John M. Bowman

Thirty-five years of Rh prophylaxis†

In 1609, a French midwife reported, in the popular Paris press, the birth of twins. 1 The first was grossly edematous (hydropic) and died promptly. The second, in better condition, became deeply jaundiced; developed neurologic symptoms (kernicterus) and died on the third day. These two conditions (hydrops fetalis and kernicterus), were not combined again until 1932, when Diamond et al. 2 came to the conclusion that they were different aspects of the same disease: severe hemolysis with the development of extramedullary erythropoiesis and the outpouring of immature nucleated erythrocytes (erythroblastosis fetalis). Diamond and coworkers had no idea of the cause of the fetal RBC hemolysis. In 1938, Ruth Darrow, 3 a Chicago pathologist who had a baby die of kernicterus, theorized that the cause of the fetal RBC hemolysis was a maternal fetal RBC antibody produced by the transplacental passage of fetal RBCs into the mother’s circulation and leading to the reverse transplacental passage of the antibody into the fetus with fetal RBC destruction. She postulated that the offending antigen was fetal Hb. She had the pathogenesis of hemolytic disease correctly identified but she had the wrong antigen. With the discovery of the Rh J blood group system by Landsteiner and Wiener 4 in 1940, and the subsequent determination by Levine et al. 5 in 1941 that D in the Rh system was the offending antigen, the pathogenesis of hemolytic disease of the fetus and newborn was elucidated. The transplacental passage of D+ fetal RBCs into the circulation of a D– mother produces anti-D. The anti-D, if IgG, traverses the placenta into the fetal circulation. This destroys the fetal RBCs, setting in motion the train of events leading to severe jaundice in the newborn or, in its most severe manifestation, hydrops fetalis with gross edema, anasarca, pulmonary edema and fetal death. Prior to 1945, 50 percent of all fetuses with hemolytic disease died of kernicterus or hydrops fetalis. It was quickly determined that if the D– mother was carrying an ABO-compatible D+ fetus, her risk of Rh immunization was 16 percent. If the D+ fetus was ABO incompatible (20% are), the risk was only 2 percent. Thus, the overall risk of Rh immunization is 13.2 percent. To clarify the importance of this disorder, in Canada in the early 1940s at a time when perinatal mortality was 40 per 1000 births, hemolytic disease of the fetus and newborn accounted for 10 percent of such deaths. There is no reason to believe that the situation in the United States, at that time, was any different. With the discovery of the cause of hemolytic disease, rapid advances in treatment occurred. Exchange transfusion, introduced by Wallerstein, 6 eradicated kernicterus and reduced the perinatal mortality to 25 percent. With the introduction of induced premature delivery, 7 amniotic fluid spectrophotometry, 8 intraperitoneal fetal transfusion, 9 fetal blood sampling, 10 and intravascular fetal transfusion, 11 perinatal mortality in tertiary unit expert hands was further reduced to 2 or 3 percent. The only way in which perinatal mortality could be reduced further is to prevent maternal Rh immunization.

Intrauterine transfusion ― intraperitoneal versus intravascular approach: a case-control comparison

Intravascular fetal transfusion has gained widespread acceptance and has supplanted the use of intraperitoneal fetal transfusion in management of severe alloimmune disease in many centers. This study compares the two methods with regard to multiple objective end points of performance, therapy, and outcome in a highly matched case-control fashion. The intravascular approach is better on almost every level. More surviving infants who are in better condition at a mature gestation and whose mothers have fewer complications and sequelae are the result. Whereas intraperitoneal transfusion should not be abandoned altogether, it is a second-line procedure used only in very limited circumstances. Intravascular fetal transfusion offers realistic prognosis for intact survival at virtually any extreme of alloimmune disease.

Controversies in Rh prophylaxis: Who needs Rh immune globulin and when should it be given?

A summary of the current recommendations for administration of Rh immune globulin after several reproductive events is presented. The risks of failure to administer Rh immune globulin after delivery or abortion, amniocentesis, and massive transplacental hemorrhage are described.

A case of double trisomy: Trisomy no. 18 and triplo-X

Summary Clinical and autopsy findings of an infant who died at 35 days of age with multiple congenital malformations are described. Cytologic studies indicate that the patient was a double trisomic individual: XXX No. 18 trisomy syndrome.

