{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:43:05Z","timestamp":1787013785984,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"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":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Benzodiazepine (BDZP) and\/or z\u2010hypnotic dispensing during pregnancy has increased globally, as have rates of autism spectrum disorder (ASD) and attention\u2010deficit hyperactivity disorder (ADHD). This systematic review and meta\u2010analysis aimed to estimate the association between gestational exposure to BDZP and\/or z\u2010hypnotics and diagnosis of ASD or ADHD in offspring.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched MEDLINE, EMBASE, and SCOPUS from inception till December 2023 for relevant English\u2010language articles. Outcomes of interest were risk of ASD and ADHD, two independent primary outcomes, in children exposed anytime during pregnancy to BDZP and\/or z\u2010hypnotics versus those unexposed. Secondary outcomes were trimester\u2010wise analyses. Using a random effects model, we pooled the overall and trimester\u2010wise hazard ratios (HRs), with 95% confidence intervals (CIs), separately for risk of ASD and ADHD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found six eligible retrospective cohort studies and no case\u2013control studies. There was no increased risk of ASD associated with anytime gestational BDZP and\/or z\u2010hypnotic exposure (primary outcome, HR, 1.10; 95% CI, 0.81\u20131.50; 4 studies;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093,783,417; 80,270 exposed, 3,703,147 unexposed) nor after first trimester exposure (HR, 1.15; 95% CI, 0.83\u20131.58; 3 studies;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091,539,335; 70,737 exposed, 1,468,598 unexposed) or later trimester exposures. A very small but significantly increased risk of ADHD was noted with anytime gestational exposure to these drugs (primary outcome, HR, 1.07; 95% CI, 1.03\u20131.12; 4 studies;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092,000,777; 78,912 exposed, 1,921,865 unexposed) and also with (only) second trimester exposure (HR, 1.07; 95% CI, 1.03\u20131.12; 3 studies;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091,539,281; 33,355 exposed, 1,505,926 unexposed). Findings were consistent in sensitivity analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Gestational exposure to benzodiazepines or z\u2010hypnotics was not associated with an increased risk of ASD and with only a marginally increased risk of ADHD in offspring. Given the likelihood of confounding by indication and by unmeasured variables in the original studies, our findings should reassure women who need these medications for severe anxiety or insomnia during pregnancy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acps.13696","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T01:58:23Z","timestamp":1715824703000},"page":"65-77","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Gestational exposure to benzodiazepines or z\u2010hypnotics and neurodevelopmental disorders in offspring: Systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"150","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)  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natarajan","family":"Varadharajan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)  Puducherry India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharmi","family":"Bascarane","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)  Puducherry India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8035-4658","authenticated-orcid":false,"given":"Vikas","family":"Menon","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)  Puducherry India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phr.2004.09.003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/aur.239"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2011.10101532"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803\u2010018\u20103834\u20100"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.2007.164.6.942"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014\u20103482"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.14344"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12884\u2010021\u201003787\u20105"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.03.014"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.43282"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.46889"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.23f14863"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2022.107078"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2022.104647"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.0674"},{"key":"e_1_2_8_19_1","unstructured":"MartinJ.The Joanna Briggs Institute Critical Appraisal Tools for Use in JBI Systematic Reviews: Checklist for Cohort Studies.2017."},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.genhosppsych.2022.12.003"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/DBP.0b013e3181e5ac93"},{"key":"e_1_2_8_22_1","unstructured":"Review Manager (RevMan) [Computer program] Version 5.4.1.The Cochrane collaboration.2020."},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000529141"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201074409\u2010x"},{"key":"e_1_2_8_25_1","first-page":"214","article-title":"Benzodiazepine pharmacology and central nervous system\u2013mediated effects","volume":"13","author":"Griffin CE","year":"2013","journal-title":"Ochsner J"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bjaceaccp\/mku013"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00737\u2010009\u20100100\u20107"}],"container-title":["Acta Psychiatrica Scandinavica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acps.13696","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,12]],"date-time":"2025-01-12T23:48:31Z","timestamp":1736725711000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acps.13696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,15]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1111\/acps.13696"],"URL":"https:\/\/doi.org\/10.1111\/acps.13696","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/ACPS.13696\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/ACPS.13696\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/ACPS.13696\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/ACPS.13696\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/ACPS.13696\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/ACPS.13696\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0001-690X","1600-0447"],"issn-type":[{"value":"0001-690X","type":"print"},{"value":"1600-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,15]]},"assertion":[{"value":"2024-01-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}