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周的中期妊娠临产前胎膜早破（midtrimester prelabour rupture of membranes, PROM）是一类严重的产科并发症，围产期并发症发生率与死亡率均处于较高水平。针对此类中期妊娠胎膜早破患者，临床曾提出采用羊膜腔内灌注术（amnioinfusion）治疗羊水过少，以期改善胎儿肺部发育及围产期结局。

材料与方法：本研究旨在开展一项系统综述与荟萃分析，纳入所有对比妊娠16+0至24+0周胎膜早破患者接受羊膜腔内灌注术与不实施干预措施的随机对照试验。研究检索了自建库起始至2021年12月的Cochrane对照试验中心注册库（Central）、Embase、Medline、ClinicalTrials.gov数据库，以及已纳入文献的参考文献。本研究的主要结局指标为围产期死亡率；次要结局指标包括新生儿结局、产妇结局，以及早产研究核心结局集所定义的长期发育结局。汇总效应量以合并相对危险度（relative risk, RR）或均数差（mean difference, MD）及对应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例受试者（羊膜腔内灌注组与不干预组各56例）。羊膜腔内灌注组的合并围产期死亡率为66.1%（37/56），不干预组为71.4%（40/56）（RR=0.92，95%CI 0.72~1.19）。两组其余新生儿及产妇核心结局指标均无显著差异，但由于事件发生数相对较少且置信区间较宽，羊膜腔内灌注术或存在具有临床意义的获益与潜在风险。在接受随访评估的儿童中，羊膜腔内灌注组的长期健康存活率为35.7%（10/28），不干预组为28.6%（8/28）（RR=1.30，95%CI 0.47~3.60，「最佳场景分析」）。

结论：基于上述研究结果，针对妊娠孕周<24周的中期妊娠胎膜早破患者实施羊膜腔内灌注术的获益尚未得到证实，其潜在风险亦未明确。