The effects of a lipid-based nutrient supplement intervention on DNA methylation in Bangladesh : insights from the Rang-Din Nutrition Study
Year: 2026
Type: dissertation
Abstract: Chronic undernutrition remains a major global health concern, particularly in early life. During this time, the resulting growth restriction and faltering are most responsive to nutrition interventions and consequential for health across the life course. Small-quantity lipid-based nutrient supplements (SQ-LNS) provide undernourished pregnant mothers and infants with micro- and macronutrients, with demonstrated benefits for growth and development in infants. These positive effects may be biologically embedded through DNA methylation (DNAm), an epigenetic marker with potential to regulate gene transcription depending on genomic context and to shape health in later life. Multiple nutrients are known to influence DNAm, yet the molecular effects of SQ-LNS intervention on genome-wide DNAm remain unclear. Given that both chronic undernutrition and DNAm patterns differ by sex, child sex may modify the potential effect of early-life nutrition on DNAm. This thesis leveraged a DNAm-profiled subset of the Rang-Din Nutrition Study (n = 194, females = 97, males = 97, age = 40–52 months), a cluster-randomized controlled effectiveness trial in rural Bangladesh, to assess whether the DNAm profiles from dried blood spots at age 4 may reflect unique early-life SQ-LNS exposures. The DNA methylome was compared with linear mixed-effects models between children who received both maternal and child SQ-LNS (Comprehensive LNS), child only SQ-LNS (Child LNS), and no SQ-LNS. At the aggregate level, small but significant genome-wide DNAm differences were observed across the different intervention groups, driven by the Child LNS and Comprehensive LNS group comparison, though no regions or individual CpGs survived multiple-test correction in epigenome-wide association analyses. The intervention-associated mean DNAm changes in sex-associated genomic regions were significantly moderated by child sex, with changes in DNAm consistent between sexes only in the Child LNS and Comprehensive LNS comparison. These findings suggest that early-life nutrition interventions can leave a detectable shift in the DNA methylome of children at age 4, with effects that differ by the timing of the intervention, mismatch of pre- and postnatal nutritional exposures, and child sex. This thesis contributes to the molecular characterization of an SQ-LNS intervention, which may help improve strategies to prevent early-life undernutrition.
DOI: 10.14288/1.0456612
Author: Waldman, Hannah
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7222438873
Cites:
Cited by:
Related to: