Supplementary Material for: Intrauterine Blood Transfusion for Parvo B19 Induced Fetal Anemia: Neuroimaging Findings and Long-Term Neurological Outcomes

INTRODUCTION: We aimed to evaluate neuroimaging findings and long-term neurodevelopment of fetuses and children following intrauterine blood transfusion [IUT] for parvo B19 infection induced anemia compared to those with RBC alloimmunization. METHODS: We conducted a retrospective cohort study including women who underwent an IUT due to fetal anemia between 2006 to 2019 in a tertiary, university-affiliated medical center. The cohort was divided into two: a study group - fetuses affected by congenital parvo-B19 infection; and a control group - fetuses affected by RBC alloimmunization. Retrospective data such as antenatal sonographic evaluations, fetal brain MRI results and short-term fetal and neonatal outcomes were collected. All children underwent a neurodevelopmental evaluation after birth using a Vineland questionnaire. Primary outcome was defined as the presence or absence of neurodevelopmental delay. Secondary outcome was defined as the presence of abnormal fetal neuroimaging findings such as cerebellar hypoplasia, polymicrogyria, intracranial hemorrhage or severe ventriculomegaly. RESULTS: Overall, 71 fetuses requiring at least one IUT were included in the study. Of these, 18 were affected by parvo B19 infection and 53 by RBC alloimmunization with various associated antibodies. Fetuses in the parvo B19 group presented at an earlier gestational age [22.91 ± 3.36 weeks vs. 27.37 ± 4.67 weeks, p=0.002] and were more affected by hydrops [93.33% vs. 16.98%, p<0.001]. Three fetuses out of the 18[16.67%] fetuses in the parvo B19 group died in utero following the IUT. Abnormal neuro-imaging findings were detected in 4/15 [26.7%] of the parvo B19 survivors vs. 2/ 53 [3.8%] of fetuses affected by RBC alloimmunization [p=0.005]. There was no difference in long-term neurodevelopmental delay rates between the children in the study and control groups, as assessed at the average age of 3.65 and 6.53 years, accordingly. CONCLUSION: Fetal anemia due to parvo B19, treated with IUT, might be associated with increased rates of abnormal neuro-sonographic findings. The correlation between those findings and long-term adverse neuro-developmental outcomes requires further investigation

研究背景：本研究旨在对比因细小病毒B19（parvovirus B19）感染引发贫血并接受宫内输血（intrauterine blood transfusion, IUT）的胎儿与儿童，以及红细胞（red blood cell, RBC）同种免疫的胎儿与儿童的神经影像学表现及长期神经发育情况。
研究方法：本研究为回顾性队列研究，纳入2006年至2019年期间，某大学附属三级医疗中心内因胎儿贫血接受宫内输血的孕妇。研究队列分为两组：研究组为先天性细小病毒B19感染胎儿；对照组为红细胞同种免疫胎儿。回顾性收集产前超声评估、胎儿脑部磁共振成像（magnetic resonance imaging, MRI）结果，以及短期胎儿与新生儿结局数据。所有儿童于出生后采用文兰问卷（Vineland questionnaire）进行神经发育评估。本研究的主要结局指标为是否存在神经发育迟缓；次要结局指标为是否存在异常胎儿神经影像学表现，包括小脑发育不全、多小脑回、颅内出血或重度脑室扩张。
研究结果：本研究共纳入71例需接受至少1次宫内输血的胎儿，其中18例为细小病毒B19感染胎儿，53例为合并多种相关抗体的红细胞同种免疫胎儿。细小病毒B19组胎儿的就诊胎龄更早（22.91±3.36周 vs. 27.37±4.67周，p=0.002），且水肿发生率更高（93.33% vs. 16.98%，p<0.001）。细小病毒B19组的18例胎儿中，有3例（16.67%）在接受宫内输血后死产。细小病毒B19组存活胎儿中，4例（26.7%）存在异常神经影像学表现，而红细胞同种免疫组存活胎儿中仅2例（3.8%）出现异常，组间差异具有统计学意义（p=0.005）。在平均随访年龄分别为3.65岁和6.53岁时，研究组与对照组儿童的长期神经发育迟缓发生率无显著差异。
研究结论：因细小病毒B19感染引发的胎儿贫血，经宫内输血治疗后，可能与异常神经超声表现发生率升高相关。此类影像学表现与长期不良神经发育结局之间的关联，仍需进一步研究探讨。