Supplementary Material for: Amnioinfusion versus usual care in women with prelabour rupture of membranes in midtrimester: a systematic review and meta-analysis of short and long-term outcomes

Introduction: Midtrimester prelabour rupture of membranes (PROM) between 16 and 24 weeks’ gestational age is a major obstetric complication with high rates of perinatal morbidity and mortality. Amnioinfusion has been proposed in women with midtrimester PROM to target oligohydramnios and subsequently enhance pulmonary development and perinatal outcomes. Material and methods: The purpose of this study was to perform a systematic review and meta-analysis including all randomized clinical trials investigating amnioinfusion versus no intervention in women with PROM between 16+0 and 24+0 weeks gestational age. Databases Central, Embase, Medline, ClinicalTrials.gov and references of identified articles were searched from inception of database to December 2021. The primary outcome was perinatal mortality. Secondary outcomes included neonatal, maternal and long-term developmental outcomes as defined in the core outcome set for preterm birth studies. Summary measures were reported as pooled relative risk (RR) or mean difference (MD) with corresponding 95% of confidence interval (CI). Results: Two studies (112 patients, 56 in the amnioinfusion group and 56 in the no intervention group) were included in this review. Pooled perinatal mortality was 66.1% (37/56) in the amnioinfusion group compared with 71.4% (40/56) in no intervention group (RR 0.92, 95% CI 0.72 - 1.19). Other neonatal and maternal core outcomes were similar in both groups although, due the relatively small number of events and wide confidence intervals, there is possibility that amnioinfusion can be associated with clinically important benefits and harms. Long-term healthy survival was seen in 35.7% (10/28) of children assessed for follow-up and treated with amnioinfusion versus 28.6% (8/28) after no intervention (RR 1.30, 95% CI 0.47 - 3.60, ‘best case scenario’). Conclusions: Based on these findings the benefits of amnioinfusion for midtrimester PROM <24 weeks gestational age are unproven and the potential harms remain undetermined.

引言：妊娠16至24周的中期妊娠产前胎膜早破（prelabour rupture of membranes, PROM）是一种严重的产科并发症，围产儿发病率与死亡率均处于较高水平。针对中期妊娠PROM患者，临床已提出采用羊膜腔灌注（amnioinfusion）治疗羊水过少，以期改善胎儿肺部发育及围产结局。
材料与方法：本研究旨在开展一项系统综述与荟萃分析，纳入所有对比羊膜腔灌注与无干预措施、针对孕周16+0至24+0周PROM患者的随机对照临床试验。本研究检索了Central、Embase、Medline、ClinicalTrials.gov数据库以及已纳入文献的参考文献，检索时限为各数据库建库至2021年12月。主要结局指标为围产儿死亡率；次要结局指标包括新生儿、产妇及长期发育结局，均参照早产研究核心结局集的定义进行设定。合并效应量采用合并相对危险度（relative risk, RR）或均数差（mean difference, MD）及其对应的95%置信区间（confidence interval, CI）进行报告。
结果：本综述共纳入2项研究，合计112例患者，其中羊膜腔灌注组与无干预组各56例。羊膜腔灌注组的合并围产儿死亡率为66.1%（37/56），无干预组为71.4%（40/56）（RR=0.92，95%CI：0.72~1.19）。两组其余新生儿与产妇核心结局指标均无显著差异，但由于事件数相对较少且置信区间较宽，羊膜腔灌注仍有可能存在具有临床意义的获益或风险。在接受随访评估的儿童中，羊膜腔灌注组的长期健康存活率为35.7%（10/28），无干预组为28.6%（8/28）（RR=1.30，95%CI：0.47~3.60，‘最佳情景分析’）。
结论：基于上述研究结果，针对孕周<24周的中期妊娠PROM患者实施羊膜腔灌注的获益尚未得到证实，其潜在风险仍有待明确。