IZOIMMUNIZATION. PATHOLOGICAL STATES IN INFANTS’ PERIOD. ASPHYXIA OF NEW-BORN. TOXICO-SEPTIC DISEASES OF INFANTS. METHODS OF INTENSIVE THERAPY AND REANIMATION OF NEW-BORN. DEFENSE OF FEMALE CASE HISTORY.
Prepared by I.Kuziv
Hemolysis from Isoimmunization
In 1892, Ballantyne established clinicopathological criteria for the diagnosis of hydrops fetalis. In 1932, Diamond, Blackfan, and Baty reported that fetal anemia characterized by numerous circulating erythroblasts was associated with this syndrome. Certainly ranking as a major contribution to medicine is the subsequent delineation of the pathogenesis of most cases of hemolytic disease in the fetus and newborn, including the related discovery of the rhesus factor by Landsteiner and Weiner in 1940. In 1941, Levine and associates confirmed that erythroblastosis was due to maternal isoimmunization with paternally inherited fetal factors, and the subsequent development of effective maternal prophylaxis was attributed to Finn and associates (1961) in England, and Freda and co-workers (1963) in the United States.
The CDE antigens are complex, and more than 400 other red cell antigens have been identified. Although some of them are immunologically and genetically important, fortunately many are so rare as to be of little clinical significance.
Individuals who lack a specific red cell antigen can potentially produce an antibody when exposed to that antigen. The antibody may prove harmful to the individual in the case of a blood transfusion or to a fetus during pregnancy. The vast majority of humans have at least one such factor inherited from their father and lacking in their mother. In these cases, the mother could be sensitized if enough erythrocytes from the fetus were to reach her circulation to elicit an immune response. That the disease is identified in very few pregnancies is a result of several circumstances. These include (1) varying rates of occurrence of red cell antigens, (2) their variable antigenicity, (3) insufficient transplacental passage of antigen or antibody across the placenta, (4) the variability of maternal response to the antigen, and (5) protection from isoimmunization by ABO incompatibility of fetus and mother.
A D-negative woman delivered of a D-positive, ABO-compatible infant, has a likelihood of isoimmunization of 16 percent (Bowman, 1985). About 2 percent of such women will be immunized by the time of delivery, another 7 percent will have anti-D antibody by 6 months postpartum, and the remaining 7 percent will demonstrate D-isoimmunization when challenged in a subsequent pregnancy by another D-positive fetus. ABO incompatibility confers some protection against D-isoimmunization because fetal red cells entering the mother usually are rapidly destroyed before they elicit an antigenic response (only a 2 percent chance of D-isoimmunization by 6 months postpartum).
CDE (Rhesus) Blood Group System
CDE (Rhesus) Blood Group System. The CDE, or rhesus, blood group system is of considerable clinical importance because the majority of individuals who lack its major antigenic determinant, D or Rho, become immunized after a single exposure to this erythrocyte antigen. Several nomenclature systems currently are used; however, the CDE grouping system seems easiest to use.
The CDE antigens are inherited independent of other blood group antigens and are located on the short arm of chromosome 1. There is apparently no difference in the distribution of the CDE antigens with regard to sex, however, there are important racial differences. American Indians and Chinese and other Asiatic peoples are almost all D-positive (99 percent). Among African Americans there is a lesser incidence of D-negative individuals (7 to 8 percent) than among white Americans (13 percent). Of all racial and ethnic groups studied thus far, the Basques show the highest incidence of D-negativity (34 percent).
CDE antigens other than D have low immunogenicity but may be significant if the pregnant woman has already formed an antibody to them. All pregnant women should be tested routinely for the presence or absence of D (Rho) antigen on their erythrocytes and for other irregular antibodies in their serum. Barss and colleagues (1988) have argued convincingly that this need be done only once during pregnancy in D-positive women.
ABO Blood Group System
ABO Blood Group System. The major blood group antigens A and B are the most common, but are not the most serious cause of hemolytic disease in the newborn. For example, group O women may from early life have anti-A and anti-B isoagglutinins, which may be augmented by pregnancy. Although about 20 percent of all infants have an ABO maternal blood group incompatibility, only 5 percent of them show overt signs of hemolytic disease. Moreover, when they do, the disease almost always is much milder than that with D-isoimmunization.
Although ABO isoimmunization will cause hemolytic disease of the newborn, it does not cause hydrops fetalis and is a disease of pediatric rather than obstetrical concern. The reasons for this are at least twofold. First, most species of isoantibodies to A and B antigens are immunoglobulin M, and thus not likely to gain access to fetal erythrocytes. Second, fetal red cells have a diminished number of A and B antigenic sites when compared with later in life.
Black infants are more likely to develop ABO disease than are white infants (Kirkman, 1977). Desjardins and co-workers (1979) studied a large number of infants of blood group O mothers to try to identify a relationship between the degree of red cell sensitization by antibody and the cord blood hemoglobin and bilirubin concentrations. They found that when the infant blood type was A or B, the bilirubin was higher and hemoglobin was lower than in cord blood from blood group O infants, even when no antibody was identified on the type A or B red cells. They concluded that ABO incompatibility represents a spectrum of hemolytic disease that ranges from those with little laboratory evidence of red cell sensitization to those with severe disease.
The usual criteria for diagnosis of hemolysis due to ABO incompatibility include the following: (1) the mother is blood group O, with anti-A and anti-B in her serum, while the fetus is group A, B, or AB; (2) there is onset of jaundice within the first 24 hours; (3) there are varying degrees of anemia, reticulocytosis, and erythroblastosis; and (4) there has been careful exclusion of other causes of hemolysis. Unlike the result in CDE hemolytic disease, the Coombs test in ABO incompatibility may be negative, although it is usually positive.
Because there is no adequate method of antenatal diagnosis, careful observation is essential in the neonatal period. Unlike CDE hemolytic disease, ABO disease is frequently seen in first-born infants, and it is likely to recur in subsequent pregnancies. Katz and co-workers (1982) identified a recurrence rate of 87 percent; 62 percent of the affected infants required treatment, but this was most often limited to phototherapy.
The principles of management of the newborn with ABO hemolytic disease are similar to those for the infant born with D-isoimmunization. For simple transfusion or exchange transfusion, group O blood is used. Because the incidence of stillbirths among ABO-incompatible pregnancies is not increased, there is no justification for early labor induction or for performing amniocentesis.
Other Blood Group Incompatibilities
Other Blood Group Incompatibilities. D-antigen incompatibility and ABO heterospecificity account for approximately 98 percent of all cases of hemolytic disease. The possibility of hemolytic disease from rarer blood groups may be suspected from the results of the indirect Coombs test done to screen for abnormal antibodies in maternal serum .
An idea of the frequency of some of these antibodies comes from the report of Bowell and colleagues (1986a), who screened 70,000 pregnant women over a 2-year period. They identified 677 pregnancies with atypical red cell antibodies, for an incidence of nearly 1 percent. One fourth of these were from the Lewis system, which do not cause fetal hemolysis because the antigens do not develop on erythrocytes until a few weeks after birth. Of the remaining 544 antibodies, 72 percent were of the CDE group, and anti-D was most common (158), followed by anti-E (130), anti-c (49), and anti-C (19). Antibodies to the Kell system antigens also were common (76).
In a review by Bowman and colleagues (1992b) of 459 pregnancies from 311 Kell-immunized women, 63 ended in abortion or stillbirth unrelated to anti-Kell sensitization. Of the remaining infants, 376 were unaffected. Of 20 who were affected, 12 newborns required no therapy. There were four perinatal deaths; one from kernicterus and three from hydrops. When the maternal anti-Kell titer is 1:8 or greater, it must be investigated by amniocentesis or fetal blood sampling. Weiner and Widness (1996) recommend the latter because their observations indicate anemia out of proportion to evidence of hemolysis.
The clinical importance of anti-c isoimmunization has been emphasized by Wenk (1986) and Bowell (1986b) and their colleagues. This antibody was the next most common cause of clinically significant isoimmunization following anti-D. Although anti-c isoimmunization most commonly resulted from previous pregnancies, those fetuses whose mothers had been transfused were more likely to have moderate to severe hemolysis.
In a review by Bowman and colleagues (1992a) of 120 pregnancies with either anti-C or anti-Ce alloimmunization, 22 ended in abortion or stillbirth unrelated to isoimmunization. Of 33 affected fetuses, only eight required treatment after birth and none had severe disease.
Mother as Provider of Rare Type Red Cells
Following maternal isoimmunization with a rare blood type, the possibility exists of hemolytic disease in the fetus and neonate. This could create a need for red cells devoid of the antigen or antigens to which the mother is isoimmunized. Moreover, the mother herself may require red cells, for example, because of a complication of hemorrhage at delivery. For such circumstances, even while pregnant, she can successfully donate her own red cells, which are then appropriately frozen for subsequent use, as demonstrated by the following case.
G.D., a 17-year-old gravida 2, P1, lacked immunological evidence of all CDE antigens except D, and had acquired antibodies during the previous pregnancy to C, c, E, and e. Compatible red cells available in the United States were limited to two units frozen in Portland, Oregon. Therefore, repeated phlebotomies were performed during pregnancy and the red cells promptly frozen for possible subsequent use. In spite of her small size—110 pounds nonpregnant—she tolerated quite well the removal of 6 units (3000 mL total) of blood at the rate of 500 mL every 3 to 5 weeks. Iron was provided along with supplementary folic acid. Her measured blood volume of 3800 mL was 47 percent above the nonpregnant state. Repeat cesarean delivery was accomplished without incident. Hemolytic disease in the newborn was treated with exchange transfusions using all of the red cells harvested and stored from the six phlebotomies plus the two frozen units from Portland.
Pathological Changes in Hemolytic Disease
In D-positive fetuses, maternal antibodies are both adsorbed to the D-positive erythrocytes and exist unbound in fetal serum. The adsorbed antibodies act as hemolysins, leading to an accelerated rate of red cell destruction. Maternal antibodies detectable at birth gradually disappear from the infant’s circulation over a period of 1 to 4 months. Their rate of disappearance is influenced to some extent by exchange transfusion. Detection of adsorbed antibodies is best accomplished by the direct Coombs test. If D red cells coated with anti-D antibody are typed with an anti-D saline agglutinin, they may be reported incorrectly as D-negative because of the blocking effect produced by the adsorbed antibody. Therefore, erythrocytes reported to be D-negative from an infant whose mother may be isoimmunized must always be checked by the direct Coombs test.
