Placental DNA Methylation of HSD11B2 and IGF2 Is Associated With Fetal Growth in the Cebu Longitudinal Health and Nutrition Survey

OBJECTIVES: The intrauterine environment exerts lasting impacts on fetal growth and development, with potential long-term effects on later health. We examined whether placental DNA methylation at HSD11B2 and IGF2-two key regulators of the intrauterine environment-is associated with fetal growth among participants in the Cebu Longitudinal Health and Nutrition Survey (CLHNS). METHODS: We analyzed DNA methylation in placental samples from 19 births in the CLHNS using the Illumina Infinium HumanMethylation450 BeadChip. Focusing on CpG sites within HSD11B2 and the IGF2/H19 imprinting control region (ICR), we used linear regression models adjusted for gestational age to assess associations of DNA methylation with birth weight, head circumference, length, and neonatal adiposity. RESULTS: Higher methylation at three CpG sites within HSD11B2 was significantly associated with reduced fetal growth: one site was associated with reduced birth weight and head circumference, and two sites were associated with shorter birth length. Within the IGF2/H19 ICR, two CpG sites were significantly associated with both increased birth weight and head circumference. Both CpGs overlapped with predicted CCCTC-binding factor (CTCF) binding sites, consistent with known regulatory mechanisms linking increased methylation at the ICR to increased IGF2 expression. CONCLUSIONS: These findings support the hypothesis that DNA methylation at regulatory regions of HSD11B2 and IGF2 contributes to variation in fetal growth, linking placental epigenetic patterns to birth outcomes.