Prepared by professor S.N.Heryak
Ternopol medical state univercity
by I.Y. Gorbachevsky
A wide spectrum of causes and demographic factors has been implicated in the birth of preterm infants.
· chronic tonsillitis
· urinary tract infection
· TORCH – infection
· viral infection
· chronic inflammatory diseases of the female sexual organs (vaginatis, bacterial vaginosis)
· Chorioamnionic infection caused by a variety of microorganisms has emerged as a possible explanation for many heretofore unexplained cases of ruptured membranes and/or preterm labor.
Schwarz and co-workers (1976) suggested that term labor is initiated by activation of phospholipase A2, which cleaves arachidonic acid from within fetal membranes, thereby making free arachidonic acid available for prostaglandin synthesis.
Subsequently, Bejar and colleagues (1981) reported that many microorganisms produce phospholipase A2, and thus potentially may initiate preterm labor. Bennett and Elder (1992) have shown that common genital tract bacteria do not themselves produce the prostaglandins.
Cox and associates (1989) provided data that bacterial endotoxin (lipopolysaccharide) introduced into the amniotic fluid stimulates decidual cells to produce cytokines and prostaglandins that may initiate labor.
An intense inflammatory reaction at the site of prematurely ruptured membranes was noted as early as 1950, and this suggested infection.
Proposed schematic mechanism of action for bacteria to incite preterm labor. Examples of bacterial products include cell wall lipopolysacharide (endotoxin) – Compiled from Berry, 1995.
· adrenal impairment – hyperandrogeny
· thyroid gland impairment - hypothoroidism
· placental abruption, placental previa
· pregnancy induced hypertension
· multiple pregnancy
· cigarette smoking,
· poor nutrition, and poor weight gain during pregnancy,
· use of drugs such as cocaine or alcohol have been reported to play important roles in the incidence and outcome of low-birth weight infants;
· low maternal age
· short stature
· occupational factors
· psychological stress in the mother.
Classification of early abortion:
Signs – lover abdominal pain, bloody vaginal discharge.
In bimanual examination – cervix is closed, enlargement of the uterus corresponds with gestational period
Management – conservative:
• Bed rest
• Sedative drugs – Valeriannae, Persen, Novopaside.
• Spasmolitics – No-Spani, Papaverini hydrochloride
• Analgetics – Analgin, Baralgin
• Progesterone – Utrogestan – 100 mg twice a day, Duphastone – 10 mg 2-3 times a day, Progesterone 10-25 mg in a day, Endometrin – 100mg 2 times a day
• Chorionic Gonadotropin Hormone
• Vitamines – vit. E 200 mg per os, folic acid – 0,4 mg in a day
Signs – cramp abdominal pain thanks to uterine contractions, bloody vaginal discharge till profuse hemorrhage.
In bimanual examination – cervix is dilated, products of conception are presented on cervical channel, enlargement of the uterus doesn’t correspond with gestational period – smaller
Management –surgical – uterine curettage.
Signs - lover abdominal pain, bloody vaginal discharge.
In bimanual examination – cervix is dilated or closed, enlargement of the uterus doesn’t correspond with gestational period – smaller.
Management –surgical – uterine curettage
Signs – lover abdominal pain, bloody vaginal discharge.
In bimanual examination – cervix is dilated, enlargement of the uterus doesn’t correspond with gestational period – smaller, some products of conception should be expelled out.
Management –surgical – uterine curettage
Conservative treatment of late abortion if cervical incompetence abcent
• Bed rest
• Sedative drugs – Valeriannae, Persen, Novopaside.
• Spasmolitics – No-Spani, Papaverini hydrochloride
• Tokolotic agents: Magnesii sulfatis 40 ml 25 % in 400 ml isotonic solution, b2- adrenomimetics (2 ml ginipral in 500 ml isotonic solution).
• Progesterone – Utrogestan – 100 mg twice a day, Duphastone – 10 mg 2-3 times a day.
Diagnosis of cervical incompetence at USG:
• Funneling of the cervix with the changes in forms T, Y, V, U (correlation between the length of the cervix and the changes in the cervical internal os).
• Cervix length < 25 mm
• Internal cervical os more than 10 mm
• Protrusion of the membranes.
• Presence of fetal parts in the cervix or vagina.
