title: Antenatal glucocorticoid treatment and polymorphisms of the glucocorticoid and mineralocorticoid receptors are associated with IQ and behavior in young adults born very preterm.
abstract: BACKGROUND
  Preterm survivors exhibit neurodevelopmental impairments. Whether this association is influenced by antenatal glucocorticoid treatment and glucocorticoid sensitivity is unknown.
  
  
  OBJECTIVE
  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).
  
  
  METHODS
  This study was part of the 19-year follow-up of the Project On Preterm and Small-for-gestational-age birth cohort.
  
  
  METHODS
  Multicenter study.
  
  
  METHODS
  Three hundred forty-four 19-year-olds born very preterm (gestational age < 32 wk), of whom 71 had received betamethasone antenatally.
  
  
  METHODS
  Single antenatal treatment course of betamethasone.
  
  
  METHODS
  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.affiliation: 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.
authors.forename: Bibian
authors.initials: B
authors.lastname: van der Voorn
authors.forename: Jan M
authors.initials: JM
authors.lastname: Wit
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: van der Pal
authors.forename: Joost
authors.initials: J
authors.lastname: Rotteveel
authors.forename: Martijn J J
authors.initials: MJ
authors.lastname: Finken
mesh_terms: D000374:Aggression / Q000187:drug effects* / Q000523:psychology; D001007:Anxiety / Q000209:etiology* / Q000523:psychology; D003863:Depression / Q000209:etiology* / Q000523:psychology; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D005938:Glucocorticoids / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007361:Intelligence Tests; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D047928:Premature Birth; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000235:genetics*; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid