{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:11:55Z","timestamp":1780337515337,"version":"3.54.1"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023699","name":"Health Data Research UK","doi-asserted-by":"publisher","award":["MR\/S003800\/1"],"award-info":[{"award-number":["MR\/S003800\/1"]}],"id":[{"id":"10.13039\/501100023699","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000308","name":"British Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000308","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Since asthma exacerbations during pregnancy risk maternal and fetal health, continued medication is important. However, some studies have reported adverse neurodevelopmental outcomes following prenatal exposure to asthma medication. Therefore, this systematic review aimed to collate the existing evidence on the associations between prenatal exposure to asthma medication and neurodevelopmental and educational outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>\n                      A systematic review was conducted in accordance with PRISMA guidelines and the PECO framework. PubMed, Medline and Embase databases were searched for studies investigating prenatal exposure to one or more asthma medication and neurodevelopmental or educational outcomes published, in English, between January 2003 and September 2024, and updated in November 2025. Studies of asthma medication used for other indications were excluded. Study quality was assessed using the Newcastle-Ottawa scale. Random-effects meta-analyses were conducted where appropriate and heterogeneity was evaluated using Cochran\u2019s\n                      <jats:italic>Q<\/jats:italic>\n                      and\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      tests.\n                    <\/jats:p>\n                    <jats:p>\n                      Of 16,824 studies identified by the initial search, seven were eligible for inclusion. All investigated beta-2-adrenergic agonists (B2AA), with one including B2AA as mono- and polytherapy\u2014and one study also investigated inhaled corticosteroids (ICS) exposure. Two reported associations with autism spectrum disorder (ASD) and one with attention-deficit hyperactivity disorder (ADHD). An updated search identified one additional eligible study, which examined both ADHD and ASD, as well as other neurodevelopmental disorders. The included eight studies (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093,867,170 participants) comprised cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095) and case-control (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093) designs and reported inconsistent results. Meta-analysis of three studies (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091,380,871) indicated significant associations with ASD for exposure to B2AA both preconception (aOR 1.34, 95% CI [1.19,1.52]) and during pregnancy (aOR 1.29, 95% CI [1.16,1.42]). Heterogeneity was low, with no evidence of significant publication bias. Limitations of the included studies comprised residual confounding and exposure misclassification. Additionally, studies included in the meta-analysis were few in number and did not adequately distinguish between medication effects and underlying maternal asthma.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Meta-analysis suggested an association between prenatal exposure to B2AA and ASD. An association with ADHD, reported in a single study, requires corroboration. To date, based on our search strategy, no association has been reported with communication skills, motor skills, problem-solving and personal-social skills, or cerebral palsy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1005100","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:50:33Z","timestamp":1780336233000},"page":"e1005100","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prenatal exposure to asthma medications and risk of neurodevelopmental disorders and educational difficulties: A systematic review and meta-analysis"],"prefix":"10.1371","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5406-7879","authenticated-orcid":true,"given":"Lama A.","family":"Shakhshir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0987-9974","authenticated-orcid":true,"given":"Alexia","family":"Karain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill P.","family":"Pell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4604-3319","authenticated-orcid":true,"given":"Claire E.","family":"Hastie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2185-4502","authenticated-orcid":true,"given":"Michael","family":"Fleming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"issue":"12","key":"pmed.1005100.ref001","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaip.2021.07.055","article-title":"Factors associated with asthma exacerbations during pregnancy","volume":"9","author":"MP Bokern","year":"2021","journal-title":"J Allergy Clin Immunol Pract"},{"key":"pmed.1005100.ref002","unstructured":"Members of GINA Committee. 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