Maternal health factors driving breastfeeding success: an evidence triangulation framework

Despite well-established benefits to mothers and children, breastfeeding rates fall short of WHO recommendations world-wide. Breastfeeding is a highly complex behaviour, affected by known system-level barriers and less well-established individual-level factors. We aimed to inform breastfeeding support by identifying maternal and perinatal determinants of breastfeeding outcomes and modifiable pathways linking education to breastfeeding. We used evidence triangulation design from complementary genetic and questionnaire-based analyses across four European cohorts including 72,653 mothers and 317,651 offspring. Five breastfeeding outcomes were assessed: initiation, establishment at 2 months, sustained breastfeeding at 6 months, and exclusive and overall breastfeeding duration. Cohort-specific breastfeeding GWAS were meta-analysed and used in two-sample Mendelian randomization (MR) analyses of 17 maternal and perinatal exposures. MR-based mediation assessed pathways linking educational attainment to breastfeeding, and robustness was evaluated using offspring-genotype adjustment, observational association and MR sensitivity analyses. Genetically predicted higher education, lower body-mass index (BMI), and lower liability to smoking, insomnia and depression were associated with more favorable breastfeeding outcomes. A 1SD (3.4-year) increase in education duration increased initiation odds (OR: 2.32, 95% CI: 1.94,2.77) and prolonged exclusive breastfeeding (beta=0.21SD, 95% CI: 0.17,0.24), whereas higher BMI reduced initiation (OR: 0.77, 95% CI: 0.66,0.90). Smoking, depression and BMI mediated 26%, 14% and 12% of education effect on exclusive breastfeeding, respectively. There was little evidence for effects of blood pressure, cholesterol or perinatal factors. Findings were consistent across sensitivity analyses. These findings highlight that breastfeeding support could be achieved through a more holistic approach to maternal physical and mental health before and during pregnancy, and that targeted strategies would reduce maternal and infant health inequalities.