacological therapy, and (4) patient education.
In general, women with moderate to severe asthma are instructed to measure and record peak expiratory flow rates twice daily. Predicted values range from 380 to 550 L/min and each woman has her own baseline value. Recommendations for therapy adjustments can be made using these measurements. For outpatients, treatment depends on the severity of disease. Shown in Table 48–3 are drugs and suggested doses for home management of asthma in the pregnant woman. Inhaled corticosteroids have become preferred by many because of minimal side effects (Barnes, 1995). In addition, b-agonists are administered by inhalation every 3 to 4 hours as needed. Wendel and colleagues (1996) reported a 55 percent reduction in readmissions for severe asthma exacerbations in pregnant women given inhaled corticosteroids along with b-agonist therapy. Cromolyn sodium (category B), which stabilizes mast cell membranes, has a preventive effect on asthma mediators and is used chronically. Two puffs administered by an inhaler are given four times daily for added therapy in women with moderate to severe chronic asthma.
Theophylline is a methylxanthine, and its various salts are bronchodilators. Aminophylline is the diethyleneamine salt of theophylline and the only form available for parenteral use. In the past, aminophylline was used for severe acute asthma as initial therapy or as an adjunct to b-adrenergic therapy, but currently it is being replaced by corticosteroids. Theophylline derivatives are considered useful by some for oral maintenance therapy of outpatients who do not respond optimally to inhaled b-agonists and corticosteroids. Sustained release theophylline preparations may also be helpful for use before bedtime in women with nocturnal symptoms that interfere with sleep.
Management of Acute Asthma
Treatment of acute asthma during pregnancy is similar to that for the nonpregnant asthmatic. An exception is a significantly lowered threshold for hospitalization of the pregnant woman. Most will benefit from intravenous hydration to help clear pulmonary secretions. Supplemental oxygen is given by mask after a blood gas sample is obtained. The therapeutic aim is to maintain the PO2 at greater than 60 mm Hg, and preferably normal, along with 95 percent oxygen saturation. Baseline pulmonary function testing includes FEV1 or peak expiratory flow rate. Continuous pulse oximetry may be helpful, and electronic fetal monitoring may provide useful information.
First-line pharmacological therapy of acute asthma includes use of a b-adrenergic agonist, either epinephrine, isoproterenol, terbutaline, albuterol, isoetharine, or metaproterenol (National Heart Lung and Blood Institute, 1991; Nelson, 1995). The more commonly used agents, their dosages, and routes of administration are listed in Table 48–4. These drugs bind to specific cell-surface receptors and activate adenylyl cyclase, which increases intracellular cyclic AMP to modulate bronchial smooth muscle relaxation. They are given subcutaneously, by inhalation, or orally and are also used for maintenance therapy of outpatients.
It is now recommended that corticosteroids be given early to all patients in the course of severe acute asthma (National Heart, Lung and Blood Institute, 1991). Because their onset of action is several hours, it is emphasized that steroids, whether given intravenously or by aerosol, are given along with b-agonists for treatment of acute asthma.
Further management depends on the response to therapy. If initial therapy with b-agonists is associated with return of the peak expiratory flow rate to above 70 percent of baseline, then discharge is considered. Clark and associates (1993) recommend intravenous methylprednisolone if the peak expiratory flow rate is between 40 and 70 percent after three doses of b-agonist. Our policy is to admit the woman at this point for intensive therapy including inhaled b-agonists, intravenous corticosteroids, and close observation for worsening of fatigue (Wendel and colleagues, 1996).
Status Asthmaticus and Respiratory Failure
Severe asthma of any type not responding after 30 to 60 minutes of intensive therapy is termed status asthmaticus. For nonpregnant patients with status asthmaticus, Braman and Kaemmerlen (1990) have shown that management in an intensive care unit will result in a good outcome in almost all cases. During pregnancy, consideration should be given to early intubation when the maternal respiratory status continues to decline despite aggressive treatment. Fatigue, carbon dioxide retention, or hypoxemia are indications for intubation and mechanical ventilation.
Management of Labor and Delivery
Regularly scheduled medications are continued through labor and delivery. Stress-dose corticosteroids should be considered for any woman given systemic steroid therapy within the preceding 4 weeks. The usual drug is 100 mg of hydrocortisone given intravenously every 8 hours. The peak expiratory flow rate should be determined on admission. If asthma symptoms develop, then serial measurements are taken after treatments.
In choosing an analgesic for labor, a non-histamine-releasing narcotic, such as fentanyl, may be preferable to meperidine or morphine. Epidural analgesia for labor is ideal. For surgical delivery, conduction analgesia is preferred because tracheal intubation can trigger severe bronchospasm. In the event of refractory postpartum hemorrhage, prostaglandin E2 and other uterotonics should be used in lieu of prostaglandin F2a, which has been associated with significant bronchospasm in asthmatic patients. Moreover, oxygen desaturation following 15-methyl PGF2a given for postpartum hemorrhage has been reported in women without reactive airway disease (Hankins and colleagues, 1988).
In the past, thromboembolic diseases were considered unique to the puerperium. In recent years, however, there appears to have been a decrease in the frequency of thromboembolism during the puerperium, but an increase antepartum. For example, Henderson and co-workers (1972) described 20 cases that developed antepartum among almost 30,000 pregnancies, but during the same period, only 16 were identified postpartum. Observations from Parkland Hospital indicate even more of a propensity for antepartum disease. During the 3-year period ending in 1992, 20 of 24 cases of deep venous thrombosis or pulmonary embolism were identified antepartum.
Undoubtedly, the frequency of venous thromboembolic disease during the puerperium decreased remarkably when early ambulation became widely practiced. Stasis is probably the strongest single predisposing event to deep vein thrombosis. Venous thrombosis with a significant potential for generating pulmonary emboli may originate in the deep veins of the leg, thigh, or pelvis. A thrombosis that involves only the superficial veins of the leg or thigh is very unlikely to embolize. Antecedent events that might possibly predispose to deep vein thrombosis during the antepartum period include the use of oral contraceptives before conception and the increased prevalence of women working during pregnancy at jobs in which they sit for long periods of time.
More recently, attention has been directed to a number of isolated deficiencies of proteins involved either in coagulation inhibition or in the fibrinolytic system . In some women these deficiencies can lead to hypercoagulability and recurrent venous thromboembolism. According to Hellgren and associates (1989), up to 70 percent of pregnancies in women with hereditary deficiency of antithrombin-III may experience thromboembolic complications. Trauscht-Van Horn and co-workers (1992) reported that one third of protein-C deficient women developed thromboembolism during pregnancy. Heijboer and colleagues (1990) found that 8 percent of nonpregnant patients with deep vein thrombosis had deficiencies of antithrombin-III, protein C, protein S, or plasminogen, compared with 2 percent of age- and sex-matched controls without thrombosis. More recently, Hellgren and associates (1995) found that 60 percent of pregnant women with thromboembolism had activated protein C resistance caused by a defect in the factor V gene.
Urinary Tract Infections
Infections of the urinary tract are the most common bacterial infections encountered during pregnancy. Although asymptomatic bacteriuria is more common, symptomatic infection may involve the lower tract to cause cystitis, or it may involve the renal calyces, pelvis, and parenchyma to cause pyelonephritis.
Organisms that cause urinary infections are those from the normal perineal flora. There is now evidence that some strains of Escherichia coli have pili that enhance their virulence (Svanborg-Eden, 1982). Also called adhesions or P-fimbriae, these appendages allow bacterial attachment to glycoprotein receptors on uro-epithelial cell membranes . Although pregnancy itself does not seem to enhance these virulence factors, urinary stasis apparently does, and along with vesicoureteral reflux in some women, it predisposes to symptomatic upper urinary infections.
In the early puerperium, bladder sensitivity to intravesical fluid tension is often decreased as the consequence of the trauma of labor as well as analgesia, especially epidural or spinal blockade. Sensations of bladder distension are also likely diminished by discomfort caused by a large episiotomy, periurethral lacerations, or vaginal wall hematomas. Following delivery when the oxytocin is stopped, a diuresis often follows with copious urine production and bladder distension. Overdistension, coupled with catheterization to provide relief, commonly leads to urinary infection.
Asymptomatic bacteriuria refers to persistent actively multiplying bacteria within the urinary tract without symptoms. The reported prevalence of bacteriuria during pregnancy varies from 2 to 7 percent, and depends on parity, race, and socioeconomic status. The highest incidence has been reported in African-American multiparas with sickle-cell trait, and the lowest incidence has been found in affluent white women of low parity.
Bacteriuria is typically present at the time of the first prenatal visit, and after an initial negative urine culture, one percent or less of women develop urinary infection (Whalley, 1967). A clean-voided specimen containing more than 100,000 organisms of a single uropathogen per mL is considered evidence for infection. Although smaller numbers of bacteria may represent contamination, lower colony counts may sometimes represent active infection, especially in the presence of symptoms. Thus, it seems prudent to treat lower concentrations, because pyelonephritis may occur with counts of only 20,000 to 50,000/mL of a single uropathogen (Lucas and Cunningham, 1993).
