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1. Buffered or impaired: Maternal anemia, inflammation and breast milk macronutrients in northern Kenya

   https://doi.org/10.1002/ajpa.23752  

   Fujita, Masako ; Paredes Ruvalcaba, Nerli ; Wander, Katherine ; Corbitt, Mary ; Brindle, Eleanor ( December 2018 , American Journal of Physical Anthropology)

   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.

   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.

   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).

   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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2. Nutritional, inflammatory, and ecological correlates of maternal retinol allocation to breast milk in agro‐pastoral Ariaal communities of northern Kenya

   https://doi.org/10.1002/ajhb.22961  

   Fujita, Masako ; Lo, Yun‐Jia ; Brindle, Eleanor ( January 2017 , American Journal of Human Biology)

   Vitamin A (VA) is an essential micronutrient required for a range of biological functions throughout life. VA deficiency (VAD) claims an estimated 1 million preschool children's lives annually. Human milk is enriched with VA (retinol) from the maternal blood, which originates from the hepatic reserve and dietary intake. Secreting retinol into milk will benefit the nursing infant through breast milk, but retaining retinol is also important for the maternal health. Previous studies found that the public health intervention of high‐dose VA supplementation to lactating mothers did not significantly lower child mortality. The World Health Organization (WHO) recently acknowledged that our understanding about the principle of VA allocation within the maternal system and the secretion into milk is too incomplete to devise an effective intervention.

   We present a secondary analysis of data collected among lactating mothers in VAD endemic northern Kenya (n = 171), examining nutritional, inflammatory, and ecological factors that might associate with maternal retinol allocation. Regression models were applied using the outcome milk‐retinol allocation index: milk retinol/(milk retinol + serum retinol).

   Ten percent of the sample was identified as VAD. The average milk retinol concentration was 0.1 μmo/L, grossly below what is considered minimally necessary for an infant (1 μmol/L). VAD mothers and mothers with inflammation did not seem to compromise their milk retinol even though their serum retinol was lower than non‐VAD and noninflammation mothers. Breast milk fat concentration positively correlated with milk retinol but not with serum retinol.

   This exploratory study contributes toward an understanding of maternal retinol allocation.

    

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3. Variation in breast milk macronutrient contents by maternal anemia and hemoglobin concentration in northern Kenya

   https://doi.org/10.1002/ajhb.23238  

   Corbitt, Mary ; Paredes Ruvalcaba, Nerli ; Fujita, Masako ( March 2019 , American Journal of Human Biology)

   This study explored differing levels of macronutrients in breast milk in relation to maternal anemia and hemoglobin.

   Archived milk specimens and data from a cross‐sectional sample of 208 breastfeeding mothers in northern Kenya, originally collected in 2006, were analyzed; data included milk fat, maternal hemoglobin concentration, and anemia status (anemia defined as hemoglobin <12 g/dL). Total protein and lactose were measured and energy was calculated. To explore the association between milk outcomes (fat, protein, lactose, and energy) and anemia, regression models were constructed with and without adjustment for maternal age, parity, and time (days) postpartum. The same models were constructed using hemoglobin as a continuous predictor in lieu of dichotomous anemia to explore the role of hemoglobin levels and anemia severity in predicting milk outcomes.

   The group comparison indicated significantly higher milk protein and lower milk fat for anemic mothers relative to nonanemic counterparts. After adjustment for maternal age, parity, and time postpartum, maternal anemia was associated with significantly higher milk protein (P = 0.001) and significantly lower milk fat (P = 0.025). Hemoglobin had a significant inverse relationship with milk protein (P = 0.017) and a marginally significant positive relationship with milk fat (P = 0.060) after adjusting for the maternal variables. Neither anemia nor hemoglobin was significant in predicting lactose or milk energy.

   Maternal anemia and hemoglobin concentration may be associated with complex changes in milk macronutrients. Future research should clarify the impact of maternal anemia on a range of breast milk components while accounting for other maternal characteristics.

    

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4. Bioactive factors in milk across lactation: Maternal effects and influence on infant growth in rhesus macaques ( Macaca mulatta )

   https://doi.org/10.1002/ajp.22544  

   Bernstein, Robin M. ; Hinde, Katie ( March 2016 , American Journal of Primatology)

   Among mammals, numerous bioactive factors in milk vary across mothers and influence offspring outcomes. This emerging area of research has primarily investigated such dynamics within rodent biomedical models, domesticated dairy breeds, and among humans in clinical contexts. Less understood are signaling factors in the milk of non‐human primates. Here, we report on multiple bioactive components in rhesus macaque (Macaca mulatta) milk and their associations with maternal and infant characteristics. Milk samples were collected from 59 macaques at multiple time points across lactation in conjunction with maternal and infant morphometrics and life‐history animal records. Milk was assayed for adiponectin (APN), epidermal growth factor (EGF) and its receptor (EGF‐R), and transforming growth factor beta 2 (TGF‐β₂). Regression models were constructed to assess the contributions of maternal factors on variation in milk bioactives, and on the relationship of this variation to infant body mass and growth. Maternal body mass, parity, social rank, and infant sex were all predictive of concentrations of milk bioactives. Primiparous mothers produced milk with higher adiponectin, but lower EGF, than multiparous mothers. Heavier mothers produced milk with lower EGF and EGF‐R, but higher TGF‐β₂. Mothers of daughters produced milk with higher TGF‐β₂. Mid‐ranking mothers produced milk with higher mean EGF and adiponectin concentrations than low‐ranking mothers. Milk EGF and EGF‐R were positively associated with infant body mass and growth rate. Importantly, these signaling bioactives (APN, EGF, EGF‐R, and TGF‐β₂) were significantly correlated with nutritional values of milk. The effects of milk signals remained after controlling for the available energy in milk revealing the added physiological role of non‐nutritive milk bioactives in the developing infant. Integrating analyses of energetic and other bioactive components of milk yields an important perspective for interpreting the magnitude, sources, and consequences of inter‐individual variation in milk synthesis. Am. J. Primatol. 78:838–850, 2016. © 2016 Wiley Periodicals, Inc.

    

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

   https://doi.org/10.1002/ajhb.23943  

   Caffé, Beatrice ; Blackwell, Aaron ; Fehrenkamp, Bethaney D. ; Williams, Janet E. ; Pace, Ryan M. ; Lackey, Kimberly A. ; Ruiz, Lorena ; Rodríguez, Juan M. ; McGuire, Mark A. ; Foster, James A. ; et al ( June 2023 , American Journal of Human Biology)

   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.

   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.

   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.

   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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