Intravenous Immunoglobulin for the Treatment of Severe Maternal Alloimmunization: Individual Patient Data Meta-Analysis

Objective To investigate the outcomes associated with the administration of maternal intravenous immunoglobulin (IVIG) in high-risk red blood cell (RBC) alloimmunized pregnancies. Data sources We systematically searched Medline, Embase, and Cochrane Library until June 2023. Study eligibility criteria We included studies reporting on pregnancies with severe RBC alloimmunization, defined as either a previous fetal or neonatal death or the need for IUT before 24 weeks in the previous pregnancy as a result of hemolytic disease of fetus and newborn (HDFN). Study appraisal and synthesis methods Cases were pregnancies that received IVIG, while controls did not. Individual patient data (IPD) meta-analysis was performed using the Bayesian framework. Results IPD analysis included eight studies comprising 97 cases and 97 controls. IVIG was associated with prolonged delta GA at first IUT (GA of current pregnancy – GA at prior pregnancy) (Mean Difference (MD): 3.19 weeks, 95% CrI 1.28, 5.05), prolonged GA at first IUT (MD: 1.32 weeks, 95% CrI 0.08, 2.5), reduced risk of fetal hydrops at time of first IUT (Incidence Rate Ratio (IRR): 0.19, 95% CrI 0.07, 0.45), reduced risk of fetal demise (IRR: 0.23, 95% CrI 0.10, 0.47), higher chances of live birth ≥28 weeks, ≥32 weeks, and survival at birth (IRR: 1.88, 95% CrI 1.31, 2.69; IRR: 1.93, 95% CrI 1.32, 2.83; IRR: 1.82, 9% CrI 1.30 to 2.61, respectively). There were no significant differences in numbers of IUT, hemoglobin level at birth, bilirubin level at birth, or survival at hospital discharge for live births. Conclusion IVIG treatment in pregnancies at risk of severe early HDFN seems to have a clinically relevant beneficial effect on the course and severity of the disease.