Human milk immune factors, maternal nutritional status, and infant sex: The INSPIRE study

Abstract

Objectives: Breastfeeding is an energetically costly and intense form of human parental investment, providing sole-source nutrition in early infancy and bioactive components, including immune factors. Given the energetic cost of lactation, milk factors may be subject to tradeoffs, and variation in concentrations have been explored utilizing the Trivers-Willard hypothesis. As human milk immune factors are critical to developing immune system and protect infants against pathogens, we tested whether concentrations of milk immune factors (IgA, IgM, IgG, EGF, TGFβ2, and IL-10) vary in response to infant sex and maternal condition (proxied by maternal diet diversity [DD] and body mass index [BMI]) as posited in the Trivers-Willard hypothesis and consider the application of the hypothesis to milk composition.

Methods: We analyzed concentrations of immune factors in 358 milk samples collected from women residing in 10 international sites using linear mixed-effects models to test for an interaction between maternal condition, including population as a random effect and infant age and maternal age as fixed effects.

Results: IgG concentrations were significantly lower in milk produced by women consuming diets with low diversity with male infants than those with female infants. No other significant associations were identified.

Conclusions: IgG concentrations were related to infant sex and maternal diet diversity, providing minimal support for the hypothesis. Given the lack of associations across other select immune factors, results suggest that the Trivers-Willard hypothesis may not be broadly applied to human milk immune factors as a measure of maternal investment, which are likely buffered against perturbations in maternal condition.

Figure 1

Lines show predictions of linear mixed-effects models examining variation in human milk immune factor concentrations with maternal body mass index (BMI) as a continuous predictor. Shaded areas are 95% confidence intervals for the effect. A. IgA (β = 0.010, P = 0.631) B. IgG (β = 0.010, P = 0.471) C IgM (β = 0.025, P = 0.229) D. EGF (β = 0.011, P = 0.268) E.TGFβ2(β = 0.04, P = 0.268) F. IL-10 (β = 0.020, P = 0.588) All factors follow the same overall trend of higher concentrations in milk of mothers with male infants and higher BMI scores except for IL-10, however no relationships are significant.

Figure 2

^a Diet Diversity Score = Score depicting the relative diversity of food categories consumed by participants. Lines show predictions of linear mixed-effects models examining interaction between infant sex, immune factors and maternal diet diversity score (DDS). Shaded areas are 95% confidence intervals for the effect. A. IgA (β = 0.009, P = 0.902) B.IgG (β = 0.009, P =0.037) C. IgM (β = 0.137, P =0.051) D.EGF (β = 0.007, P =0.845) E. TGFβ2 (β = 0.107, P = 0.243) F. IL-10 (β = −0.249 P =0.052) All factors follow the same overall trend of higher concentrations in milk of mothers with male infants and high diet diversity except for IL-10, however only IgG is significant.