Bibian van der Voorn

107 GR/MR VARIATION ON IQ & BEHAVIOR AFTER PREMATURITY INTRODUCTION Childrenbornprematurelyhave decreasedbrainvolumes aswell as higher frequencies of cognitive impairments and problems with internalizing behavior and attention 1,2 . During fetal maturation, development of the central nervous system follows a specific, coordinated chain of ontogenetic events 3 . Antenatal glucocorticoid treatment could disturb these processes 3,4 . Most women at risk of premature birth are treated with glucocorticoids to stimulate fetal lung maturation. This is highly effective in reducing short term mortality and morbidity 5 . However, despite these benefits, evidence from animal studies shows that exposure of the fetus to excess glucocorticoids can permanently alter neuroendocrine function, behaviorandmemory 3,4 . Accordingly, antenatal glucocorticoidtreatmentmay affect the ontogenesis of the immature brain, causing life-long deleterious effects 3,4 . In 2006, a Cochrane meta-analysis, based on six studies, reported that antenatal glucocorticoid treatment is not associatedwith long termneurodevelopmental deficits 5 . However, 3 out of the 6 studies included in this meta-analysis were not limited to very preterm subjects (GA <32wks) 6-8 . Furthermore, 3 out of the 6 studies reported on the risk to develop a psychiatric disorder or become severely handicapped, and did not take subtle impairments into account 7,9,10 . The neural actions of glucocorticoids depend on the sensitivity of brain regions to these hormones, mediated by two corticosteroid receptors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) 3,11,12 . Polymorphisms of the GR and MR genes contribute to inter-individual variations in glucocorticoid sensitivity 11,13 , cognitive performance and behavior 14,15 . Within the GR gene, the R23K (rs 6190) and N363S (rs 6195) SNPs have been associated with decreased and increased GR sensitivity, respectively 16 . Within the MR gene, the -2G/C (rs 2070951) and the I180V SNPs (rs5522) have been implicated in influencing MR sensitivity. The I180V SNP has been associated with decreased MR sensitivity and the CC-genotype of the -2G/C SNP is thought to increase MR sensitivity compared to the GG-genotype, although this was not a universal finding 17 . To date, no study has been performed in very preterm survivors, addressing the effects of antenatal synthetic glucocorticoid exposure and common variations in GR and MR genes on later cognitive and behavioral functioning. Therefore, we studied in young adults born very preterm the effects of antenatal glucocorticoid treatment, and GR and MR SNPs, as well as their interaction, on behavior and IQ.