Abstract
BackgroundMaternal prenatal health has been shown to be an important influence on children’s developmental outcomes, which has led to an increased emphasis on providing more information to support clinical decisions in pregnancy. Several systematic reviews suggest that analgesic drug use during pregnancy may have neurodisruptive properties. However, no firm conclusions have yet been drawn on the associations between prenatal analgesic drug use and children’s long-term development of neurodevelopmental disorders such 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 analgesic drug use, specifically ibuprofen, acetaminophen, aspirin, naproxen, diclofenac, and ketoprofen, on children’s neurodevelopmental disorder status. Examined drugs were restricted to those readily accessible 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 (e.g., PubMed, EMBASE, PsychINFO) from inception dates of databases to the date of data extraction, and conduct manual searches of reference lists, consultation with field experts, and scan of pre-print archives. Extracted data will also include short qualitative summaries by both reviewers. As part of quality assessment, a standardized measurement tool to assess systematic reviews (AMSTAR 2) will be used. A narrative synthesis is proposed to integrate findings from different, potentially methodologically heterogeneous, studies.DiscussionThis umbrella review of associations between maternal prenatal use of analgesic drugs and children’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 could provide 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 registrationPROSPERO CRD42020179216.
Highlights
Maternal prenatal health has been shown to be an important influence on children’s developmental outcomes, which has led to an increased emphasis on providing more information to support clinical decisions in pregnancy
Current studies show that prenatal use of drugs is frequent in pregnant women, with around 90% of them taking some form of medication during pregnancy [12]
autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) assessed by any means [11] will be included in this review
Summary
Registration and reporting information The umbrella review protocol is being reported in accordance with the reporting guidance provided in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement [24] (Additional File 5). Information extracted from each study will include first author, year of publication, reported a protocol, objective(s), reported strategies to search literature, number of databases searched and date of last search, inclusion/exclusion criteria, population, main outcomes of interest, type of study designs included (e.g., observational studies), number of included studies, number of studies reporting data for meta-analyses, effect metric(s) reported (e.g., risk ratio), methods to assess study risk of bias, additional analyses, metabias assessment (e.g., publication bias across studies), funding source, and conflicts of interest. This tool is in line with advised guidelines on the assessment of systematic reviews based on identifying methodological features such as how well the research question is defined, use of a systematic search strategy, possible publication or funding bias, selective reporting, previous quality ratings, and presence of information synthesis and conclusion [27]. Using GRADE guidelines [28, 29], the researchers will examine the following domains for a decrease in certainty: risk of bias, imprecision of true effects, inconsistency of effects, indirectness of outcomes, and publication bias
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