Objective: Prenatal exposure to excess cortisol can affect postnatal metabolic health by epigenetic mechanisms. We aimed to investigate if prenatal exposure to pharmacological glucocorticoids increases the risk of overweight/obesity in childhood.
Design: A nationwide population registry-based cohort study.
Methods: We identified 383 877 children born in Denmark (2007-2012), who underwent routine anthropometric evaluation at 5-8 years of age. Prenatal exposure to glucocorticoids was divided into systemic and topical glucocorticoids, cumulative systemic dose, and use by trimester. The comparison cohort included children without exposure, born to maternal never-users. Negative control exposures were used to investigate confounding from an underlying disease or unmeasured characteristics. Such exposures included children without glucocorticoid exposure born to maternal users of non-steroidal anti-inflammatory drugs or immunotherapy during pregnancy, maternal former users of glucocorticoids, or paternal users of glucocorticoids during the pregnancy of their partner. We estimated sex-stratified adjusted prevalence ratios (aPR) of overweight/obesity at 5-8 years of age, as epigenetic modifications have shown to be sex-specific.
Results: In the study, 21 246 (11%) boys and 27 851 (15%) girls were overweight/obese at 5-8 years of age. Overall, neither systemic nor topical glucocorticoids were associated with overweight/obesity. In boys, high-dose systemic glucocorticoids was associated with higher prevalence of overweight/obesity vs the comparison cohort (aPR: 1.41 (95% CI: 1.07-1.86), prevalence: 16% vs 11%). Negative control exposures indicated robustness to confounding.
Conclusion: Overweight/obesity might be an adverse effect of prenatal exposure to high-dose systemic glucocorticoids in boys. We found no association for neither prenatal exposure to lower doses of systemic nor topical glucocorticoids. These results merit clinical attention.