Significance. If asymptomatic bacteriuria is not treated, about 25 percent of infected women subsequently develop acute symptomatic infection during that pregnancy. Eradication of bacteriuria with antimicrobial agents has been shown to prevent most of these clinically evident infections. Although it is reasonable to perform routine screening for bacteriuria in women at high risk, screening via urine culture may not be cost effective when the prevalence is low. Less expensive tests such as the leukocyte esterase-nitrite dipstick have been shown to be cost effective with prevalences of 2 percent (Rouse and colleagues, 1995). Another approach for the low-risk population is to perform screening cultures selected by historical factors. Gratacos and associates (1994) reported a decreased incidence of pyelonephritis from 1.8 to 0.6 percent in their population following the introduction of a screening and treatment program for asymptomatic bacteriuria.
In addition to causing symptomatic infection, covert bacteriuria has been associated in some studies with a number of other adverse pregnancy outcomes. In early studies by Kass (1962), the incidence of preterm births, defined as birthweight of 2500 g or less, was 27 percent among 95 bacteriuric women given placebo during pregnancy, whereas it was only 7 percent among 84 women treated with antimicrobial agents. The corresponding perinatal death rates were 14 and 0 percent, respectively. Kincaid-Smith and Bullen (1965) also reported an increased incidence of low-birthweight infants among untreated bacteriuric women, but they were unable to reduce this with antimicrobial therapy.
In other studies, bacteriuria has been linked to an increased incidence of pregnancy-induced hypertension and anemia. Using multivariate analysis for a perinatal registry cohort of 25,746 mother–infant pairs, Schieve and colleagues (1994) reported increased risks for low birthweight, preterm delivery, hypertension or preeclampsia, and maternal anemia. These findings are at variance with those of Gilstrap and colleagues (1981b), who compared pregnancy outcomes in 248 pregnant woman in whom they localized asymptomatic infection to the bladder or kidney. There was no association of bacteriuria with anemia or pregnancy-induced hypertension, as well as low-birthweight infants from growth restriction or preterm delivery.
Bacteriuria persists after delivery in many of these women, and there is also a significant number with pyelographic evidence of chronic infection, obstructive lesions, or congenital urinary abnormalities (Kincaid-Smith and Bullen, 1965; Whalley and associates, 1965).
Women with asymptomatic bacteriuria may be given treatment with any of several antimicrobial regimens. Selection can be chosen on the basis of in vitro susceptibilities, but most often is empirical. For example, treatment for 10 days with nitrofurantoin macrocrystals, 100 mg daily, has proved effective in most women. Other regimens include ampicillin, amoxicillin, a cephalosporin, nitrofurantoin, or a sulfonamide given four times daily for 3 days . Single-dose antimicrobial therapy for bacteriuria has also been used with success (Andriole and Patterson, 1991). The recurrence rate for all of these regimens is about 30 percent. Failure of single-dose regimens may be an indication of upper tract infection and the need for more protracted therapy such as nitrofurantoin 100 mg at bedtime for 21 days (Lucas and Cunningham, 1994). For women with persistent or frequent bacteriuria recurrences, suppressive therapy for the remainder of pregnancy may be indicated. One regimen that has been successful is nitrofurantoin, 100 mg at bedtime.
Cystitis and Urethritis
There is evidence that bladder infection during pregnancy develops without antecedent covert bacteriuria (Harris and Gilstrap, 1981). Typically, cystitis is characterized by dysuria, urgency, and frequency. There are few associated systemic findings. Usually there is pyuria as well as bacteriuria. Microscopic hematuria is common, and occasionally there is gross hematuria. Although asymptomatic infection is associated with renal bacteriuria in half of cases, more than 90 percent of the cases of cystitis are limited to the bladder (Harris and Gilstrap, 1981). Although cystitis is usually uncomplicated, the upper urinary tract may become involved by ascending infection. Certainly, 40 percent of pregnant women with acute pyelonephritis have preceding symptoms of lower-tract infection (Gilstrap and associates, 1981a). Finally, Fakhoury and co-workers (1994) described two pregnant women with severe hemorrhagic cystitis. They recommend continuous bladder irrigation; one woman required blood transfusions.
Women with bacterial cystitis respond readily to any of several regimens. Harris and Gilstrap (1981) reported a 97 percent cure rate with a 10-day ampicillin regimen. Sulfonamides, nitrofurantoin, or a cephalosporin also are effective when given for 10 days. Recently, as with covert bacteriuria, there has been a trend to use a 3-day course of therapy. Single-dose therapy as described for asymptomatic bacteriuria has been shown effective for both nonpregnant and pregnant women, but concomitant pyelonephritis must be confidently excluded.
Frequency, urgency, dysuria, and pyuria accompanied by a “sterile” urine culture may be the consequence of urethritis caused by Chlamydia trachomatis, a common pathogen of the genitourinary tract. Muco-purulent cervicitis usually coexists. Erythromycin therapy usually is effective .
Acute pyelonephritis is the most common serious medical complication of pregnancy, occurring in 1 to 2 percent of pregnant women. According to the Professional Activities Study Database (1987), more than 85,000 pregnant women were hospitalized in the United States in 1985 for this complication. The population incidence varies and depends on the prevalence of covert bacteriuria and whether it is treated. For example, at Parkland Hospital, nearly 90 percent of women attend prenatal clinics where bacteriuria screening is performed and treatment given for the 8 percent who are infected. Before we began routine screening, nearly 3 percent of pregnancies were complicated by pyelonephritis; but with screening and attempts to eradicate bacteriuria, acute renal infection now complicates only about 1 percent of pregnancies. This is similar to the incidence reported by Gratacos and associates (1994) after they instituted a screening program.
Pyelonephritis is more common after midpregnancy. It is unilateral and right-sided in more than half of cases, and bilateral in one fourth. In most women, renal parenchymal infection is caused by bacteria that ascend from the lower tract. Between 75 and 90 percent of renal infections are caused by bacteria that have P-fimbriae adhesions (Stenqvist and associates, 1987).
The onset of pyelonephritis is usually rather abrupt. Symptoms include fever, shaking chills, and aching pain in one or both lumbar regions. There may be anorexia, nausea, and vomiting. The course of the disease may vary remarkably with fever to as high as 40°C or more and hypothermia to as low as 34°C. Tenderness usually can be elicited by percussion in one or both costovertebral angles. The urinary sediment frequently contains many leukocytes, frequently in clumps, and numerous bacteria. In a survey of 190 women admitted to Parkland Hospital, E coli was isolated from the urine in 77 percent, Klebsiella pneumoniae in 11 percent, and Enterobacter or Proteus each in 4 percent (Cunningham, 1988). Culture results were similar from 120 women with antepartum pyelonephritis treated at Los Angeles County–University of Southern California Medical Center (Millar and colleagues, 1995). Importantly, about 15 percent of women with acute pyelonephritis also have bacteremia.
Although the diagnosis usually is apparent, pyelo-nephritis may be mistaken for labor, chorioamnionitis, appendicitis, placental abruption, or infarcted myoma, and in the puerperium, for metritis with pelvic cellulitis.
Almost all clinical findings in these women are ultimately caused by endotoxemia, and so are the serious complications of acute pyelonephritis. A frequent and sometimes dramatic finding is thermoregulatory instability characterized by high spiking fever followed by hypothermia. Commonly, temperatures fluctuate from as low as 34°C to as high as 42°C (Fig )
Twickler and associates (1994) have shown a significantly decreased systemic vascular resistance and increased cardiac output in women with acute infection. These are mediated by cytokines that are elaborated by macrophages in response to endotoxin. These include interleukin-1, previously termed endogenous pyrogen, or tumor necrosis factor (Parrillo, 1993).
Plasma creatinine should be measured early in the course of therapy. Acute pyelonephritis in some pregnant women causes a considerable reduction in the glomerular filtration rate that is reversed by effective treatment and recovery. From 1 to 2 percent of women with antepartum pyelonephritis develop varying degrees of respiratory insufficiency caused by endotoxin-induced alveolar injury and pulmonary edema (Cunningham and associates, 1987; Sanchez-Ramos and colleagues, 1995). In some women, pulmonary injury is severe with resultant adult respiratory distress syndrome. Occasionally, tracheal intubation with mechanical ventilation is lifesaving (Fig. ).
Graham and associates (1993) confirmed that institution of antimicrobial treatment in these women was followed by increased uterine activity. This likely is due to endotoxin release. For women given b-agonist tocolysis, Towers and co-workers (1991) reported that 8 percent developed respiratory insufficiency. Ridgway and colleagues (1991) observed that plasma colloid osmotic pressure reaches a nadir 24 hours after treatment is begun.
Endotoxin-induced hemolysis is also common, and about one third develop acute anemia (Cox and colleagues, 1991). Recent evidence is indicative that acute pyelonephritis does not affect erythropoietin production either acutely or during the next several days of infection (Cavenee and colleagues, 1994).
MacMillan and Grimes (1991) have questioned the clinical utility and cost effectiveness of pretreatment urine and blood cultures. Intravenous hydration to insure adequate urinary output is essential. Because 15 percent of these women have bacteremia, during the first day or so of therapy they should be watched carefully to detect symptoms of endotoxin shock or its sequelae. Urinary output, blood pressure, and temperature are monitored closely. High fever should be treated, usually with a cooling blanket.
