Predictors of milk cortisol in North American women.

OBJECTIVES: Human milk content varies across mother-child dyads, environments, and populations. Among the hormones in milk is cortisol, a glucocorticoid; its impact on the breastfeeding child is unknown. Milk cortisol may constitute a signal to the child's developing physiology which can shape characteristics (e.g., growth, temperament) to prevailing environmental conditions. This exploratory study evaluated the maternal, breastfeeding, and infant characteristics associated with milk cortisol. METHODS: We evaluated archived milk specimens for cortisol using enzyme immunoassay and employed an information-theoretic approach to assess associations between milk cortisol and participant characteristics with linear regression modeling. Because we employed secondary data, information for some variables likely to impact milk cortisol variation (e.g., time of day, socioeconomic status, maternal or infant body mass index, milk energy density) was unavailable. RESULTS: Participants were 48 lactating mothers from upstate New York, aged 21-40 years. Milk cortisol ranged from 0.098 to 1.007 µg/dL. Child age ranged from 1 to 26 months. In linear regression employing best fit modeling criteria, milk cortisol increased with child age (B: 0.069; p: .000; a 7.1% increase in milk cortisol for each month of child age), while child symptoms of illness (B: -0.398; p: .057; a 33% decrease) and consumption of complementary foods (B: -.525; p: .020; a 41% decrease) were associated with lower milk cortisol. CONCLUSIONS: We speculate that increasing milk cortisol with child age plays a role in signaling development (e.g., as increasing independence increases risk for injury and other negative health outcomes), independent of the maternal stressors we could capture.

Maternal and infant predictors of proinflammatory milk immune activity in Kilimanjaro, Tanzania.

OBJECTIVES: The 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. METHODS: We characterized milk in vitro interleukin-6 (IL-6) responses to Salmonella enterica (a target of protective immune activity; N = 96) and Escherichia 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. RESULTS: In all models, IL-6 responses to S. enterica increased with maternal age and decreased with gravidity. In mixture models, IL-6 responses to E. coli declined with maternal age and increased with gravidity. No other considered variables were consistently associated with IL-6 responses. CONCLUSIONS: The 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.

Associations between milk cortisol and activity of the immune system of milk.

OBJECTIVES: Both the immune system of human milk and milk cortisol have complex short- and long-term effects on child health and development. As understanding continues to grow of the independent effects of each of these components of milk, it is also important to investigate their intersection, including how milk cortisol affects the immune system of milk. We began this important endeavor through secondary analyses of archived milk specimens. METHODS: Participants were 31 lactating mothers from upstate New York. We estimated milk cortisol concentrations via enzyme immunoassay. We assessed milk proinflammatory cytokine (interleukin-6, IL-6) responses to pathogenic (Salmonella) and commensal (Escherichia, Lactobacillus, Bifidobacterium) bacteria via in vitro stimulation. We estimated ordered logistic regression models to assess associations between milk cortisol and IL-6 responses to bacteria. RESULTS: Milk cortisol ranged from 0.098 to 1.007 µg/dL. Milk cortisol was positively associated with IL-6 responses to S. enterica (B: 4.035; 95% CI: 0.674, 7.395) and B. breve (B: 3.675; 95% CI: 0.426, 6.924); this association persisted after controlling for child age. Results were less clear for associations between milk cortisol and IL-6 responses to L. acidophilus (B: 2.318; 95% CI: -1.224, 5.859) and E. coli (B: 2.366; 95% CI: -0.960, 5.692). CONCLUSIONS: Complex interactions between cortisol and the immune system extend to milk. Milk cortisol was positively associated with proinflammatory responses to some bacteria in vitro. This may suggest that milk cortisol is causally upstream of protective immune activity.

Does the immune system of milk increase activity for infants experiencing infectious disease episodes in Kilimanjaro, Tanzania?