RhD Hemolytic Disease of the Newborn

Hemolytic disease of the fetus and newborn was first described in 1609 in a set of twins by a French midwife: the first twin was hydropic and stillborn, and the second was deeply jaundiced and subs...

Severe Rh disease—Poor outcome is not inevitable

Most centers report only moderate success in the intrauterine treatment of severe Rh-isoimmune hemolytic disease. For the hydropic fetus, the prognosis is poor. Innovations in the assessment, treatment, and follow-up of the severely affected fetus have yielded more encouraging results. Among the 24 fetuses receiving a refined management plan, instituted in June, 1980, survival rates were 100% in the nonhydropic fetus and 75% in the hydropic fetus. Improved fetal evaluation by means of extensive real-time ultrasonography allows more exact assessment of stage of disease, safer performance of intrauterine transfusion, and a direct picture of the fetal response to treatment. The intrauterine transfusion procedure differs in many aspects from those used in other centers and is notable mostly because of the absence of traumatic fetal death since the present program began. This improvement and the absence of neonatal death have resulted in 92% survival rate among the fetuses transfused. The success of this integrated team approach suggests revision of the pessimism toward the fetus with severe Rh disease.

Anti‐Rh(D) IgG Subclasses and Severity of Rh Hemolytic Disease of the Newborn

Abstract. The influence of anti‐Rh(D) IgG subclasses on the severity of hemolytic disease of the newborn was examined in 98 pregnancies. Disease was severe in 19 of 32 cases in which only IgG1 was detected, 40 of 63 cases in which IgG1 and IgG3 were found and 0 of 3 cases in which only IgG3 was detected. When both IgG1 and IgG3 anti‐D were present, hemolytic disease was more severe than when IgG1 alone was detected. The earliest onset of hydrops was at 20 weeks gestation in the IgG1+IgG3 anti‐Rh group, and at 27 weeks gestation in the IgG1 group.

Severe anti-C hemolytic disease of the newborn

Objective: Because of referral of a C-alloimmunized pregnant woman with a previous hydropic death whose fetus survived after four intraperitoneal transfusions, prevalence and severity of anti-C hemolytic disease of the newborn were investigated. Study Design: The numbers of C- or Ce-alloimmunized pregnancies in Manitoban women and their outcome for the 28-year period ending Oct. 31, 1990, were reviewed. The literature relating to C or Ce alloimmunization from 1944 to 1990 was surveyed. Results: In Manitoba for the period reviewed there were 120 pregnancies in 80 C- or Ce-alloimmunized women. Twenty-two ended in abortion and two in fetal death unrelated to anti-C or anti-Ce. Of the remaining 96, 33 fetuses of 32 pregnancies were affected but only eight (6.7%) required treatment after birth. None were severely affected. In the literature there are only three other reported deaths from C or Ce hemolytic disease; two of the three may have been the same patient. The prevalence of C or Ce alloimmunization reported in various series, including our own, ranged from 8.7 to 185 per 100,000 pregnancies. Conclusions: Because on rare occasions, C or Ce alloimmunization can cause severe hemolytic disease, criteria for investigative measures such as amniocentesis or cordocentesis do not differ from the criteria for instituting these measures in Rh o (D)—alloimmunized pregnancies.

Absorption of red cells from the peritoneal cavity of an hydropic twin.

A pair of monozygotic erythroblastotic twins, one with hydrops, the other without, were treated by intrauterine transfusion. The twins had a monochorionic, diamniotic placenta with gross surface vascular anastomoses; at birth their circulating blood was of a single composition. The composition established that the presence of ascites per se does not inhibit absorption of blood from the peritoneal cavity.

HEMOLYTIC DISEASE OF THE NEWBORN

Hemolytic disease of the newborn (HDN) was first described in a set of twins in 1609 by a French midwife. One was hydropic and stillborn; the other became intensely jaundiced and died at three days of age, undoubtedly of kernicterus. The cause of hemolytic disease was elucidated by Levinel, following the discovery of the Rh blood group system by Landsteiner and Weiner2. A woman, following a hydropic stillbirth, had a reaction after transfusion of her husband’s blood. She was shown to be Rh(D) negative with a powerful antibody against her husband’s Rh positive red cells and the red cells of a panel of Rh positive Caucasians’. In the early 19403, when perinatal mortality in Canada was 40 per thousand births, 10% of these deaths were due to HDN.