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Background: 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. Methods and findings: 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;]; p = 0.735) or age at first MACE (adjusted hazard ratio 0.58, 95% CI [0.23, 1.49]; p = 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. Conclusions: 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. Anthony G B Walters and colleagues assess cardiovascular outcomes fifty years after antenatal exposure to betamethasone, in long-term follow-up of a randomised double-blind, placebo-controlled trial. Author summary: Why was this study done?: Antenatal corticosteroids (ANC) are given to pregnant persons at risk of preterm birth to reduce the risk of death and breathing difficulty for their offspring. Animal studies have shown later adverse effects of ANC on offspring, particularly on their cardiovascular health in adulthood. There is little robust evidence about long-term effects in humans. This study aimed to provide evidence about the long-term effects of ANC on offspring cardiovascular health in adulthood. What did the researchers do and find?: We assessed participants at 50 years of age who had been exposed to ANC or placebo during the first randomised clinical trial of this treatment. We compared cardiovascular disease and cardiovascular risk factors between those exposed to ANC and placebo in 424 participants (46% of those still alive), using a questionnaire and routinely collected administrative data. We found no differences in cardiovascular outcomes between those exposed to ANC and those who were not. What do these findings mean?: There is no evidence that ANC has adverse effects on the cardiovascular health outcomes of offspring up to 50 years of age. The main limitation was the follow-up rate of less than 50% and the use of health questionnaires and routinely collected data rather than in-person assessments. [ABSTRACT FROM AUTHOR]

Two letters to the editor in response to articles published in previous issues including an article on the Women's Health Initiative calcium and vitamin D study, published in a previous issue and its response and an editorial on calcium, vitamin D and cardiovascular risk, published in a previous issue are presented.

The article discusses a research conducted to determine whether calcium supplements, with or without vitamin D, leads to cardiovascular diseases. A randomised, placebo controlled trial of calcium and vitamin D in postmenopausal women was conducted on 29000 participants and it found that calcium supplements increased the risk of myocardial infarction by about 25 percent and the risk of stroke by about 15 percent.

The article discusses a study which investigated the effect of calcium supplements without coadministered vitamin D on the risk of cardiovascular events. The authors analysed randomised placebo controlled trials of calcium supplements published in Medline, Embase, and the Cochrane Central Register of Controlled trials. It was suggested by a previous randomised placebo controlled trial that there was an association between an increased risk of myocardial infarction and calcium supplements, which was confirmed by the current study.