INTRODUCTION: Multiple studies have reported that milk immune content increases for infants experiencing infectious disease (ID) episodes, suggesting that the immune system of milk (ISOM) offers enhanced protection when needed to combat ID. METHODS: To test the hypothesis that ISOM content and/or activity increases during an infant's ID episode, we characterized milk secretory immunoglobulin A (sIgA; a major ISOM constituent) and in vitro interleukin-6 (IL-6) responses to Salmonella enterica and Escherichia coli, as system-level biomarkers of ISOM activity, in a prospective study among 96 mother-infant dyads in Kilimanjaro, Tanzania. RESULTS: After control for covariates, no milk immune variables (sIgA, Coef: 0.03; 95% CI -0.25, 0.32; in vitro IL-6 response to S. enterica, Coef: 0.23; 95% CI: -0.67, 1.13; IL-6 response to E. coli, Coef: -0.11; 95% CI: -0.98, 0.77) were associated with prevalent ID (diagnosed at the initial participation visit). Among infants experiencing an incident ID (diagnosed subsequent to the initial participation), milk immune content and responses were not substantially higher or lower than the initial visit (sIgA, N: 61; p: 0.788; IL-6 response to S. enterica, N: 56; p: 0.896; IL-6 response to E. coli, N: 36; p: 0.683); this was unchanged by exclusion of infants with ID at the time of initial participation. CONCLUSION: These findings are not consistent with the hypothesis that milk delivers enhanced immune protection when infants experience ID. In environments with a high burden of ID, dynamism may be less valuable to maternal reproductive success than stability in the ISOM.

Maternal stress and hair cortisol among pregnant women following hurricane Florence.

Natural disasters represent major stressors, resulting in psychological distress and physiological responses such as increased cortisol. During pregnancy, this impacts not only maternal well-being, but also fetal development. In 2018, Hurricane Florence caused extensive damage across the eastern United States. Studies indicated that compared to married pregnant women, unmarried pregnant women had higher risk of distress. Here we assess hair cortisol among a subsample of participants, and variations based on marital status. METHODS: We analyzed multiple stress measures among 37 participants who were pregnant during Hurricane Florence. We used questionnaires modeled on previous studies to assess hardship associated with the hurricane, psychological distress, sociodemographic characteristics, social support, and food security. We analyzed cortisol concentrations in proximal and distal hair sections, representing stress around the time of the disaster (distal) and 3-4 months following the disaster (proximal). We used linear regression to test relationships between hair cortisol and self-report stress measures, and variations based on marital status. RESULTS: Self-report measures of distress and hardship were similar among married and unmarried participants. Mean cortisol levels in distal and proximal sections were higher among unmarried participants. Controlling for confounding variables, hardship was not associated with hair cortisol. Distress predicted cortisol in distal sections (ß = .482, p = .018), with a trend for proximal sections (ß = .368, p = .055). Marital status was a significant predictor of distal (ß = .388, p = .027) and proximal (ß = .333, p = .047) hair cortisol, explaining 8.6%-11.7% of unique variance. CONCLUSIONS: Preexisting and intersecting risk factors likely place unmarried pregnant individuals at risk of stress during and following a disaster.

Matriliny reverses gender disparities in inflammation and hypertension among the Mosuo of China.

Women experience higher morbidity than men, despite living longer. This is often attributed to biological differences between the sexes; however, the majority of societies in which these disparities are observed exhibit gender norms that favor men. We tested the hypothesis that female-biased gender norms ameliorate gender disparities in health by comparing gender differences in inflammation and hypertension among the matrilineal and patrilineal Mosuo of China. Widely reported gender disparities in health were reversed among matrilineal Mosuo compared with patrilineal Mosuo, due to substantial improvements in women's health, with no concomitant detrimental effects on men. These findings offer evidence that gender norms limiting women's autonomy and biasing inheritance toward men adversely affect the health of women, increasing women's risk for chronic diseases with tremendous global health impact.

Human milk lactoferrin variation in relation to maternal inflammation and iron deficiency in northern Kenya.

BACKGROUND: Milk lactoferrin is a multi-functional, iron-binding glycoprotein with immunomodulatory effects, protecting infants against infectious diseases. AIMS: This study explored how maternal inflammation/infection and iron-deficiency anemia (IDA) might influence human milk lactoferrin. Lactoferrin might be elevated with maternal inflammation resulting from infectious disease processes. Conversely, lactoferrin might decrease with IDA, corresponding to scarce maternal iron for transfer in milk. In these two hypothesized scenarios, the degree of lactoferrin elevation or decrease might vary with infant vulnerability to infectious diseases or malnutrition. Alternatively, lactoferrin might be unassociated with inflammation/infection or IDA if mothers could buffer it against these conditions. MATERIALS & METHODS: We used cross-sectional data from Ariaal mothers of northern Kenya (n = 200) to evaluate associations between milk lactoferrin and maternal inflammation/infection, IDA, infant age/sex, and the mother-infant variable interactions in multivariate regression models. RESULTS: Maternal inflammation was associated with higher lactoferrin for younger infants (<~5 months of age) but with lower lactoferrin for older infants. Maternal IDA was unassociated with lactoferrin alone or in interaction with infant variables. DISCUSSION & CONCLUSION: Results suggest that mothers of vulnerable young infants deliver more lactoferrin when they have inflammation/infection but mothers with older infants do not, and that maternal delivery of lactoferrin is unaffected by their IDA. Longitudinal research should verify these findings.

Labor migration is associated with lower rates of underweight and higher rates of obesity among left-behind wives in rural Bangladesh: a cross-sectional study.

BACKGROUND: Among Bangladeshi men, international labor migration has increased ten-fold since 1990 and rural to urban labor migration rates have steadily increased. Labor migration of husbands has increased household wealth and redefined women's roles, which have both positively and negatively impacted the health of wives "left behind". We examined the direct and indirect effects of husband labor migration on chronic disease indicators and outcomes among wives of labor migrants. METHODS: We collected survey, anthropometric, and biomarker data from a random sample of women in Matlab, Bangladesh, in 2018. We assessed associations between husband's migration and indicators of adiposity and chronic disease. We used structural equation modeling to assess the direct effect of labor migration on chronic disease, undernutrition, and adiposity, and the mediating roles of income, food security, and proportion of food purchased from the bazaar. Qualitative interviews and participant observation were used to help provide context for the associations we found in our quantitative results. FINDINGS: Among study participants, 9.0% were underweight, 50.9% were iron deficient, 48.3% were anemic, 39.6% were obese, 27.3% had a waist circumference over 35 in., 33.1% had a high whole-body fat percentage, 32.8% were diabetic, and 32.9% had hypertension. Slightly more women in the sample (55.3%) had a husband who never migrated than had a husband who had ever migrated (44.9%). Of those whose husband had ever migrated, 25.8% had a husband who was a current international migrant. Wives of migrants were less likely to be underweight, and more likely to have indicators of excess adiposity, than wives of non-migrants. Protection against undernutrition was attributable primarily to increased food security among wives of migrants, while increased adiposity was attributable primarily to purchasing a higher proportion of food from the bazaar; however, there was a separate path through income, which qualitative findings suggest may be related to reduced physical activity. CONCLUSIONS: Labor migration, and particularly international labor migration, intensifies the nutrition transition in Bangladesh through increasing wealth, changing how foods are purchased, and reducing physical activity, which both decreases risk for undernutrition and increases risk for excess adiposity.

High-altitude adaptations mitigate risk for hypertension and diabetes-associated anemia.

BACKGROUND: Human populations native to high altitude exhibit numerous genetic adaptations to hypobaric hypoxia. Among Tibetan plateau peoples, these include increased vasodilation and uncoupling of erythropoiesis from hypoxia. OBJECTIVE/METHODS: We tested the hypothesis that these high-altitude adaptations reduce risk for hypertension and diabetes-associated anemia among the Mosuo, a Tibetan-descended population in the mountains of Southwest China that is experiencing rapid economic change and increased chronic disease risk. RESULTS: Hypertension was substantially less common among Mosuo than low-altitude Han populations, and models fit to the Han predicted higher probability of hypertension than models fit to the Mosuo. Diabetes was positively associated with anemia among the Han, but not the Mosuo. CONCLUSION: The Mosuo have lower risk for hypertension and diabetes-associated anemia than the Han, supporting the hypothesis that high-altitude adaptations affecting blood and circulation intersect with chronic disease processes to lower risk for these outcomes. As chronic diseases continue to grow as global health concerns, it is important to investigate how they may be affected by local genetic adaptations.

