Maternal BMI associations with cord blood DNA methylation and mid-childhood adiposity.
Level 3 - non-randomized controlled study
Prospective observational birth cohort follow-up study
PubMed 42070037 · doi:10.1186/s13148-026-02119-8
What was done
Investigators conducted an epigenome-wide association study (EWAS) and mediation analysis using cord blood DNA methylation (Infinium MethylationEPIC 850K BeadChip) from the prospective, multicenter Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and its follow-up study (HAPO FUS). Linear regression models adjusted for population substructure, cell counts, and maternal and child covariates with Bonferroni correction. Mediation analysis assessed whether maternal BMI-associated CpG sites explained the relationship between maternal BMI and offspring BMI z-score at a mean follow-up age of 11.5 years (offspring aged 10–14 years).
What was found
In 3,116 mother-child pairs (48% White, 21% Asian, 19% Black, 12% Hispanic; 36% of mothers and 28.3% of children overweight or obese), maternal BMI was significantly associated with DNA methylation at 7 CpG sites: cg00579423, cg07138793, cg12188424, cg19345626, cg20020844, cg02988288, and cg26974062 (including two sites on the TXNIP gene). Cord blood DNA methylation at cg20020844 (SP6) mediated 1.2% of the association between maternal BMI and child BMI z-score.
Why it matters
This study provides multi-ethnic evidence that maternal BMI is linked to altered cord blood DNA methylation at birth. However, the finding that the top site mediated only 1.2% of the child BMI association demonstrates that single-site cord blood methylation explains very little of the transgenerational adiposity relationship.
Limits
The observational design cannot establish causal fetal programming. The proportion of the association mediated was extremely small (1.2%), leaving most of the maternal-child BMI relationship unexplained by these epigenetic marks. The abstract omits effect sizes, beta coefficients, and confidence intervals for the 7 CpG sites, and measurements in cord blood leukocytes may not mirror methylation patterns in target metabolic tissues.
Cited by
- context Children born to obese mothers are epigenetically predisposed toward developing obesity and type 2 diabetes.