Summary: In a 50-year follow-up of the Auckland Steroid Trial, the adult grandchildren of pregnancies randomised to antenatal betamethasone showed no significant difference in BMI or in metabolic, cardiovascular, respiratory, neurodevelopmental, or mental-health outcomes, a reassuring result on intergenerational safety.
PICO Summary
| Element | Detail |
|---|---|
| Population | Second-generation adults (grandchildren) of Auckland Steroid Trial participants; 213 enrolled, 144 with BMI data. |
| Intervention | Grandparental randomisation to antenatal betamethasone (parent exposed in utero). |
| Comparison | Grandparental randomisation to placebo. |
| Outcome | No difference in BMI z-score (0.63 vs 0.41; adjusted difference 0.16; 95% CI -0.37 to 0.69) and no evidence of difference in overweight, diabetes, respiratory disease, cardiometabolic risk, neurodevelopmental, mental-health, or social outcomes, though confidence intervals were wide. |
Antenatal Steroids and the Next Generation
RCT 50-year follow-up · grandchildren
At 50 years, grandchildren of antenatal-betamethasone pregnancies showed no difference in BMI or in metabolic, cardiovascular, respiratory, neurodevelopmental, or mental-health outcomes. A reassuring null result on intergenerational safety, though confidence intervals were wide.
Expert Commentary
This is a reassuring null result, and it is important to state that plainly, because the earlier version of this page had the conclusion exactly backwards. The study did not show transgenerational metabolic harm in grandchildren; it looked for it and did not find it. BMI z-score was no different between the betamethasone and placebo lineages, and no signal emerged across diabetes, cardiometabolic, respiratory, neurodevelopmental, or mental-health outcomes. Given genuine theoretical concern from animal work about glucocorticoid effects programmed across generations, finding none in humans at 50 years is a genuinely valuable, and welcome, piece of evidence. My one honest caveat is statistical: the confidence intervals are wide, so this is best read as no evidence of a clinically important effect rather than proof of absolutely none, and very small effects cannot be excluded. Can I use this with my patients? Yes, as reassurance. Antenatal corticosteroids for threatened preterm birth are strongly beneficial and life-saving, and this long-term follow-up supports their intergenerational safety, while still favouring giving them only when genuinely indicated rather than just in case. A clear example of why negative findings deserve accurate reporting.
References
Lord LG, Walters AGB, Crowther CA, et al. Second generation effects of antenatal corticosteroid exposure: 50-year follow-up of the Auckland Steroid Trial. J Dev Orig Health Dis. 2025;16:e25. doi:10.1017/S204017442510007X