These serious urinary infections usually respond quickly to intravenous hydration and antimicrobial therapy. The choice of drug is empirical, and ampicillin, a cephalosporin, or an extended-spectrum penicillin is satisfactory (Cox and Cunningham, 1988b). Ampicillin resistance of E coli has become common; Duff (1984) reported a 27 percent clinical failure rate in 131 women given ampicillin. In a recent audit of urine cultures from 130 women admitted to Parkland Hospital for antepartum pyelonephritis, only half of E coli strains were sensitive to ampicillin but 90 percent were sensitive to cefazolin (Horsager and Cox, 1994). For these reasons, many prefer to give gentamicin or another aminoglycoside with ampicillin. Serial determinations of serum creatinine are important if nephrotoxic drugs are given. Finally, some prefer a cephalosporin or extended-spectrum penicillin, which have been shown to be effective in 95 percent of infected women (Cox and Cunningham, 1988b; Dunlow and Duff, 1990; Sanchez-Ramos and associates, 1995).
Clinical symptoms for the most part resolve during the first 2 days of therapy; but even though the symptoms promptly abate, many recommend therapy for a total of 7 to 10 days. Cultures of urine usually become sterile within the first 24 hours. Because changes in the urinary tract induced by pregnancy persist, reinfection is possible. If subsequent cultures of the urine are positive remote from therapy, we give nitrofurantoin, 100 mg at bedtime for the remainder of pregnancy.
Angel and associates (1990) described a randomized clinical trial in which they compared oral versus intravenous antimicrobial therapy for 90 women with antepartum pyelonephritis. Their purpose was to simulate outpatient therapy. They excluded women with underlying medical complications, those who could not tolerate oral medications, those with possible sepsis, and at least retrospectively, those 15 percent with bacteremia. The women generally did well, and one in each group developed a serious complication; one had permeability pulmonary edema and the other developed hemolytic anemia. Sanchez-Ramos and co-workers (1995) found that a single daily dose of intravenous ceftriaxone, 1 g, was effective therapy for hospitalized women. They suggested that such a regimen used with a 23-hour stay may be ideal. Millar and colleagues (1995) randomized 120 women less than 24 weeks to inpatient versus outpatient treatment. The latter were observed 4 to 24 hours to verify that they could take oral hydration. All of these women did well. In another study, Cook and collaborators (1996) observed a 25 percent failure rate of inpatient oral therapy. Careful home managed health care and close observation is mandatory if patients are discharged before they are afebrile.
During normal pregnancy the gastrointestinal tract and its appendages undergo changes, both anatomical and functional, that can appreciably alter the criteria for diagnosis and treatment of several diseases to which they are susceptible. For example, nausea and vomiting are frequent symptoms early in normal pregnancy, but if these symptoms are erroneously attributed to a normal physiological change, then gastrointestinal disease can be overlooked. Conversely, persistent nausea and vomiting in late pregnancy always should prompt a search for underlying pathology. In another example, most obstetricians, but not most internists or gastroenterologists, are aware that upper abdominal pain—epigastric or right upper quadrant—can be an ominous sign of severe preeclampsia. During advanced pregnancy, gastrointestinal symptoms become difficult to assess, and physical findings are often obscured by the large uterus and its contents.
Laparotomy and surgical treatment may be life saving for certain conditions, acute appendicitis being the most common. Nearly 1 of every 500 pregnant women will undergo laparotomy. Citing data from the Swedish Registry, Mazze and Källén (1989) reported that abdominal surgery was performed in 1331 of 720,000 pregnancies—about 1 in every 500 pregnancies. Kort and associates (1993) reported that a total of 78 women in over 49,500 births had nonobstetrical surgery during pregnancy, an incidence of 1 in 635. The most common indications for surgery were appendicitis, adnexal masses, and cholecystitis. From 1989 through 1991, 62 abdominal operations unrelated to pregnancy were performed at Parkland Hospital in nearly 45,000 pregnant women. Although about half of these were for adnexal masses, most of the remainder were for gastrointestinal lesions.
Disorders of the Upper Gastrointestinal Tract
Nausea and vomiting of moderate intensity are especially common until about 16 weeks’ gestation. Klebanoff and colleagues (1985) reported that slightly over half of 9000 women had vomiting in early pregnancy.
Fortunately, hyperemesis gravidarum has become uncommon. This syndrome is defined as vomiting sufficiently pernicious to produce weight loss, dehydration, acidosis from starvation, alkalosis from loss of hydrochloric acid in vomitus, and hypokalemia. It appears to be related to high or rapidly rising serum levels of chorionic gonadotropin or estrogens. Goodwin and associates (1994) described significantly higher total as well as free b-subunits of chorionic gonadotropin concentrations in women with hyperemesis compared with asymptomatic controls. Hyperemesis may lead to transient hepatic dysfunction.
Management. Dehydration is corrected as well as fluid and electrolyte deficits and acidosis or alkalosis. This requires appropriate amounts of sodium, potassium, chloride, lactate or bicarbonate, glucose, and water, all of which should be administered parenterally until vomiting has been controlled. Vomiting may be frequent and severe. Schwartz and Rossoff (1994) described a woman whose retching led to bilateral pneumothoraces and pneumomediastinum. A number of anti-emetics may be given to alleviate nausea and vomiting such as promethazine, prochlorperazine, and chlorpromazine. Nageotte and colleagues (1996) reported success with intravenous droperidol-diphenhydramine. For severe disease, metoclopramide may be given parenterally. This stimulates motility of the upper intestinal tract without stimulating gastric, biliary, or pancreatic secretions. Its anti-emetic properties apparently result from central antagonism of dopamine receptors. With persistent vomiting, appropriate steps should be taken to diagnose other diseases, such as gastroenteritis, cholecystitis, pancreatitis, hepatitis, peptic ulcer, pyelonephritis, and fatty liver of pregnancy.
In many instances, social and psychological factors contribute to the illness (Deuchar, 1995). With correction of these circumstances, the woman usually improves remarkably while hospitalized, only to relapse after discharge. Positive assistance with psychological and social problems is beneficial.
Godsey and Newman (1991) studied 140 women admitted for hyperemesis to the Medical University of South Carolina Hospital. In 27 percent of these women, multiple admissions were necessary. In some women with persistent and severe disease, parenteral nutrition is used (Levine and Esser, 1988). Enteral nutrition also has been successfully used after acute nausea and vomiting subside (Boyce, 1992).
Heartburn, also called pyrosis, is a common symptom in late pregnancy. The retrosternal burning sensation is caused by esophagitis from gastroesophageal reflux related to relaxation of the lower esophageal sphincter (Hytten, 1991).
Common heartburn during pregnancy is seldom severe enough to warrant diagnostic investigation. Raising the head of the bed and ingestion of oral antacids usually suffices to relieve symptoms. If severe symptoms persist despite these simple measures, an H2-receptor antagonist is prescribed. Both cimetidine and ranitidine are category B drugs (Briggs and associates, 1990). If there is then no relief, endoscopy should be considered.
Mazze and Källén (1991) described findings from 720,000 Swedish registry deliveries and reported that 778 (about 1 in 1000 pregnancies) of these women underwent appendectomy during pregnancy. Appendicitis was confirmed in 65 percent, or about 1 in 1500 pregnancies.
Pregnancy often makes the diagnosis of appendicitis more difficult because: (1) Anorexia, nausea, and vomiting that accompany normal pregnancy are fairly common symptoms of appendicitis. (2) As the uterus enlarges, the appendix commonly moves upward and outward toward the flank, so that pain and tenderness may not be prominent in the right lower quadrant
Fig. 1. (3) Some degree of leukocytosis is the rule during normal pregnancy. (4) During pregnancy especially, other diseases may be confused with appendicitis, such as pyelonephritis, renal colic, placental abruption, and degeneration of a uterine myoma. (5) Pregnant women, especially those late in gestation, frequently do not have symptoms considered “typical” for nonpregnant patients with appendicitis.
As the appendix is pushed progressively higher by the growing uterus, containment of infection by the omentum becomes increasingly unlikely, and appendiceal rupture is more likely to cause generalized peritonitis. Acute appendicitis in the last trimester, therefore, may carry a poor prognosis, and it is worth emphasizing that in some series maternal mortality approaches 5 percent (Sharp, 1994). Increased fetal and maternal morbidity and mortality is almost invariably due to surgical delay (Cunningham and McCubbin, 1975).
Effects on Pregnancy Outcome
Effects on Pregnancy Outcome. Appendicitis increases the likelihood of abortion or preterm labor, especially if there is peritonitis. Mazze and Källén (1991) found that spontaneous labor ensued with greater frequency if surgery for appendicitis was performed after 23 weeks. Fetal loss is increased in most series, and overall it is about 15 percent. In the Swedish study, fetal loss was 22 percent if surgery was performed after 23 weeks’ gestation. Mays and colleagues (1995) have suggested a link between maternal–fetal sepsis and neonatal neurological injury.
Diagnosis and Management
Diagnosis and Management. Persistent abdominal pain and tenderness are the most reproducible findings. If appendicitis is suspected, treatment, regardless of the stage of gestation, is immediate surgical exploration. The diagnosis is a clinical one, and few laboratory tests are helpful. Graded compression using ultrasound imaging has been demonstrated to be effective in the diagnosis of appendicitis in nonpregnant patients (Chesbrough and co-workers, 1993; Puylaert and colleagues, 1987). Landwehr and associates (1996) correctly predicted appendicitis in 4 of 5 pregnant women using graded-compression ultrasound. Even though diagnostic errors sometimes lead to the removal of a normal appendix, it is better to operate unnecessarily than to postpone intervention until generalized peritonitis has developed. In most reports, the diagnosis is verified in about half of women who undergo surgical exploration (Sharp, 1994). In the Swedish study of 778 women operated for suspected appendicitis, the diagnosis was confirmed in 65 percent (Mazze and Källén, 1991). In the first trimester, 77 percent of diagnoses were correct; however, in the latter two trimesters, only 57 percent of diagnoses were confirmed at surgery.