Preterm labor is classified according to clinic duration as:
· Threatened preterm labor
· Initial preterm labor
· Inevitable preterm labor
Threatened preterm labor is characterized by:
- symptoms of pelvic pressure, low back pain;
- increase uterine tone;
- absence of cervical effacement and dilation in vaginal examination.
Initial preterm labor is characterized by:
- irregular crampy – like painful uterine contractions;
- presence of cervical effacement and dilation of the cervix till 3-4 cm in vaginal examination;
- amniotic fluid gush is present very often.
Inevitable preterm labor is characterized by:
- regular uterine contractions;
- cervical dilation more than 3-4 cm.
Because uterine contractions alone may be misleading, Herron and associates (1982) require the following criteria to document preterm labor: regular uterine contractions after 20 weeks or before 37 weeks, which are 5 to 8 minutes apart or less, and accompanied by one or more of the following: (1) progressive change in the cervix, (2) cervical dilatation of 2 cm or more, or (3) cervical effacement of 80 percent or more.
Peculiarities of Preterm labor duration:
1. Preterm Ruptured Membranes
Known risk factors for preterm rupture of the membranes include:
- preceding preterm labor;
- occult amnionic fluid infection;
- multiple fetuses;
- abruptio placentae.
2. Uterine contractions abnormalities: uterine inertia, uterine hyperactivity, discoordination.
3. Precipitatous preterm labor as a result of cervical incompetence.
4. Vaginal bleeding as a result of placental abruption or placenta previa is most common complication in labor.
5. Fetal hypoxia is more common in labor
6. Infectious complications are very common in labor (chorionamnionitis) and postpartum period (endometritis, phlebitis).
Diagnosis of preterm labor includes:
1. To learn the cause of preterm labor and its elimination.
2. To estimate gestational age of pregnancy and probable fetal weight, its lie, presentation, visus.
3. To diagnose uterine activity (presence or absence regular uterine contractions).
4. To perform vaginal examination for learning cervical effacement and dilation, preterm ruptured membranes and to put correct diagnose of the preterm labor stage.
Management of preterm labor
1. Expectant Management - nonintervention or expectant management, in which nothing is done and spontaneous labor is simply awaited
2. Active Management - intervention that may include corticosteroids, given with or without tocolytic agents to arrest preterm labor in order that the corticosteroids have sufficient time to induce fetal maturation.
Indications for expectant management:
· threatened and initial preterm labor;
· intact membranes;
· gestational age of pregnancy till 36 weeks of gestation;
· satisfactory maternal and fetal conditions;
· cervical dilation till 2-4 cm;
· absence of infection, regular uterine contractions, serious obstetric and extragenital pathology.
· 28-34 weeks of pregnancy with preterm ruptured membranes, absence of regular uterine contractions and infection.
· 28-34 weeks of gestation, intact membranes, 100 % cervical effacement and cervical dilation till 3-4 cm.
Expectant Management of Preterm labor in the case of Ruptured amniotic membranes:
Pregnancy complicated by preterm rupture of the membranes is managed as follows:
1. One sterile speculum examination is performed to identify fluid coming from the cervix or pooled in the vagina. Demonstration of visible fluid or a positive Nitrazine test is indicative of ruptured membranes. Attempts are made to visualize the extent of cervical effacement and dilatation, but a digital examination is not performed. A cervicovaginal specimen is taken and culture sent for Neisseria gonorrhoeae.
2. Ultrasound examination is performed to help confirm gestational age, identify the presenting part, and assess amniotic fluid volume.
3. If the gestational age is 34 completed weeks or less and there are no other maternal or fetal indications for delivery, the woman is observed closely in Labor and Delivery, with continuous fetal heart rate monitoring to look for evidence of cord compression, especially if labor supervenes.
1. If there is no evidence of fetal jeopardy, or if labor does not begin, the woman is transferred to the High Risk Pregnancy Unit for close observation for signs of labor, infection, or fetal jeopardy.
2. General blood analysis – twice a day determination of leucocytes number, urine, vaginal smear, bacteriological examination once a 5 days.
3. If the gestational age is greater than 34 completed weeks and if labor has not begun spontaneously in 12 hours, a time period that provides for adequate evaluation, labor is induced with intravenous oxytocin. A breech presentation or transverse lie are contraindications for induction. If induction fails, cesarean delivery is performed.
