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

Importance: Women with a history of 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. Objective: Examine associations between maternal lifetime history of depression and maternal DNA methylation at the oxytocin receptor gene (OXTR), and associations between maternal OXTR DNA methylation and breastfeeding outcomes. Design: Longitudinal observational data from the Norwegian Mother, Father and Child Cohort Study (MoBa) were analysed. Setting: MoBa is a population-based nationwide pregnancy cohort study conducted by the Norwegian Institute of Public Health.Participants: N=3,607 participants selected from three subsets of the MoBa cohort for whom DNA methylation data was available. Exposures: Lifetime history of major depression was self-reported during pregnancy (week 15) using 6 items that closely correspond to the DSM-III criteria for lifetime major depression. Main outcomes and measures: Blood samples were collected at week 16-18 of pregnancy, and DNA methylation was measured using the Illumina Methylation EPIC BeadChip 850K 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 post-birth), breastfeeding maintenance (breastmilk given to child for 6 months or more) and breastfeeding problems.Results: Maternal lifetime history of depression was not associated with DNA methylation at the OXTR gene. There was some evidence that maternal DNA methylation at the OXTR gene was associated with breastfeeding outcomes. The strongest evidence was for an association between the CpG site cg26455676 and the maintenance of breastfeeding to 6 months after birth (odds ratio=1.59, 95% confidence intervals=1.11-2.27, raw p=0.01, adjusted p=0.04). Higher levels of maternal DNA methylation at CpG cg26455676 was associated with a greater likelihood of maintaining breastfeeding to 6 months after birth. Conclusions and relevance: This highly novel study highlights the intriguing possibility that maternal DNA methylation at genes important for breastfeeding may be associated with breastfeeding experiences. Further understanding of why women have vastly differing breastfeeding experiences would assist with the targeting of efforts to support breastfeeding women, particularly those who are vulnerable, such as mothers who have depression.