Perinatal outcomes in RhD-negative pregnant women in Japan

Abstract

Managing RhD-negative pregnancies is vital for preventing hemolytic disease of the fetus and newborn, which occurs when RhD-negative mothers develop anti-D antibodies after exposure to RhD-positive fetal blood. This retrospective cohort study evaluated the proportion of RhD-negative pregnancies and newborns in Japan by assessing current management practices and outcomes. This study included RhD-negative pregnant women who delivered at 22 weeks or later at 47 Japanese facilities between April 2018 and March 2023. Pregnancies with unknown newborn RhD status were excluded. Data were obtained from medical records. Among the 1088 RhD-negative women, 1062 met the inclusion criteria. RhD-negative pregnancies comprised 0.71% of the total cohort, with 8.7% RhD-negative newborns. Anti-D immunoglobulin was administered in 96.5% of pregnancies, with a maternal spontaneous sensitization rate of 0.6% before 28 weeks and no sensitization detected from 28 weeks to postpartum. Sensitized RhD-negative women had higher cesarean section, preterm delivery, and neonatal hemolytic anemia rates than the non-sensitized group, leading to increased neonatal intensive care unit admissions. Despite the low incidence of RhD-negative pregnancies, this study underscores the need for tailored management strategies, suggesting that non-invasive prenatal diagnosis of fetal RhD status could prevent unnecessary anti-D immunoglobulin administration, improving outcomes and resource utilization in Japan.

Keywords: Anti-D immunoglobulin; Hemolytic disease of the fetus and newborn; Maternal sensitization; Neonatal hemolytic anemia; Non-invasive prenatal diagnosis; RhD-negative pregnancies.

Fig. 1

Study flow chart. Among the 152,526 pregnant women who delivered after 22 weeks at 47 facilities, 1088 were RhD-negative. Ninety-five of the 1091 newborns were RhD-negative.

Fig. 2

Status and results of irregular antibody testing. More than 90% of cases were tested in the first trimester and at approximately 28 weeks of gestation; however, the proportion dropped substantially postpartum. No cases were tested after 1 month postpartum. The results of the indirect Coombs test were notably affected by anti-D human immunoglobulin administration.

Fig. 3

Maternal anti-D antibody sensitization status. Some cases of spontaneous sensitization to anti-D antibodies during pregnancy have occurred, although the proportion is relatively small. Specifically, 850 represents the number of patients who underwent the indirect Coombs test at approximately 10 and 28 weeks of gestation, with available results. In contrast, 347 represents the number of patients who underwent the indirect Coombs test immediately postpartum and at approximately 28 weeks of gestation, with available results.