During surgery and recovery, intravenous antimicrobials are given if there is gangrene, perforation, or a periappendiceal phlegmon. If generalized peritonitis does not develop, then the prognosis is quite good. Seldom is cesarean delivery indicated at the time of appendectomy. Uterine contractions are common if there is peritonitis. Although some recommend tocolytic agents for these women, we do not. De Veciana and colleagues (1994) reported that increased intravenous fluid administration and tocolytic use increased the risk for pulmonary injury with antepartum appendicitis.
Undiagnosed appendicitis often stimulates labor. The large uterus frequently helps to contain infection locally, but after delivery when the uterus rapidly empties, the walled-off infection is disrupted with spillage of free pus into the peritoneal cavity. In these cases, an acute surgical abdomen is encountered within a few postpartum hours.
Simply because it is coincidental, appendicitis during the early puerperium is rare. In some cases, especially with early appendicitis, diagnosis is particularly difficult because of the normally robust leukocytosis as well as the frequency of other puerperal disorders with similar signs and symptoms. Anorexia with any evidence of peritoneal irritation, such as distension and adynamic ileus, should suggest appendicitis. Puerperal pelvic infections typically do not cause peritonitis.
A number of infectious agents can cause acute inflammation of the colon. Viral gastroenteritis is most common, and the Norwalk virus accounts for up to one third of epidemics in developed countries (Bennett, 1995). In many cases, the principal diagnostic dilemma is to exclude new-onset inflammatory bowel disease. Infectious colitis often presents with bloody diarrhea, but its hallmark is the demonstration of numerous leukocytes in the stool.
Traveler’s diarrhea, usually due to enterotoxigenic Escherichia coli, afflicts as many as one third of foreign travelers. Symptoms appear abruptly, with urgent diarrhea, abdominal cramping, nausea, and low-grade fever. Fluid loss may be impressive and treatment is to insure adequate hydration given along with bismuth subsalicylate. Women with severe diarrhea are also given trimethoprim-sulfamethoxazole. Amebiasis may present as colitis and bloody diarrhea, and the diagnosis should be suspected in foreign-born nationals or in women who have recently traveled outside of the United States
Acute bacillary dysentery is caused by Shigella, nontyphoidal Salmonellae, or Campylobacter species. These invasive organisms characteristically affect the colon and terminal ileum and destroy segments of mucosa. Along with numerous small-volume stools of blood, pus, and mucus, they also usually have associated systemic symptoms. Diagnosis is by stool culture. Intravenous hydration should be provided, and unless symptoms are severe, most do not recommend antibacterial and antiperistaltic agents (Bennett, 1995).
Antibiotic-associated colitis, which in its worst form is termed pseudomembranous colitis is caused by the toxin of Clostridium difficile, which overgrows after treatment is given with any of a large number of antimicrobials.
According to Kelly and colleagues (1994), ampicillin or amoxicillin, cephalosporins, and clindamycin are the most common agents that induce such colitis. Although fewer than 1 percent of adults are colonized with C. difficile, almost 25 percent of adults recently treated with antibiotics are colonized. Fortunately, the majority remain asymptomatic (Kelly and associates, 1994). Severe colitis is characterized clinically by profuse diarrhea, abdominal pain and distention, fever, anorexia, and hypovolemia. Diagnosis can be confirmed by using sigmoidoscopy; more severe cases have pseudomembrane formation. In its most severe form, a toxic-megacolon syndrome is characterized by an acute abdomen and an obviously ill patient. The diagnosis of associated perforation is especially problematic during pregnancy. Abdominal radiography should be performed to assess for colonic distention and possibly free air. Computed tomography may be useful in pregnancy . Therapy with intravenous fluids and metronidazole or vancomycin is given, but occasionally colectomy is necessary.
Diseases of the Liver
It has become customary to divide liver diseases into those coincidental to pregnancy, those specifically related to pregnancy, and chronic liver disease upon which pregnancy supervenes. Liver diseases complicating pregnancy more often than not are coincidental, as with acute viral hepatitis or drug-induced hepatic failure. There are some diseases that are induced by pregnancy that disappear following delivery. These include intrahepatic cholestasis of pregnancy with or without icterus gravidarum, acute fatty liver of pregnancy, hepatocellular damage of varying intensity that is the direct consequence of severe preeclampsia and eclampsia, and hepatic dysfunction associated with hyperemesis gravidarum. Finally, pregnancy may be superimposed on chronic hepatitis or cirrhosis, or more recently, may follow liver transplantation.
Pregnancy induces physiological changes that often confuse the diagnosis of several hematological disorders and the assessment of their treatment. This is especially true for anemia. A number of marked pregnancy-induced hematological changes are discussed in detail in Chapter 8. One of the most significant changes is that of blood volume expansion by a mean of 50 percent. Plasma volume increases disproportionately compared with red cell mass, resulting in physiological decrease in hematocrit. During this time, iron requirements for mother and fetus average nearly 1000 mg.
Definition of Anemia
A precise definition of anemia in women is complicated by normal differences in the concentrations of hemoglobin between women and men, between white and black women, between women who are pregnant and those who are not, and between pregnant women who receive iron supplements and those who do not.
Extensive hematological measurements have been made in healthy nonpregnant women, none of whom were iron deficient because each had histochemically proven iron stores, and none were folate deficient because marrow erythropoiesis remained normoblastic. On the basis of data , anemia in nonpregnant women is defined as hemoglobin concentration less than 12 g/dL and less than 10 g/dL during pregnancy or the puerperium. The hemoglobin concentration is lower in midpregnancy. Early in pregnancy and again near term, the hemoglobin level of most healthy women with iron stores is 11 g/dL or higher. For these reasons, the Centers for Disease Control (1990) defined anemia as less than 11 g/dL in the first and third trimesters, and less than 10.5 g/dL in the second trimester.
The modest fall in hemoglobin levels observed during pregnancy in healthy women not deficient in iron or folate is caused by a relatively greater expansion of plasma volume compared with the increase in hemoglobin mass and red cell volume. The disproportion between the rates at which plasma and erythrocytes are added to the maternal circulation is normally greatest during the second trimester. The long-used term physiological anemia to describe this process is an oxymoron and should be discarded. Late in pregnancy, plasma expansion essentially ceases while hemoglobin mass continues to increase .
During the puerperium, in the absence of excessive blood loss, hemoglobin concentration is not appreciably less than predelivery. After delivery the hemoglobin level typically fluctuates to a modest degree around the predelivery value for a few days and then rises to the higher nonpregnant level. The rate and magnitude of increase early in the puerperium are the result of the amount of hemoglobin added during pregnancy and the amount lost by blood loss at delivery and modified by a puerperal decrease in plasma volume.
Frequency of Anemia
Although anemia is somewhat more common among indigent pregnant women, it is by no means restricted to them. The frequency of anemia during pregnancy varies considerably, depending primarily upon whether supplemental iron is taken during pregnancy. For example, at Parkland Hospital the hemoglobin level at the time of delivery among women who took iron supplements averaged 12.4 g/dL, whereas it was only 11.3 g/dL among those who were not taking iron. Moreover, in none of the group receiving iron supplements was the hemoglobin less than 10 g/dL, but it was below this level in 16 percent of those who took no supplements . Taylor and associates (1982) reported similar observations, that is, hemoglobin levels at term averaged 12.7 g/dL among women who received supplemental iron compared with 11.2 g/dL for women who did not.
Etiology of Anemia. Any disorder causing anemia encountered in childbearing-age women may complicate pregnancy. A classification based primarily on etiology and including most of the common causes of anemia in pregnant women is shown in Table TABLE . CAUSES OF ANEMIA DURING PREGNANCY
Anemia caused by acute blood loss
Anemia of inflammation or malignancy
Acquired hemolytic anemia
Aplastic or hypoplastic anemia
Hereditary hemolytic anemias
Effects of Anemia on Pregnancy
The etiology of anemia is important when evaluating its effects on pregnancy outcome. For example, maternal and perinatal outcomes are altered markedly in women with sickle-cell anemia. Currently, there is no evidence that adverse outcomes are related to the anemia itself but rather to the vascular complications of sickling.
Most studies of the effects of anemia on pregnancy, describe large populations, and at least ostensibly deal with nutritional anemias, specifically those due to iron deficiency. Klebanoff and co-workers (1991) studied nearly 27,000 women and found a slightly increased risk of preterm birth with midtrimester anemia. Lieberman and collaborators (1987) found a positive association with low hematocrit and preterm birth in black women, and suggested that anemia was a marker for nutritional deficiencies. Godfrey and colleagues (1991) suggested a link between maternal iron-deficiency anemia with low birthweight and subsequent adult hypertension developing in the infant.