The pathological changes in the organs of the fetus and newborn infant vary with the severity of the process. The severely affected fetus or infant may show considerable subcutaneous edema as well as effusion into the serous cavities—hydrops fetalis. At times, the edema is so severe that the diagnosis can be easily identified using sonography . In these cases, the placenta is also markedly edematous, appreciably enlarged and boggy, with large, prominent cotyledons and edematous villi. Excessive and prolonged hemolysis serves to stimulate marked erythroid hyperplasia of the bone marrow as well as large areas of extramedullary hematopoiesis, particularly in the spleen and liver, which may in turn cause hepatic dysfunction (Nicolini and associates, 1991). Histological examination of the liver may also disclose fatty degenerative parenchymal changes as well as deposition of hemosiderin and engorgement of hepatic canaliculi with bile. There may be cardiac enlargement and pulmonary hemorrhages. Ascites, hepatomegaly and splenomegaly, may be so massive as to lead to severe dystocia as the consequence of the greatly enlarged abdomen. Hydrothorax may be so severe as to compromise respirations after birth.
The precise pathophysiology of hydrops remains obscure. Theories of its causation include heart failure from profound anemia, capillary leakage caused by hypoxia from severe anemia, portal and umbilical venous hypertension from hepatic parenchymal disruption by extramedullary hematopoiesis, and decreased colloid oncotic pressure from hypoproteinemia caused by liver dysfunction. To study this, Nicolaides and colleagues (1985) performed percutaneous umbilical artery blood sampling in 17 severely D-isoimmunized fetuses at 18 to 25 weeks. All fetuses with hydrops had hemoglobin values of less than 3.8 g/dL as well as plasma protein concentrations less than 2 standard deviations from the mean for normal fetuses of the same age. The hydropic fetuses also had substantive protein concentrations in ascitic fluid collected at fetoscopy. Conversely, all nonhydropic fetuses had hemoglobin values that exceeded 4 g/dL; however, 6 of 10 had hypoproteinemia of the same magnitude as the hydropic fetuses. These investigators concluded that the degree and duration of anemia influence the severity of ascites, and this is made worse by hypoproteinemia. They also hypothesized that severe chronic anemia causes tissue hypoxia with resultant capillary endothelial leakage with protein loss.
Fetuses with hydrops may die in utero from profound anemia and circulatory failure (Fig. ). A sign of severe anemia and impending death is a sinusoidal fetal heart rate pattern . The live-born hydropic infant appears pale, edematous, and limp at birth, often requiring resuscitation. The spleen and liver are enlarged, and there may be widespread ecchymoses or scattered petechiae. Dyspnea and circulatory collapse are common.
Less severely affected infants may appear well at birth, only to become jaundiced within a few hours. Marked hyperbilirubinemia, if untreated, may lead to central nervous system damage, especially to the basal ganglia or kernicterus. Anemia, in part resulting from impaired erythropoiesis, may persist for many weeks to months in the infant who had demonstrated hemolytic disease at birth. In the absence of hypoxia, erythrocyte production normally falls after birth, especially in the preterm infant.
The number of perinatal deaths from hemolytic disease caused by D-isoimmunization has dramatically dropped. The most common reason for this is that the administration of D-immune globulin during or immediately after pregnancy to D-negative women has eradicated most D-isoimmunization. Another reason is that the fetus who is most likely to be seriously affected can be treated by intraperitoneal or direct intravascular transfusions or be delivered preterm. The favorable impact on reducing perinatal mortality as the consequence of these procedures is exemplified by experiences in Manitoba. In that Canadian province, the number of perinatal deaths from hemolytic disease decreased from 29 in 1964 to only 1 in 1975 (Bowman and colleagues, 1977).
Immune Globulin Prophylaxis for the D-Negative, Nonsensitized Mother
Anti-D immune globulin is a 7S immune globulin G extracted by cold alcohol fractionation from plasma containing high-titer D-antibody. Each dose provides not less than 300 mg of D-antibody as determined by radioimmunoassay.
Freda and co-workers (1975) summarized their 10 years of clinical experience with D-immune globulin, confirming their original observations that such globu-lin given to the previously unsensitized D-negative woman within 72 hours of delivery is highly protective. D-negative women undergoing abortion should also be treated, because up to 2 percent having spontaneous abortions and 5 percent having elective terminations become isoimmunized without D-immune globulin. Likewise, women with ectopic pregnancies or hydatidiform moles should be treated. The observation of Blajchman and co-workers (1974) of detectable fetal-maternal hemorrhage after 6 percent of amniocenteses has provided support for a policy that all unsensitized D-negative women suspected of having a D-positive fetus should receive D-immune globulin following such a procedure. For similar reasons, such women should also receive D-immune globulin following external cephalic version (Boucher and associates, 1996).
D-negative women who receive blood or blood fractions are at risk of becoming sensitized. Red cells can supply massive amounts of foreign antigen if the cells are D-positive and their recipient is D-negative. Moreover, platelet transfusions and plasmapheresis can provide sufficient D-antigen to cause sensitization, which can be prevented by an injection of D-antiglobulin. Freda (1973), as well as Bowman (1985), emphasize that when in doubt whether to give anti-D immune globulin, then it should be given.
While adherence to the above guidelines dramatically decreased the risk of maternal isoimmunization, the problem was not eliminated. Bowman and Pollock (1978) identified 1.8 percent of women who became isoimmunized in spite of adherence to the above recommendations. They found that failures were the consequence of spontaneous silent fetal-maternal bleeds before delivery and before the administration postpartum of D-immune globulin. To avoid isoimmunization from fetal-maternal bleeds remote from term, 300 mg of antibody routinely was administered intramuscularly to all nonsensitized D-negative women at 28 weeks, again at 34 weeks, as well as at the time of amniocentesis or uterine bleeding. If the infant was D-positive, a third dose of the immunoglobulin was administered to the mother after delivery. This program was followed by a reduction in the incidence of D-isoimmunization during pregnancy from 1.8 percent to 0.07 percent. A single dose at about 28 weeks proved to be almost as effective as were the two doses antepartum, and only 2 of 1799 D-negative women developed D-isoimmunization despite antenatal prophylaxis. The small amount of antibody that crosses the placenta results at times in a weakly positive direct Coombs test in cord and infant blood; however, none of the infants showed evidence of anemia or exaggerated hyperbilirubinemia.
Chavez and associates (1991), in a review of the epidemiology of CDE hemolytic disease in the United States, estimated an incidence of 10.6 per 10,000 live births. They concluded that CDE hemolytic disease still contributed significantly to both neonatal morbidity and mortality.
Appropriate concern has been raised for the possibility that the human immunodeficiency virus or other viruses may be transmitted by plasma-derived products such as D-immunoglobulin. Exclusion of individuals who are antibody or antigen positive for various hepatitis viruses should significantly reduce the risk of the spread of these infections by various immunoglobulin preparations. The human immunodeficiency virus should be inactivated by the manufacturing process itself .
A single intramuscular dose of 300 mg of D-immunoglobulin is administered routinely to all D-negative, nonimmunized women at 28 to 32 weeks, and again within 72 hours of the birth of a D-positive infant. A similar dose is also given at the time of amniocentesis and whenever there is uterine bleeding, unless the routine dose at 28 to 32 weeks had been given very recently. If a massive fetal–maternal hemorrhage is recognized, more immune globulin should be given, as described below. One dose of 300 mg will protect the mother against a bleed of up to 15 mL of D-positive red cells, or 30 mL of fetal blood.
Ness and colleagues (1987) provided data for the incidence of excessive fetal–maternal hemorrhage that may cause isoimmunization despite postpartum immune globulin administration. Using the enzyme-linked antiglobulin test, they studied almost 800 D-negative mothers giving birth to D-positive infants, and found evidence in 1 percent of the mothers for fetal bleeding in excess of 30 mL. Another 5.6 percent of these pregnancies had fetal-maternal bleeds of between 11 and 30 mL. Thus, at least 1 percent, and perhaps more, of susceptible mothers would have been given insufficient immune globulin if not tested. Importantly, they identified no risk factors that predicted excess bleeding, and recommended that all women be tested at delivery. Stedman and co-workers (1986), utilizing the erythrocyte rosette test, reported similar results.
In most institutions the rosette or similar test is routinely performed on postpartum maternal blood samples of D-negative women delivering D-positive infants to identify those women requiring more than the standard dose of D-immunoglobulin. In women who potentially require repeated injections of D-immunoglobulin—for example, repeated, unexplained uterine bleeding in the first or second trimester—an indirect Coombs test will, if positive, allow the confirmation of antibody excess from the last immunoglobulin injection and avoid the need for additional prophylaxis.
Whether to provide routinely D-antiglobulin prophylaxis for Du-positive women is controversial. Bowman (1985) cites five instances in 750,000 pregnancies in which a Du-positive mother produced anti-D antibody. Fortunately, in none of these was the fetus severely affected. If there is any doubt about D-antigen status, then globulin should be given.
Large Fetal to Maternal Bleed
In the case of a larger fetal–maternal hemorrhage, the D-positive erythrocytes may, by careful examination, be identified at times as clumps in the crossmatch of the erythrocytes from maternal blood and the D-immune globulin. However, the acid-elution technique for identifying erythrocytes that contain appreciable hemoglobin is best used to identify a major bleed and to approximate its magnitude.
When the acid-elution test is performed, red cells rich in fetal hemoglobin are easy to identify . A careful differential count will serve to approximate closely the percentage of fetal cells in the maternal blood. From this value, as described on page 982, an estimate of the volume of fetal red cells in the maternal circulation can be made. The volume of fetal red cells calculated is then divided by 15 (volume of red cells effectively neutralized by 300 mg of antibody), and this provides a reasonable estimate of the number of 300 mg ampules of D-immune globulin required for protection. In practice, in cases of fetal-maternal hemorrhage, sensitization of the mother can be prevented by injecting sufficient D-immune globulin intramuscularly to provide demonstrable free antibody in the maternal serum.
Rarely, the D-negative woman will have been exposed in utero to D-antigen from her mother and become sensitized as the consequence. As with fetal–maternal bleeds, a major blood group (ABO) incompatibility offers appreciable protection against D-sensitization. Jennings and Clauss (1978), in a study of 105 D-negative infants born to D-positive mothers, identified a maternal–fetal bleed in only two instances. Jennings and Clauss (1978) and Bowman (1985), on the basis of their extensive studies, do not believe that D-immune globulin prophylaxis is warranted for D-negative babies born to D-positive mothers.
The management of isoimmunization, except for ABO incompatibility, is similar regardless of the inciting antigen. Because D-isoimmunization is most common, general management for this clinical situation is discussed.
