Context: Preterm birth is associated with postnatal growth failure, abdominal fat accumulation, insulin resistance and hypertension, resembling increased glucocorticoid bioactivity.

Objective: We tested the effects of the R23K and N363S polymorphisms in the glucocorticoid receptor gene, associated with decreased and increased sensitivity to cortisol, respectively, on linear growth and the adult metabolic profile in a cohort (n=249) of men and women born <32 gestational weeks and followed prospectively from birth until 19 years of age.

Design and participants: Birth cohort study that included 249 19-year-old survivors born at a gestational age <32 weeks from the Dutch Project On Preterm and Small-for-gestational-age infants (POPS) cohort.

Setting: Multicenter-study.

Main outcome measures: Linear growth and adult body composition, fasting cortisol, glucose, insulin and cholesterol concentrations, and blood pressure.

Results: The 23K variant (n=24) was associated with lower fasting insulin levels (mean difference after log-transformation: -0.09 (95% CI: -0.16; -0.01) mU/l) and a lower HOMA-IR (mean difference after log-transformation: -0.09 (95% CI: -0.16; -0.01)), as well as with a taller stature departing from the age of 1 year onwards. 23K carriers showed complete catch-up growth between the ages of 3 months and 1 year and attained height was similar to the population reference mean, whereas stature in non-carriers was on average 0.5 SD below this mean. In contrast, the N363S polymorphism was not associated with any of the outcomes.

Conclusions: Carriers of the 23K variant are, at least in part, protected against postnatal growth failure and insulin resistance after preterm birth.