Intra-amniotic inflammation and child neurodevelopment: a systematic review protocol

Background: Intra-amniotic inflammation is associated with adverse pregnancy and neonatal outcomes. However, the impact on child neurodevelopment remains unclear. We aim to assess the effect of intra-amniotic inflammation on neurodevelopmental outcomes in children. Methods: The databases MEDLINE, Embase, CINAHL, and Cochrane will be searched from their inception until November 2017. Randomized trials and cohort studies in which inflammatory markers were measured in amniotic fluid collected by amniocentesis and in which infant's neurodevelopment was assessed will be eligible. Two reviewers will independently select eligible studies, assess their risk of bias, and extract data. Results will be compared and a third party will be consulted in case of disagreement. Our primary outcome of interest is child neurodevelopment, assessed with either a validated tool or by revision of medical records for specific diagnosis. Secondary outcomes will include abnormal brain imaging. Relative risks will be pooled and sensitivity analyses will be performed for the indication of amniocentesis, gestational age at amniocentesis, gestational age at delivery, and fetal sex. Risk of bias will be assessed using the Cochrane Collaboration's tool for assessing the risk of bias in randomized trials or an adapted version of the ROBINS-1 for the risk of bias in non-randomized studies. Discussion: This systematic review will report the current evidence regarding the association between amniotic inflammation and child neurodevelopment, and the modifiers of this association. The review will generate new hypotheses on pathological pathways and will guide future research.