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

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 (ß = 0.077, p = .022) and NIDA (ß = 0.083, p = .100) predicted higher total protein (ln). IDA (ß = -0.293, p = .002), NIDA (ß = -0.313, p = .047), and inflammation (ß = -0.269, p = .007) each predicted lower fat (ln); however, anemia accompanying inflammation predicted higher fat (ß = 0.655, p = .007 for IDA and ß = 0.468, p = .092 for NIDA). NIDA predicted higher lactose (ß = 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 anemia and inflammation). This study demonstrates the foundational importance of maternal micronutrient health and inflammation or infection for advancing the ecological understanding of human milk nutrient variation.

A test of the optimal iron hypothesis among breastfeeding Ariaal mothers in northern Kenya.

OBJECTIVE: The optimal iron hypothesis posits a trade-off in iron nutrition-iron deficiency restricts iron available to infectious agents, protecting against severe infection, but also compromises immune defense-such that mild-to-moderate iron deficiency may be more adaptive than either iron-replete or severe deficiency in environments with high infectious disease load. This hypothesis has not been tested among adults. MATERIALS AND METHODS: A secondary analysis of data and specimens from 220 lactating mothers in northern Kenya was conducted. Elevated serum C-reactive protein (CRP > 2 or >5 mg/l) was utilized to identify prevalent subclinical infection/inflammation. Iron deficiency was identified with transferrin receptor in archived dried blood spots (TfR > 5.0 mg/l). The absence of iron deficiency or anemia (Hemoglobin < 12 g/l) defined the iron replete state. Iron-deficient erythropoiesis (IDE, mild-to-moderate iron deficiency) was defined as iron deficiency without anemia; iron deficiency anemia (IDA, severe iron deficiency) as iron deficiency with anemia; and noniron-deficiency anemia (NIDA) as anemia without iron deficiency. RESULTS: The prevalence of elevated inflammation (subclinical infection) was lowest in IDE. In logistic regression, IDE was inversely associated with inflammation (for CRP > 2 mg/l: adjusted odds ratio, aOR = 0.30; p = 0.02; for CRP > 5 mg/l: aOR = 0.27; p = 0.10), compared to the iron replete state. The protective effect of IDE differed in the presence of vitamin A deficiency or underweight. CONCLUSIONS: We interpret these patterns as tentative support for the optimal iron hypothesis in breastfeeding women in the infectious disease ecology of northern Kenya. Iron deficiency may interact in important ways with other forms of malnutrition that are known to affect immune protection.

Hay fever, asthma, and eczema and early infectious diseases among children in Kilimanjaro, Tanzania.

OBJECTIVES: To investigate the hygiene (or "old friends") hypothesis in a high-infectious disease (ID) environment, rural Kilimanjaro, Tanzania. METHODS: Among a cross-sectional sample of 2- to 7-year-old children, we collected physician-diagnosed hay fever, asthma, and eczema, history of hospitalization, family size, and household environment information via questionnaire; performed active and passive surveillance for ID; and, evaluated total immunoglobulin E (IgE) and biomarkers of inflammation in dried blood spot specimens. We used regression models to describe patterns in allergic diseases. RESULTS: Complete information was available for 280 children: 12.5% had been diagnosed with hay fever; 18.9% with eczema; 2.1% with asthma. There was a positive association between hay fever and eczema diagnoses (π2 : 4.07; P = 0.044); total IgE was positively associated with eczema (ß: 0.24; P = 0.100) and allergic diseases together (ß: 0.26; P = 0.042). ID were common: the incidence of any ID diagnosis was 28 per 100 children per month. Hay fever was inversely associated with household animals (OR: 0.27; P = 0.006), and positively associated with earth housing materials (OR: 1.93; P = 0.079) and hospitalization in infancy with an ID (3.16; P = 0.066); patterns were similar when allergic disease outcomes were considered together. Few associations between these predictors and eczema or asthma alone were apparent. CONCLUSIONS: Allergic diseases were common among children in Kilimanjaro. The inverse association between household animals and allergy is consistent with the hygiene/old friends hypothesis; however, positive associations between allergic diseases and earth housing materials and early hospitalization with ID bear further explanation.