4. Inhibiting preterm labor drugs are prescribed - Spasmolytics, b-adrenergic inhibitors.
8. Accelerated Maturation of Pulmonary Function - Dexamethasone, 5 mg, is given intramuscularly every 12 hours for 4 doses for enhancement of fetal maturation. This dosage is repeated every 7 days.
9. Antimicrobial Therapy - ampicillin 2 g, is given intravenously every 6 hours prior to delivery for prevention of group B streptococcus infection in the neonate.
The greatest concern with prolonged membrane rupture is the risk of maternal or fetal infection. If chorioamnionitis is diagnosed, prompt efforts to effect delivery, preferably vaginally, are initiated.
Unfortunately, fever is the only reliable indicator for making this diagnosis; a temperature of 38°C or higher accompanying ruptured membranes implies infection. Maternal leukocytosis by itself has been found to be unreliable by most investigators, and this has also been our experience.
10. Labor and delivery are managed so as to minimize maternal hypotension and fetal hypoxia and acidosis, as well as infection.
Indications for active management:
· preterm ruptured membranes;
· regular uterine contractions;
· presence of infection;
· fetal jeopardy, hypoxia;
· severe maternal diseases;
· birth defects of the fetus;
· obstetric complications of pregnancy (severe pregnancy induced hypertension, polyhydramnios).
Vaginal delivery is indicated in cephalic presentations, cesarean section is performed in the case of breech presentation and transverse lie.
Antepartum management of women with signs and symptoms of preterm labor and intact membranes is much the same as already described for pregnancies with preterm ruptured membranes. That is, the cornerstone of treatment is to avoid delivery prior to 35 weeks if possible.
Expectant Management of Preterm labor in the case of Intact amniotic membranes:
1. Diagnosis of the cause of preterm labor and its elimination.
2. Methods Used to Inhibit Preterm Labor
1) Bed Rest
2) Beta-adrenergic Receptor Agonists
There are two classes of b-adrenergic receptors: b1-receptors, dominant in the heart and intestines; and b2-receptors, dominant in the myometrium, blood vessels, and bronchioles. A number of compounds generally similar in structure to epinephrine have been evaluated in the search for one that ideally would provide optimal stimulation of myometrial b2-receptors and thus inhibit uterine contractions while simultaneously causing few adverse effects from stimulation of receptors elsewhere.
3. Bricanil (Terbutaline) 0.5 mg is dissolved in 250-400 ml isotonic solution. Toxicity—especially maternal pulmonary edema and glucose intolerance—have been evident with its use (Angel and associates, 1988).
4. Partusistene (Fenoterol, Berotek) - 0.5 mg is dissolved in 250-400 ml isotonic solution and prescribed slowly i/v.
3) Calcium Channel-blocking Drugs
Smooth muscle activity, including myometrium, is directly related to free calcium within the cytoplasm, and a reduction in calcium concentration inhibits contraction. – Nifedipine – 40 mg in one hour. From the nest day 20 mg three time a day
It has been recognized for some time that ionic magnesium in a sufficiently high concentration can alter myometrial contractility in vivo as well as in vitro. Its role is presumably that of a calcium antagonist.
Steere and Petrie (1977) concluded that intravenously administered magnesium sulfate, 4 g given as a loading dose followed by a continuous infusion of 2 g/hr, will usually arrest labor. Elliott (1983), in a retrospective study, found tocolysis with magnesium sulfate to be successful, inexpensive, and relatively nontoxic.
5) Prostaglandin Inhibitors
Antiprostaglandin agents may act by inhibiting the synthesis of prostaglandins or by blocking the action of prostaglandins on target organs. Several drugs are known to block this system, including aspirin and other salicylates, indomethacin, naproxen, and sulindac.
Unfortunately, prostaglandin synthase inhibitors may adversely affect the fetus, and this has prevented widespread use of these agents for tocolysis. Complications include closure of the ductus arteriosus, necrotizing enterocolitis, and intracranial hemorrhage (Norton and co-workers, 1993).
6) Atosiban - a nonapeptide oxytocin analog. Atosiban has been shown to be a competitive oxytocin-vasopressin antagonist capable of inhibiting oxytocin-induced uterine contractions.
7 ) Nitric Oxide Donor Drugs
Nitric oxide is a potent endogenous smooth-muscle relaxant in the vasculature, the gut, and the uterus. Nitroglycerin is an example of a nitric oxide donor drug.
