Antenatal glucocorticoid treatment and polymorphisms of the glucocorticoid and mineralocorticoid receptors are associated with IQ and behavior in young adults born very preterm

Context: Preterm survivors exhibit neurodevelopmental impairments. Whether this association is influenced by antenatal glucocorticoid treatment and glucocorticoid sensitivity is unknown. Objectives: To study the effects of antenatal glucocorticoid treatment and glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) polymorphisms on behavior and IQ. Design: Follow-up of the Project On Preterm and Small-for-gestational-age (POPS) birth cohort Setting: Multicenter study Patients: 344 19-year-olds born very preterm (gestational age <32 wks), of whom 71 had received betamethasone antenatally. Intervention: single antenatal treatment course of betamethasone. Main outcome measures: Behavior (Young Adult Self-Report and Young Adult Behavior Checklist for parents) and IQ (digital Multicultural Capacity Test-Intermediate Level). Data were analyzed by linear regression and presented as regression coefficient (95% CI). Results: Sex ratio, GR (R23K; N363S) and MR (-2G/C; I180V) genotypes were equally distributed between treated and non-treated subjects. Independent of treatment, R23K carriers had improved IQ-scores (9.3 [3.4; 15.1]) and a tendency towards more favorable total problem behavior scores (-8.5 [-17.3; 0.2]); -2G/C CC-carriers had poorer IQ-scores (-6.2 [-10. 5; -1.9]); I180V carriers had more favorable internalizing behavior scores -2.0 (-3.9; -0.1). Antenatal glucocorticoid treatment was associated with more unfavorable behavior scores, especially internalizing behavior (2.4 [0.3; 4.5]). Interaction between GR and MR polymorphisms and antenatal glucocorticoid treatment was observed, with poorer IQ-scores for exposed N363S-carriers; poorer intellectual subdomain-scores for exposed I180V-carriers; more favorable total problem behavior scores for exposed R23K-carriers. Conclusions: Genetic variations in glucocorticoid sensitivity and antenatal glucocorticoid treatment are associated with IQ and behavior in young adult preterm survivors.