According to the World Health Organization, anemia has been implicated as contributory in up to 40 percent of maternal deaths in third-world countries (Viteri, 1994). Ironically, in otherwise healthy women, higher hemoglobin concentrations are more likely associated with adverse pregnancy outcome. In these cases, the normal blood volume expansion of pregnancy appears to have been curtailed. Murphy and colleagues (1986) reported findings from the Cardiff Birth Survey of over 54,000 singleton pregnancies and described excessive perinatal mortality with high hemoglobin concentrations. Specifically, women whose hemoglobin concentration exceeded 13.2 g/dL at 13 to 18 weeks had excessive perinatal mortality, low-birthweight infants, and preterm delivery, as well as preeclampsia in nulliparas. Similarly, Lu and associates (1991) studied the relationship between hematocrit and pregnancy outcome in over 17,000 iron- and folate-supplemented women and found a relationship between fetal growth restriction and a high hematocrit.
The two most common causes of anemia during pregnancy and the puerperium are iron deficiency and acute blood loss. Not infrequently, the two are intimately related, because excessive blood loss with its concomitant loss of hemoglobin iron and exhaustion of iron stores in one pregnancy can be an important cause of iron-deficiency anemia in the next pregnancy.
In a typical gestation with a single fetus, the maternal need for iron induced by pregnancy averages close to 800 mg; about 300 mg for the fetus and placenta and about 500 mg, if available, for maternal hemoglobin mass expansion. Approximately 200 mg more are shed through the gut, urine, and skin. This total amount—1000 mg—considerably exceeds the iron stores of most women. Unless the difference between the amount of stored iron available to the mother and the iron requirements of normal pregnancy cited is compensated for by absorption of iron from the gastrointestinal tract, iron-deficiency anemia develops.
With the rather rapid expansion of blood volume during the second trimester, iron lack is often manifested by an appreciable drop in hemoglobin concentration. Although the rate of expansion of blood volume is not so great in the third trimester, the need for iron is still increased because augmentation of maternal hemoglobin mass continues, and considerable iron is now transported to the fetus. Because the amount of iron diverted to the fetus from an iron-deficient mother is not much different from the amount normally transferred, the newborn infant of a severely anemic mother does not suffer from iron-deficiency anemia. Iron stores in the infant are influenced much more by when and how the cord is clamped rather than by maternal iron stores .
Classical morphological evidence of iron-deficiency anemia—erythrocyte hypochromia and microcytosis—is less prominent in the pregnant woman compared with the nonpregnant woman with the same hemoglobin concentration. Moderate iron-deficiency anemia during pregnancy—for example, a hemoglobin concentration of 9 g/dL—usually is not accompanied by obvious morphological changes in erythrocytes. With this degree of anemia from iron deficiency, however, serum ferritin levels are lower than normal, and there is no stainable bone marrow iron. The serum iron-binding capacity is elevated, but by itself this is of little diagnostic value because it also is elevated during normal pregnancy in the absence of iron deficiency. Moderate normoblastic hyperplasia of the bone marrow also is found to be similar to that in normal pregnancy. Thus, iron-deficiency anemia during pregnancy is the consequence primarily of expansion of plasma volume without normal expansion of maternal hemoglobin mass.
The initial evaluation of a pregnant woman with moderate anemia should include measurements of hemoglobin, hematocrit, and red cell indices, careful examination of a well-prepared smear of the peripheral blood, a sickle-cell preparation if the woman is of African origin, and the measurement of the serum iron concentration or serum ferritin level, or both. Carriaga and colleagues (1991) reported that normal serum ferritin concentration excludes iron deficiency but that decreased values do not confirm it. In their study, the mean serum ferritin concentration during pregnancy was 14.3 mg/L, compared with 25 to 30 mg/L in nonpregnant women. The diagnosis of iron deficiency in moderately anemic pregnant women usually is presumptive and based largely on the exclusion of other causes of anemia.
When the pregnant woman with moderate iron-deficiency anemia is given adequate iron therapy, a hematological response is detected by an elevated reticulocyte count. The rate of increase of hemoglobin concentration or hematocrit varies considerably, but usually it is slower than in nonpregnant women. The reason is related largely to the differences in blood volumes, and during the latter half of pregnancy, newly formed hemoglobin is added to the characteristically much larger volume.
The objectives of treatment are correction of the deficit in hemoglobin mass and eventually restitution of iron stores. Both of these objectives can be accomplished with orally administered, simple iron compounds—ferrous sulfate, fumarate, or gluconate—that provide a daily dose of about 200 mg of elemental iron. There is no need to prescribe ascorbic acid or fruit juices or to withhold food to enhance iron absorption, nor is there any advantage from delayed-release or sustained-release medication. If the woman cannot or will not take oral iron preparations, then parenteral therapy is given. To replenish iron stores, oral therapy should be continued for 3 months or so after the anemia has been corrected.
Transfusions of red cells or whole blood seldom are indicated for the treatment of iron-deficiency anemia unless hypovolemia from blood loss coexists or an emergency operative procedure must be performed on a severely anemic woman.
Anemia from Acute Blood Loss
Anemia resulting from recent hemorrhage is more likely to be evident during the puerperium. Both abruptio placentae and placenta previa may be sources of serious blood loss and of anemia before as well as after delivery. Earlier in pregnancy, anemia caused by acute blood loss is common in instances of abortion, ectopic pregnancy, and hydatidiform mole. Massive hemorrhage demands immediate treatment to restore and maintain perfusion of vital organs . Even though the amount of blood replaced commonly does not completely repair the hemoglobin deficit created by the hemorrhage, in general, once dangerous hypovolemia has been overcome and hemostasis has been achieved, the residual anemia should be treated with iron. For the moderately anemic woman whose hemoglobin is more than 7 g/dL, whose condition is stable, who no longer faces the likelihood of further serious hemorrhage, who can ambulate without adverse symptoms, and who is not febrile, iron therapy for at least 3 months rather than blood transfusions is the best treatment.
This and the preceding 19 editions of Williams Obstetrics provide witness that the 20th century has been a remarkable time for the diabetic woman who becomes pregnant. At the beginning of the century, diabetic women suffered from infertility, and the rare woman achieving pregnancy faced a dismal prognosis. Maternal death was a real threat, and perinatal survival a mere 40 percent. The availability of insulin, beginning in 1922, restored fertility and virtually abolished maternal mortality. At the same time, perinatal survival did not change appreciably.
To improve this dismal perinatal mortality, obstetricians increasingly focused on both timing and mode of delivery, so that by the 1930s, awareness of fetal macrosomia and intrapartum deaths led to frequent cesarean delivery (White and colleagues, 1939). Some improvement followed, but unexplained late antepartum deaths continued to be a problem and led to early delivery with resultant neonatal immaturity and its consequences. The development of the White Classification in 1949, by which fetal risk was shown to be proportional to the severity of maternal diabetes, permitted individualized timing of delivery, and helped reduce perinatal mortality. These management landmarks improved perinatal survival to about 85 percent by the late 1950s (White, 1978b). In the ensuing years, up to the present, several refinements in management of diabetic women and their fetuses or infants have resulted in a perinatal mortality rate, excluding malformations, nearly equivalent to that observed in normal pregnancies.
Diabetes is classified as type 1 (insulin dependent) or type 2 (noninsulin dependent) according to whether the patient requires exogenous insulin to prevent ketoacidosis. Type 1 diabetes is immune mediated and develops in genetically susceptible persons. This predisposition is permissive rather than causal and disease presumably is triggered by a viral infection. There is inflammatory insulitis with lymphocytic infiltration of islets. Subsequently, there is immune stimulation of antibodies against the b-cell. The b-cell membrane becomes susceptible to autoimmune cytotoxic antibodies, which leads to eventual destruction of the cell and resultant diabetes. The genetics of type 1 diabetes is complex, but there is general agreement that there is an association with the HLA-D histocompatibility complex located on chromosome 6. There is a low vertical transmission rate in type 1 disease. Moreover, the concordance rate for diabetes in monozygous twins, rather than being nearly 100 percent if diabetes were solely genetic in origin, is less than 50 percent .
There has been no HLA association discovered with type 2 noninsulin-dependent diabetes. The disease has a familial occurrence and concordance in monozygotic twins is 100 percent. Nearly 40 percent of siblings and one third of offspring develop abnormal glucose tolerance or obvious diabetes (Foster, 1994). Its pathophysiology is abnormal insulin secretion and insulin resistance in target tissues. Most patients are overtly obese, and there is speculation that peripheral insulin resistance induced by obesity leads to b-cell exhaustion.
Diabetes is the most common medical complication of pregnancy. Patients can be separated into those who were known to have diabetes before pregnancy (overt) and those diagnosed during pregnancy (gestational). In 1993, a total of 102,234 American women had pregnancies complicated by diabetes, representing 2.6 percent of all live births in the nation (Ventura and colleagues, 1995). It is estimated that 90 percent of all pregnancies complicated by diabetes are due to gestational diabetes. Thus, in 1993, approximately 10,000 American women with overt diabetes, and 90,000 with gestational diabetes, delivered live births.
Classification During Pregnancy
In the 1986 classification, women diagnosed to have gestational diabetes are subdivided according to their degree of glycemia. Specifically, those with fasting hyperglycemia (105 mg/dL or greater) are placed into class A2. Approximately 5 percent of women with gestational diabetes will exhibit fasting hyperglycemia (Magee and co-workers, 1993). Women in classes B to H, corresponding to the White classification (1978a), have overt diabetes antedating pregnancy. The White system emphasizes that end-organ derangements, especially involving the eyes, kidneys, and heart, have significant effects on pregnancy outcome.