The mother who is sufficiently immunized to produce enough antibody to cause overt hemolytic disease in the fetus and newborn will have detectable D-antibody in her serum by 36 weeks. From early studies, if no treatment was given for the sensitized D-negative woman with a D-positive fetus, the perinatal mortality rate was about 30 percent . With aggressive management, including diagnostic amniocenteses or studies performed on fetal blood obtained by cordocentesis, repeated ultrasound examinations, intrauterine transfusions in selected cases, and early delivery in most cases, the perinatal mortality rate can be lowered remarkably. For optimal outcome, management is individualized and aided by the following information:
1. Past obstetrical history, with emphasis on fetal outcome and how that outcome was achieved.
2. Accurate knowledge of fetal age.
3. The paternal D-antigen status, because if he is negative, then the fetus cannot be affected.
4. Maternal antibody determinations repeated throughout pregnancy.
5. Spectrophotometric analyses of amnionic fluid, or sonographically-directed fetal blood sampling.
An antibody titer, performed using the indirect Coombs test, that is no higher than 1:16 almost always means that the fetus will not die in utero from hemolytic disease. A titer higher than this indicates the possibility of severe hemolytic disease. It is emphasized that the titer in the previously sensitized woman may, during a subsequent pregnancy, rise infrequently to high levels even though her fetus is D-negative—the so-called amnestic response. Whenever the antibody titer is sufficiently elevated to be clinically significant, fetal evaluation is warranted. In most institutions this critical titer is considered to be 1:16 or greater; however, in some centers, if the titer remains below 1:32, then a good fetal outcome is anticipated.
Prior to the mid-1980s, indirect evaluation of fetal hemolytic disease was almost always accomplished by determining the amount of bilirubin pigment in amnionic fluid by spectrophotometric analysis. There is now reasonable experience with sonographically-directed fetal blood sampling to warrant, in some cases, direct assessment of the degree of hemolysis and anemia, as well as identifying the presence or absence of the suspected antigen.
The absorbance of breakdown pigments, mostly bilirubin, in the supernatant of amnionic fluid, when measured in a continuously recording spectrophotometer, is demonstrable as a hump with maximum absorbance at 450 nm wavelength, as shown in Figure 42–10. Because the change in optical density is measured, this is referred to as DOD450. The magnitude of the increase in optical density above baseline at 450 nm most often, but not always, correlates well for any gestational age with the intensity of the hemolytic disease.
Liley (1964) constructed a graph that provides for reasonably precise prediction of the severity of hemolysis, a modification of which is demonstrated in Figure 42–11. Depending on the severity of disease, amniocenteses are repeated at 1- to 3-week intervals (American College of Obstetricians and Gynecologists, 1990). In general such amniocenteses are initiated at 24 to 26 weeks. Prior to this time, there is limited data regarding normal values for amnionic fluid optical density readings (Queenan and co-workers, 1993). Thus, in mothers with a history of early fetal hydrops or death from isoimmunization, cordocentesis and direct fetal blood analysis is often appropriate. Although some clinicians with extensive experience in cordocentesis have abandoned amnionic fluid analysis altogether in favor of serial cordocentesis, such an approach has not been demonstrated to be superior and its routine use remains controversial. Not only do risks of cordocentesis exceed those of amniocentesis, but the degree of isoimmunization may increase following this procedure .
Optical density values in zone 1 generally indicate an unaffected fetus, one who will only have mild disease, or a D-negative fetus. Values in zone 3 indicate a severely affected fetus, and death within 7 to 10 days may be expected. Transfusion or delivery is indicated. In zone 2, the prognosis is less accurate, but the fetus is at moderate to severe risk and repeated amniocentesis or fetal blood sampling may be required to establish the actual condition of the fetus. In lower zone 2, the expected fetal hemoglobin concentration is between 11.0 and 13.9 g/dL, whereas in upper zone 2, the anticipated hemoglobin level ranges from 8.0 to 10.9 g/dL.
Ananth and Queenan (1989), in a study of 32 women with D-isoimmunized pregnancies at 16 to 20 weeks, reported that amnionic fluid DOD450 values greater than 0.15 were predictive of severe fetal hemolysis, while those less than 0.09 had mild or no disease. Values between these two were not predictive and require further evaluation.
Fetal Blood Sampling
Nicolaides and colleagues (1986) studied 59 D-isoimmunized pregnancies at 18 to 25 weeks, and reported poor correlation in nonhydropic fetuses between the degree of fetal anemia and the trend in amnionic fluid analysis using the Liley graph. Nicolaides and Snijders (1992) concluded that the only reliable method to determine severity in the second trimester is direct measurement of fetal hemoglobin. Nicolaides and co-workers (1988) recommend that transfusions be commenced when the hemoglobin deficit exceeds 2 g/dL from the mean for normal fetuses of corresponding gestational age . Despite these concerns, amnionic fluid analysis remains an important and accepted means of managing the isoimmunized woman. Queenan and associates (1993) provided data regarding the utility of amnionic fluid analysis as early as 14 weeks.
Intraperitoneal Fetal Transfusions
The refinement in prognostic precision furnished by amnionic fluid analysis led Liley (1963) to try, in apparently hopeless cases, intrauterine blood transfusion into the fetal peritoneal cavity. With such transfusions, the overall survival rate in more recent years was probably about 50 percent. The team in Winnipeg, however, has been much more successful. They reported 100 percent survival of nonhydropic fetuses and 75 percent survival of hydropic fetuses when treated with intrauterine transfusion, or an overall survival rate of 92 percent (Harman and co-workers, 1983). Watts and colleagues (1988) reported similar results. Both groups emphasized improved fetal evaluation through the use of real-time sonography before, during, and after fetal transfusion.
At Winnipeg Center, 731 fetal transfusions have been carried out on 302 fetuses since the first transfusion was attempted in 1964. Mortality has decreased progressively as follows: 1964 to 1968, 55 percent; 1968 to 1972, 34 percent; 1972 to 1976, 34 percent; 1976 to 1980, 29 percent; and the recent study cited earlier, 8 percent. Importantly, the publicly funded anti-D prophylaxis program in Manitoba has lowered the risk of sensitization of mothers in that province from 13 percent to 0.18 percent, and in turn the frequency of intrauterine transfusions.
In a comparison of 44 intraperitoneal versus 44 intravascular transfusions, Harman and colleagues (1990) reported that the intravascular approach resulted in significantly more surviving infants (91 versus 66 percent), fewer infants with Apgar scores of less than 7 at 5 minutes (14 versus 38 percent), and increased frequency of vaginal delivery (83 versus 50 percent). They concluded that although intraperitoneal transfusion should not be abandoned, it was relegated a second-choice procedure for very limited circumstances (Harman and colleagues, 1990).
Intravascular Fetal Transfusions
In 1981, the group from Lewisham Hospital in London described a technique for direct intravascular blood transfusion using fetoscopy (Rodeck and colleagues, 1981). Subsequent to this (1984), they reported results from 25 severely D-isoimmunized fetuses, including 15 with hydrops, who were given intravascular transfusions between 19 and 32 weeks. They again used fetoscopy, but some of these transfusions were now accomplished using sonographically-directed needle placements. Those fetuses in whom treatment was begun before 25 weeks had a remarkable 84 percent survival. Since this time, investigators from Yale (Grannum and colleagues, 1986) and Mount Sinai in New York (Berkowitz and co-workers, 1988) have also reported their successes with the method, which is shown in Figure 42–13. In many centers, this procedure has largely replaced the intraperitoneal technique for transfusion.
Ney and co-workers (1991) reported an overall survival of 85 percent with intravascular transfusion in severely isoimmunized fetuses. Survival was not significantly different comparing hydropic fetuses with non-hydropic fetuses in their study. Weiner and colleagues (1991a) reported an overall survival rate of 96 percent when intravascular transfusion was given for severe fetal anemia defined as a hematocrit of 30 percent or less.
Nicolini and associates (1990) described fetal blood sampling and intravascular transfusion utilizing the fetal intrahepatic vein. A fetal blood sample was successfully obtained in 91 percent of attempts, and the fetal hematocrit was raised to satisfactory levels in approximately 90 percent of the transfusions. The survival rate in 42 fetuses who were transfused was 86 percent.
Although intravascular transfusion is a relatively safe procedure, it is not without risk. In a review of 594 diagnostic cordocenteses and 156 intravascular transfusions, Weiner and associates (1991b) reported that duration of bleeding was greater with arterial than venous puncture and with intravascular transfusions compared with diagnostic venipuncture. Preterm prematurely ruptured membranes and amnionitis developed overall in 0.4 percent and 0.5 percent of procedures, respectively. Fetal bradycardia was identified in 7 percent of all cases, and the perinatal loss rate as 0.8 percent. Other complications include hyperkalemia (Thorp and associates, 1990), development of a porencephalic cyst (Dildy and colleagues, 1991), and depressed neonatal erythropoiesis (Millard and co-workers, 1990; Thorp and collaborators, 1991). Radunovic and co-workers (1992) have reported increased mortality in hydropic fetuses who had acute hematocrit increases associated with intravascular transfusions. Schumacher and Moise (1996) recently reviewed fetal transfusions for red cell alloimmunization.
Molecular Genetics and Isoimmunization
Molecular Genetics and Isoimmunization. Work by Dildy (1996), Fisk (1994), Rossiter (1994), and van den Veyer (1996) and their colleagues demonstrates the feasibility of fetal D-antigen typing from amniocytes or chorionic villi, using polymerase chain reaction. Such techniques will most likely allow women whose partners are heterozygous for the D antigen to determine fetal blood type without cordocentesis, and potentially avoid unnecessary invasive procedures.
Subsequent Child Development
In Bowman’s experience (1978), the great majority of fetal transfusion survivors developed normally; 74 of 89 tested when 18 months of age or older were completely normal, four were abnormal, whereas development in 11 appeared somewhat delayed, perhaps because of preterm birth.
Other Methods to Try to Minimize Fetal Hemolysis
In an attempt to prevent D-antibody formation, to remove antibody already formed, or to block antibody action on the red cell, a number of techniques have been tried without consistent success. Plasmapheresis does not appear to provide benefits that outweigh the risks and the costs. Promethazine in large doses has been cited by some as being beneficial (Charles and Blumenthal, 1982); however, this is unproven. D-positive erythrocyte membrane in enteric coated capsules has been administered orally to sensitized women throughout pregnancy on the basis that such treatment might induce T-suppressor cell formation that would in turn reduce antibody response to challenges by the antigen. This also does not appear to provide any benefit (Gold and co-workers, 1983). Attempts at immunosuppression with corticosteroids have proven to be of no benefit.
Method of Delivery
The fetus who is to be delivered remote from term because of evidence of hemolytic disease will sometimes benefit from cesarean section. By doing so, the time of birth is set and the most experienced personnel can be assembled to provide for optimal treatment.
Exchange Transfusion in the Newborn
Cord blood analysis should be carried out immediately for any pregnancy in which the D-negative mother is known to be sensitized. Cord blood hemoglobin concentration and direct Coombs test are of considerable importance when the infant is D-positive. If the infant is overtly anemic, it is often best to carry out the initial exchange promptly to correct anemia. Type O, D-negative red cells, recently collected, are used. For infants who are not overtly anemic, the need for exchange transfusion is determined by the rate of increase in bilirubin concentration, the maturity of the infant, and the presence or absence of other complications.
