Behavioural outcomes following in utero exposure to anti-seizure medication: protocol for a systematic review

IntroductionPrenatal exposure to certain antiseizure medications (ASMs) has been associated with increased risk of adverse neurodevelopmental outcomes in offspring. While the cognitive and intellectual outcomes of ASM-exposed offspring have been well-described, the long-term behavioural and functional sequalae in these children have received less attention. This systematic review aims to synthesise evidence on the relationship between prenatal ASM exposure and postnatal adverse neurodevelopmental outcomes, focusing on non-cognitive and intellectual domains of neurodevelopment including reduced social, emotional, behavioural, and adaptive functioning, as well as the frequency of neurodevelopmental and psychiatric disorders. This will have meaningful clinical implications for how we counsel women taking ASMs in pregnancy. Methods and analysisStudies reporting predefined neurodevelopmental outcomes will be identified by electronic searches of MEDLINE, PsychINFO, EMBASE, as well as additional manual and grey literature searches. Eligible studies will report outcomes of offspring exposed to ASMs in utero either prospectively or retrospectively from 1990 to present, with screening performed in duplicate. We will use the Newcastle-Ottawa Scale to conduct methodological quality assessments of included observational studies. A narrative synthesis will be used to report on the review findings. Meta-analysis is not anticipated. Ethics and disseminationEthics clearance is not required for the current study. The systematic review will be prepared as a journal article and published in a peer-reviewed journal upon completion. PROSPERO registration numberPROSPERO CRD42021281919 Article SummaryStrengths and limitations of this study O_LIThis protocol was developed and written according to the PRISMA-P guidelines C_LIO_LIPublication of this protocol ensures transparency and reproducibility of the methods of the systematic review, as well as reduces the likelihood of review duplication C_LIO_LIRestricting publications to English only may introduce bias whereby some relevant data is not included C_LIO_LIMeta-analysis is not likely to be possible due to heterogeneity in study methodology, reducing the strength of the conclusions that can be drawn C_LIO_LITargeting psychosocial and behavioural outcomes allows for a more nuanced understanding of the long-term clinical consequences of prenatal ASM-exposure C_LI