Second generation effects of antenatal corticosteroid exposure: 50-year follow-up of the Auckland Steroid Trial

Antenatal corticosteroids are given to pregnant people at risk of preterm birth to reduce newborn morbidity, including respiratory distress syndrome. However, there has been concern surrounding potential adverse effects on subsequent generations. Animal studies have demonstrated endocrine and metabolic changes in those exposed to corticosteroids in utero (<i>F</i>₁) and in the second generation (<i>F</i>₂). We aimed to assess the effects of parental antenatal corticosteroid exposure on health of the second generation (<i>F</i>₂) of Auckland Steroid Trial (AST) participants. In the AST, women (<i>F</i>₀) expected to birth between 24 and 36 weeks' gestation were randomised to betamethasone or placebo. When their children (<i>F</i>₁) were 50 years old, they and their children (<i>F</i>₂) were followed up with a self-report questionnaire and data linkage. The primary outcome for this analysis was body mass index (BMI) z-score in the <i>F</i>₂ generation. Secondary outcomes included respiratory, cardiovascular, neurodevelopmental, mental and general health, and social outcomes. Of the 213 <i>F</i>₂ participants, 144 had BMI data available. There was no difference in BMI z-score between participants whose parent was exposed to betamethasone versus placebo (mean (<i>SD</i>) 0.63 (1.45), <i>N</i> = 77 vs 0.41 (1.28), <i>N</i> = 67, adjusted mean difference (95% confidence interval) = 0.16 (-0.37, 0.69)). There was no evidence of a difference in rates of overweight, diabetes, respiratory disease, cardiometabolic risk factors, neurodevelopmental difficulties, mental health difficulties and social outcomes between parental betamethasone versus placebo exposure groups, but confidence intervals were wide. These findings are reassuring regarding the intergenerational safety of antenatal corticosteroids.