Disposal of Bilirubin
Before birth, unconjugated or free bilirubin is readily transferred across the placenta from fetal to maternal circulation—and vice versa, if the maternal plasma level of unconjugated bilirubin is high. Whereas bilirubin glucuronide is water soluble and normally is excreted into the bile by the liver and into the urine by the kidney when the plasma level is elevated, unconjugated bilirubin is not excreted in the urine or to any extent in the bile.
The great concern over unconjugated hyperbilirubinemia in the newborn, especially the premature, is its association with kernicterus. The yellow staining of the basal ganglia and hippocampus is indicative of profound degeneration in these regions. Surviving infants show spasticity, muscular incoordination, and varying degrees of mental retardation. There is a positive correlation between kernicterus and unconjugated bilirubin levels above 18 to 20 mg/dL, although kernicterus may develop at much lower concentrations, especially in very preterm infants.
Factors other than the serum bilirubin concentration contribute to the development of kernicterus. Hypoxia and acidosis enhance bilirubin toxicity. Both hypothermia and hypoglycemia predispose the infant to kernicterus by raising the level of nonesterified fatty acids, which compete with bilirubin for the binding sites on albumin and inhibit bilirubin conjugation. Sepsis contributes to kernicterus, although the mechanism is not clear. Although it is extremely unlikely that they lead to kernicterus, sulfonamides and salicylates may increase the level of bilirubin because they compete with unconjugated bilirubin for protein-binding sites. Sodium benzoate, in injectable diazepam, furosemide, and gentamicin, displaces bilirubin from albumin. Excessive doses of vitamin K analogues may be associated with hyperbilirubinemia. The importance of the serum albumin concentration and the binding sites so provided is obvious.
Breast Milk Jaundice
Breast milk jaundice has been attributed to the excretion of pregnane-3a,20b-diol into breast milk by some mothers. This steroid was reported by Arias and colleagues (1964) to block bilirubin conjugation by inhibiting glucuronyl transferase activity. Breast milk samples from mothers of infants with hyperbilirubinemia have been described to have an unusually high lipolytic activity and liberate large quantities of fatty acids that inhibit bilirubin conjugation (Foliot and co-workers, 1976). Another explanation is that bilirubin is broken down in the intestine to form free bilirubin, which can be reabsorbed. Usually, bovine milk and human milk appear to block the reabsorption of free bilirubin, whereas the milk of mothers with jaundiced offspring does not, and may even enhance its reabsorption. With breast milk jaundice, the serum bilirubin level rises from about the fourth day after birth to a maximum by 15 days. If breast feeding is continued, the high levels persist for another 10 to 14 days and slowly decline over the next several weeks. No cases of overt bilirubin encephalopathy have been reported caused by this phenomenon (Maisels, 1979).
By far the most common form of unconjugated nonhemolytic jaundice is so-called physiological jaundice. In the mature infant, the serum bilirubin increases for 3 to 4 days to achieve serum levels up to 10 mg/dL or so and then falls rapidly. In preterm infants, the rise is more prolonged and may be more intense. Jaundice in the newborn should not be ignored as being physiological in the following circumstances:
1. The infant is visibly jaundiced in the first 24 hours after birth.
2. The total bilirubin concentration in serum is increasing daily by more than 5 mg/dL.
3. The total bilirubin concentration is above 15 mg/dL.
4. Jaundice is visible for more than 1 week in a term infant or 2 weeks in a preterm infant.
Exchange transfusion for severe hyperbilirubinemia is not associated with a mortality rate of less than 1 percent when moribund, hydropic, and kernicteric infants are excluded from analysis.
Phototherapy is now widely used to treat hyperbilirubinemia. In most instances, its use leads to a lower bilirubin level from its oxidation. Light that penetrates the skin also increases peripheral blood flow, which enhances photo-oxidation. By some unknown mechanism, light seems to promote hepatic excretion of unconjugated bilirubin. As much surface area as possible should be exposed, and the infant should be turned every 2 hours with close temperature monitoring to prevent dehydration. The fluorescent bulbs must be appropriate wavelength and the eyelids should be closed and completely shielded from light. Serum bilirubin should be monitored for at least 24 hours after discontinuance of phototherapy.
Isoimmunization can involve many of the several hundred blood group systems. This disorder is frequently referred to as Rh isoimmunization, because the Rhesus (Rh) system is most frequently involved. For the sake of this discussion, the Rh system will be used as an example, although it should be remembered that isoimmunization can and does develop with many other blood systems such as Kell, Duffy, Kidd, and others.
Within the Rh system, there are several specific antigens, the one most commonly associated with hemolytic disease being the D antigen. If a fetus is Rh+, having received the genes for the Rh D antigen from its father, and the mother lacks the Rh antigen (i.e., she is Rh-), the conditions exist for the development of isoimmunization. In the woman's first such pregnancy, the infant typically has no complications (unless the mother has had a previous blod transfusion with Rh positive blood). At the time of delivery, however, if the mother's blood is exposed to fetal red cells, even minuscule amounts, the woman can develop antibodies to the Rh D antigen. Antibody development occurs in approximately 15% of cases of an Rh- mother and Rh+ fetus. In a subsequent pregnancy, passage of minute amounts of fetal blood across the placenta, which occurs quite frequently, can lead to an anamnestic response of maternal antibody production.
If the mother produces immunoglobulin M (IgM)-type antibodies, the molecules do not cross the placenta, because they are too large. In the case of Rh factor, however, the maternal antibody is predominantly the smaller IgG-type, which can freely cross the placenta and enter the fetal circulation. Once in the fetal vascular system, the antibody attaches to the Rh+ red blood cells and hemolyzes them. The bilirubin produced in this hemolytic process is transferred back across the placenta to the mother and metabolized. The condition of the fetus is determined by the amount of maternal antibody transferred across the placenta and the ability of the fetus to replace the red blood cells that have been destroyed.
In the first affected pregnancy, the infant may be anemic at delivery and may soon develop elevated levels of bilirubin, because hemolysis continues after birth and the newborn must now rely on its own, somewhat immature, liver to metabolize the bilirubin. In subsequent pregnancies, with an Rh+ fetus, the process of antibody production and transfer may be accelerated, leading to the development of more significant anemia. In such cases, the fetal liver can manufacture additional red cells. Because of fetal blod destruction, the newborn will usually develop jaundice. Jaundice occurs because the increased red cell destruction releases larger amounts of hemoglobin than normal. Hemoglobin is broken down to bilirubin pigments, which normally would be metabolized by the liver to form bilirubin glucoronide. In the fetus the excess bilirubin is passed back through the placenta and the mother’s liver excretes it into her bile. In the newborn, the glucoronase transferase enzyme system in the liver is not mature enough to metabolize the larger amounts of bilirubinBilirubin thus builds up in the blood, producing the typical bronzed color of the skin as we recognize as “jaundice”.
However, this activity reduces the amount of proteins manufactured by the fetal liver. In turn, the reduced protein production can lead to a decreased oncotic pressure within the fetal vascular system, resulting in fetal ascites and subcutaneous edema. At the same time, the severe fetal anemia can lead to high output cardiac failure. This combination of findings is referred to as hydrops fetalis.
Kernicterus (brain damage caused by bilirubin): Most biliribin is bound to albumin in the newborn’s blood. When the concentration of bilirubin in the newborn blood exceeds in-term fetus – 307,8 – 342 mkmoll/L, in pre-term fetus – 153-205 mkmoll/L, the albumin binding sites are all filled, and bilirubin molecules are then freed to enter the tissues. Biliribin is a cytological poison, nad it is a preferentially taken up by the cells of the basal ganglia. When a sufficient number of basal ganglia neurons are damaged by the larger amount bilirubin, the function of the basal ganglia is destroyed. The clinical picture is one of motor handicap (similar to cerebral palsy). Once this pathophysiology was understood, methods of management and later prevention were developed.
The tendency is for each subsequent baby to be more severely affected, but this is not always the case. The level of fetal disturbance may remain the same or, occasionally, may even be less than in the previous pregnancy. If subsequent fetuses are Rh-, which is commonly the case if the father is a hétérozygote, the fetus is not affected at all.
Rhesus (Rh) isoimmunization is an immunologic disorder that occurs in a pregnant, Rh-negative patient carrying an Rh-positive fetus. The immunologic system in the mother is stimulated to produce antibodies to the Rh antigen, which then cross the placenta and destroy red blood cells.
Risk of Rh Sensitization: mismatched blood transfusion (90-95 %), full-term delivery, Abo-compatible or incompatible (14-17 %), induced abortion ( 5-6 %), spontaneous abortion (3-4 %), amniocentesis (1-3 %), full-term pregnancy (1-2 %), eectopic pregnancy (< 1 %).
Pathophysiology. The “Rh disease ” results from the Rh negative mother becoming isoimmunized to an Rh antibody from the red cells of her first child.
1) the first Rh positive pregnancy is almost never affected unless the mother has had a previous blood transfusion with Rh positive blood;
2) once immunized, the mother’s immune system responds by manufacturing anti Rh isoantibodies with a second pregnancy;
3) If the second pregnancy is one in which the fetus is Rh positive, the mother’s anti Rh Isoantibodies are transferred to the fetus across the placenta.
Stages of hemolytic disease of infant severity:
Anemia, hemoglobin level in umbilical cord (g/L)
Jaundice, bilirubin level in umbilical cord (mkmol/L)
Edema of subcutaneous fat and ascites
Isoimmunization can often be diagnosed on the basis of history. A woman with a previous diagnosis of isoimmunization or with a previous birth in which the neonatal course was consistent with this disorder is at risk for recurrence. As part of routine antenatal laboratory evaluation include such methods of diagnostics as:
· Maternal blood is tested for presence of a variety antibodies that may cause significant disturbances in fetus – “antibody screening test”, “indirect” and “direct Coomb’s tests”. Mild isoimmunization – antibody titer below 1:16. Rarely produce fetal hydrops and usually do not require any intervention in the pregnancy. The newborn may be anemic and develop hyperbilirubinemia. Severe isoimmunization - titer of over 1:16 or greater is generally considered the critical point at which there is sufficient risk of fetal jeopardy to warrant additional evaluation. This should be done amniocentesis or percutaneous umbilical blood sampling (PUBS).
During this testing process, other antibodies may be discovered that do not cause significant fetal/neonatal problems. The two most common of these are the anti-Lewis and anti-I. When these antibodies are found, titers are not reported because of their lack of clinical importance.
· Determination of the father's Rh status is extremely helpful. If he is Rh-, the fetus is not affected. If he is Rh+, genotype testing can determine whether he is homozygous or heterozygous. Recently, direct Rh testing of the fetus has become possible using cells floating within the amniotic cavity.
