Duration of human milk feeding, human milk oligosaccharides, and child development at five years of age: a cohort study of urban Chinese mother-child dyads

Abstract

Background: While human milk is known to support child development, the specific roles of its bioactive components, like human milk oligosaccharides (HMOs), are still being uncovered. Evidence for HMO benefits is mostly limited to the first two years of life, with their long-term impacts on developmental outcomes remaining largely unknown.

Objective: To investigate the associations of human milk feeding duration and HMO composition with child development at five years.

Methods: Seventeen HMOs were measured in 309 milk samples from 156 urban Chinese mothers during 0-5, 10-15, 40-45, 200-240, and 300-400 days postpartum. Human milk and formula feeding data were collected during infancy. Child development was assessed at approximately five years using the Griffiths Mental Development Scales for China. Multivariable general linear models with cluster-robust standard errors were applied, accounting for repeated HMO measurements.

Results: Longer duration of human milk feeding without formula (≥12 vs. <6 months) was associated with significantly higher Z-scores in personal-social and practical reasoning domains. The relative abundance of key HMOs, including 2'-fucosyllactose (2'-FL) and 3'-sialyllactose (3'-SL), remained relatively stable throughout lactation. Each SD increase in 2'-FL and 3'-SL relative abundance was associated with a 0.28-point (95% CI: 0.02, 0.54; P = 0.034) and 0.19-point (95% CI: 0.06, 0.33; P = 0.007) increase in locomotor Z-scores, respectively. These positive associations were modified by infant feeding practice, appearing significant only in the human milk and formula-fed group, not in their human milk-fed peers (P_difference <0.05).

Conclusions: Feeding human milk beyond 12 months was associated with improved developmental outcomes at five years. Notably, higher relative abundances of 2'-FL and 3'-SL were associated with modest improvements in locomotor skills only in infants receiving both human milk and formula. These findings suggest that HMOs, acting alongside other modifiable factors, may contribute to long-term child development.

Keywords: 2'-fucosyllactose; child development; cohort study; human milk feeding; human milk oligosaccharides.