{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:25:17Z","timestamp":1785306317727,"version":"3.55.0"},"reference-count":72,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006636","name":"Forskningsr\u00c3\u00a5det om H\u00c3\u00a4lsa, Arbetsliv och V\u00c3\u00a4lf\u00c3\u00a4rd","doi-asserted-by":"publisher","award":["2023-01238"],"award-info":[{"award-number":["2023-01238"]}],"id":[{"id":"10.13039\/501100006636","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003793","name":"Hj\u00c3\u00a4rt-Lungfonden","doi-asserted-by":"publisher","award":["20240328"],"award-info":[{"award-number":["20240328"]}],"id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","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>While maternal congenital heart disease (CHD) is associated with increased risks of adverse pregnancy outcomes, its impact on long-term child development remains unknown. This study aimed to investigate if in-utero exposure to maternal CHD is associated with child developmental vulnerability at school entry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>This population-based cohort study included 256,629 singleton offspring born in British Columbia, Canada between January 1, 1995 and December 31, 2016, with follow up through linkage to teacher-rated Early Development Instrument (EDI) surveys administered in kindergarten around 5\u20136 years of age. Over 90% children enrolled in participating schools completed the questionnaire. Developmental vulnerability was defined as a score &lt;10th percentile in any two of the five EDI domains: physical health and wellbeing, social competence, emotional maturity, language and cognitive development, and communication and general knowledge. The association between maternal CHD and child developmental vulnerability was examined using modified Poisson regression models, adjusted for maternal age at delivery, parity, country of birth, marital status, neighborhood income quintiles, preexisting psychiatric disorders, and pre-gestational diabetes. A counterfactual four-way decomposition method was used to quantify potential mediation and moderation by preterm birth. Of the 256,629 children (51.4% female) included in the analysis, 456 (0.2%) were exposed to maternal CHD. Developmental vulnerability was identified among 25.2% children exposed to maternal CHD compared with 16.6% among the unexposed. In the adjusted model, maternal CHD was associated with 28% higher risk of developmental vulnerability (aRR 1.28; 95% CI [1.11, 1.48]) compared with no maternal CHD. The increased risk was observed across multiple developmental domains related to physical health and wellbeing (aRR 1.31; 95% CI [1.11, 1.54]), social competence (aRR 1.22; 95% CI [1.02, 1.45]), language and cognitive development (aRR 1.39; 95% CI [1.13, 1.70]), and communication and general knowledge (aRR 1.33; 95% CI [1.09, 1.63]). Preterm birth mediated only about 8% of the overall association. Severe CHD was more strongly associated with developmental vulnerability (aRR 1.98; 95% CI [1.31, 3.00]) compared to mild CHD (aRR 1.19; 95% CI [1.00, 1.42]). However, the study had limited capacity to separate intrauterine effects from potential genetic and postnatal familial influences. Some degree of CHD misclassification is possible, which would likely bias the association toward the null.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this population-based study, maternal CHD was associated with child developmental vulnerability at school entry. While further research is required to elucidate the mechanisms, enhanced clinical monitoring and tailored support to reproductive age women with CHD may help reduce the risk of developmental vulnerability in their children.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1004890","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:28:32Z","timestamp":1783013312000},"page":"e1004890","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Maternal congenital heart disease and risk of child developmental vulnerability in early school age: A population-based cohort study"],"prefix":"10.1371","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9078-419X","authenticated-orcid":true,"given":"Muhammad Zakir","family":"Hossin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Gadermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edit","family":"Nagy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8937-1736","authenticated-orcid":true,"given":"Randip","family":"Gill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique Gagn\u00e9","family":"Petteni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4727-5998","authenticated-orcid":true,"given":"Jonas","family":"Fax\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neda","family":"Razaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"pmed.1004890.ref001","first-page":"2982","article-title":"Global burden of cardiovascular diseases and risk factors, 1990-2019: Update from the GBD 2019 study","volume":"76","author":"GA Roth","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"pmed.1004890.ref002","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1161\/CIRCULATIONAHA.123.064400","article-title":"Survival from birth until young adulthood among individuals with congenital heart defects: CH STRONG","volume":"148","author":"KF Downing","year":"2023","journal-title":"Circulation"},{"key":"pmed.1004890.ref003","doi-asserted-by":"crossref","first-page":"101249","DOI":"10.1016\/j.eclinm.2021.101249","article-title":"Global, regional, and national time trends in mortality for congenital heart disease, 1990-2019: an age-period-cohort analysis for the Global Burden of Disease 2019 study","volume":"43","author":"Z Su","year":"2022","journal-title":"EClinicalMedicine"},{"key":"pmed.1004890.ref004","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1093\/eurheartj\/ehy340","article-title":"2018 ESC guidelines for the management of cardiovascular diseases during pregnancy","author":"V Regitz-Zagrosek","year":"2018","journal-title":"Eur Heart J"},{"key":"pmed.1004890.ref005","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1093\/eurheartj\/ehac669","article-title":"Prevalence, trends, and outcomes of cardiovascular diseases in pregnant patients in the USA: 2010\u201319","volume":"44","author":"M Majmundar","year":"2023","journal-title":"Eur Heart J"},{"key":"pmed.1004890.ref006","first-page":"100507","article-title":"Time trends and birth rates in women with congenital heart disease; 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