· Amniocentesis denotes the amount of blood destruction by estimating the amount of bilirubin pigments in the amniotic fluid;
Indications to amniocentesis are:
1) Antenatal fetal death and isoimminization in previous pregnancies;
2) Hemolytic infant disease in the previous pregnancies;
3) Increasing of antibodies titer to 1: 32.
Contraindications to amniocentesis are:
1) Threatened abortus and preterm labor;
3) Abnormal uterine development.
· Percutaneous umbilical blood sampling (PUBS) under ultrasound guidance – fetal blood can be taken for hematocrit, hemoglobin, blood gases, pH, bilirubin levels;
· Amniotic fluid spectrophotometry – there is an excellent correlation between the amount of biliary pigment in the amniotic fluid and the fetal hematocrit beginning at 27 weeks’ gestation. Liley chart can be used – it is a spectrophotometric graph based on the correlation of cord blood hemoglobin concentrations at birth and the amniotic fluid change in optical density at 450m.
Amniotic fluid assessment is of great value in managing the isoimmunized patient. Practical use of amniotic fluid analysis became a reality in about 1960, when Liley found that the level of bilirubin in the amniotic fluid accurately reflects the condition of the fetus. The mechanism by which bilirubin enters the amniotic fluid from the fetal compartment is still not understood. However, in the second half of normal pregnancy, the level of bilirubin normally decreases progressively. The level of bilirubin in an affected, isoimmunized patient can be evaluated in relation to natural decline. The level of bilirubin in the amniotic fluid is determined using a spectrophotometer. Normal amniotic fluid subjected to spectrophotometric analysis has a characteristic curve, based on optical density (OD). The presence of bilirubin causes a characteristic deviation in this curve, at 450 nm. Experience has shown how optical density relates to the severity of fetal problems, as shown in the figure.
Amniotic fluid is obtained from the patient by amniocentesis at periodic intervals between the twentieth and thirtieth weeks of pregnancy, depending on the history of previous pregnancies. OD values are then plotted on a curve, which allows estimation of the degree of severity of the anemia in the fetus. Based on this level of severity, in conjunction with the gestational age, a decision about expected management, transfusion of the fetus, or delivery can be made.
· Ultrasonic detection – both the placenta and the fetal liver are enlarged with hydrops. Fetal hydrops is easily diagnosed by the characteristic appearance of one or more of the following: ascites, pleural effusion, pericardial effusion, skin edema. Appearance of these factors during ultrasonic examination eliminates the need for diagnostic amniocentesis and necessitates therapeutic intervention based on fetal gestational age. Assessment of the affected fetus by periodic ultrasonography can be very helpful in detecting severe signs of the hemolytic process, namely subcutaneous edema and ascites. Under ultrasound guidance, the umbilical cord can be sampled directly percutaneous umbilical blood sampling (PUBS)] and fetal blood can be taken for hematocrit determination to assess the severity of anemia. Later in pregnancy, general tests of fetal well-being are used in the isoimmunized patient, because the ability of an affected fetus to withstand the stresses of pregnancy and labor may be compromised.
US- examination in Rh-isoimmunization
US- examination in Rh-isoimmunization
· Percutaneous Fetal Blood Sampling - allows measurement of fetal Hb, Hct, pH, reticulocytes
Middle cerebral artery peak velocity
Middle Cerebral Artery peak systolic velocity
· Direct fetal intravascular transfusion
· New techniques for evaluating fetal Rh Status: 1) determination of fetal RhD blood type by DNA amplification using a single fetal nucleated erythrocyte isolated from maternal blood; 2) determination of fetal RhD genotype from amniotic fluid or chorionic villus cells using DNA amplification. MANAGEMENT
Antibody titers would seem to be good markers of maternal antibody production, but in fact, such titers are of limited usefulness. In the first sensitized pregnancy, titers do seem to be helpful, but thereafter, they are of virtually no value because they do not reflect the current fetal condition. Even in the initial sensitized pregnancy, the greatest value is in distinguishing those pregnancies for which antibody production is so low as to be nonthreatening to the fetus from those for which there are likely to be significant consequence. A titer of 1:16 or greater is generally considered the critical point at which there is sufficient risk of fetal jeopardy to warrant additional evaluation.
Management of the patients with isoimmunization in female dyspansery:
1. To determine Rh-titer in the blood once a week until 32 weeks of pregnancy, from 32 to 35 weeks 0 twice a waak, then every week.
2. Perform blood investigation on presence blood type immune antibodies (in pregnants with 0 blood type, in husband – A, B, AB).
3. Prescribe desensitizing therapy (three courses during 10 days in the terms of 10-12, 22 -24, 32-34 weeks of pregnancy in all Rh-negative patients, even in the case of absence in their blood Rh-antibodies).
Desensitizing therapy include:
· cocarboxylase 100.0 mg intravenous;
· rutin 0,02 x 3 times per day per os;
· teonical 0.15 x3 times per day per os;
· calcii gluconate 0.5 x 3 times per day
· antihistaminic drugs are prescribed before sleeping (dimedroli, suprastini).
In specializing obstetrics department:
1. Plasmopheresis should be started from early terms of pregnancy gestation under control antibodies titer every two weeks. The course of treatment include 4-5 times of plasmopheresis with interval 1-2 days. Such method of treatment eliminates circulating immune complexes, and antibodies from blood thanks to special apparatus “Hemos PH-12”.
· Donor’s immunoglobulin in the dose of 4, 5 ml once a day with interval 3 days ¹ 3 injections should prescribed intramuscularly.
· Normal human immunoglobulin in the dose 150 mg on 1 kg of weight intravenous.
· Ultraviolet radiation of blood – 5-10 times on the course of treatment.
· Treatment of placental dysfunction: Tivortin i/v, Riboxin i/v
3. Transabdominal amniocentesis.
Pregnant women undergo cesarean section in such cases as:
· Severe form of hemolytic infant disease in the term 34-35 weeks after previous antenatal prevention of fetal hyaline membranes syndrome;
· Hydrops fetalis in any gestation term because of interm pregnancy would provoke antenatal fetal death.
In all other cases the labor are finished through birth canal. Such as hemolytic fetus response to hemorrhage, in the second stage of labor pudendal anesthesia and episiotomy are indicated (they decreasing fetal traumatization).
In the all others cases pregnant women with the diagnosis of Rh- disease undergo delivery in the term of 37-38 weeks of gestation. Estrogens, glucose, calcii. and vitamins have been prescribed during 5 days with the following labor induction. Induction of labor is performen by prostaglandin (in the case of immature uterine cervix) or by intravenous oxytocin infusion administration (in the case of mature uterine cervix). The success of locally applied prostaglandin gels in changing the cervix from unfavorable to favorable is encountered for future practice, although some studies have failed to confirm it efficacy.
Transfusion of Rh- red blood cells to the fetus is indicated when, on the basis of the fetus is in significant jeopardy for hydrops or fetal death. Traditionally, blood was transfused into the fetal abdominal cavity where absorption of the transfused cells takes place over subsequent days. More recently, direct fetal transfusions into the umbilical cord (PUBS) under ultrasonography guidance are being used more frequently, with positive results. Physicians experienced and skilled in this technique are critical to its success. The procedure carries with it a risk of fetal death of up to 3%, a risk that must be weighed against the predicted future course for the fetus in utero and the potential adverse consequences of preterm delivery. The quantity of red blood cells to be transferred can be calculated using the gestational age and size of the fetus and the fetal hematocrit. Because the transferred cells are Rh-, they are not affected by the transplacental maternal antibody. Timing of subsequent transfusions can be determined based on the severity of disease and the predicted life span of the transfused cells.
Indications to exchange blood transfusion in infants:
In -term fetus
Indirect bilirubin, mkmoll/L
Indirect bilirubin per hour, mkmoll/L
WHAT IS NEONATAL ASPHYXIA?
Newborn infants normally start to breathe without assistance and often cry after delivery. By 1 minute most infants are breathing well. If an infant fails to establish adequate, sustained respiration after birth, the infant is said to have NEONATAL ASPHYXIA.
NEONATAL ASPHYXIA IS DEFINED AS THE FAILURE OF AN INFANT TO CRY OR BREATHE WELL AFTER DELIVERY
Neonatal asphyxia is an important cause of neonatal death if not managed correctly.
WHAT IS HYPOXIA?
Hypoxia is defined as TOO LITTLE OXYGEN IN THE CELLS OF THE BODY. Hypoxia may occur in the fetus or the newborn infant. If the placenta fails to provide the fetus with enough oxygen, hypoxia will result and cause fetal distress. Similarly, with failure to breathe well after delivery (i.e. neonatal asphyxia) the infant will develop hypoxia. As a result of hypoxia the heart rate falls, central cyanosis develops and the infant becomes hypotonic (floppy) and unresponsive.
Note that neonatal asphyxia and hypoxia are not the same although they often occur together. Fetal hypoxia may result in neonatal asphyxia while neonatal asphyxia will result in hypoxia if the infant is not rapidly resuscitated.
HYPOXIA IS DEFINED AS TOO LITTLE OXYGEN IN THE CELLS OF THE BODY
The Apgar score is a method of assessing an infant's clinical condition after delivery. The Apgar score is based on 5 vital signs:
1. Heart rate.
2. Respiratory effort.
3. Presence or absence of central and peripheral cyanosis.
4. Muscle tone.
5. Response to stimulation.
Each vital sign is given a score of 0 or 1 or 2. A score of 2 is normal, a score of 1 is mildly abnormal and a score of 0 is severely abnormal. The individual vital sign scores are then totalled to give the Apgar score out of 10. The best possible Apgar score is 10 and the worst 0. An infant with a score of 0 shows no sign of life.
Normally the Apgar score is of 7 to 10. Infants with a score between 4 and 6 have moderate depression of their vital signs while infants with a score of 0 to 3 have severely depressed vital signs and are at great risk of dying unless actively resuscitated.
Due to the presence of peripheral cyanosis in most infants at delivery, it is unusual for a normal infant to score 10 at 1 minute. By 5 minutes most infants will have a score of 10. If the Apgar score is guessed and not correctly assessed, too high a score is usually given.
*** The Apgar score is named after the late Dr. Virginia Apgar, an anaesthetist, who described the scoring method in 1953.
The Apgar score should be performed on all infants at 1 minute after birth to record the infant's clinical condition and to assess whether the infant requires resuscitation. If the 1 minute Apgar score is below 7, then the Apgar score should be repeated at 5 minutes to document the success or failure of the resuscitation efforts. If the 5 minute Apgar score is still low, it should be repeated every 5 minutes until a normal Apgar score of 7 or more is achieved. In many hospitals, the Apgar score is often routinely repeated at 5 minutes even if the 1 minute score was normal. This is not necessary and the infant should rather be handed to the mother.
WHAT CAUSES A LOW APGAR SCORE?
