Fetal Erythroblastosis

The first pregnancy, the one that induces maternal sensitivity evolves normally. Ulterior pregnancies are characterized by hemolytic disease in the fetus, leading to anemia, immature fetal red blood cells released into circulation, hypoalbuminemia caused by hepatic dysfunction, high-output heart failure and ultimately fetal death. The amniotic fluid is rich in bilirubin and has a yellowish color. Fetal echography shows evidence of hydrops: pericardial and pleural effusions and ascites. Hydrops does not occur until the hemoglobin level drops to 4 g/dl. The biophysical profile becomes worse as the disease progresses. The severity of the hemolytic disease can be predicted using Liley diagrams [1].

If the disease is not as severe and the fetus survives, the newborn develops icterus during the first day of life, that may be as severe as to induce kernicterus. Also, the newborn will be anemic and pale and present splenomegaly and hepatomegaly, caused by extramedullary hematopoiesis. Portal hypertension has the same cause.

The placenta will be enlarged, and transplacental transport is compromised by the edema.

The mother is asymptomatic during the pregnancy and after delivery.

Usual prenatal consultations establish which pregnancies are at risk, namely those of Rh negative women impregnated by Rh positive men. In selected cases, blood workup will include blood type, Coombs test [2], Rh and anti-Rh antibody testing in the mother and blood type and Rh testing in the father [3]. In the mother, measurements are to be repeated every 2 weeks after 20 weeks of gestation.

The fetus is to be monitored by ultrasound regarding middle cerebral blood flow in order to determine if high output heart failure, an indicator of anemia, is present. If so, the fetal Rh should be determined by umbilical blood sampling.

Fetal Rh genotype can be tested using fetal cells or cell-free deoxyribonucleic acid in maternal circulation [4] [5] by polymerase chain reaction.

The newborn will have increased unconjugated bilirubin levels, that are rapidly rising and manifesting as icterus during the first days of life. Sometimes conjugated bilirubin levels are also high, due to hepatic dysfunction. He or she will be anemic, with increased reticulocyte count, anisocytosis, spherocytosis, and young (nucleated, immature) red blood cells released into circulation. Coombs test is positive [6]. Schistocytes, as a sign of disseminated intravascular coagulation and burr cells, are present, as well as neutropenia and thrombocytopenia. Other associated findings include hypoglycemia [7], hypokalemia or hyperkalemia and hypocalcemia. High carboxyhemoglobin levels also point to the presence of hemolysis [8].

Also, the newborn will have peripheral edema and other liquid accumulations, like ascites, pleurisy, and pericardial effusion.

1. Liley AW. Liquor amnii analysis in management of pregnancy complicated by rhesus immunization. Am J Obstet Gynecol. 1961;82:1359-1371.
2. Romano EL, Hughes-Jones NC, Mollison PL. Direct antiglobulin reaction in ABO-haemolytic disease of the newborn. Br Med J. 1973;1(852):524-526.
3. Pirelli KJ, Pietz BC, Johnson ST, et al. Molecular determination of RHD zygosity: predicting risk of hemolytic disease of the fetus and newborn related to anti-D. Prenat Diagn. 2010;30(12-13):1207-1212.
4. Bianchi DW, Avent ND, Costa JM, et al. Noninvasive prenatal diagnosis of fetal Rhesus D: ready for Prime(r) Time. Obstet Gynecol. 2005;106(4):841-844.
5. Rouillac-Le Sciellour C, Puillandre P, Gillot R, et al. Large-scale pre-diagnosis study of fetal RHD genotyping by PCR on plasma DNA from RhD-negative pregnant women. Mol Diagn. 2004;8(1):23-31.
6. Murray NA, Roberts IA. Haemolytic disease of the newborn. Arch Dis Child Fetal Neonatal Ed. 2007;92(2):F83-F88.
7. Vidnes J, Finne H. Immunoreactive insulin in amniotic fluid from Rh-immunized women. Biol Neonate. 1977;31(1-2):1-6.
8. Lozar-Krivec J, Bratanic B, Paro-Panjan D. The role of carboxyhemoglobin measured with CO-oximetry in the detection of hemolysis in newborns with ABO alloimmunization. J Matern Fetal Neonatal Med. 2016;29(3):452-456.