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Topical Area: Maternal, Perinatal and Pediatric Nutrition

Maternal, Perinatal and Pediatric Nutrition (I) (Poster Session)

(P07-011-23) Amnion DNA Methylation Is Strongly Associated With Birth Anthropometry in Guatemalan Mother-Infant Dyads: The Women First Preconception Maternal Nutrition Trial

Saturday, July 22, 2023
12:00 PM – 1:00 PM ET
Location: Poster Board 128
Disclosure(s):
Sarah J. Borengasser, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Stephanie P. Gilley, MD, PhD: Bobbie, Inc: Grant/Research Support (Ongoing)
Stephanie W. Waldrop, MD, MPH: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: DNA methylation (DNAme) at birth is a major factor associated with fetal growth and development. We tested if DNAme from amnion tissue, the innermost placental layer and represents fetal tissue, was associated with gestational-age adjusted z-scores for birth length (LGAZ), weight (WGAZ), weight-for-length (WLGAZ), and head circumference (HCGAZ) in a subset of Guatemalan mother-infant dyads for whom 80% of mothers are stunted and 49% are overweight from the Women First Preconception Maternal Nutrition Trial (WF).

Methods: Women were randomized to either: Arm 1) women consumed a daily small quantity lipid-based nutrition supplement (sqLNS) > 3 months prior to conception until delivery; Arm 2) women consumed the same sqLNS starting at 12 weeks gestation until delivery; or Arm 3) no sqLNS. Here, dyads were equally represented across study arms. Bisulfite-converted DNAme libraries were constructed using Roche SeqCap Epi CpGiant probes and sequenced via 2 x 150 paired end reads. We assessed the relationship between differentially methylated positions (DMPs) and regions (DMRs) with birth anthropometry (N = 83). All statistical models accounted for multiple testing using false discovery rate (FDR) for DMPs and Sidák correction for DMRs and adjusted for study arm, pre-pregnancy BMI, maternal age, maternal smoke exposure, infant sex, infant genetics, and cellular heterogeneity. Gene set enrichment analyses were performed via Enrichr for DMRs that annotated to genes.

Results: In this subset, mean z-scores were: LGAZ = -0.59, WGAZ = -0.75, WLGAZ = -1.0, and HCGAZ = -0.13, indicating mild fetal growth restriction. We identified 3 DMPs and 647 DMRs associated with LGAZ; 1 DMP and 565 DMRs with WGAZ; 270 DMRs with WLGAZ; and 142 DMRs with HCGAZ (FDR or Sidák < 0.05). DMRs annotated to genes enriched in biologically relevant pathways and processes that included bone morphogenesis, embryonic limb development, and skeletal system morphogenesis (p < 0.05). Metabolic-related pathways were also enriched and included thermogenesis, lipid metabolism, and insulin resistance (p < 0.05).

Conclusions: Our findings indicate that amnion DNAme at birth was strongly associated with all measures of birth anthropometry and annotated to biologically relevant genes involved in growth, development, and metabolism.

Funding Sources: Bill & Melinda Gates Foundation and NIH NICHD/ODS and NIDDK