8) Spasmolytic agents - No-spani, Papaverini hydrochloridi, Baralgin
3. Accelerated Maturation of Pulmonary Function
1. Glucocorticoid Therapy – is recommended from 24 to 34 weeks for gestation
The mechanism by which betamethasone or other corticosteroids are currently thought to reduce the frequency of respiratory distress involves induction of proteins that regulate biochemical systems within type II cells in the fetal lung that produce surfactant (Ballard and Ballard, 1995). The reported physiological effects of glucocorticoids on the developing lungs include increased alveolar surfactant, compliance, and maximal lung volume.
- betamethasone (12 mg intramuscularly in two doses 24 hours apart) to prevent respiratory distress in the subsequently delivered preterm infant.
- dexamethasone, 24 mg intramuscularly general dose was introduced for selected women at risk for preterm birth between 24 and 34 weeks.
- prednizolone in the dose 60 mg in a day during 2 days.
2. Thyrotropin-releasing Hormone for Fetal Maturation
Knight and colleagues (1994) from New Zealand reported that administration of thyrotropin-releasing hormone (400 mg given intravenously) in addition to betamethasone augmented fetal lung maturation compared with betamethasone used alone. This effect is based on experimental observations that tri-iodothyronine enhances surfactant synthesis.
3. Induction of prenatal lung stimulation by Lazolvan, Mucosolvan – 1000 mg a day during 3-5 days.
In general, the more immature the fetus, the greater the risks from labor and delivery.
Labor. Whether labor is induced or spontaneous, abnormalities of fetal heart rate and uterine contractions should be sought, preferably by continuous electronic monitoring.
Delivery. In the absence of a relaxed vaginal outlet, a liberal episiotomy for delivery is advantageous once the fetal head reaches the perineum. Pudendal anesthesia for perineal muscles relaxation in performed obligatory by 0.25 % Novocaine in every side. Perineal protective maneuvers don’t apply.
“Postterm”, “postdate” pregnancy is signify pregnancies that have exceeded a duration considered to be the upper limit of normal - more than 42 completed weeks (294 days) with signs of Placental Dysfunction and delivery of the fetus with signs of postmaturity.
“Prolonged “ pregnancy is signify pregnancies that have exceeded a duration considered to be the upper limit of normal - more than 42 completed weeks (294 days) with absence signs of Placental Dysfunction and delivery of the fetus without signs of postmaturity.
“Postmature” should be used to describe the infant with recognizable clinical features indicating a pathologically prolonged pregnancy.
Signs of Postmature Infant.
Clifford’s 1954 divided postmaturity into three stages: in stage 1 the amniotic fluid was clear, in stage 2 the skin was stained green, and in stage 3 the skin discoloration was yellow-green. Signs of infant’ postmaturity:
- wrinkled, patchy peeling skin. Skin wrinkling can be particularly prominent on the palms and soles. The nails are typically quite long.
- a long, thin body suggesting wasting,
- open-eyed, unusually alert, old, and worried-looking.
Skin changes of postmaturity were due to loss of the protective effects of vernix caseosa. His second hypothesis that continues to influence contemporary concepts attributes postmaturity syndrome to placental senescence
The postterm fetus may continue to gain weight and thus be an unusually large infant at birth. That the fetus continues to grow serves to suggest that placental function is not compromised. Indeed, continued fetal growth, although at a slower rate, is characteristic between 38 and 42 weeks (Fig. 35–4 ). Nahum and colleagues (1995) have confirmed that fetal growth continues at least up until 42 weeks.
Diagnosis of postdate pregnancy:
1. Taking female history.
2. Estimation of probable day of labor by all methods.
3. Clinical evaluation of the patient:
- decreasing of maternal weight
- decreasing of maternal skin tone
- decreasing of circumference of the maternal abdomen
- decreasing of fetal movement
4. Laboratory signs of fetal distress:
- viscous meconium, decreased umbilical cord diameter in ultrasonograophy and late decelerations in electronic monitoring.
- signs of oligohydramnios which is estimated by ultrasonography - the smaller the amnionic fluid pocket, the greater the likelihood that there was clinically significant oligohydramnios.
