Anti-epileptic drug exposure during pregnancy and neonatal birth weight outcomes: protocol for a systematic review and meta-analysis

Background: The prevalence of epilepsy in pregnant women is estimated at 0.3-1%. Anti-epileptic drug (AED) exposure in-utero has been associated with various adverse health outcomes in neonates, including adverse birth weight outcomes. Objective: This review aims to summarize the published evidence on the association between AED exposure in pregnancy and adverse birth weight outcomes Methods: Studies assessing AED exposure in pregnancy and neonatal birth weight outcomes, including small for gestational age (SGA), low birth weight (LBW), birth weight (BW), length, head circumference, and cephalization index will be identified in MEDLINE (R), EMBASE, Cochrane Library, Scopus, Cumulative Index of Nursing and Allied Health Literature (CINAHL), International Pharmaceutical Abstracts (IPA), and Global Health. Open grey, Theses Canada, and ProQuest Dissertations will be used to locate gray literature. Eligible study designs will include both intervention and non-interventional studies. We will not impose any time limit in the review. We will use the Newcastle-Ottawa Scale to assess the methodological quality of observational studies and quasi-experimental studies included in the review. The risk of bias of experimental studies will be appraised using the Cochrane risk-ofbias tool for randomized trials (RoB 2). A meta-analysis will be conducted using a random-effects model. Discussion: The results from this review could improve clinicians' prescribing decisions by highlighting the safest AEDs for women who are pregnant or planning to conceive based on the evidence currently available.