Diagnosis of Overt Diabetes During Pregnancy
The woman with high plasma glucose levels, glucosuria, and ketoacidosis presents no problem in diagnosis. Similarly, women with a random plasma glucose level greater than 200 mg/dL plus classical signs and symptoms such as polydipsia, polyuria, and weight loss should be considered to have overt diabetes (American Diabetes Association, 1991). The woman at the opposite end of the spectrum, with only minimal metabolic derangement, may be difficult to identify. The likelihood of impaired carbohydrate metabolism is increased appreciably in women who have a strong familial history of diabetes, have given birth to large infants, demonstrate persistent glucosuria, or have unexplained fetal losses.
Reducing substances are commonly found in the urine of pregnant women. Unless a method that is specific for glucose is used, often the substance identified is lactose, which is not a source of concern. Commercially available dipsticks may be used to identify glucosuria while avoiding a positive reaction from lactose. Even then, glucosuria most often does not reflect impaired glucose tolerance, but rather augmented glomerular filtration. Nonetheless, the detection of glucosuria during pregnancy warrants further investigation (Gribble and co-authors, 1995).
Detection of Gestational Diabetes
Gestational diabetes mellitus is defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy. This definition applies regardless of whether or not insulin is used for treatment. Undoubtedly, some women with gestational diabetes have previously unrecognized overt diabetes. Because gestational diabetes is typically a disorder of late gestation, hyperglycemia during the first trimester usually means overt diabetes (American Diabetes Association, 1995).
There is no agreement as to the most appropriate diagnostic criteria for gestational diabetes, nor even the most appropriate selection of women to be screened for this disorder.
Traditionally, obstetricians have relied on historical and clinical risk factors to identify those women most likely to develop gestational diabetes. These risk factors have included age over 30; family history of diabetes; a prior macrosomic, malformed, or stillborn infant; obesity; hypertension; or glucosuria (American College of Obstetricians and Gynecologists, 1986). Use of these risk factors has been criticized because up to half of women with gestational diabetes would be missed (Coustan and co-workers, 1989). The 1990 Chicago Workshop Conference on Gestational Diabetes recommended that all pregnant women should be screened (universal screening) using a 50-g oral glucose tolerance test between 24 and 28 weeks without regard to time of day or last meal, and that a plasma value at 1 hour exceeding 140 mg/dL be used as the cutoff for performing the diagnostic 100-g 3-hour oral glucose tolerance test (described later). Women with a previous history of gestational diabetes may benefit from earlier screening. If screening in early pregnancy yields a normal result, subsequent screening should be performed at 24 to 28 weeks (American College of Obstetricians and Gynecologists, 1994).
Owen and colleagues (1995) surveyed obstetrics and gynecology residency programs in the United States and found that 97 percent were using universal screening between 24 and 28 weeks. According to the American College of Obstetricians and Gynecologists (1994), the sensitivity of screening may be improved by using a 130 mg/dL threshold, rather than 140 mg/dL, to define an abnormal response to the 50-g test. Use of the lower threshold value may increase detection of gestational diabetes from 90 percent to nearly 100 percent but at the expense of subjecting 25 percent of pregnant women to the 3-hour test. Surprisingly, only 40 percent of respondents in the survey by Owen and colleagues (1995) were using the 140 mg/dL threshold that is most commonly recommended.
The day-to-day reproducibility of the 50-g screening test has also been tested (Espinosa and co-workers, 1993). Approximately 90 percent of normal results were reproducible the next day but only 83 percent of abnormal tests were reproducible. Murphy and colleagues (1994) studied the accuracy and precision of recent-generation reflectance photometers (Accu-Check III) for screening. Use of the glucometer required redefining the circumstances for testing as well as threshold values for abnormal results. It seems best to avoid these devices for screening.
There is international disagreement as to the optimal glucose tolerance test for the definitive diagnosis of gestational diabetes. In the United States, the 100-g 3-hour oral glucose tolerance test performed after an overnight fast remains the standard for diagnosis of gestational diabetes (American College of Obstetricians and Gynecologists, 1994). Catalano and co-workers (1993) found that the 100-g 3-hour test was not reproducible in 24 percent of women when repeated 1 week after the initial test. They attributed this to increased norepinephrine-mediated gluconeogenesis due to maternal stress at initial testing.
There is not a consensus as to which glucose threshold values to use for diagnosis of gestational diabetes. Plasma values suggested by the American College of Obstetricians and Gynecologists (1994) are shown in Table 52–3 and permit use of normative data suggested by the National Diabetes Data Group (1979) as well as those of Carpenter and Coustan (1982). Diagnosis of gestational diabetes is generally made in either set of criteria when any two values are met or exceeded. Berkus and Langer (1993), however, suggest that only one abnormal value is sufficient. Rust and colleagues (1996) studied the effects of lowering glucose-tolerance test thresholds or using one abnormal test value to diagnose gestational diabetes in 434 women with abnormal 50-g screening results. They concluded that liberalizing the criteria for diagnosis of gestational diabetes led to overdiagnosis with no improvement in perinatal outcomes. At the 2nd International Symposium on Diabetes and Pregnancy (1995), Langer suggested that the lack of consensus could be resolved if “we lock the top recognized specialists in a room until they come out and agree on diagnostic criteria.” According to the survey by Owen and colleagues (1995), 77 percent of residency programs use the National Diabetes Data Group (1979) criteria and 96 percent require two or more abnormal values. These are the diagnostic criteria in use at Parkland Hospital. About 15 percent of all pregnant women have an abnormal 1-hour screening test and 15 percent of these will be found to have gestational diabetes defined by at least two abnormal values using the 3-hour test.
“Gestational” diabetes implies that this disorder is induced by pregnancy, perhaps due to exaggerated physiological changes in glucose metabolism . An alternative explanation is that gestational diabetes is maturity-onset or type 2 diabetes unmasked or discovered during pregnancy. For example, Harris (1988) found that the prevalence of undiagnosed glucose intolerance in nonpregnant American women between the ages of 20 and 44 years was virtually identical to the prevalence of gestational diabetes. Berkus and associates (1996) also concluded that gestational diabetes was likely maturity-onset diabetes rather than a distinct diabetic state due to pregnancy. Carpenter and colleagues (1996) and Curet and co-workers (1996) observed that women diagnosed to have gestational diabetes have preexisting aberrations in insulin economy. Similarly, Peters and associates (1996) found that a subsequent pregnancy in women with prior gestational diabetes accelerated the development of maturity-onset diabetes. They hypothesized that pregnancy induced episodes of insulin resistance contributed to a preexisting decline in b-cell function.
The American Diabetes Association convened three workshop–conferences on gestational diabetes between 1979 and 1990. These conferences and the published proceedings have had major influences on current management. In 1990, the Third International Workshop– Conference on Gestational Diabetes (1991) was held in Chicago. Use of the diagnostic term gestational diabetes was encouraged in order to communicate the need for increased surveillance and to convince women of the need for further testing postpartum. The likelihood of fetal death with appropriately treated gestational diabetes was found no different than in the general population. The most important perinatal concern was excessive fetal growth, which may result in birth trauma. Importantly, more than half of women with gestational diabetes ultimately develop overt diabetes in the ensuing 20 years, and there is mounting evidence for long-range complications that include obesity and diabetes in their offspring. The 1990 Workshop recommendations have been largely adopted by the American College of Obstetricians and Gynecologists (1994).
There has been an important shift in focus concerning adverse fetal consequences of gestational diabetes. Importantly, unlike in women with overt diabetes, fetal anomalies are not increased (Reece and Hobbins, 1986). Similarly, whereas pregnancies in women with overt diabetes are at greater risk for fetal death, this danger is not apparent for those with postprandial hyperglycemia only, that is, class A1 (Lucas and co-workers, 1993). In contrast, gestational diabetes with elevated fasting glucose (class A2), has been associated with unexplained stillbirth similar to overt diabetes (Johnstone and colleagues, 1990).
The perinatal focal point now is avoidance of difficult delivery due to macrosomia, with concomitant birth trauma due to shoulder dystocia. Except for the brain, most fetal organs are affected by macrosomia that commonly (but not always) characterizes the fetus of a diabetic woman. Modanlou and colleagues (1982) observed that macrosomic infants of diabetic mothers Fig.
were anthropometrically different from other large-for-age infants because those whose mothers had diabetes had excessive fat deposition on the shoulders and trunk, predisposing these fetuses to shoulder dystocia. Similarly, Bernstein and Catalano (1994), using measurements of subscapular and triceps skin-fold thickness, found that fat infants of diabetic women more often required cesarean delivery for cephalopelvic disproportion. Fortunately, shoulder dystocia is uncommon, even in women with gestational diabetes. For example, Magee and colleagues (1993) diagnosed shoulder dystocia in 3 percent of women with class A1 diabetes. None of these infants sustained brachial plexus injuries.
Macrosomia in these infants is compatible with the long-recognized association between fetal hyperinsulinemia resulting from maternal hyperglycemia, which in turn stimulates excessive somatic growth. Similarly, hyperinsulinemia in the infant may provoke hypoglycemia within minutes of birth. The incidence varies greatly depending on the threshold used to define significant neonatal hypoglycemia. According to the American Diabetes Association (1995), values less than 35 mg/dL at term are abnormal. A lower value is considered abnormal in preterm infants, because glycogen stores have not reached term levels. Magee and co-workers (1993) reported that 4 percent of infants of women with gestational diabetes required intravenous glucose therapy for hypoglycemia.