Oligohydramnios commonly develops as pregnancy advances beyond 42 weeks. It is also likely that fetal release of meconium into an already reduced amnionic fluid volume is the reason for the thick, viscous meconium implicated in meconium aspiration syndrome. Diminished urine production was found to be associated with oligohydramnios was found by Trimmer and co-workers (1990). It was hypothesized, however, that decreased fetal urine flow was likely the result of preexisting oligohydramnios that limited fetal swallowing of amnionic fluid. Veille and co-workers (1993), using pulsed Doppler waveforms, reported that fetal renal blood flow is reduced in postterm pregnancies with oligohydramnios.
MANAGEMENT OF POSRTERM PREGNANCY
Labor is a particularly dangerous time for the postterm fetus. Therefore, it is important that women whose pregnancies are known or suspected to be postterm come to the hospital as soon as they suspect they are in labor. Upon arrival, while being observed for possible labor, we recommend that fetal heart rate and uterine contractions be monitored electronically for variations consistent with fetal distress.
When a cervix is not favorable, intravaginal prostaglandin E2 gel (dinoprostone; Prepidil gel) has been used to ripen the cervix, and indeed, labor often ensues without the need of oxytocin stimulation. A dose of 0.5 mg of prostaglandin gel is inserted next to the cervix every 4 to 6 hours. The main concern in the use of prostaglandin is uterine hyperstimulation, which in turn may cause uteroplacental insufficiency and, rarely, uterine rupture. Prostaglandin gel is relatively contraindicated in patients with concurrent asthma. Another method to ripen the cervix is insertion of laminaria.
In the case of postdate pregnancy at 42 weeks or more induction is recommended unless the cervix is unfavorable, in which case cervical ripening agents or fetal surveillance are acceptable options.
Induction of labor is usually carried out with several ways:
· intravenous administrated 5 units (1 ml) oxytocin in 500 ml 0,9 % isotonic solution NaCl (dilute intravenous solution) with the initiated dose 6-8 drops per minute to 40 drops per minute;
· intravenous administrated 5 mg (1 ml) prostaglandin F2a in 500 ml 0,9 % isotonic solution NaCl with the initiated dose 6-8 drops per minute to 25-30 drops per minute;
· combine intravenous administration of 2,5 units of oxytocin and 2,5 mg of prostaglandin F2a in 500 ml 0,9 % isotonic solution NaCl with the initiated dose 6-8 drops per minute to 40 drops per minute.
The mother should never be left alone while the oxytocin infusion is running. Uterine contractions must be evaluated continually and oxytocin shut off immediately if contractions exceed 1 minute in duration or if the fetal heart rate decelerate significantly. When either occurs, immediate discontinuation of the oxytocin nearly always correct the disturbances, preventing harm to mother and fetus. The oxytocin concentration in plasma rapidly falls, since the mean half-loaf of oxytocin is approximately 5 minutes.
Caution: oxytocin has potent antidiuretic action. Whenever 20 mV per min or more of oxytocin is infused, water intoxication may lead to convulsion, coma, and even death.
In the case of prolonged pregnancies have included use of prostaglandin E2 for cervical ripening with the follow induction of labor.
In the case of oligohydramnios amniotomy is precede induction of labor. When to perform amniotomy is problematic. Further reduction in fluid volume following amniotomy can certainly enhance the possibility of cord compression. On the other hand, amniotomy will aid diagnosis of thick meconium, which may be dangerous to the fetus if aspirated. Moreover, once the membranes are ruptured, a scalp electrode and intrauterine pressure catheter can be placed, which usually provide more precise data concerning fetal heart rate and uterine contractions.
Identification of thick meconium in the amnionic fluid is particularly worrisome. The viscosity probably signifies the lack of liquid and thus oligohydramnios. Aspiration of thick meconium may cause severe pulmonary dysfunction and neonatal death This may be minimized but not eliminated by effective suctioning of the pharynx as soon as the head is delivered but before the thorax is delivered. If meconium is identified, the trachea should be aspirated as soon as possible after delivery. Immediately thereafter, the infant should be ventilated as needed. The likelihood of successful vaginal delivery is reduced appreciably for the nulliparous woman who is in early labor with thick meconium-stained amnionic fluid. Therefore, when the woman is remote from delivery, strong consideration should be given to prompt cesarean section, especially when cephalopelvic disproportion is suspected or either hypotonic or hypertonic dysfunctional labor is evident. Some choose to avoid oxytocin use in these cases.
At times, the continued growth of the fetus postterm will result in a large-for-gestational-age infant, and shoulder dystocia may develop. Therefore, an obstetrician experienced in managing this complication should be available to effect delivery.