{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:44:42Z","timestamp":1780548282514,"version":"3.54.1"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,9]],"date-time":"2025-03-09T00:00:00Z","timestamp":1741478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Psychiatr Scand"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Gestational exposure to valproate has been associated with a wide range of adverse pregnancy outcomes, including major congenital malformations in offspring. However, to date, no meta\u2010analysis has comprehensively examined the risk of autism spectrum disorder (ASD) and attention\u2010deficit\/hyperactivity disorder (ADHD) in children gestationally exposed to valproate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched MEDLINE, Embase, and Scopus\u00a0from inception until 15 May 2024 for relevant English\u2010language articles. Primary outcomes of interest were the risk of ASD and ADHD, two independent primary outcomes, in children exposed to valproate anytime during pregnancy relative to unexposed children. Secondary outcomes were trimester\u2010wise analyses of risk. We used a random effects model to pool the overall and trimester\u2010wise hazard ratios (HRs) and obtained 95% confidence intervals (CIs), separately for the risks of ASD and ADHD. Study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eight cohort studies (pooled\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20096,033,300) met our search criteria. Anytime gestational exposure to valproate was associated with a large increase in the risk of ASD (adjusted HR [aHR], 3.10; 95% confidence interval [CI], 2.24\u20134.28;\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20091,841,198) and a modest increase in the risk of ADHD (aHR, 1.62; 95% CI, 1.30\u20132.01;\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200924,295). The findings in sensitivity analyses for both outcomes were generally consistent with those of the main analyses. Notably, anytime gestational exposure to high\u2010dose valproate (&gt;\u20091.0 to 1.1\u2009g\/day) was associated with a substantially elevated risk of ASD (aHR, 6.32; 95% CI, 3.12\u201312.80,\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20091,719,825). Likewise, in monotherapy (aHR, 4.21; 95% CI, 2.97\u20135.95;\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20091,745,253) and discordant sibling pair (aHR, 6.42; 95% CI, 2.02\u201320.42;\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20091133) analyses, the risk of ASD was substantially elevated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Gestational exposure to valproate was associated with an increased risk of ASD and ADHD; the risks for ASD were greater at doses \u2265\u20091000\u2009mg\/day. These findings add to the literature that strongly discourages the use of valproate by women of childbearing age, especially during pregnancy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acps.13797","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T23:42:20Z","timestamp":1741736540000},"page":"668-679","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Gestational Exposure to Valproate and Autism Spectrum Disorder or Attention\u2010Deficit\/Hyperactivity Disorder in Offspring: Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","volume":"151","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1526-567X","authenticated-orcid":false,"given":"Chittaranjan","family":"Andrade","sequence":"first","affiliation":[{"name":"Department of Clinical Psychopharmacology and Neurotoxicology National Institute of Mental Health and Neurosciences (NIMHANS)  Bangalore 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