Trial reportThe American journal of clinical nutrition2022
Intake of mother's milk by very-low-birth-weight infants and variation in DNA methylation of genes involved in neurodevelopment at 5.5 years of age.
Trial report in The American journal of clinical nutrition, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02759809 (Optimizing Mothers' Milk for Preterm Infants), which is not on this map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Optimizing Mothers' Milk for Preterm Infants (OptiMoM) Program of Research: Study 1-Impact of Donor Milk at Kindergarten
Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Breastfeeding in Infancy and Adult Health: A Narrative Review.Children (Basel, Switzerland) · 2026Review
- Blood and adipose tissue DNA methylation in adults born preterm with a very low birth weight - a sibling comparison study.Epigenomics · 2026Article
- Impact of Enteral Nutrition on Clinical Outcomes in Very Low Birth Weight Infants in the NICU: A Single-Center Retrospective Cohort Study.Nutrients · 2025Article
- Genome-Wide Association Analysis Revealed Candidate Genes Related to Early Growth Traits in Inner Mongolia Cashmere Goats.Veterinary sciences · 2025Article
- Where does the time go? Temporal patterns of pumping behaviors in mothers of very preterm infants vary by sociodemographic and clinical factors.Frontiers in nutrition · 2024Article
- Human Milk Feeding and Direct Breastfeeding Improve Outcomes for Infants With Single Ventricle Congenital Heart Disease: Propensity Score-Matched Analysis of the NPC-QIC Registry.Journal of the American Heart Association · 2023Article
- Review
- Human milk feeding and direct breastfeeding improve outcomes for infants with single ventricle congenital heart disease: Propensity score matched analysis of the NPC-QIC registry.medRxiv : the preprint server for health sciences · 2023Article
- Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMechanisms responsible for associations between intake of mother's milk in very-low-birth-weight (VLBW, <1500 g) infants and later neurodevelopment are poorly understood. It is proposed that early nutrition may affect neurodevelopmental pathways by altering gene expression through epigenetic modification. Variation in DNA methylation (DNAm) at cytosine-guanine dinucleotides (CpGs) is a commonly studied epigenetic modification.
objectivesWe aimed to assess whether early mother's milk intake by VLBW infants is associated with variations in DNAm at 5.5 y, and whether these variations correlate with neurodevelopmental phenotypes.
methodsThis cohort study was a 5.5-y follow-up (2016-2018) of VLBW infants born in Ontario, Canada who participated in the Donor Milk for Improved Neurodevelopmental Outcomes trial. We performed an epigenome-wide association study (EWAS) to test whether percentage mother's milk (not including supplemental donor milk) during hospitalization was associated with DNAm in buccal cells during early childhood (n = 143; mean ± SD age: 5.7 ± 0.2 y; birth weight: 1008 ± 517 g). DNAm was assessed with the Illumina Infinium MethylationEPIC array at 814,583 CpGs. In secondary analyses, we tested associations between top-ranked CpGs and measures of early childhood neurodevelopment, e.g., total surface area of the cerebral cortex (n = 41, MRI) and Full-Scale IQ (n = 133, Wechsler Preschool and Primary Scale of Intelligence-IV).
resultsEWAS analysis demonstrated percentage mother's milk intake by VLBW infants during hospitalization was associated with DNAm at 2 CpGs, cg03744440 [myosin XVB (MYO15B)] and cg00851389 [metallothionein 1A (MT1A)], at 5.5 y (P < 9E-08). Gene set enrichment analysis indicated that top-ranked CpGs (P < 0.001) were annotated to genes enriched in neurodevelopmental biological processes. Corroborating these findings, DNAm at several top identified CpGs from the EWAS was associated with cortical surface area and IQ at 5.5 y (P < 0.05).
conclusionsIn-hospital percentage mother's milk intake by VLBW infants was associated with variations in DNAm of neurodevelopmental genes at 5.5 y; some of these DNAm variations are associated with brain structure and IQ.This trial was registered at isrctn.com as ISRCTN35317141 and at clinicaltrials.gov as NCT02759809.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.