{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:00:46Z","timestamp":1791925246904,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.pmed.1004378","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000}}],"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021732","name":"Aotearoa Foundation","doi-asserted-by":"publisher","award":["9909494"],"award-info":[{"award-number":["9909494"]}],"id":[{"id":"10.13039\/501100021732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001511","name":"Auckland Medical Research Foundation","doi-asserted-by":"publisher","award":["1421003"],"award-info":[{"award-number":["1421003"]}],"id":[{"id":"10.13039\/501100001511","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001515","name":"Cure Kids","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001515","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["19\/690"],"award-info":[{"award-number":["19\/690"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]}],"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>Antenatal corticosteroids for women at risk of preterm birth reduce neonatal morbidity and mortality, but there is limited evidence regarding their effects on long-term health. This study assessed cardiovascular outcomes at 50 years after antenatal exposure to corticosteroids.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>We assessed the adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (RDS) (1969 to 1974). The first 717 mothers received 2 intramuscular injections of 12 mg betamethasone or placebo 24 h apart and the subsequent 398 received 2 injections of 24 mg betamethasone or equivalent volume of placebo. Follow-up included a health questionnaire and consent to access administrative data sources. The co-primary outcomes were the prevalence of cardiovascular risk factors (any of hypertension, hyperlipidaemia, diabetes mellitus, gestational diabetes mellitus, or prediabetes) and age at first major adverse cardiovascular event (MACE) (cardiovascular death, myocardial infarction, coronary revascularisation, stroke, admission for peripheral vascular disease, and admission for heart failure). Analyses were adjusted for gestational age at entry, sex, and clustering. Of 1,218 infants born to 1,115 mothers, we followed up 424 (46% of survivors; 212 [50%] female) at mean (standard deviation) age 49.3 (1.0) years. There were no differences between those exposed to betamethasone or placebo for cardiovascular risk factors (159\/229 [69.4%] versus 131\/195 [67.2%]; adjusted relative risk 1.02, 95% confidence interval [CI] [0.89, 1.18;]; <jats:italic>p<\/jats:italic> = 0.735) or age at first MACE (adjusted hazard ratio 0.58, 95% CI [0.23, 1.49]; <jats:italic>p<\/jats:italic> = 0.261). There were also no differences in the components of these composite outcomes or in any of the other secondary outcomes. Key limitations were follow-up rate and lack of in-person assessments.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>There is no evidence that antenatal corticosteroids increase the prevalence of cardiovascular risk factors or incidence of cardiovascular events up to 50 years of age. Established benefits of antenatal corticosteroids are not outweighed by an increase in adult cardiovascular disease.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1004378","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T17:48:03Z","timestamp":1711993683000},"page":"e1004378","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cardiovascular outcomes 50 years after antenatal exposure to betamethasone: Follow-up of a randomised double-blind, placebo-controlled trial"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9129-6024","authenticated-orcid":true,"given":"Anthony G. B.","family":"Walters","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0412-3203","authenticated-orcid":true,"given":"Greg D.","family":"Gamble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9079-4451","authenticated-orcid":true,"given":"Caroline A.","family":"Crowther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart R.","family":"Dalziel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl L.","family":"Eagleton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1088-9467","authenticated-orcid":true,"given":"Christopher J. 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Preterm labour and birth. London: National Institute for Health and Care Excellence (UK); 2015. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK327571\/."},{"key":"pmed.1004378.ref003","first-page":"CD004454","article-title":"Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth","volume":"12","author":"Cochrane Pregnancy and Childbirth Group","year":"2020","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"pmed.1004378.ref004","first-page":"1","article-title":"The effect of antenatal steroids for fetal maturation on perinatal outcomes","volume":"12","year":"1994","journal-title":"NIH Consensus Statement"},{"key":"pmed.1004378.ref005","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1097\/MOP.0000000000000191","article-title":"Developmental origins of health and disease: a paradigm for understanding disease cause and prevention","volume":"27","author":"JJ Heindel","year":"2015","journal-title":"Curr Opin 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Gatford","year":"2000","journal-title":"Clin Sci (London, England)"},{"key":"pmed.1004378.ref015","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1042\/cs0980137","article-title":"Antenatal corticosteroid therapy and blood pressure at 14 years of age in preterm children","volume":"98","author":"LW Doyle","year":"2000","journal-title":"Clin Sci (London, England)"},{"key":"pmed.1004378.ref016","doi-asserted-by":"crossref","first-page":"F442","DOI":"10.1136\/adc.2007.128470","article-title":"Antenatal glucocorticoid treatment is not associated with long-term metabolic risks in individuals born before 32 weeks of gestation","volume":"93","author":"MJJ Finken","year":"2008","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"pmed.1004378.ref017","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/1471-0528.17316","article-title":"The effect of antenatal corticosteroid use on offspring cardiovascular function: a systematic review","volume":"130","author":"A 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