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1. 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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2. Characterizing the extent human milk folate is buffered against maternal malnutrition and infection in drought‐stricken northern Kenya

   https://doi.org/10.1002/ajpa.24603  

   Fujita, Masako ; Wander, Katherine ; Tran, Tin ; Brindle, Eleanor ( August 2022 , American Journal of Biological Anthropology)

   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.

   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.

   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.

   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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3. Steroid hormone concentrations in milk predict sex‐specific offspring growth in a nonhuman primate

   https://doi.org/10.1002/ajhb.23315  

   Petrullo, Lauren ; Hinde, Katie ; Lu, Amy ( August 2019 , American Journal of Human Biology)

   In humans and other mammals, maternal hormones are transferred to offspring during lactation via milk and may regulate postnatal development, including the pace of early growth. Here, we used a nonhuman primate model to test the hypotheses that milk cortisol and dehydroepiandrosterone‐sulfate (DHEAS) concentrations reflect maternal characteristics, and that changes in these hormones across lactation are associated with early postnatal growth rates.

   Demographic information, morphometrics, and milk samples were collected from rhesus macaque mothers and their infants at the California National Primate Research Center in Davis, California. Using linear models, we examined the relationship between maternal traits and milk hormone concentrations (N = 104 females) and explored the effect of milk hormones on the rate of offspring growth (N = 72 mother‐infant dyads), controlling for available milk energy.

   Contrary to previous studies, we found that milk cortisol concentrations were categorically higher in multiparous females than in primiparous females. However, milk DHEAS concentrations decreased with maternal parity. Neither milk cortisol nor DHEAS were related to maternal rank. Finally, changes in milk hormones predicted offspring growth in a sex‐specific and temporal manner: increases in cortisol from peak to late lactation predicted faster female growth, and increases in DHEAS concentrations from early to peak and peak to late lactation predicted faster male growth.

   Our findings shed light on how hormonal components of milk have sex‐specific effects on offspring growth during early postnatal life with varying temporal windows of sensitivity.

    

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4. 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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5. Infant respiratory sinus arrhythmia and maternal depressive symptoms predict toddler sleep problems

   https://doi.org/10.1002/dev.21480  

   Gueron‐Sela, Noa ; Propper, Cathi B. ; Wagner, Nicholas J. ; Camerota, Marie ; Tully, Kristin P. ; Moore, Ginger A. ( October 2016 , Developmental Psychobiology)

   This study examined the direct and interactive effects of infants’ respiratory sinus arrhythmia (RSA) and maternal depressive symptoms (MDS) during the first 6 months of life in the prediction of children's sleep problems at age 18 months. Participants included 156 children and their mothers who were followed from 3 to 18 months of age. At ages 3 and 6 months, infants’ cardiac activity was recorded at rest and during the still‐face paradigm, a mother–child social challenge task, and estimates of infant baseline RSA (RSAB) and RSA withdrawal (RSAW) were calculated. Mothers reported about their depressive symptoms at 3, 6, and 18 months, and about infants’ sleep problems at age 18 months. Less RSAW and higher levels of MDS predicted more sleep problems at age 18 months. Additionally, RSAB moderated the link between MDS and children's sleep problems such that MDS were related to more sleep problems only for infants with high levels of RSAB. Results illustrate the importance of RSA as both a direct predictor and a moderator of maternal influences in the prediction of early sleep problems.

    

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