Abdominal Fat Accumulation in Adults Born Preterm Exposed Antenatally to Maternal Glucocorticoid Treatment Is Dependent on Glucocorticoid Receptor Gene Variation

Abstract

Abstract Context: Preterm birth is associated with short stature, abdominal adiposity, insulin resistance, and hypertension, resembling effects of increased glucocorticoid bioactivity. Although antenatal glucocorticoid treatment does not substantially contribute to these associations, it is unknown whether genetic variants in the glucocorticoid receptor gene could modulate the effects of antenatal glucocorticoid treatment on the above phenotype. Objective: Our objective was to test the effects of the R23K and N363S variants, associated with decreased and increased sensitivity to cortisol, respectively, on the metabolic profile in adults born preterm of whom some had been treated with glucocorticoids antenatally and/or in the early postnatal phase. Design and Participants: This was a prospective follow-up study that included 263 19-year-olds born at a gestational age under 32 wk from the Dutch Project on Preterm and Small-for-Gestational-Age Infants cohort. Setting: This was a nationwide multicenter follow-up study. Main Outcome Measures: Adult height and body composition, fasting serum glucose, insulin and cholesterol levels, and blood pressure were evaluated. Results: At 19 yr of age, waist circumference was 1.67 ± 0.90 sd score in 363S carriers who had been treated antenatally with glucocorticoids (n = 4), which was much higher than that of the other groups (P for interaction = 0.03). A similar association was found for the waist-to-hip ratio sd score (P = 0.03). Similar associations were absent with the R23K polymorphism. There was no interaction between these genotypes and postnatal glucocorticoid treatment on serum levels of glucose, insulin, and cholesterol or blood pressure. Conclusions: In prematurely born individuals carrying the 363S variant, antenatal glucocorticoid treatment predisposes to abdominal adiposity at age 19 yr.