There are many causes of a low Apgar score. These include:
1. Fetal distress due to hypoxia before delivery.
2. Maternal anaesthesia or recent analgesia.
3. Preterm infant.
4. Difficult or traumatic delivery.
5. Excessive suctioning of the pharynx after delivery.
6. Severe respiratory distress.
Note that fetal distress due to hypoxia during labour is only one of the many causes of neonatal asphyxia. However, neonatal asphyxia will result in hypoxia after delivery if the infant is not rapidly resuscitated.
It is important to always try and find the cause of a low Apgar score.
Resuscitation is a series of actions taken to establish normal breathing, heart rate, colour, tone and activity in an infant with depressed vital signs (i.e. a low Apgar score).
All infants who do not breathe well after delivery (i.e. infants with neonatal asphyxia) or have a 1 minute Apgar score below 7 need immediate resuscitation. The lower the Apgar score the more resuscitation is usually needed. Any infant who stops breathing or has depressed vital signs at any time after delivery or in the nursery also requires resuscitation.
ALL INFANTS WITH A 1 MINUTE APGAR SCORE BELOW 7 REQUIRE RESUSCITATION
The following clinical situations often lead to the delivery of an infant with neonatal asphyxiated and a low Apgar score at 1 minute:
1. Signs of fetal distress during labour.
2. Delivery before 37 weeks of gestation.
3. Abnormal presentation of the fetus.
4. Difficult or traumatic delivery.
5. General anaesthesia or recent analgesia (pethidine or morphine within the last 4 hours).
Remember that any infant can be born with neonatal asphyxia without prior warning. It is essential, therefore, to be prepared to resuscitate any newborn infant. Anyone who delivers an infant must be able to perform resuscitation.
ANY INFANT CAN HAVE NEONATAL ASPHYXIA WITHOUT WARNING SIGNS DURING LABOUR
EQUIPMENT DO YOU NEED FOR INFANT RESUSCITATION?
It is essential that you have all the basic equipment needed for simple infant resuscitation. The equipment must be in working order and immediately available. The equipment must be checked daily.
A warm, well lit corner of the delivery room should be available for resuscitation. A heat source, such as an overhead radiant warmer, is needed to keep the infant warm. A good light, such as an angle poise lamp, is required so that the infant can be closely observed during resuscitation.
The following essential equipment must be available in the delivery room:
1. SUCTION APPARATUS: An electric or wall vacuum suction apparatus is ideal but the vacuum pressure should not exceed 200 cm water (i.e. 20 kPa or 200 mbar). Soft 10 end hole suction catheters are needed.
2. OXYGEN: Whenever possible a cylinder or wall source of 100% oxygen should be available. However, infants can be resusciteted without oxygen.
3. RESUSCITATOR: A neonatal ventilation bag (e.g. Laerdal, Ambu Penlon or Cardiff) or simple Samson resuscitator must be available to provide ventilation.
4. ENDOTRACHEAL TUBES: 2,0 mm, 2,5 mm and 3,0 mm tubes, straight or shouldered, must be available. Introducers are also needed. Cuffed endotracheal tubes must not be used in newborn infants.
5. LARYNGOSCOPE: A laryngoscope with a small, straight blade (Miller 0 and 1 blades). Spare batteries and bulbs must be kept with the laryngoscope. This is the only expensive piece of equipment that is essential for all hospitals and clinics where deliveries are done.
6. NALOXONE: Ampoules of naloxone (Narcan). Syringes and needles will be needed to administer the drug.
7. WALL CLOCK or watch: To time the Apgar scoring.
*** Ampoules of 4% sodium bicarbonate and ampoules of 1:1000 adrenaline.
HOW SHOULD YOU STIMULATE RESPIRATION IMMEDIATELY AFTER BIRTH?
After birth all infants must be quickly dried in a warm towel and then placed in a second warm, dry towel before starting resuscitation. This prevents rapid heat loss due to evaporation. Handling and rubbing the newborn infant with a dry towel is usually all that is needed to stimulate the onset of breathing. Gently flicking under the infant's feet may be helpful in stimulating breathing. Stimulation alone will start breathing in most infants. There is no need to smack newborn infants.
Infants who breathe well at delivery should NOT be routinely suctioned as suctioning sometimes causes apnoea. Infants born by caesarean section also need not be routinely suctioned.
IT IS NOT NECESSARY TO ROUTINELY SUCTION THE MOUTH AND NOSE OF INFANTS AFTER DELIVERY
HOW DO YOU RESUSCITATE AN INFANT?
If the infant fails to respond to stimulation, then the infant must be actively resuscitated. The most experienced person, irrespective of rank, should resuscitate the infant. However, all staff who conduct deliveries must be able to resuscitate infants. It is very helpful to have an assistant.
There are 4 main steps in the basic resuscitation of a newborn infant. They can be easily remembered by thinking of the first 4 letters of the alphabet, i.e. "ABCD" - AIRWAY - BREATHING - CIRCULATION - DRUGS.
STEP 1. OPEN AND CLEAR THE AIRWAY.
1. OPEN THE AIRWAY by placing the infant’s head in the neutral position with the neck slight extended. Do not flex or over extend the neck.
2. GENTLY CLEAR THE THROAT. The infant may be unable to breathe because the airway is blocked by mucus or blood. Therefore, if the infant fails to breathe after stimulation, gently suction the back of the mouth and throat with a soft F 10 catheter. Excessive suctioning, especially if too deep in the region of the vocal cords, may result in apnoea and bradycardia by stimulating the vagal nerve. This can be prevented by holding the catheter 5 cm from the tip when suctioning the infant's throat. Do not suction the nose before suctioning the mouth or throat as this often causes the infant to gasp.
If stimulation, positioning and suctioning fail to start breathing, the infant needs mask ventilation. Do not waste time by giving oxygen without also applying mask ventilation.
VENTILATION IS THE MOST IMPORTANT STEP IN NEWBORN RESUSCITATION
STEP 2. START THE INFANT BREATHING BY PROVIDING ADEQUATE VENTILATION.
1. MASK VENTILATION: If the infant still fails to breathe adequately, some form of artificial ventilation (breathing) is required. Most infants can be adequately ventilated with a bag and mask. The mask must be held tightly over the infant's nose and mouth. Make sure the head is in the correct position and the airway is clear. Even if breathing is not started, most infants can be kept alive with face mask ventilation until help arrives. Intubation and ventilation are needed if adequate chest movement cannot be achieved with mask ventilation.
2. INTUBATION AND VENTILATION: The most effective method of ventilation is via an endotracheal tube. All staff who frequently deliver infants should learn this simple technique. Infants who fail to respond to mask ventilation must be intubated. Ventilate the infant at a rate of about 40 breaths a minute. Make sure that the infant's chest moves with each breath and that good, bilateral air entry is heard. Adequate ventilation is by far the most important step in resuscitating an infant with severe neonatal asphyxia. Respiratory stimulants such as Vandid must not be used as they are dangerous and do not help.
MOST INFANTS CAN BE ADEQUATELY VENTILATED WITH A BAG AND MASK
The method of mask ventilation and tracheal intubation is described in skills workshop 16.
STEP 3. OBTAIN A GOOD CIRCULATION WITH CHEST COMPRESSIONS.
Apply chest compressions (external cardiac massage) at about 80 times a minute if the heart rate remains below 60 beats per minute after effective ventilation has been started. Place the fingers of one or two hands under the infant's back and press on the lower half of the sternum with your thumb or thumbs. Usually two chest compressions is followed by a breath.
The method of giving cardiac massage is described in skills workshop 16.
STEP 4. DRUGS TO REVERSE PETHIDINE AND MORPHINE.
If the mother has received either pethidine or morphine during the 4 hour period before delivery, the infant's poor breathing may be due to narcotic depression. If so, the depressing effect of the analgesia on respiration can be rapidly reversed with Narcan (a 1 ml ampoule contains 0,4 mg naloxone). Narcan 0,1 mg/kg (i.e. 0,25 ml/kg) can be given by intramuscular injection into the anterolateral aspect of the thigh. Do not use Neonatal Narcan as this preparation requires too big a volume. Narcan will not help resuscitate an infant if the mother has not received a narcotic analgesic during labour, or has only received a general anaesthetic, barbiturates or other sedatives.
*** Narcan acts more rapidly if injected directly into the umbilical vein or if given down the endotracheal tube. Flumazenil (Anexate) will reverse the depressant effect of benzodiazepines such as diazepam (Valium).
*** With experience and further training, additional drugs can be given if the above steps fail to resuscitate the infant:
1. The injection of 2 ml/kg of 4% sodium bicarbonate into the umbilical vein to correct acidosis and stimulate the cardiorespiratory system. Sodium bicarbonate should only be given once adequate ventilation has been achieved. An 8% solution must never be used as it is extremely hypertonic. Never give sodium bicarbonate down the endotracheal tube.
2. Adrenalin 1:10 000 given intravenously or placed down the endotracheal tube stimulates the myocardium if cardiac massage fails to improve the heart rate. One ml of adrenalin 1:1000 must first be diluted with 9 ml normal saline to give a 1:10 000 solution. One ml of the diluted solution can then be given to term infants and 0,5 ml to preterm infants (recommended dose is 0,2 ml/kg of diluted adrenalin).
3. If the infant remains shocked with poor peripheral perfusion despite all other attempts at resuscitation, a plasma volume expander such as stabilized human serum, Haemacceel or Plasmolyte B or Normal Saline can be given. The required volume is usually 10 ml/kg over 10 minutes.
A summary of the method of resuscitating a newborn infant is shown in flow diagram 16-1.
The 4 steps in resuscitation are followed step by step until the 3 most important vital signs of the Apgar score have returned to normal:
1. A PULSE RATE ABOVE 100 BEATS PER MINUTE. Easily assessed by palpating the base of the umbilical cord or listening to the chest with a stethoscope.
2. A GOOD CRY OR GOOD BREATHING EFFORTS. This assures adequate breathing.
3. A PINK TONGUE. This indicates a good oxygen supply to the brain. Do not rely on the colour of the lips or buccal mucosa.
DOES THE MECONIUM STAINED INFANT NEED SPECIAL CARE?
Yes. All infants that have meconium stained amniotic fluid (liquor) at birth need special care to prevent severe meconium aspiration. Whenever possible all these at risk infants should be identified before delivery, especially infants with thick meconium in the amniotic fluid.
WHY DOES THE MECONIUM STAINED INFANT NEED SPECIAL CARE?
As a result of hypoxia before delivery, the fetus may make gasping movements and also pass meconium. Meconium can, therefore, be sucked into the upper airways together with amniotic fluid. Fortunately most of the meconium is unable to reach the fluid filled alveoli of the fetus. Only after delivery, when the infant inhales air, does meconium enter the small airways and alveoli.
Meconium contains enzymes from the fetal pancreas that can cause severe lung damage and even death if inhaled into the alveoli after delivery. Meconium also obstructs the airways.
