Maternal Variants in the MFGE8 Gene are Associated with Perceived Breast Milk Supply

Background: The World Health Organization recommends exclusive breastfeeding for ≥6 months, but many mothers are unable to meet this goal. A major reason why mothers undergo early, unplanned breastfeeding cessation is perceived inadequate of milk supply (PIMS). We hypothesized that defining genetic polymorphisms associated with PIMS could aid early identification of at-risk mothers, providing an opportunity for targeted lactation support. Materials and Methods: This prospective observational cohort study followed 221 breastfeeding mothers for 12 months, collecting medical, demographic, and breastfeeding characteristics. Eighteen mammary secretory genes were assessed for single-nucleotide polymorphisms in 88 women (45 with PIMS and 43 with perceived adequate milk supply [PAMS]), matched by age/race/parity. Hierarchical regressions were used to assess the ability of genotype to aid PIMS prediction. Results: Mothers with PIMS exclusively breastfed for a shorter period (7 ± 12 weeks; p = 0.001) and reported lower milk production (17.6 ± 13.3 oz/day; p = 0.001), and their infants displayed reduced weight-for-length Z-score gains (0.74 ± 1.4; p = 0.038) relative to mothers with PAMS (22 ± 19 weeks; 27.03 ± 12.2 oz/day; 1.4 ± 1.5). Maternal genotype for the rs2271714 variant within milk fat globule EGF and factor V/VIII domain containing gene (MFGE8) was associated with PIMS status (p = 0.009, adjusted p = 0.09, likelihood ratio = 9.33) and duration of exclusive breastfeeding (p = 0.009, adjusted p = 0.09, χ² = 9.39). Addition of MFGE8 genotype to a model employing maternal characteristics (age, parity, previous breast-feeding duration, body mass index, education, and depression status) significantly increased predictive accuracy for PIMS status (p = 0.001; χ² = 13.5; area under the curve = 0.813 versus 0.725). Conclusions: Genotyping one lactogenic gene aided identification of mothers at risk for PIMS. If validated in a larger cohort, such an approach could be used to identify mothers who may benefit from increased lactation support.