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Abstract Background and objectivesThe optimal iron hypothesis (OIH) posits that risk for infection is lowest at a mild level of iron deficiency. The extent to which this protection results from arms race dynamics in the evolution of iron acquisition and sequestration mechanisms is unclear. We evaluated the OIH with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an emerging infectious agent. MethodologyWe tested 304 healthcare workers at baseline for iron deficiency (zinc protoporphyrin:heme), anemia (hemoglobin), and SARS-CoV-2 (salivary PCR), and followed them for ~3 months with biweekly SARS-CoV-2 tests. We fit logistic regression models based on Akaike Information Criterion. ResultsAdequate data were available for 199 participants. Iron replete (OR: 2.87, 95% CI: 0.85, 9.75) and anemia (OR: 2.48; 95% CI: 0.82, 7.85) were associated with higher risk for SARS-CoV-2 infection after control for covariates. Logistic regression and Cox proportional hazards models of the SARS-CoV-2 outcome were similar. Anemia (OR: 1.81; 95% CI: 0.88, 3.71) was associated with respiratory symptoms regardless of SARS-CoV-2 infection. Conclusions and implicationsThese findings provide partial support for the OIH: SARS-CoV-2 infection risk was elevated at the high end of the range of iron availability; however, the elevated risk among those with anemia was not, as expected, specific to severe iron deficiency. Narrowly, for COVID-19 epidemiology, these findings accord with evidence that SARS-CoV-2’s ability to establish infection is enhanced by access to iron. More broadly, these findings suggest that the OIH does not hinge on a long history of evolutionary arms race dynamics in access to host iron. 

Abstract ObjectivesThe immune system of milk (ISOM) creates a mother–infant immune axis that plays an important role in protecting infants against infectious disease (ID). Tradeoffs in the immune system suggest the potential for both protection and harm, so we conceive of two dimensions via which the ISOM impacts infants: promotion of protective activity and control of activity directed at benign targets. High variability in ISOM activity across mother–infant dyads suggests investment the ISOM may have evolved to be sensitive to maternal and/or infant characteristics. We assessed predictors of appropriate and misdirected proinflammatory ISOM activity in an environment of high ID risk, testing predictions drawn from life history theory and other evolutionary perspectives. MethodsWe characterized milk in vitro interleukin‐6 (IL‐6) responses toSalmonella enterica(a target of protective immune activity;N = 96) andEscherichia coli(a benign target;N = 85) among mother–infant dyads in rural Kilimanjaro, Tanzania. We used ordered logistic regression and mixture models to evaluate maternal and infant characteristics as predictors of IL‐6 responses. ResultsIn all models, IL‐6 responses toS.entericaincreased with maternal age and decreased with gravidity. In mixture models, IL‐6 responses toE.colideclined with maternal age and increased with gravidity. No other considered variables were consistently associated with IL‐6 responses. ConclusionsThe ISOM's capacities for appropriate proinflammatory activity and control of misdirected proinflammatory activity increases with maternal age and decreases with gravidity. These findings are consistent with the hypothesis that the mother–infant immune axis has evolved to respond to maternal life history characteristics. 

Abstract ObjectivesThis study explored differing levels of macronutrients in breast milk in relation to maternal anemia and hemoglobin. MethodsArchived 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. ResultsThe 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. ConclusionsMaternal 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. 

Abstract BackgroundMaternal 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. MethodsA 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. ResultsIDA (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). ConclusionsMilk 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.