Bibian van der Voorn1, Jan M Wit, Sylvia M van der Pal, Joost Rotteveel, Martijn J J Finken. 1. Department of Pediatrics (B.v.d.V., J.R., M.J.J.F.), VU University Medical Center, 1007 MB Amsterdam, The Netherlands; Department of Pediatrics (J.M.W.), Leiden University Medical Center, 2333 ZA Leiden, Netherlands; and TNO, Child Health (S.M.v.d.P.), 2316 ZL Leiden, The Netherlands.
Abstract
CONTEXT: Preterm survivors exhibit neurodevelopmental impairments. Whether this association is influenced by antenatal glucocorticoid treatment and glucocorticoid sensitivity is unknown. OBJECTIVES: This study aimed to study the effects of antenatal glucocorticoid treatment and glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) polymorphisms on behavior and intelligence quotient (IQ). DESIGN: This study was part of the 19-year follow-up of the Project On Preterm and Small-for-gestational-age birth cohort. SETTING: Multicenter study. PATIENTS: Three hundred forty-four 19-year-olds born very preterm (gestational age < 32 wk), 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% confidence interval [CI]). RESULTS: Sex ratio, GR (R23K; N363S) and MR (-2G/C; I180V) genotypes were equally distributed 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 toward more favorable 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 had more favorable internalizing behavior scores (β -2.0; 95% CI, -3.9 to -0.1). Antenatal glucocorticoid treatment 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 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.
CONTEXT: Preterm survivors exhibit neurodevelopmental impairments. Whether this association is influenced by antenatal glucocorticoid treatment and glucocorticoid sensitivity is unknown. OBJECTIVES: This study aimed to study the effects of antenatal glucocorticoid treatment and glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) polymorphisms on behavior and intelligence quotient (IQ). DESIGN: This study was part of the 19-year follow-up of the Project On Preterm and Small-for-gestational-age birth cohort. SETTING: Multicenter study. PATIENTS: Three hundred forty-four 19-year-olds born very preterm (gestational age < 32 wk), 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% confidence interval [CI]). RESULTS: Sex ratio, GR (R23K; N363S) and MR (-2G/C; I180V) genotypes were equally distributed 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 toward more favorable 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 had more favorable internalizing behavior scores (β -2.0; 95% CI, -3.9 to -0.1). Antenatal glucocorticoid treatment 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 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.
Authors: Martijn J J Finken; Bibian van der Voorn; Jonneke J Hollanders; Charlotte A Ruys; Marita de Waard; Johannes B van Goudoever; Joost Rotteveel Journal: Ann Nutr Metab Date: 2017-03-17 Impact factor: 3.374
Authors: Sandra Van der Auwera; Johanna Klinger-König; Katharina Wittfeld; Jan Terock; Anke Hannemann; Robin Bülow; Matthias Nauck; Uwe Völker; Henry Völzke; Hans Jörgen Grabe Journal: Eur Arch Psychiatry Clin Neurosci Date: 2022-05-17 Impact factor: 5.270
Authors: Krystle A Frahm; Melanie E Peffer; Janie Y Zhang; Soumya Luthra; Anish B Chakka; Matthew B Couger; Uma R Chandran; A Paula Monaghan; Donald B DeFranco Journal: Mol Endocrinol Date: 2015-11-25