*** Meconium often burns the infant's skin and digests away the infant's eye lashes! Therefore, imagine the damage meconium can cause to the delicate lining of the bronchi and alveoli.
HOW CAN YOU PREVENT MECONIUM ASPIRATION AT VAGINAL DELIVERY?
Many cases of meconium aspiration syndrome can be prevented with the correct care of the infant during delivery. A suction apparatus and a F 10 end hole catheter must be ready at the bedside. If possible, the person conducting the delivery should have an assistant to suction the infant's mouth when the head delivers.
After delivery of the head, the shoulders should be held back and the mother asked to pant to prevent delivery of the trunk. The infant's face is then turned toward the assistant so that the mouth and pharynx can be well suctioned. Only when no more meconium can be cleared, should the infant be completely delivered. If the infant cries well after delivery, no further resuscitation or suctioning is needed. However, some infants develop apnoea and bradycardia as a result of the suctioning and, therefore, need ventilation after delivery.
If an infant needs ventilation, the pharynx should again be suctioned, preferably under direct vision using a laryngoscope, before ventilation is started. If the infant is intubated, direct suction can be applied to the endotracheal tube. Withdraw the endotracheal tube while applying suction Repeat until no more meconium is obtained. This aggressive method of suctioning is very successful in preventing severe meconium aspiration but should not be used when resuscitating infants that are not meconium stained.
MECONIUM STAINED INFANTS MUST BE SUCTIONED BEFORE DELIVERY OF THE SHOULDERS
When a meconium stained infant is delivered by caesarean section, the mouth and pharynx must be suctioned with a F10 end hole catheter, BEFORE the shoulders are delivered from the uterus. After complete delivery, move the infant immediately to the resuscitation table. If the infant does not breathe spontaneously, further suctioning under direct vision is needed before stimulating respiration or applying ventilation. Infants who breathe well after delivery do not need to be suctioned again.
WHEN IS FURTHER RESUSCITATION HOPELESS?
Every effort should be made to resuscitate all infants that show any sign of life at delivery. The severity of neonatal asphyxia at 1 and 5 minutes is not a good indicator of the likelihood of hypoxic brain damage or the possibility of an unsuccessful resuscitation. If the Apgar score remains low after 5 minutes, efforts at resuscitation must be continued. However, if the infant has not started to breathe, or only gives occasional gasps by 20 minutes, the chance of death or brain damage is extremely high. The exception is when the infant is sedated by maternal drugs. It is preferable if an experienced person decides when to abandon further attempts at resuscitation.
*** Some people claim that resuscitating infants with severe neonatal asphyxia is contra-indicated as they survive with brain damage. Research has indicated that this claim is not correct as the majority of severely neonatal asphyxiated infants that are aggressively resuscitated and survive recover completely.
WHAT POST RESUSCITATION CARE IS NEEDED?
All infants that require resuscitation must be carefully observed for at least 4 hours. Their temperature, pulse and respiratory rate, colour and activity should be recorded and their blood glucose levels checked. Keep these infants warm and provide fluid and energy either intravenously or orally. Usually these infants are observed in a closed incubator. Do not bath the infant until the infant has fully recovered.
If the infant has signs of respiratory difficulty or is centrally cyanosed in room air after resuscitation, it is essential to provide oxygen while the infant is being moved to the nursery. Some infants may even require ventilation during transport.
Careful notes must be made describing the infant's condition at birth, the resuscitation needed and the probable cause of the neonatal asphyxia.
WHAT CARE SHOULD YOU GIVE TO MECONIUM STAINED INFANTS IN THE NURSERY?
All heavily meconium stained infants should be observed in the nursery for a few hours after delivery as they may show signs of hypoxic damage or meconium aspiration syndrome. Most meconium stained infants have swallowed meconium before delivery. Meconium is a very irritant substance and causes meconium gastritis. This results in repeated vomits of meconium stained mucus. Infants with lightly meconium stained amniotic fluid who appear well after delivery can be kept with their mothers.
Meconium gastritis may be prevented by washing out the stomach tube with 2% sodium bicarbonate (mix 4% sodium bicarbonate with an equal volume of sterile water). Five ml of 2% sodium bicarbonate is repeated injected into the stomach via a nasogastric tube and then aspirated until the gastric aspirate is clear All heavily meconium stained infants should have a stomach washout on arrival in the nursery. This should be followed by a feed of colostrum. Routine stomach washouts in preterm infants or infants born by caesarean section are not needed.
*** Colostrum contains phagocytic cells that ingest any meconium that remains in the stomach. This reduces the chance of further vomiting.
A STOMACH WASHOUT IS ONLY NEEDED IF THE INFANT IS COVERED WITH THICK MECONIUM
WHAT IS THE DANGER OF FETAL DISTRESS DUE TO PRENATAL HYPOXIA?
If the cells of the fetus do not receive adequate oxygen during pregnancy or labour, many organs may be damaged. This may result in either:
1. Transient damage which will recover completely after delivery.
2. Permanent damage that will not recover fully after birth.
3. Death of the fetus or newborn infant.
WHAT ORGANS ARE COMMONLY DAMAGED BY HYPOXIA?
1. The BRAIN needs a lot of oxygen and, therefore, is very sensitive to hypoxia either before or after delivery.
2. The KIDNEYS may be damaged, resulting in haematuria, proteinuria and decreased urine output for the first few days after delivery. Occasionally renal failure may result.
3. The HEART may be damaged causing heart failure. This presents with hepatomegaly, respiratory distress and poor peripheral perfusion.
4. The GUT may be damaged causing necrotising enterocolitis.
5. The LUNGS may be damaged resulting in respiratory distress with pulmonary artery spasm (persistent pulmonary hypertension).
Newborn care principles
When a baby is born to a mother being treated for complications, the management of the newborn will depend on:
· whether the baby has a condition or problem requiring rapid treatment;
· whether the mother’s condition permits her to care for her newborn completely, partially or not at all.
· If the newborn has an acute problem that requires treatment within 1 hour of delivery, health care providers in the labour ward will be required to give the care. Problems or conditions of the newborn requiring urgent interventions include:
- gasping or not breathing;
- breathing with difficulty (less than 30 or more than 60 breaths per minute, indrawing of the chest or grunting)
- central cyanosis (blueness);
- pretern or very low birth weight (less than 1 500 g);
- hypothermia/cold stress (axillary temperature less than 36.5�C);
· The following conditions require early treatment:
- low birth weight (1500 g - 2500 g)
- possible bacterial infection in an apparently normal newborn whose mother had prelabour or prolonged rupture of membranes or amnionitis;
- possible congenital syphilis (mother has positive serologic test or is symptomatic).
• If the newborn has a malformation or other problem that does not require urgent (labour ward) care:
· If the newborn has no apparent problems, provide routine initial newborn care, including skin-to-skin contact with the mother and early breastfeeding.
· If the mother’s condition permits, keep the baby in skin-to-skin contact with the mother at all times;
· If the mother’s condition does not permit her to maintain skin-to-skin contact with the baby after the delivery (e.g. caesarean section):
- Wrap the baby in a soft, dry cloth, cover with a blanket and ensure the head is covered to prevent heat loss;
- Observe frequently.
· If the mother’s condition requires prolonged separation from the baby, transfer the baby to the appropriate service to care for newborns (see below).
· Keep the baby warm. Wrap the baby in a soft, dry cloth, cover with a blanket and ensure the head is covered to prevent heat loss.
· Transfer the baby in the arms of a health care provider if possible. If the baby requires special treatment such as oxygen, transfer in an incubator or bassinet.
· Initiate breastfeeding as soon as the baby is ready to suckle or as soon as the mother’s condition permits.
· f breastfeeding has to be delayed due to maternal or newborn problems, teach the mother to express breastmilk as soon as possible and ensure that this milk is given to the newborn.
· Ensure that the service caring for the newborn receives the record of the labour and delivery and of any treatments given to the newborn.
*** At the onset of hypoxia, blood is shunted away from the kidneys, gut and lungs to the brain and heart. This mechanism to protect the brain and heart may cause ischaemic damage to the kidneys, gut and lungs. The increased blood flow to the brain may cause intraventricular haemorrhage in preterm infants. With severe, prolonged hypoxia, cardiac output falls and as a result the brain and myocardium may also suffer ischaemic damage.
HAEMATURIA IN THE NEWBORN INFANT IS A USEFUL CLINICAL MARKER OF PRENATAL HYPOXIA
WHAT DAMAGE IS DONE TO THE BRAIN BY HYPOXIA?
Different types of brain damage can occur depending on the gestational age of the fetus and the severity of the hypoxia:
1. INTRAVENTRICULAR HAEMORRHAGE. Hypoxia may damage small blood vessels around the ventricles of the brain in preterm infants. These vessels may bleed into the ventricles which can damage the surrounding brain. An intraventricular haemorrhage usually presents within the first 2 days after delivery. A mild haemorrhage is usually asymptomatic but a severe haemorrhage causes apnoea, shock and death. The clinical diagnosis of intraventricular haemorrhage can be confirmed with ultrasonography of the brain.
2. Hypoxia may cause decreased blood flow (ISCHAEMIA) which results in INFARCTION (death) of part of the brain. In preterm infants this usually causes spastic diplegia (spastic weakness of both legs). In term infants hypoxia usually causes convulsions, mental retardation and cerebral palsy.
3. In term infants, hypoxia and ischaemia of the brain presents in the first 72 hours as NEONATAL ENCEPHALOPATHY (hypoxic ischaemic encephalopathy) with poor feeding, increased or decreased tone, and convulsions.
4. Hypoxia may also cause blindness, deafness or learning and behaviour problems at school.
Immediate newborn conditions or problems
· The newborn has serious conditions or problems:
- not breathing or is gasping;
- breathing with difficulty (less than 30 or more than 60 breaths per minute, indrawing of the chest or grunting);
- cyanosis (blueness);
- preterm or very low birth weight (less than 32 weeks gestation or less than 1 500 g);
· The newborn has other conditions or problems that require attention in the delivery room:
- low birth weight (1 500–2 500 g);
- possible bacterial infection in an apparently normal newborn whose mother had prelabour or prolonged rupture of membranes;
- possible congenital syphilis in newborn whose mother has a positive serologic test for syphilis or is symptomatic.
Three situations require immediate management: no breathing (or gasping, below), cyanosis (blueness) or breathing with difficulty.
NO BREATHING OR GASPING
· Dry the baby, remove the wet cloth and wrap the baby in a dry, warm cloth.
· Clamp and cut the cord immediately if not already done.
· Move the baby to a firm, warm surface under a radiant heater for resuscitation.
To avoid delays during an emergency situation, it is vital to ensure that equipment is in good condition before resuscitation is needed:
· Have the appropriate size masks available according to the expected size of the baby (size 1 for a normal weight newborn and size 0 for a small newborn).