There is extensive, although largely indirect, evidence that insulin and the insulin-like growth factors I (IGF-I) and II (IGF-II) have a role in the regulation of fetal growth (Verhaeghe and co-authors, 1993). Insulin is secreted by fetal pancreatic b-cells primarily during the second half of gestation, and is believed to stimulate somatic growth and adiposity. These growth factors, which structurally are proinsulin-like polypeptides, are produced by virtually all fetal organs and are potent stimulators of cell differentiation and division. Verhaeghe and co-workers (1993) measured cord serum insulin-like growth factors and insulin (c-peptide) concentrations throughout gestation in women without diabetes and found that levels were associated with birthweight (Fig. 52–2 ). Large-for-age infants had significantly increased levels of these factors.
Maternal obesity is an independent and more important risk factor for large infants in women with gestational diabetes than is glucose intolerance (Lucas and colleagues, 1993; Leonardi and Bottoms, 1996). Moreover, maternal obesity is itself an important confounding factor in the diagnosis of gestational diabetes. Johnson and colleagues (1987) reported that 8 percent of 588 women who weighed more than 250 pounds had gestational diabetes compared with less than 1 percent of women who weighed less than 200 pounds. Landon and colleagues (1994) and Zhang and co-workers (1995) found that the risk of gestational diabetes was increased in women with truncal obesity.
Women with gestational diabetes can be divided into two functional classes depending on their level of fasting glycemia . Insulin therapy is usually recommended when standard dietary management does not consistently maintain the fasting plasma glucose at less than 105 mg/dL or the 2-hour postprandial plasma glucose at less than 120 mg/dL (American College of Obstetricians and Gynecologists, 1994). Conversely, women without persistent fasting hypoglycemia (class A1), are usually treated by diet alone. They are typically seen at 1- to 2-week intervals, and fasting and/or postprandial plasma glucose levels are measured to insure that the glucose thresholds for insulin therapy have not been exceeded. Huddleston and colleagues (1993), however, concluded in an analysis of 194 women with gestational diabetes that the 2-hour postprandial glucose measurement was unnecessary for surveillance as long as the fasting glucose remained less than 105 mg/dL.
Nutritional counselling is a cornerstone in management. The goals of such therapy are (1) to provide the necessary nutrients for the mother and fetus, (2) to control glucose levels, and (3) to prevent starvation ketosis. Proposed daily caloric intakes and pregnancy weight gain for women with gestational diabetes are shown in Table 52–4. These recommendations pertain to women treated with insulin as well as dietary restrictions. Significant caloric restriction to 1200 to 1800 kcal/day has been studied in overweight women with gestational diabetes (Dornhorst and colleagues, 1991). Although maternal weight gain and fetal macrosomia may be decreased, the safety of this approach has not been established, and is not recommended by the American College of Obstetricians and Gynecologists (1994).
Exercise. A liberal exercise program is encouraged. Jovanovic-Peterson and associates (1989) have shown that a program of cardiovascular-conditioning exercise improves glycemic control when compared with diet alone. Appropriate exercises are those that use the upper-body muscles or place little mechanical stress on the trunk region during exercise (Durak and co-workers, 1990). It is proposed that when the lower body is kept from an excessive weight-bearing load, the work effort can be increased safely, permitting a cardiovascular workout without fear of fetal distress. Jovanovic-Peterson (1990) reported that such upper body cardiovascular training resulted in lower glucose levels. The effects of exercise on glucose levels only become apparent after 4 weeks of exercise.
Most American practitioners—93 percent according to Owen and colleagues (1995)—initiate insulin therapy in women with gestational diabetes if fasting hyperglycemia greater than 105 mg/dL persists despite diet therapy. Usually, institution of insulin therapy requires hospitalization to safely titrate the dosage and educate the woman on self-administration and measurement of capillary glucose levels.
Experts differ in their approach to insulin therapy in gestational diabetes. A total dose of 20 to 30 units given once daily, before breakfast, is commonly used to initiate therapy. The total dose is usually divided into two thirds intermediate-acting insulin (NPH or Lente) and one third short-acting insulin (regular).
Once insulin therapy has been initiated, it must be recognized that the level of glycemia necessary to reduce fetal and neonatal complications of gestational diabetes has not been established (American College of Obstetricians and Gynecologists, 1994). DeVeciana and colleagues (1995) randomized 66 women with fasting hyperglycemia (class A2 gestational diabetes) and treated with insulin to glucose surveillance using either preprandial or postprandial (1-hour after each meal) capillary blood glucose concentrations measured by glucometer. Postprandial surveillance was shown to be superior because blood glucose control was significantly improved with less neonatal hypoglycemia (3 versus 21 percent for postprandial versus preprandial surveillance), less macrosomia (12 versus 42 percent), and fewer cesarean deliveries for dystocia (24 versus 39 percent). Bansal and co-authors (1996), however, have challenged these conclusions, because the women analyzed had prestudy fasting glucose values consistent with overt diabetes.
Prophylactic insulin given to decrease complications related to macrosomia in women with fasting euglycemia (class A1) has not been proven to be beneficial and is not widely practiced in the United States. Langer and co-authors (1994) reviewed 23 reports from 1979 through 1993 and found that none demonstrated improved perinatal outcomes related to any management approach, including prophylactic insulin given to the mother. There were only two randomized studies. Thompson and colleagues (1990) randomized 108 gestational diabetics to diet alone or diet plus insulin and showed a significant birthweight reduction in the insulin-treated group. In contrast, Nordlander and co-workers (1989) randomized 261 gestational diabetics to diet or diet plus insulin and found no neonatal benefits from insulin therapy.
Langer and colleagues (1994) managed 1145 women with gestational diabetes using an “intensified” approach guided by glucometer measurements seven times each day. Goals included fasting glucose levels between 60 and 90 mg/dL and postprandial levels less than 120 mg/dL. In contrast, another 1316 women in the “conventional” management group had the same glucose control goals, but without glucometers because there were insufficient instruments available. Women in both groups underwent glucose surveillance for an average of 12 weeks and a similar number of glucose measurements (approximately 350 per patient) were performed in each study group. Although mean glucose values were not different between the “intensive” and “conventional” management groups, macrosomia, cesarean delivery, and shoulder dystocia were significantly reduced in women managed intensively. Unfortunately, it is unclear exactly how the two treatment approaches differed in this largest study, to date, on insulin therapy for gestational diabetes.
In general, women with gestational diabetes who do not require insulin seldom require early delivery or other interventions (American College of Obstetricians and Gynecologists, 1994). There is no consensus regarding whether antepartum fetal testing is necessary, and if so, when to begin such testing in women with class A1 gestational diabetes. This is based on the low risk of fetal death. Elective induction, compared with spontaneous labor, after sonographic diagnosis of fetal macrosomia to prevent shoulder dystocia is controversial. Conway and Langer (1996) found that elective delivery reduced the rate of shoulder dystocia from 2.2 to 0.7 percent. In contrast, Combs and colleagues (1993b) and Adasheck and associates (1996) found no advantages. Women who require insulin therapy for fasting hyperglycemia, however, typically receive fetal testing and are managed as if they had overt diabetes.
If fasting hyperglycemia develops during pregnancy, diabetes is more likely to persist postpartum. For example, in women with fasting glucose levels of 105 to 130 mg/mL, 43 percent were found to be overtly diabetic (Metzger and colleagues, 1985). When fasting glucose exceeded 130 mg/dL during pregnancy, 86 percent of women became overtly diabetic. Similarly, Dacus and co-workers (1994) and Greenberg and colleagues (1995) have also concluded that insulin therapy during pregnancy, and especially before 24 weeks, is a powerful predictor of diabetes after the pregnancy.
Recurrence of gestational diabetes in subsequent pregnancies was documented in 20 of 30 women reported by Philipson and Super (1989). Obese women were more likely to have impaired glucose intolerance in subsequent pregnancies.
According to the American Diabetes Association (1995), at the first postpartum checkup 6 to 8 weeks after delivery, or shortly after the woman stops breast feeding, all women with previous gestational diabetes should undergo a 2-hour 75-g oral glucose tolerance test. It is also recommended that those women whose 75-g test is normal receive, at the minimum, yearly fasting plasma glucose measurements. Dietary management, and specifically, weight reduction in obese women can significantly reduce the risk of subsequent overt diabetes
Most skin diseases are encountered with similar frequency in pregnant and nonpregnant women. There are, however, a number of skin changes induced by the hormonal influences of pregnancy. For example, episodes of pruritus are common during pregnancy, and in many instances, itching is not accompanied by a skin eruption. A common etiology is intrahepatic cholestasis and bile salt retention, commonly known as pruritus gravidarum (Chap. 50 ). In addition, there are a number of pregnancy-specific dermatoses that usually are symptomatic and thus may be alarming. Importantly, some of these may be associated with adverse pregnancy outcomes.
Physiological Skin Changes in Pregnancy
Hormonal changes induced by normal pregnancy may have rather profound influences on the skin. Similarly, there are profound changes in the availability or concentrations of some adrenal steroids, including cortisol, aldosterone, and deoxycorticosterone. Presumably related to enlargement of the intermediate lobe of the pituitary gland, plasma levels of melanocyte-stimulating hormone (MSH) become remarkably elevated by the end of the second month of pregnancy. Finally, production of pro-opiomelanocortin has been demonstrated in placental extracts, and this ultimately is a source of a- and b-melanocyte-stimulating hormone.
