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1. 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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2. 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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3. Immunological Effects of Adding Bovine Lactoferrin and Reducing Iron in Infant Formula: A Randomized Controlled Trial

   https://doi.org/10.1097/MPG.0000000000003367  

   Björmsjö, Maria ; Hernell, Olle ; Lönnerdal, Bo ; Berglund, Staffan K. ( December 2021 , Journal of Pediatric Gastroenterology and Nutrition)

   Compared to formula‐fed infants, breastfed infants have a lower risk of infections. Two possible reasons for this are the presence of the anti‐infective and anti‐inflammatory protein lactoferrin and the lower level of iron in breast milk. We explored how adding bovine lactoferrin and reducing the iron concentration in infant formula affect immunology and risk of infections in healthy infants.

   In a double‐blind controlled trial, term formula‐fed (FF) Swedish infants (n = 180) were randomized to receive, from 6 weeks to 6 months of age, a low‐iron formula (2 mg/L) with added bovine lactoferrin (1.0 g/L) (Lf+; n = 72); low‐iron formula with no added lactoferrin (Lf−; n = 72); and standard formula at 8 mg/L iron and no added lactoferrin (control formula [CF]; n = 36). Cytokines, infections, and infection related treatments were assessed until 12 months of age.

   No adverse effects were observed. There were no apparent effects on transforming growth factor beta (TGF‐β)1, TGF‐β2, tumor necrosis factor alfa (TNF‐α) or interleukin2 (IL‐2) at 4, 6, or 12 months, except of higher TGF‐β2 at 6 months in the CF group in comparison to the low iron groups combined (P= 0.033). No significant differences in otitis, respiratory infections, gastroenteritis, or other monitored infections and treatments were detected for any of the study feeding groups during the first 6 months and only a few and diverging effects were observed between 6 and 12 months.

   Adding bovine lactoferrin and reducing iron from 8 to 2 mg/L in infant formula was safe. No clinically relevant effects on cytokines or infection related morbidity were observed in this well‐nourished and healthy population.

    

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4. Epigenetic tuning of brain signal entropy in emergent human social behavior

   https://doi.org/10.1186/s12916-020-01683-x  

   Puglia, Meghan H. ; Krol, Kathleen M. ; Missana, Manuela ; Williams, Cabell L. ; Lillard, Travis S. ; Morris, James P. ; Connelly, Jessica J. ; Grossmann, Tobias ( December 2020 , BMC Medicine)

   null (Ed.)

   Abstract Background How the brain develops accurate models of the external world and generates appropriate behavioral responses is a vital question of widespread multidisciplinary interest. It is increasingly understood that brain signal variability—posited to enhance perception, facilitate flexible cognitive representations, and improve behavioral outcomes—plays an important role in neural and cognitive development. The ability to perceive, interpret, and respond to complex and dynamic social information is particularly critical for the development of adaptive learning and behavior. Social perception relies on oxytocin-regulated neural networks that emerge early in development. Methods We tested the hypothesis that individual differences in the endogenous oxytocinergic system early in life may influence social behavioral outcomes by regulating variability in brain signaling during social perception. In study 1, 55 infants provided a saliva sample at 5 months of age for analysis of individual differences in the oxytocinergic system and underwent electroencephalography (EEG) while listening to human vocalizations at 8 months of age for the assessment of brain signal variability. Infant behavior was assessed via parental report. In study 2, 60 infants provided a saliva sample and underwent EEG while viewing faces and objects and listening to human speech and water sounds at 4 months of age. Infant behavior was assessed via parental report and eye tracking. Results We show in two independent infant samples that increased brain signal entropy during social perception is in part explained by an epigenetic modification to the oxytocin receptor gene ( OXTR ) and accounts for significant individual differences in social behavior in the first year of life. These results are measure-, context-, and modality-specific: entropy, not standard deviation, links OXTR methylation and infant behavior; entropy evoked during social perception specifically explains social behavior only; and only entropy evoked during social auditory perception predicts infant vocalization behavior. Conclusions Demonstrating these associations in infancy is critical for elucidating the neurobiological mechanisms accounting for individual differences in cognition and behavior relevant to neurodevelopmental disorders. Our results suggest that an epigenetic modification to the oxytocin receptor gene and brain signal entropy are useful indicators of social development and may hold potential diagnostic, therapeutic, and prognostic value. 

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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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