The Association Between Non-prescription Analgesic Drug Use in Pregnancy and Neurodevelopmental Disorders: Protocol for an Umbrella Review

BackgroundMaternal prenatal health has been shown to bean important influence on children’s developmental outcomes, which has led to an increased emphasis onprovidingmore information to supportclinical decisions in pregnancy. Several systematic reviewssuggest that analgesic drug use during pregnancy may haveneurodisruptive properties. However, no firm conclusions have yet been drawn onthe associations between prenatal analgesic drug use and children’s long-term development of neurodevelopmental disorderssuch as Autism Spectrum Disorder (ASD) or Attention-Deficit Hyperactivity Disorder (ADHD). Therefore, an umbrella review is proposed for the purpose of examining the associations between maternal analgesic drug use during pregnancy and diagnoses of neurodevelopmental disorders.MethodsIncluded systematic reviews will consist of studies examining the effect of maternal prenatal non-prescription analgesic drug use on children’s neurodevelopmental disorder status. Examined drugs will be restricted to those readilyaccessible and frequently used by pregnant women, and with characteristics that allow them to cross the placenta and directly affect fetal development. Outcomes will be restricted to formal clinical diagnoses of ASD and/or ADHD. Two reviewers will independently identify eligible reviews from six databases and a manual search of reference lists, consultation with field experts, and scan of pre-print archives.A third researcher will be consulted when consensus cannot be reached.Search strategy and data extraction will be based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocol and PRISMA-P checklist. Extracted data will also include short qualitative summaries by both reviewers. As part of quality assessment, astandardised measurement tool to assess systematic reviews (AMSTAR 2) will be used. A narrative synthesis is proposed to integrate findingsfrom different, potentially methodologically heterogeneousstudies. DiscussionThis umbrella review of associations between maternal prenatal use of non-prescription analgesic drugs andchildren’s neurodevelopmental disorders could allow for firmer conclusions to be drawn through the synthesis of all relevant published research. The synthesis of findings using high-quality evidence couldprovide more accurate healthcare information on the long-term effects of analgesic drugs on neurodevelopment, to better guide future clinical decisions during pregnancy. This review will also allow gaps and methodological differences in the literature to be identified, informing recommendations for future research.Systematic review registrationPROSPEROregistration number CRD42020179216.