According to Wong and Ellis (1984), some degree of skin darkening is observed in 90 percent of all pregnant women. Its exact cause is not known, but it is doubtful that elevated serum levels of melanocyte-stimulating hormone are responsible. Estrogens play a role in melanogenesis in mammals and may be the inciting factor. Hyperpigmentation is evident beginning early in pregnancy, and this is more marked in dark-skinned women. These effects, as perhaps expected, are more pronounced in naturally hyperpigmented areas such as the areolae, perineum, and umbilicus. Areas prone to friction, including the axillae and inner thighs, may also become darkened. The linea alba becomes pigmented and is now called the linea nigra.
Pigmentation of the face, referred to as the mask of pregnancy, is also called chloasma or melasma, and is seen in at least half of pregnant women. Melasma is aggravated by sunlight or other ultraviolet light exposure; its severity may be altered by avoiding excessive exposure and using sunscreens. It is caused by melanin deposition into epidermal or dermal macrophages, and although the former usually regresses postpartum, dermal melanosis may persist up to 10 years in one third of women (Wong and Ellis, 1984). Oral contraceptives may aggravate melasma and should be avoided in susceptible women. If particularly disfiguring, topical application of 2 to 5 percent hydroxyquinone or 0.1 percent tretinoin ointment or cream may provide some improvement (Griffiths and colleagues, 1993; Kimbrough-Green and co-workers, 1994). Sunscreen use should be continued.
Nevi. All persons have some form of benign or melanocytic nevi. During pregnancy, these pigmented cutaneous tumors commonly enlarge and darken, and thus may be confused for a malignant melanoma. Although cutaneous nevi are shown histologically to have enlarged melanocytes and increased melanin deposition, there is no evidence that they undergo malignant transformation as a result of pregnancy (Winton and Lewis, 1982). According to the study by the World Health Organization Melanoma Program, the average malignant tumor is slightly but significantly thicker when discovered during pregnancy (MacKie and colleagues, 1991). These authors concluded that this represents either a delay in identification or pregnancy-induced melanoma stimulation.
Augmented cutaneous blood flow in pregnancy is associated with marked decreases in peripheral vascular resistance (Spetz, 1964). This is thought to serve to dissipate excess heat generated by increased metabolism. There are a number of presumably estrogen-induced changes in the small vessels that are encountered with some frequency. Spider angiomas are found in two thirds of white women and about 10 percent of African Americans during pregnancy (Wong and Ellis, 1984). Most of these vascular lesions regress postpartum. Palmar erythema is likewise more commonly noticed in whites (two thirds) than blacks (one third). Capillary hemangiomas, especially of the head and neck, are seen in about 5 percent of women during pregnancy.
One vascular condition that may be distressing is pregnancy gingivitis, which is caused by growth of the gum capillaries. This so-called epulis of pregnancy may become more severe as gestation progresses, but it may be controlled by proper dental hygiene and avoidance of trauma. Epulis should not be confused with pyogenic granuloma of pregnancy, which is also called granuloma gravidarum. These lesions are typical pyogenic granulomas, which are found in the oral cavity and often arise from the gingival papillae. Powell and colleagues (1994) described laser excision of a large granuloma in a 37-week pregnant woman.
Dermatoses of Pregnancy
A number of dermatological conditions have been identified as unique to pregnancy, or if not unique, encountered with a greater frequency during gestation. In a population of nearly 3200 pregnant women who were carefully studied over one year, Roger and colleagues (1994) found that 1.6 percent had significant pruritus. Of the 51 women, 22 (0.6 percent of the total) had pruritus gravidarum, which is probably a mild variant of intrahepatic cholestasis of pregnancy . The gross appearances and clinical presentation of these dermatoses may be confusing. In addition, terminology has been very inconsistent.
Pruritic Urticarial Papules and Plaques of Pregnancy
Pruritic urticarial papules and plaques of pregnancy (PUPPP), referred to as polymorphic eruption of pregnancy in the United Kingdom, is the most common pruritic dermatosis of pregnancy. In the study by Roger and co-workers (1994) cited earlier, 25 women (0.8 percent of the total) had this dermatosis during pregnancy. It is characterized by an intensely pruritic cutaneous eruption that usually appears late during pregnancy . Erythematous urticarial papules and plaques (Fig. 56–1) first develop on the abdomen, usually in the periumbilical area, and spread to the thighs and extremities (Alcalay and associates, 1987; Yancey and colleagues, 1984).
Pruritus may be severe. In some women the urticarial component predominates, while in others the erythematous pattern is prominent. The erythematous patches are widespread. The face is usually spared, and seldom is there excoriation. The disease is more common in nulliparas and seldom recurs in subsequent pregnancies. It may resemble herpes gestationis, but there are no vesicles or bullae. Weiss and Hull (1992) describe a familial tendency and attribute the maternal response to a circulatory paternal factor.
On biopsy, there is no immunoglobulin or complement deposition seen using immunofluorescent staining of dermis. Rather, there is a mild nonspecific lymphohistiocytic perivasculitis with an eosinophilic component. The absence of a linear band of C3 in the basement membrane differentiates this dermatosis from herpes gestationis. Alcalay and associates (1988) found no differences between serum concentrations of b-chorionic gonadotropin, estradiol, and cortisol or urinary estriol excretion in 11 women with this dermatosis when compared with gestational-age-matched controls.
Some women obtain relief from oral antihistamines and skin emollients, but most require topical corticosteroid creams or ointments for relief. Oral corticosteroids are given if these fail to relieve severe itching. The lesions invariably regress within 1 to 4 weeks following delivery. Beltrani and Beltrani (1992) described a woman at 35 weeks whose pruritus was refractory to prednisone and whose symptoms were so severe that delivery by cesarean section was done. Pruritus improved within hours and was resolved by 2 days. There is no evidence that perinatal morbidity is increased (Aronson and Halaska, 1995).
Also called pemphigoid gestationis, herpes gestationis is similar to bullous pemphigoid seen in elderly patients (Fine, 1995). Severe herpes gestationis can be serious, but fortunately it is rare. The previously reported incidence of about 1 in 50,000 pregnancies may have been an underestimate. Roger and colleagues (1994) identified the condition in 1 in 1700 pregnancies, and Zurn and associates (1992) reported it to be 1 in 7000. It may accompany gestational trophoblastic disease. Unlike the name implies, it is not a viral-induced illness. This pruritic blistering skin eruption usually presents in multiparous women in late pregnancy, but may begin early in pregnancy or up to a week postpartum.
Herpes gestationis is characterized by an extremely pruritic widespread eruption with lesions that vary from erythematous and edematous papules to large, tense vesicles and bullae (Figs. 2 ).
Common sites of involvement are the abdomen and the extremities. Exacerbations and remissions throughout pregnancy are common, and up to 80 percent of women suffer postpartum exacerbations (Shornick and colleagues, 1993). In subsequent pregnancies the disease invariably recurs, and it usually does so earlier and is more severe. Baxi and colleagues (1991) reported a woman in whom recurrence was documented in five pregnancies; however, each time the disease was less severe. Although morphological changes may develop in the small intestinal mucosa similar to those of adult celiac disease, they do not appear to cause significant malabsorption.
Katz and co-workers (1976) described a herpes gestationis serum factor, which is a thermostable immunoglobulin G protein. This serum factor reacts with amnionic tissue, and has been demonstrated to react with a 180-kd human epidermal antigen (Morrison and colleagues, 1988). Histologically, the classical finding in herpes gestationis is subepidermal edema with infiltrates of lymphocytes, histocytes, and eosinophils. Direct immunofluorescent techniques applied to a skin biopsy are of value for confirming the diagnosis, and C3 complement and sometimes IgG are deposited along the basement membrane zone.
Although the etiology of herpes gestationis is unknown, there is an inherited predisposition to its development. There is a markedly increased incidence of HLA-DR3 and HLA-DR4 antigens in affected women. Although over half of women with herpes gestationis have these antigens, they are found in only 3 percent of unaffected women. According to Shornick and co-workers (1993), these antigens are also associated with Graves disease and Hashimoto thyroiditis. Shornick and Black (1992b) reported that 11 percent of 75 women with herpes gestationis also had Graves disease. Shornick and associates (1993) demonstrated anti-HLA antibodies in all 39 women with biopsy-proven herpes gestationis. The incidence of these antibodies in normal nulliparous women is 15 to 20 percent.
Treatment. Pruritus may be quite severe. Some women obtain relief from topical steroids and antihistamines. If unsuccessful, orally administered prednisone, 1 mg/kg daily, usually brings relief promptly and inhibits the formation of new lesions. The healed sites usually are not scarred but frequently are hyperpigmented. Dapsone has been used to treat women who cannot tolerate corticosteroid therapy (Fine, 1995).
Effect on Pregnancy. It is unclear if herpes gestationis causes adverse fetal outcomes. Holmes and Black (1984) reviewed 50 pregnancies, and Shornick and Black (1992a) reviewed 74, undoubtedly many from the same reports. They reported an increased incidence of preterm delivery and small-for-gestational age infants, but not perinatal mortality.
Lesions similar to those of the mother develop in up to 10 percent of neonates. These usually clear spontaneously within a few weeks (Shornick, 1987). C3 complement deposited at the basement membrane of the newborn’s skin, and herpes gestationis factor in cord serum, were described by Katz and associates (1976).