· Block the mask by making a tight seal with the palm of your hand and squeeze the bag:
- If you feel pressure against your hand, the bag is generating adequate pressure;
- If the bag reinflates when you release the grip, the bag is functioning properly.
OPENING THE AIRWAY
· Position the newborn (Fig S-28):
- Place the baby on its back;
- Position the head in a slightly extended position to open the airway;
- Keep the baby wrapped or covered, except for the face and upper chest.
Correct position of the head for ventilation; note that the neck is less extended than in adults
· Clear the airway by suctioning first the mouth and then the nostrils. If blood or meconium is in the baby’s mouth or nose, suction immediately to prevent aspiration.
Note: Do not suction deep in the throat as this may cause the baby’s heart to slow or the baby may stop breathing.
· Reassess the baby:
- If the newborn starts crying or breathing, no further immediate action is needed. Proceed with initial care of the newborn;
- If the baby is still not breathing, start ventilating (see below).
VENTILATING THE NEWBORN
· Recheck the newborn’s position. The neck should be slightly extended (Fig S-28).
· Position the mask and check the seal (Fig S-29):
- Place the mask on the newborn’s face. It should cover the chin, mouth and nose;
- Form a seal between the mask and the face;
- Squeeze the bag with two fingers only or with the whole hand, depending on the size of the bag;
- Check the seal by ventilating twice and observing the rise of the chest.
Ventilation with bag and mask
· Once a seal is ensured and chest movement is present, ventilate the newborn. Maintain the correct rate (approximately 40 breaths per minute) and the correct pressure (observe the chest for an easy rise and fall):
- If the baby’s chest is rising, ventilation pressure is probably adequate;
- If the baby’s chest is not rising:
- Recheck and correct, if necessary, the position of the newborn (Fig S-28);
- Reposition the mask on the baby’s face to improve the seal between mask and face;
- Squeeze the bag harder to increase ventilation pressure;
- Repeat suction of mouth and nose to remove mucus, blood or meconium from the airway.
· If the mother of the newborn received pethidine or morphine prior to delivery, consider administering naloxone after vital signs have been established (Box S-9).
· Ventilate for 1 minute and then stop and quickly assess if the newborn is breathing spontaneously:
- If breathing is normal (30–60 breaths per minute) and there is no indrawing of the chest and no grunting for 1 minute, no further resuscitation is needed. Proceed with initial care of the newborn;
- If the newborn is not breathing, or the breathing is weak, continue ventilating until spontaneous breathing begins.
· If the newborn starts crying, stop ventilating and continue observing breathing for 5 minutes after crying stops:
- If breathing is normal (30–60 breaths per minute) and there is no indrawing of the chest and no grunting for 1 minute, no further resuscitation is needed. Proceed with initial care of the newborn;
- If the frequency of breathing is less than 30 breaths per minute, continue ventilating;
- If there is severe indrawing of the chest, ventilate with oxygen, if available (Box S-10). Arrange to transfer the baby to the most appropriate service for the care of sick newborns.
· If the newborn is not breathing regularly after 20 minutes of ventilation:
- Transfer the baby to the most appropriate service for the care of sick newborns;
- During the transfer, keep the newborn warm and ventilated, if necessary.
· If there is no gasping or breathing at all after 20 minutes of ventilation, stop ventilating; the baby is stillborn. Provide emotional support to the family.
Counteracting respiratory depression in the newborn caused by narcotic drugs
If the mother received pethidine or morphine, naloxone is the antidote for counteracting respiratory depression in the newborn caused bythese drugs.
Note: Do not administer naloxone to newborns whose mothers are suspected of having recently abused narcotic drugs.
· If there are signs of respiratory depression, begin resuscitation immediately:
- After vital signs have been established, give naloxone 0.1 mg/kg body weight IV to the newborn;
- Naloxone may be given IM after successful resuscitation if the infant has adequate peripheral circulation. Repeated doses may be required to prevent recurrent respiratory depression.
If there are no signs of respiratory
depression, but pethidine
or morphine was given within 4 hours of delivery, observe the baby
CARE AFTER SUCCESSFUL RESUSCITATION
· Prevent heat loss:
- Place the baby skin-to-skin on the mother’s chest and cover the baby’s body and head;
- Alternatively, place the baby under a radiant heater.
· Examine the newborn and count the number of breaths per minute:
- If the baby is cyanotic (bluish) or is having difficulty breathing (less than 30 or more than 60 breaths per minute, indrawing of the chest or grunting), give oxygen by nasal catheter or prongs (below).
· Measure the baby’s axillary temperature:
- If the temperature is 36�C or more, keep the baby skin-to-skin on the mother’s chest and encourage breastfeeding;
- If the temperature is less than 36�C, rewarm the baby.
· Encourage the mother to begin breastfeeding. A newborn that required resuscitation is at higher risk of developing hypoglycaemia:
- If suckling is good, the newborn is recovering well;
- If suckling is not good, transfer the baby to the appropriate service for the care of sick newborns.
· Ensure frequent monitoring of the newborn during the next 24 hours. If signs of breathing difficulties recur, arrange to transfer the baby to the most appropriate service for thecare of sick newborns.
· If the baby is cyanotic (bluish) or is having difficulty breathing (less than 30 or more than 60 breaths per minute, indrawing of the chest or grunting) give oxygen by nasal catheter or prongs:
- Suction the mouth and nose to ensure the airways are clear;
- Give oxygen at 0.5 L per minute by nasal catheter or nasal prongs (Box S-10);
- Transfer the baby to the appropriate service for the care of sick newborns.
· Ensure that the baby is kept warm. Wrap the baby in a soft, dry cloth, cover with a blanket and ensure the head is covered to prevent heat loss.
Use of oxygen
When using oxygen, remember:
· Supplemental oxygen should only be used for difficulty in breathing or cyanosis;
· If the baby is having severe indrawing of the chest, is gasping for breath or is persistently cyanotic, increase the concentration of oxygen by nasal catheter, nasal prongs or oxygen hood.
Note: Indiscriminate use of supplemental oxygen for premature infants has been associated with the risk of blindness.
Many serious conditions in newborns—bacterial infections, malformations, severe asphyxia and hyaline membrane disease due to preterm birth—present in a similar way with difficulty in breathing, lethargy and poor or no feeding.
It is difficult to distinguish between the conditions without diagnostic methods. Nevertheless, treatment must start immediately even without a clear diagnosis of a specific cause. Babies with any of these problems should be suspected to have a serious condition and should be transferred without delay to the appropriate service for the care of sick newborns.
VERY LOW BIRTH WEIGHT OR VERY PRETERM BABY
If the baby is very small (less than 1 500 g or less than 32 weeks), severe health problems are likely and include difficulty in breathing, inability to feed, severe jaundice and infection. The baby is susceptible to hypothermia without special thermal protection (e.g. incubator).
Very small newborns require special care. They should be transferred to the appropriate service for caring for sick and small babies as early as possible. Before and during transfer:
· Ensure that the baby is kept warm. Wrap the baby in a soft, dry cloth, cover with a blanket and ensure the head is covered to prevent heat loss.
· If maternal history indicates possible bacterial infection, give first dose of antibiotics:
- gentamicin 4 mg/kg body weight IM (or give kanamycin);
- PLUS ampicillin 100 mg/kg body weight IM (or give benzyl penicillin).
· If the baby is cyanotic (bluish) or is having difficulty breathing (less than 30 or more than 60 breaths per minute, indrawing of the chest or grunting), give oxygen by nasal catheter or prongs.
If the baby is lethargic (low muscular tone, does not move), it
is very likely that the baby has a severe illness and should be transferred to
the appropriate service for the care of sick
Hypothermia can occur quickly in a very small baby or a baby who was resuscitated or separated from the mother. In these cases, temperature may quickly drop below 35C. Rewarm the baby as soon as possible:
· If the baby is very sick or is very hypothermic (axillary temperature less than 35C):
- Use available methods to begin warming the baby (incubator, radiant heater, warm room, heated bed);
- Transfer the baby as quickly as possible to the appropriate service for the care of preterm or sick newborns;
- If the baby is cyanotic (bluish) or is having difficulty breathing (less than 30 or more than 60 breaths per minute, indrawing of the chest or grunting), give oxygen by nasal catheter or prongs (page S-146).
· If the baby is not very sick and axillary temperature is 35�C or more:
- Ensure that the baby is kept warm. Wrap the baby in a soft, dry cloth, cover with a blanket and ensure the head is covered to prevent heat loss;
- Encourage the mother to begin breastfeeding as soon as the baby is ready;
- Monitor axillary temperature hourly until normal;
- Alternatively, the baby can be placed in an incubator or under a radiant heater.
Convulsions in the first hour of life are rare. They could be caused by meningitis, encephalopathy or severe hypoglycaemia.
· Ensure that the baby is kept warm. Wrap the baby in a soft, dry cloth, cover with a blanket and ensure the head is covered to prevent heat loss.
· Transfer the baby to the appropriate service for the care of sick newborns as quickly as possible.
MODERATELY PRETERM OR LOW BIRTH WEIGHT BABY
Moderately preterm (33–38 weeks) or low birth weight (1 500–2 500 g) babies may start to develop problems soon after birth.
· If the baby has no breathing difficulty and remains adequately warm while in skin-to-skin contact with the mother:
- Keep the baby with the mother;
- Encourage the mother to initiate breastfeeding within the first hour if possible.
· If the baby is cyanotic (bluish) or is having difficulty breathing (less than 30 or more than 60 per minute, indrawing of the chest or grunting), give oxygen by nasal catheter or prongs.
· If axillary temperature drops below 35C, rewarm the baby.
The following are suggested guidelines which may be modified according to local situations:
· If the mother has clinical signs of bacterial infection or if membranes were ruptured for more than 18 hours before delivery even if the mother has no clinical signs of infection:
- Keep the baby with the mother and encourage her to continue breastfeeding;
- Make arrangements with the appropriate service that cares for sick newborns to take a blood culture and start the newborn on antibiotics.
· If these conditions are not met, do not treat with antibiotics. Observe the baby for signs of infection for three days:
- Keep the baby with the mother and encourage her to continue breastfeeding;
- If signs of infection occur within 3 days, make arrangements with the appropriate service that cares for sick newborns to take a blood culture and start the newborn on antibiotics.
· If the newborn shows signs of syphilis, transfer the baby to the appropriate service for the care of sick newborns. Signs of syphilis include:
- generalized oedema;
- skin rash;
- blisters on palms or soles;
- anal condylomata;
- enlarged liver/spleen;
- paralysis of one limb;
- spirochetes seen on darkfield examination of lesion, body fluid or cerebrospinal fluid.
· If the mother has a positive serologic test for syphilis or is symptomatic but the newborn shows no signs of syphilis, whether or not the mother was treated, give benzathine penicillin 50 000 units/kg body weight IM as a single dose.