Bibian van der Voorn

106 CHAPTER 8 ABSTRACT BACKGROUND Preterm survivors exhibit neurodevelopmental impairments. Whether this associa- tion is influenced by antenatal glucocorticoid treatment and glucocorticoid sensitivity is unknown. This study aimed to study the effects of antenatal glucocorticoid treat- ment and glucocorticoid receptor ( GR ) and mineralocorticoid receptor ( MR ) poly- morphisms on behavior and intelligence quotient (IQ). METHODS This multicenter study was part of the 19-year follow-up of the Project On Preterm and Small-for-gestational-age birth cohort. Three hundred forty-four 19-year-olds born very preterm (gestational age < 32 wk), of whom 71 had re- ceived a single antenatal treatment course of betamethasone. Main Outcome Measures: Behavior (Young Adult Self Report and Young Adult Behavior Check- list 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 distribut- ed between treated and nontreated subjects. Independent of treatment, R23K carriers had improved IQ scores (β 9.3; 95%CI, 3.4 to 15.1) and a tendency towardmore favor- able total problem behavior scores (β -8.5;95%CI,-17.3 to 0.2) ; -2G/C CC carriers had poorer IQ scores (β -6.2;95%CI,-10.5 to -1.9); I180V carriers hadmore favorable inter- nalizing behavior scores (β -2.0; 95% CI, -3.9 to -0.1). Antenatal glucocorticoid treat- ment was associated with more unfavorable behavior scores, especially internalizing behavior (β 2.4; 95% CI, 0.3 to 4.5). Interaction between GR and MR polymorphisms and antenatal glucocorticoid treatment was observed, with poorer IQ scores for ex- posed N363S carriers; poorer intellectual subdomain scores for exposed I180V-car- riers; more favorable total problem behavior scores for exposed R23K carriers. CONCLUSIONS Genetic variations in glucocorticoid sensitivity and antenatal glucocorticoid treat- ment are associated with IQ and behavior in young adult preterm survivors.