IMMUNOHEMATOLOGY ABO hemolytic disease of the fetus and newborn: an iatrogenic complication of heterologous assisted reproductive technology-induced pregnancy Antonio Alberto Zuppa, Valentina Cardiello, Marco Lai, Luigi Cataldi, Vito D’Andrea, and Costantino Romagnoli BACKGROUND: ABO hemolytic disease of the fetus and newborn (ABO HDFN) may manifest itself in cases of mothers belonging to blood group O and newborns of groups A or B and more frequently in group A and less so in group B. CASE STUDY: The case subjects are twin-birth new- borns with ABO HDFN, of group AB born to a mother of group O. These cases of ABO HDFN prove inconsistent with Mendel’s law of segregation. RESULTS AND CONCLUSION: This case study finds its explanation in new methods of assisted reproduc- tion, particularly heterologous in vitro fertilization with ovodonation. O ur case revolves around twins, one male and one female, born to a 45-year-old primi- gravida at the 36th week of gestation of a dichorionic-diamniotic pregnancy; the infants were delivered by cesarean section as a result of the podalic positioning of one of the twins. They were reported in good clinical condition and both received a Apgar score of 1’9 and 5’10. The first newborn weighed 2820 g, the second weighed 2810 g, and both were appro- priate for gestational age, between the 50th and 90th percentiles. 1 Approximately 21 hours after birth, tests to measure total bilirubin levels were conducted in response to the appearance of premature cutaneous jaundice in both infants. Spectrophotometry showed total bilirubin levels of 10.6 mg/dL with a hematocrit (Hct) of 51% in the first twin and 10.7 mg/dL with 50% Hct in the second twin. Given the elevated levels of total bilirubin, tests were carried out to measure direct bilirubin levels in both twins. Direct antiglobulin test (DAT) and blood type tests were carried out on the umbilical cord blood of both newborns as well as gathering information on the blood types of their mother and father. The mother’s blood group was determined to be group O+, the father’s was group AB+; the DAT of the twins’ umbilical cord blood gave weak posi- tive readings with normal direct bilirubin levels (0.48 and 0.50 mg/dL, respectively) while both twins were found to be group AB–. Suspecting jaundice brought on by ABO hemolytic disease of the fetus and newborn (ABO HDFN), at 22 hours of life, the twins underwent 74 hours of phototherapy. 2-4 In their second day of life, the twins’ peripheral blood was subjected to a hemogram with reticulocyte count, an indirect antiglobulin test (IAT), a DAT, and a blood smear. The hemogram carried out on the twins’ second day of life showed normal levels in both twins with mild reticulocytosis (8% in the first twin and 7.5% in the second) 5 and marked macrocytosis and aniso- cytosis. The peripheral blood smear showed normal read- ings for both twins: 32% lymphocytes, 8% monocytes, 50% neutrophils, 2 erythroblasts for every 100 cells counted, and some metamyelocytes; thrombocytes were numerous in the examined field. The second DAT was negative. According to the mother’s medical history, the pregnancy had proceeded normally, but had been inducted by in vitro fertilization with ovodonation (IVF) for maternal ste- rility of unknown origin. In cases of newborns resulting from assisted reproductive technology (ART)-induced pregnancies, ABBREVIATIONS: ABO HDFN = ABO hemolytic disease of the fetus and newborn; ART = assisted reproductive technology; IVF = in vitro fertilization with ovodonation. From the Department of Pediatrics, Division of Neonatology, and the Immunohematology Laboratory,Transfusion Centre, Catholic University of Sacred Heart, Rome, Italy. Address reprint requests to: Prof. Antonio Alberto Zuppa, Department of Pediatrics, Division of Neonatology, Catholic University of the Sacred Hearth, Largo Agostino Gemelli 8, 00168 Rome, Italy; e-mail: zuppaaa@rm.unicatt.it. Received for publication February 7, 2010; revision received March 16, 2010, and accepted March 18, 2010. doi: 10.1111/j.1537-2995.2010.02698.x TRANSFUSION 2010;50:2102-2104. 2102 TRANSFUSION Volume 50, October 2010