# Associations between lifetime history of depression, prenatal OXTR DNA methylation and breastfeeding outcomes

## TL;DR

This study explores how depression and DNA methylation in the OXTR gene during pregnancy may affect breastfeeding outcomes.

## Contribution

It is the first to investigate prenatal OXTR DNA methylation as a potential link between maternal depression and breastfeeding challenges.

## Key findings

- Maternal lifetime history of depression was not associated with OXTR DNA methylation.
- Higher methylation at CpG cg26455676 was linked to better breastfeeding maintenance for 6 months.
- Prenatal OXTR DNA methylation showed some evidence of association with breastfeeding outcomes.

## Abstract

Women with depression are less likely to breastfeed and experience more breastfeeding challenges. Potential biological mechanisms that link maternal depression with poor breastfeeding outcomes have not been investigated. This study examined associations between lifetime history of depression (LHD), prenatal oxytocin receptor gene (OXTR) DNA methylation, and breastfeeding outcomes.

Longitudinal observational data from the Norwegian Mother, Father and Child Cohort Study (MoBa) were analysed (N = 3607). LHD was self-reported during pregnancy (week 15). Blood samples were collected at 16–18 weeks of pregnancy, and DNA methylation was measured using the Illumina Methylation EPIC BeadChip 850 K array. This array includes 22 CpG sites on the OXTR gene, which were used in analyses. Mothers self-reported breastfeeding initiation (breastmilk given to child in first month), breastfeeding maintenance (breastmilk given to child for 6 months or more) and breastfeeding problems. Maternal LHD was not associated with OXTR DNA methylation. There was some evidence that prenatal OXTR DNA methylation was associated with breastfeeding outcomes. There was an association between CpG cg26455676 and breastfeeding maintenance to 6 months (odds ratio = 1.59, 95% confidence intervals = 1.11–2.27, raw p = 0.01, adjusted p = 0.04). Higher levels of DNA methylation at CpG cg26455676 was associated with a greater likelihood of maintaining breastfeeding to 6 months.

This highly novel study highlights the intriguing possibility that maternal prenatal DNA methylation at genes important for breastfeeding may be associated with breastfeeding experiences. Further understanding of vastly differing breastfeeding experiences would assist with the targeting efforts to support breastfeeding women, particularly those who are vulnerable, such as mothers who have depression.

The online version contains supplementary material available at 10.1186/s13148-025-02030-8.