Antenatal glucocorticoid treatment and polymorphisms of the glucocorticoid and mineralocorticoid receptors are associated with IQ and behavior in young adults born very preterm
van der Voorn, B.
van der Pal, S.M.
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.
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CH - Child Health
ELSS - Earth, Life and Social Sciences
Healthy for Life
Journal of Clinical Endocrinology & Metabolism, 100 (2), 500-507