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Maternal fat intake during pregnancy affects fetal growth, but mechanisms underlying this relationship are unclear. We performed an exploratory study of the associations of fat consumption during pregnancy with cord blood DNA methylation of the insulin‐like growth factor 2 ( IGF2 ) and  H19  genes. We used data from 96 uncomplicated full‐term pregnancies of mothers of whom majority had normal body mass index (BMI) (66%) in Project Viva, a prospective pre‐birth cohort. We assessed maternal diet with validated food frequency questionnaires during the first and second trimesters and measured DNA methylation in segments of the  IGF2 ‐ and  H19 ‐differentially methylated regions (DMRs) by pyrosequencing DNA extracted from umbilical cord blood samples. Mean (SD) age was 32.8 (4.1) years and prepregnancy BMI was 24.0 (4.4) kg/m 2 . Mean DNA methylation was 56.3% (3.9%) for  IGF2 ‐DMR and 44.6% (1.9%) for  H19 ‐DMR. Greater first trimester intake of omega‐6 polyunsaturated fat (effect per 1% of calories at the expense of carbohydrates) was associated with lower DNA methylation of  IGF2 ‐DMR (−1.2%; 95% confidence interval [CI]: −2.2%, −0.2%) and higher DNA methylation at  H19 ‐DMR (0.8%; 95% CI: 0.3%, 1.3%). On the other hand, greater first trimester intake of omega‐3 polyunsaturated fat was associated with lower DNA methylation of the  H19 ‐DMR (−4.3%; 95% CI: −7.9%, −0.8%). We did not find significant associations of  IGF2  and  H19  methylation with IGF2 cord blood levels. Our findings suggest that early prenatal fat intake (omega‐3, omega‐6, and saturated fatty acids) may influence DNA methylation at the  IGF2  and  H19  locus, which could impact fetal development and long‐term health.

Dietary fat intake during early pregnancy is associated with cord blood DNA methylation at IGF2 and H19 genes in newborns