Breastfeeding over two years is associated with longer birth intervals, but not measures of growth or health, among children in Kilimanjaro, TZ.

OBJECTIVES: Breastfeeding has been associated with numerous health and well-being benefits for both children and their mothers, including prolonging the birth interval to the subsequent sibling. The clearest associations between breastfeeding and health outcomes, per se, reflect exclusive breastfeeding in the first months of postnatal life and are most evident during infancy. Fewer studies explore the consequences of breastfeeding for multiple years. In this article, we ask whether breastfeeding for more than 2 years is associated with discernible health and well-being benefits to children. METHODS: Data were collected from 315 children, aged 2 to 7, and their caretakers residing in Kilimanjaro, Tanzania. Basic demographic and health information was solicited, and anthropometric and blood markers of health were evaluated. RESULTS: Our results indicate a strong positive relationship between breastfeeding for 2 or more years and interbirth interval, but little evidence for a relationship between prolonged breastfeeding and several indicators of child growth and health. CONCLUSIONS: We suggest that these relationships may support the recently rekindled birth spacing hypothesis, positing selection for longer interbirth intervals, rather than, or in addition to, more direct health benefits associated with breastfeeding for 2 or more years. Our results may indicate attenuating health benefits associated with longer breastfeeding.

Correction: Betel quid use is associated with anemia among both men and women in Matlab, Bangladesh.

[This corrects the article DOI: 10.1371/journal.pgph.0001677.].

The evolutionary ecology of early weaning in Kilimanjaro, Tanzania.

Public health recommendations promote prolonged breastfeeding of all children; however, parental investment (PI) theory predicts that breastfeeding will be allocated among a mothers' offspring to maximize her reproductive success. We evaluated PI in terms of risk for weaning before age two among 283 children in Kilimanjaro, Tanzania. Results demonstrate: (i) a Trivers-Willard effect--high socioeconomic status (SES) females and low SES males were more likely to be weaned early; (ii) later-born children were less likely to be weaned early; (iii) higher birthweight children were less likely to be weaned early, and (iv) no effect of cattle (a source of supplementary milk) ownership. These associations were largely independent and remained significant in models controlling for potential confounders; however, the inverse association between early weaning and birth order lost significance in the model containing birthweight. These patterns were observed despite public health recommendations encouraging breastfeeding for at least two years.

Predictors of delayed-type hypersensitivity to Candida albicans and anti-Epstein-Barr virus antibody among children in Kilimanjaro, Tanzania.

We evaluated sex, age, nutritional status, and infectious disease (ID) as predictors of two biomarkers of cell-mediated immunity (CMI), delayed-type hypersensitivity to Candida albicans (DTH-Candida), and anti-Epstein-Barr virus antibody (EBV Ab), among 200 children in Kilimanjaro, Tanzania. DTH-Candida, which decreases with compromised CMI, was positively associated with age (OR: 1.27; 95% CI: 1.02, 1.57) and triceps skinfold (TSF; OR: 1.16; 95% CI: 1.02, 1.26), and inversely associated with height-for-age Z score (HAZ; OR: 0.86; 95% CI: 0.68, 1.08) and diagnosed ID (OR: 0.48; 95% CI: 0.22, 1.08). There was significant interaction between TSF and ID: DTH-Candida exhibited a strong inverse association with ID among children with low TSF (OR: 0.16; 95% CI: 0.05, 0.50) and a strong positive association with TSF among children with ID (OR: 2.64; 95% CI: 1.29, 5.42). EBV Ab, which increases with compromised CMI, was inversely associated with male sex (ß: -0.47; 95% CI: -0.70, -0.24) and TSF (ß: -0.04; 95% CI: -0.08, 0.00), and positively associated with HAZ (ß: 0.06; 95% CI: -0.03, 0.15). Among males, EBV Ab was positively associated with anemia. Among normal HAZ children, EBV Ab was inversely associated with TSF. There was no association between DTH-Candida and EBV Ab. While DTH-Candida provides a direct measure of CMI, our results suggest that interpretation of EBV-Ab among Kilimanjaro children was complicated by its indirect relationship with CMI. Among our sample, CMI increased with age and adequate nutrition and was compromised during acute ID. The suggestive CMI-compromising effect of increasing height-for-age may bear further exploration.

