The aim of this study is to understand how fetal growth influences neurocognitive function. We hypothesize that the outcome on IQ is mediated by birth weight in interaction with polymorphisms of certain SNPs of the BDNF gene.

Methods: In the large Asian cohort study of SCORM we have analysed six hundred fifty three children aged 7-9 years old, recruited from 3 schools in Singapore, who were followed yearly from 1999 onwards. Birth parameters were recorded by health personnel. Childhood IQ was measured with the Raven's Standard Progressive Matrices at ages 8 to 12. Buccal DNA was collected and single nucleotide polymorphisms for BDNF were obtained from the Illumina 550K beadchip.

Results: In SCORM we found that the BDNF gene show significant interactions between rs6265 (p=0.000) and rs11030104 (p=0.000) and birth weight (corrected for gestational age) on IQ. In children with TC (p=0.033) and TT (0.045) alleles of BNDF rs6265 and CC (0.054) and TC (0.029) alleles of the BNDF 11030104 a lower birth weight is associated with a lower IQ, while a higher birth weight is associated with a higher IQ.

These findings could implicate that improved fetal growth reduces the risk for lower IQ and improved developmental outcomes in children with certain alleles of BDNF genotypes. We would like to replicate these findings in the large Western cohort of ALSPAC.

Satistical Analysis:

Categorical data will be analyzed using the chi-square test. Differences between gender in age, birth weight and IQ are measured with t-tests. Genotype differences for continuous variables are evaluated using one-way analysis of variance. Birth weight will be corrected for gestational age. The interaction effects of SNP * Birth weight (corrected for gestational age) on IQ are examined with lineair regression. Posthoc analyses are performed if the relationship was found to be significant by subgroup analyses. All p values are two-tailed and considered statistically significant when the values were below 0.05. All statistical procedures used SPSS version 16.0 (SPSS Inc, Chicago, USA).