Cardiovascular outcomes 50 years after antenatal exposure to betamethasone: Follow-up of a randomised double-blind, placebo-controlled trial.

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.

Betamethasone for Preterm Birth: Auckland Steroid Trial Full Results and New Insights 50 Years on.

OBJECTIVES: The objective of this study was to use modern analysis and reporting methods to present the full results of the first randomized trial of antenatal corticosteroids, performed 50 years ago. STUDY DESIGN: In this single-center trial, women at risk of preterm birth at 24 to less than 37 weeks of gestation were randomized to receive 2 doses of betamethasone or placebo, 24 hours apart. Women and their caregivers were blinded to treatment allocation. The primary outcome was respiratory distress syndrome. Secondary outcomes included measures of neonatal mortality and morbidity, mode of birth, and maternal infection. RESULTS: Between 1969 and 1974, 1115 women (1142 pregnancies) were randomized, 560 pregnancies (601 infants) to betamethasone and 582 (617 infants) to placebo. The risk of respiratory distress syndrome was significantly reduced in the betamethasone group compared with placebo (8.8% vs 14.4%, adjusted relative risk 0.62, 95% CI 0.45-0.86, P = .004). Subgroup analyses indicated greater efficacy in male than female infants but no effect of tocolytic therapy or doubling of betamethasone dose. Fetal or neonatal death, neonatal or maternal infection, neonatal hypoglycaemia, cesarean delivery, and lactation status at discharge were not different between the groups. CONCLUSIONS: Antenatal betamethasone administered to women at risk of preterm birth between 24 and less than 37 weeks of gestation reduces the incidence of respiratory distress syndrome, with greater effect in male than in female infants. Doubling the dose of betamethasone does not provide additional benefit.

Endocrine adverse effects of immune checkpoint inhibitors.

Immune checkpoint inhibitors are increasingly being utilised as an effective therapy for a variety of cancers. However, they have the potential to cause serious autoimmune toxicities in multiple organ systems termed 'immunotherapy-related adverse events'. Endocrine toxicities are common, can occur well after commencement of therapy and can result in significant morbidity and mortality if not recognised. This makes it important for all physicians, in addition to endocrinologists and oncologists, to understand the nature of these reactions and the general approach to their diagnosis and management. This review aims to provide an overview of the epidemiology, pathophysiology, clinical presentation and management of the endocrine adverse events.