Does gender structure social networks across domains of cooperation? An exploration of gendered networks among matrilineal and patrilineal Mosuo.

Cooperative networks are essential features of human society. Evolutionary theory hypothesizes that networks are used differently by men and women, yet the bulk of evidence supporting this hypothesis is based on studies conducted in a limited range of contexts and on few domains of cooperation. In this paper, we compare individual-level cooperative networks from two communities in Southwest China that differ systematically in kinship norms and institutions-one matrilineal and one patrilineal-while sharing an ethnic identity. Specifically, we investigate whether network structures differ based on prevailing kinship norms and type of gendered cooperative activity, one woman-centred (preparation of community meals) and one man-centred (farm equipment lending). Our descriptive results show a mixture of 'feminine' and 'masculine' features in all four networks. The matrilineal meals network stands out in terms of high degree skew. Exponential random graph models reveal a stronger role for geographical proximity in patriliny and a limited role of affinal relatedness across all networks. Our results point to the need to consider domains of cooperative activity alongside gender and cultural context to fully understand variation in how women and men leverage social relationships toward different ends. This article is part of the theme issue 'Cooperation among women: evolutionary and cross-cultural perspectives'.

Market integration, income inequality, and kinship system among the Mosuo of China.

Increased access to defensible material wealth is hypothesised to escalate inequality. Market integration, which creates novel opportunities in cash economies, provides a means of testing this hypothesis. Using demographic data collected from 505 households among the matrilineal and patrilineal Mosuo in 2017, we test whether market integration is associated with increased material wealth, whether increased material wealth is associated with wealth inequality, and whether being in a matrilineal vs. patrilineal kinship system alters the relationship between wealth and inequality. We find evidence that market integration, measured as distance to the nearest source of tourism and primary source of household income, is associated with increased household income and 'modern' asset value. Both village-level market integration and mean asset value were associated negatively, rather than positively, with inequality, contrary to predictions. Finally, income, modern wealth and inequality were higher in matrilineal communities that were located closer to the centre of tourism and where tourism has long provided a relatively stable source of income. However, we also observed exacerbated inequality with increasing farm animal value in patriliny. We conclude that the forces affecting wealth and inequality depend on local context and that the importance of local institutions is obscured by aggregate statistics drawn from modern nation states.

Betel quid use is associated with anemia among both men and women in Matlab, Bangladesh.

Anemia accounts for 8.8% of total disability burden worldwide. Betel quid use among pregnant women has been found to increase anemia risk. Betel quid is prepared by wrapping the betel (or areca) nut, with spices and other additions, in betel or tobacco leaf and it is chewed or placed in the mouth. We explored the association between betel quid use and anemia among men and non-pregnant women. We collected data from a random sample of women and their husbands in Matlab, Bangladesh. Participants reported their current betel quid use and individual characteristics. We assessed hemoglobin (a biomarker of anemia) with a hemoglobinometer and soluble transferrin receptor (a biomarker of iron deficiency) and C-reactive protein (a biomarker of inflammation) in dried blood spots via enzyme immunoassay. We estimated logistic regression models to evaluate the association between betel quid use and anemia and structural equation models (SEM) to evaluate mediating roles of iron deficiency and elevated inflammation. A total of 1133 participants (390 men and 743 non-pregnant women) were included. After controlling for important confounders, any betel quid use was positively associated with anemia among men (OR: 1.80; 95% CI: 1.12, 2.89). Among women, betel quid use was associated with anemia only among the most frequent users (OR: 1.62; 95% CI: 1.03, 2.53). SEM did not reveal indirect paths through inflammation or iron deficiency. Betel quid use may contribute to the burden of anemia among adults in Bangladesh. Our findings suggest the burden of disease attributed to betel quid use has been underestimated.