JMIR Publications

ABSTRACT

Background:

Hemolytic disease of the fetus and newborn (HDFN) is a life-threatening condition resulting from maternal-fetal erythrocyte antigen incompatibility. Although anti-RhD prophylaxis has reduced RhD-associated cases, HDFN persists due to non-RhD antibodies and gaps in prevention. Population-based data on maternal, neonatal, and recurrence patterns are limited.

Objective:

To characterize maternal and neonatal outcomes, healthcare utilization patterns, and recurrence of HDFN across pregnancies.

Methods:

We conducted a retrospective cohort study of 464,711 pregnancies within Kaiser Permanente Southern California (01/01/2008-06/30/2022). HDFN diagnoses were confirmed using validated natural language processing-assisted manual chart review and followed through 2023. Maternal characteristics, neonatal outcomes, and healthcare utilization were compared by HDFN status, and recurrence risk were evaluated among individuals with ≥2 pregnancies. Chi-square tests and t-tests were used to compare characteristics between HDFN and non-HDFN pregnancies. Adjusted P-values were used to assess the significance of recurrence risk, with P<0.05 considered statistically significant.

Results:

Among all pregnancies, 139 (3 per 10,000) were diagnosed with HDFN. Women with an HDFN diagnosis (compared to those without) were more likely to be older (≥35 years: 30.2% vs. 20.9%) and multiparous (87.1% vs. 57.0%). HDFN-affected infants had higher rates of preterm birth (28.4% vs. 9.5%), low birthweight (<2,500 g: 15.6% vs. 7.1%), and neonatal jaundice (65.2% vs. 36.4%) compared to non-HDFN infants. Delivery hospitalizations (median 5.0 vs. 2.0 days) and NICU stays (median 4.0 vs. 0.0 days) were longer, and maternal non-delivery hospitalizations were more frequent (19.4% vs. 5.0%) in pregnancies complicated by HDFN. Among women with a prior HDFN-affected pregnancy, 83.3% experienced recurrence in a subsequent pregnancy. Of these, 32.0% were severe, and 75.0% involved fetal anemia requiring at least one intrauterine transfusion.

Conclusions:

HDFN was rare but associated with substantial maternal and neonatal morbidity, including elevated rates of preterm birth, increased NICU admissions, and greater healthcare utilization. Recurrence was frequent and clinically significant, underscoring the importance of early surveillance and proactive management strategies.