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.