Abstract
ABSTRACT
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.