{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:56:38Z","timestamp":1789732598416,"version":"4.0.1"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004319","name":"Shin Kong Wu Ho-Su Memorial Hospital","doi-asserted-by":"publisher","award":["109GB006-1"],"award-info":[{"award-number":["109GB006-1"]}],"id":[{"id":"10.13039\/501100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>STUDY QUESTION<\/jats:title>\n                  <jats:p>Is parental fertility status and use of IVF associated with the risk of pediatric cardiovascular diseases among offspring aged 0\u201313\u2009years, and is this association mediated by perinatal factors?<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SUMMARY ANSWER<\/jats:title>\n                  <jats:p>Children conceived through IVF and those born to parents with subfertility (defined as one partner with an infertility diagnosis and not using ART for the study pregnancy) have an increased risk for congenital heart defects, partly explained by multiple gestations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                  <jats:p>Evidence indicates that children born following IVF have an increased risk of premature vascular aging. However, the risk of developing cardiovascular diseases during childhood and the extent to which such risks are associated with adverse perinatal outcomes remains uncertain.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                  <jats:p>This nationwide, population-based, nested case\u2013control study included registry data from 2\u00a0228\u00a0073 parents\u2013child triads in Taiwan from 1 January 2004 to 31 December 2017. Offspring were categorized into three groups based on their parents\u2019 fertility status (fertile [achieved spontaneous conception, no infertility diagnosis], subfertility, and IVF [conception via IVF, including ICSI]). The three groups were followed from birth (between 1 January 2004 and 31 December 2017) until they developed the outcomes of interest, met any exclusion criteria, died, or until the end of the study period (31 December 2017), whichever came first.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                  <jats:p>In the study cohort, we identified 41\u00a0113 children with newly diagnosed pediatric cardiovascular diseases and used incidence density sampling to match each case to four controls (n\u2009=\u2009169\u00a0850), based on age, sex, mother\u2019s residential township at delivery, and the calendar date of the pediatric cardiovascular disease diagnosis. Pediatric cardiovascular diseases included diagnoses of congenital heart defects, hypertensive diseases, cardiomyopathy, and arrhythmia. Conditional logistic regression was performed to examine the association between fertility status and pediatric cardiovascular diseases. Causal mediation analysis was used to test for mediation by multiple gestations, preterm birth, and low birth weight.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                  <jats:p>During 11.5 million person-years of follow-up (median [interquartile range, IQR], 6\u2009years [2\u201310]), IVF conception was associated with an increased risk of congenital heart defects compared with subfertility (odds ratio [OR], 1.47; 95% CI, 1.36\u20131.60; incidence rate difference [IRD], 375.1 per 100\u00a0000 person-years [95% CI, 331.8\u2013418.3]) and fertile group (OR, 1.72; 95% CI, 1.60\u20131.85; IRD, 445.7 per 100\u00a0000 person-years [95% CI, 403.0\u2013488.3]). Subfertility was associated with a 1.19-fold higher risk of congenital heart defects (95% CI, 1.16\u20131.23; IRD, 70.6 per 100\u00a0000 person-years [95% CI, 61.9\u201379.4]) than fertile group. Multiple gestations accounted for 31.16% of the association between IVF and congenital heart defects compared with subfertility and for 54.26% of the association compared with fertile group. No significant associations were found between fertility status and hypertensive diseases, cardiomyopathy, or arrhythmias.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                  <jats:p>Although the national data with a long follow-up period were used, the duration may still be insufficient to detect potential risks for hypertensive diseases, cardiomyopathy, and arrhythmia. Lack of data on pregnancy terminations could lead to underestimation of congenital heart defects risk.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                  <jats:p>These findings suggest that a reduction in the occurrence of multiple gestations may help reduce the risk of congenital heart defects related to IVF conception. IVF conception should prompt consideration of fetal echocardiography, particularly in mothers with multiple gestations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                  <jats:p>This study was supported by grants from Shin Kong Wu Ho-Su Memorial Hospital (No. 109GB006-1). The funders had no role in the study design, data collection, analysis, interpretation, report writing, or the decision to submit the article for publication. The authors have no competing interests to disclose.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                  <jats:p>N\/A.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/humrep\/deaf161","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T18:35:21Z","timestamp":1755801321000},"page":"1980-1989","source":"Crossref","is-referenced-by-count":2,"title":["Fertility status and risk of pediatric cardiovascular diseases: a population-based nested case\u2013control study"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7949-1663","authenticated-orcid":false,"given":"Shiue-Shan","family":"Weng","sequence":"first","affiliation":[{"name":"Institute of Public Health, National Yang Ming Chiao Tung University , Taipei 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