Routine prenatal anti-Rhesus D (RhD) prophylaxis offers the potential to prevent a substantial proportion of fetal and neonatal hemolytic disease, a study of Swedish women showed.
About half of RhD-immunized women became sensitized during pregnancy or while giving birth to their first child, and another third became sensitized with their second-born child. Three-fourths of RhD-immunized women developed anti-D antibodies during the second or third trimester, and another fifth developed antibodies at term or birth, said Eleonor Tiblad, MD, of Karolinska University Hospital in Stockholm, and colleagues.
More than half of infants with RhD-immunized mothers required treatment for hemolytic disease during the pregnancy or at birth, they reported online in Acta Obstetricia et Gynecologica Scandinavica.
"Based on our study, at least half of the cases (of hemolytic disease) could potentially have been avoided by routine antenatal anti-D prophylaxis in the beginning of the third trimester," Tibald's group concluded. "To optimize the beneficial effects of new prevention programs, we propose providing anti-D prophylaxis in gestational week 28 to 30 selectively to all RhD-negative women with RhD-positive fetuses."
Fetal and neonatal hemolytic diseases related to RhD immunization remains a severe, albeit infrequent, complication of pregnancy. Upon immunization during pregnancy, RhD-negative women have an increased risk of giving birth to RhD-positive infants in subsequent pregnancies.
Development of effective postnatal anti-D prophylaxis has led to substantial reductions in the risk of sensitization from 13% to ~1%, the authors noted. Subsequently, the introduction of routine prenatal anti-D prophylaxis has reduced the prevalence of RhD immunization to 0.2% to 0.3% in several countries. Sweden has not adopted routine prenatal RhD prophylaxis, and the prevalence of anti-D antibodies in pregnant women remains about 1%.
First-trimester fetal genetic RHD screening has demonstrated good accuracy, facilitating selective anti-D prophylaxis during the third trimester or earlier in the case of miscarriage, pregnancy termination, or invasive prenatal testing.
However, the optimal time for fetal RHD screening during pregnancy remains unclear, and the authors sought to clarify the issue by analyzing a contemporary cohort of RhD-immunized pregnant women in Stockholm County.
They retrospectively reviewed records for RhD-immunized women identified from 1990 to 2008. Only patients who received all of their care at Karolinska University Hospital were included.
Sweden introduced postdelivery anti-D prophylaxis of non-immunized women in 1969. Additionally, anti-D prophylaxis was administered during pregnancy when interventions posed a risk of fetomaternal hemorrhage. Since 1975, standard practice has been to administer anti-D prophylaxis after surgical termination of pregnancy and after spontaneous or induced abortion beyond 12 weeks of gestation.
The primary outcomes were timing of sensitization and frequency of fetal and neonatal hemolytic disease. Secondary outcomes included perinatal outcomes and number of children following the pregnancy when sensitization occurred.
Data analysis identified 290 pregnant women with anti-D antibodies during the study period. In 147 (51%) cases, sensitization occurred with the first-born child and with the second-born child in an additional 96 (33%) cases. Anti-D antibodies were detected during the second or third trimester in 212 (73%) of the women and at term or after delivery in 61 (21%) of the women.
Almost half (132, 46%) of the women became immunized during the third trimester and 13% (38) during the second trimester, including a fourth of women who became immunized during their second pregnancy.
Among women who became immunized with their first-born child, or during a third or subsequent pregnancy, a third of infants required phototherapy during the neonatal period. The proportion increased to 50% among women who became immunized during their second pregnancy (P=0.04).
Among women who were immunized during pregnancy with their first-born child, 36 (24%) had a history of first-trimester pregnancy termination or miscarriage.
A majority of women (203 of 290) gave birth at least once following the pregnancy associated with RhD immunization, including 89% of the first-birth group, 48% of the second-birth group, and 38% of women who became immunized during a third or subsequent pregnancy. Perinatal outcomes were similar across the three groups.
The authors found that 56% of neonates required treatment for hemolytic disease, including intrauterine transfusion in 20% and postnatal exchange transfusion in 26%. Premature delivery before 34 weeks occurred in 12 of 557 pregnancies (2%). Nine perinatal deaths were caused by or associated with treatment for hemolytic disease.
"Our study shows that without routine antenatal anti-D prophylaxis, approximately half of RhD-immunized women are sensitized during pregnancy or delivery of their first-born child and a third with their second-born child," the authors said. "The majority of immunizations occur before delivery, and the frequency of hemolytic disease of the fetus or neonate in subsequent pregnancies is high."
"At least half of the cases of RhD immunizations could potentially have been avoided by routine antenatal anti-D prophylaxis in the beginning of the third trimester," they added. "Noninvasive determination of fetal RHD genotype in the first trimester of pregnancy enables more efficient prevention strategies, providing anti-D prophylaxis selectively to women with RHD-positive fetuses."
The authors reported no conflicts of interest.
- Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Acta Obstetricia et Gynecologica ScandinavicaSource Reference: Tiblad E, et al "Consequences of being Rhesus D immunized during pregnancy and how to optimize new prevention strategies" Acta Obstet Gynecol Scand 2013; DOI: 10.1111/aogs.12193.