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Title: Bioactive factors in milk across lactation: Maternal effects and influence on infant growth in rhesus macaques ( Macaca mulatta )
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NSF-PAR ID:
10236357
Author(s) / Creator(s):
 ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
American Journal of Primatology
Volume:
78
Issue:
8
ISSN:
0275-2565
Format(s):
Medium: X Size: p. 838-850
Size(s):
p. 838-850
Sponsoring Org:
National Science Foundation
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  1. Abstract Objectives

    Lactational programming, through which milk‐borne bioactives influence both neonatal and long‐term biological development, is well established. However, almost no research has investigated how developmental stimuli during a mother's early life may influence her milk bioactives in adulthood. Here, we investigated the association between maternal birth weight and milk epidermal growth factor (EGF) and epidermal growth factor receptor (EGF‐R) in later life. We predicted there would be a decrease in both milk EGF and EGF‐R in the milk produced by mothers who were themselves born low birth weight.

    Methods

    Study participants are from the Cebu Longitudinal Health and Nutrition Survey. Mothers (n= 69) were followed longitudinally since birth with prospective data collection. Anthropometrics, health, and dietary recalls were collected with early morning milk samples when mothers were 24 to 25 years of age. Milk samples were analyzed for EGF and its receptor (EGF‐R). Analysis of variance was used to test for differences in milk EGF and EGF‐R between low and average birthweight mothers after adjustment for parity, age, and maternal dietary energy intake.

    Results

    Mothers who were low birth weight produced milk with significantly less EGF and more EGF‐R which resulted in a lower ratio of EGF to EGF‐R. These associations persisted after adjustment for infant age, maternal adiposity, and dietary energy.

    Conclusions

    While this is a small sample size, these preliminary findings suggest that maternal early life characteristics, such as birth weight, may be important contributors to variation in milk bioactives. Future work is necessary to understand how variation in maternal early life may influence milk composition in adulthood.

     
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  2. 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.

     
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  3. Abstract Background

    Maternal anemia has adverse consequences for the mother‐infant dyad. To evaluate whether and how milk nutrient content may change in ways that could “buffer” infants against the conditions underlying maternal anemia, this study assessed associations between milk macronutrients and maternal iron‐deficiency anemia (IDA), non‐iron‐deficiency anemia (NIDA), and inflammation.

    Methods

    A secondary analysis of cross‐sectional data and milk from northern Kenya was conducted (n = 204). The combination of hemoglobin and transferrin receptor defined IDA/NIDA. Elevated serum C‐reactive protein defined acute inflammation. The effects of IDA, NIDA, and inflammation on milk macronutrients were evaluated in regression models.

    Results

    IDA (β = 0.077,p =.022) and NIDA (β = 0.083,p =.100) predicted higher total protein (ln). IDA (β = −0.293,p =.002), NIDA (β = −0.313,p =.047), and inflammation (β = −0.269,p =.007) each predicted lower fat (ln); however, anemia accompanying inflammation predictedhigherfat (β = 0.655,p =.007 for IDA and β = 0.468,p =.092 for NIDA). NIDA predicted higher lactose (β = 1.020,p =.003).

    Conclusions

    Milk macronutrient content both increases and decreases in the presence of maternal anemia and inflammation, suggesting a more complicated and dynamic change than simple impairment of nutrient delivery during maternal stress. Maternal fat delivery to milk may be impaired under anemia. Mothers may buffer infant nutrition against adverse conditions or poor maternal health by elevating milk protein (mothers with IDA/NIDA), lactose (mothers with NIDA), or fat (mothers with anemiaandinflammation). This study demonstrates the foundational importance of maternal micronutrient health and inflammation or infection for advancing the ecological understanding of human milk nutrient variation.

     
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  4. Abstract Objectives

    Folate is an essential nutrient fundamental to human growth and development. Human milk maintains high folate content across the maternal folate status range, suggesting buffering of milk folate with prioritized delivery to milk at the expense of maternal depletion. We investigated whether and how the extent of this buffering may diminish under prolonged nutritional and/or disease stress, while taking into consideration infants' varying vulnerability to malnutrition‐related morbidity/mortality.

    Methods

    A cross‐sectional study analyzed milk specimens from northern Kenyan mothers (n = 203), surveyed during a historic drought and ensuing food shortage. Multiple regression models for folate receptor‐α (FOLR1) in milk were constructed. Predictors included maternal underweight (BMI < 18.5), iron‐deficiency anemia (hemoglobin <12 g/dl and dried‐blood‐spot transferrin receptor >5 mg/L), folate deficiency (hyperhomocysteinemia, homocysteine >12 or 14 μmol/L), inflammation (serum C‐reactive protein >5 mg/L), infant age and sex, and mother‐infant interactions.

    Results

    In adjusted models, milk FOLR1 was unassociated with maternal underweight, iron‐deficiency anemia and inflammation. FOLR1 was positively associated with maternal folate deficiency, and inversely associated with infant age. There was interaction between infant age and maternal underweight, and between infant sex and maternal folate deficiency, predicting complex changes in FOLR1.

    Conclusions

    Our results suggest that mothers buffer milk folate against their own nutritional stress even during a prolonged drought; however, the extent of this buffering may vary with infant age, and, among folate‐deficient mothers, with infant sex. Future research is needed to better understand this variability in maternal buffering of milk folate and how it relates to folate status in nursing infants.

     
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  5. Synopsis

    Among mammals, primipara who initiate reproduction before full maturity can be constrained in their maternal investment, both due to fewer somatic resources and tradeoffs between their own continued development and reproductive effort. Primipara are particularly limited in their capacity to synthesize milk during lactation, the costliest aspect of reproduction for most mammals, especially primates due to long periods of postnatal development. Due to reduced milk transfer, Firstborns may be at elevated risk for long-term consequences of deficits in early life endowment from their primiparous mothers. Here we investigated mass, growth, stature, and lactation performance among N = 273 adult daughters across N = 335 reproductions, who were their own mother’s Firstborn or Laterborn progeny, among rhesus macaques (Macaca mulatta) at the California National Primate Research Center. We further explored mass during infancy of the offspring of Firstborn and Laterborn mothers. Firstborns had accelerated growth during infancy, but had slowed growth during juvenility, compared to Laterborns. Although both Firstborns and Laterborns were the same age at reproductive debut, Firstborns had lower body mass, an effect that persisted throughout the reproductive career. Available milk energy, the product of milk energetic density and milk yield, was on average 16% lower for Firstborns compared to Laterborns, a difference that was only partially mediated by their lower mass. Despite differences in their mothers’ energy provision through milk, the mass of infants of Firstborn and Laterborn mothers did not differ at peak lactation, suggesting that infants of Firstborns devote a higher proportion of milk energy to growth than infants of Laterborns. To date few studies have explored how early life conditions shape capacities to synthesize milk and milk composition. Our findings contribute new information among primates on how early life maternal endowments are associated with persistent effects long after the period of maternal dependence well into reproductive maturity.

     
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