Bibian van der Voorn

116 CHAPTER 8 reported behavior, since preterm survivors appear to underreport deviating behavior 23,28,39 and parents provide data with a high validity 39 . A limitation of our study is that there was an underrepresentation of subjects who followed special education and subjects with a severe handicap 19 . However, if these individuals with unfavorable outcomes had participated, this would probably have enhanced the effects found. Another weakness is that genotypes were not known for the entire birth cohort. Therefore, we were unable to rule out a survival advantage associated with GR or MR carriage 15,40 . However, the allele frequencies in our sample were similar to the normal Caucasian population. Furthermore, most results were consistent with expectations based on in vitro receptor signaling studies 16,17 . In the interpretation of genetic association studies several other factors which affect the outcome must be acknowledged, including challenges during life and health status. Last, in our cohort numbers of exposed GR SNP carriers were small, as only 8 R23K carriers and 4 N363S carriers were exposed to antenatal glucocorticoid treatment. Even though, statistically significant differences were found. Furthermore, also the numbers with intercourse compound variation were low. In conclusion, our data provide evidence for a possible mechanism explaining the association between prematurity and impairments in cognitive functioning and behavior. We showed that individual variations in glucocorticoid sensitivity and antenatal exposure to synthetic glucocorticoids during a critical period of neural ontogenesis were associated with IQ and behavior in young adults with a history of very pretermbirth. Replication of these findings in independent samples is warranted.