Neonatal outcomes among pregnancies with red cell alloimmunization requiring doppler monitoring without intrauterine transfusion: A retrospective cohort study

Abstract

Introduction: Red cell alloimmunization in pregnancy occurs when a pregnant person develops antibodies against red blood cell antigens that are foreign to her. These antibodies can cross the placenta and cause hemolytic disease in the fetus and newborn (HDFN), which can lead to complications ranging from anemia and hyperbilirubinemia to stillbirth. Historically managed with invasive monitoring via amniocentesis, the approach shifted toward non-invasive Doppler ultrasound of the middle cerebral artery—using a middle cerebral artery peak systolic velocity (MCA PSV) threshold of 1.5 multiples of the median (MoM)—as a sensitive method to detect moderate to severe fetal anemia. However, more data are needed on neonatal outcomes when intrauterine transfusion is not performed. This study aimed to evaluate the characteristics and outcomes of red cell alloimmunized pregnancies requiring MCA PSV Doppler monitoring but not requiring intrauterine transfusion (IUT) and to investigate prenatal associations or predictors among neonates who required postnatal therapy for HDFN. Methods: This was a retrospective cohort study of a single center of level IV maternity and neonatal care units in the United States between January 2018 and December 2023. We included pregnancies with red cell alloimmunization requiring MCA PSV Doppler monitoring for which the fetus or neonate was shown to be at risk either antenatally or postnatally but did not require an IUT procedure. We excluded red cell alloimmunized pregnancies for which no testing was done either antenatally or postnatally to show whether the fetus or neonate was at risk, which required IUT, and which involved multiple gestations. Descriptive statistics were reported for the entire cohort. We then performed a bivariate comparison between two groups: neonates who received postnatal treatment for HDFN and those who did not. Multivariable logistic regression was performed to investigate prenatal associations or predictors among the neonates who required postnatal therapy for HDFN. Results: A total of 40 eligible pregnancies reached critical titers and needed MCA PSV Doppler monitoring, from which 39 neonates were included in the final analysis. A total of 18 (46.2%) of the at-risk neonates were admitted to the NICU. A total of 22 neonates (56.4%) required phototherapy of any kind (bililights and/or biliblanket), 1 neonate (2.6%) required exchange transfusion, and 5 neonates (12.8%) required IVIG. A total of 13 neonates (33.3%) only required phototherapy. No neonates received IVIG or exchange transfusion as isolated therapy. A total of 11 neonates (28.2%) required RBC transfusions to treat anemia. Only two neonates (5.1%) received RBC transfusion(s) as isolated therapy. Neonates requiring postnatal therapy for HDFN had higher rates of NICU admission (66.7% vs. 13.3%, p = 0.002) and longer NICU stays (median days 7, IQR 0, 19.5 vs. 0; p < 0.001). The multivariable logistic regression analysis showed that antibody titer at pregnancy onset was a significant predictor (OR = 16.33, 95% CI: 1.35–197.77, p = 0.03), while earlier MCA Doppler monitoring showed a non-significant trend toward reduced treatment need (OR = 0.095, 95% CI: 0.006–1.498, p = 0.09). Conclusion: This study confirms earlier studies in clinical predictive data for neonatal outcomes in red cell alloimmunization and highlights the importance of structured postnatal monitoring and timely follow-up.