Perinatal survival following intrauterine transfusion for red cell alloimmunized pregnancies: systematic review and meta-regression

OBJECTIVE: Red blood cell (RBC) alloimmunization is one of the major causes of fetal anemia, often resulting in hydrops and, in extreme cases, intrauterine fetal demise (IUFD).1 Intrauterine transfusion (IUT) has emerged as a widely utilized intervention to enhance survival rates in severe cases. Our study aims to assess the perinatal outcomes of RBC alloimmunized pregnancies following IUT and explore potential predictors of perinatal survival. STUDY DESIGN: In this systematic review and meta-regression analysis, we conducted a comprehensive search of PubMed, Scopus, and Web of Science databases, spanning the period from January 1990 to December 2021. Our inclusion criteria encompassed studies reporting on perinatal outcomes following IUT for fetal anemia resulting from RBC alloimmunization. To synthesize the findings, we employed a random-effects model for pooling the outcome variables. In addition, univariate and multivariate meta-regression analyses were conducted to explore potential predictors of perinatal outcomes. For a detailed description of the methodology, please refer to the Supplementary Material. RESULTS: We screened 434 articles and analyzed 38 studies with 2323 fetuses and 5688 IUTs from 18 countries. Mean gestational age (GA) at first IUT was 26.21 weeks (95% confi- dence interval [CI], 25.36-27.07; I2=97.5%), pretransfusion hemoglobin (Hb) was 6.01 g/dL (95% CI, 5.38-6.64; I2=95.5%), and hydrops at diagnosis was reported in 32.36% (95% CI, 24.94-40.78; I2=84.3%). The perinatal survival rate was 82.39% (95% CI, 77.92-86.12; I2=80.4%), mean GA at delivery was 33.67 weeks (95% CI, 32.93-34.40; I2=96.0%) and mean Hb at birth was 11.62 g/dL (95% CI, 10.57-12.66; I2=88.0%). On univariate meta-regression, pretransfusion Hb, absence of hydrops, higher World Bank income (WBI) class of the country at the time of the study, and total number of procedures were significantly associated with improved survival. Multivariate meta-regression showed WBI class and total number of procedures were associated with survival. CONCLUSION: Following IUT for RBC alloimmunized pregnancies, perinatal survival was 82.4%. Multivariate metaregression revealed that the WBI class of the studied country and the total number of transfusions performed were significant predictors of perinatal survival. The WBI class may reflect socioeconomic status and healthcare system infrastructure, whereas the number of transfusions reflects team expertise. In line with previous studies, our univariate meta-regression showed associations between low GA at first transfusion, pretransfusion Hb level, and hydrops with low perinatal survival;1-4 however, these associations did not remain significant in multivariate analysis. These variables may indirectly relate to socioeconomic status. Our findings suggest that investment in healthcare infrastructure has the potential to address barriers such as delayed presentation and limited access to screening and advanced care. Furthermore, our study reveals a perinatal death rate of 1 in 5, indicating the need for further investigation and interventions to improve outcomes.