Joann M. McDermid

The mammary gland produces nutrient-rich human milk (HM), yet how mammary functional state shapes HM composition and infant outcomes remains poorly understood. We used HM multi-omics - metabolomics, proteomics, micronutrients, macronutrients, and HM oligosaccharides - across 1,543 samples from three cohorts, including two randomized trials, as a noninvasive readout of mammary functional state. Trajectory modeling and multi-omic integration showed that maternal supplementation improved recovery from early growth faltering and revealed a shared HM compositional axis linking maternal nutrition to infant growth. Machine learning, with Human Protein Atlas–informed proteomics, identified seven HM biomarkers reflecting variation across key mammary domains, indexing milk synthesis, barrier integrity, and immune/repair activity. Elevated valerylcarnitine and low pantothenic acid emerged as metabolic signals linking mammary functional state to infant growth.

Background: Stunting among children in low-resource settings is associated with enteric pathogen carriage and micronutrient deficiencies. Our goal was to test whether administration of scheduled antimicrobials and daily nicotinamide improved linear growth in a region with a high prevalence of stunting and enteric pathogen carriage. Methods and findings: We performed a randomized, 2 × 2 factorial, double-blind, placebo-controlled trial in the area around Haydom, Tanzania. Mother–child dyads were enrolled by age 14 days and followed with monthly home visits and every 3-month anthropometry assessments through 18 months. Those randomized to the antimicrobial arm received 2 medications (versus corresponding placebos): azithromycin (single dose of 20 mg/kg) at months 6, 9, 12, and 15 and nitazoxanide (3-day course of 100 mg twice daily) at months 12 and 15. Those randomized to nicotinamide arm received daily nicotinamide to the mother (250 mg pills months 0 to 6) and to the child (100 mg sachets months 6 to 18). Primary outcome was length-for-age z-score (LAZ) at 18 months in the modified intention-to-treat group. Between September 5, 2017 and August 31, 2018, 1,188 children were randomized, of whom 1,084 (n = 277 placebo/placebo, 273 antimicrobial/placebo, 274 placebo/nicotinamide, and 260 antimicrobial/nicotinamide) were included in the modified intention-to-treat analysis. The study was suspended for a 3-month period by the Tanzanian National Institute for Medical Research (NIMR) because of concerns related to the timing of laboratory testing and the total number of serious adverse events (SAEs); this resulted in some participants receiving their final study assessment late. There was a high prevalence of stunting overall (533/1,084, 49.2%). Mean 18-month LAZ did not differ between groups for either intervention (mean LAZ with 95% confidence interval [CI]: antimicrobial: −2.05 CI −2.13, −1.96, placebo: −2.05 CI −2.14, −1.97; mean difference: 0.01 CI −0.13, 0.11, p = 0.91; nicotinamide: −2.06 CI −2.13, −1.95, placebo: −2.04 CI −2.14, −1.98, mean difference 0.03 CI −0.15, 0.09, p = 0.66). There was no difference in LAZ for either intervention after adjusting for possible confounders (baseline LAZ, age in days at 18-month measurement, ward, hospital birth, birth month, years of maternal education, socioeconomic status (SES) quartile category, sex, whether the mother was a member of the Datoga tribe, and mother’s height). Adverse events (AEs) and SAEs were overall similar between treatment groups for both the nicotinamide and antimicrobial interventions. Key limitations include the absence of laboratory measures of pathogen carriage and nicotinamide metabolism to provide context for the negative findings. Conclusions: In this study, we observed that neither scheduled administration of azithromycin and nitazoxanide nor daily provision of nicotinamide was associated with improved growth in this resource-poor setting with a high force of enteric infections. Further research remains critical to identify interventions toward improved early childhood growth in challenging conditions. Trial registration: ClinicalTrials.gov NCT03268902.

Recurrent enteric infections and micronutrient deficiencies, including deficiencies in the tryptophan–kynurenine–niacin pathway, have been associated with environmental enteric dysfunction, potentially contributing to poor child growth and development. We are conducting a randomized, placebo-controlled, 2 × 2 factorial interventional trial in a rural population in Haydom, Tanzania, to determine the effect of 1) antimicrobials (azithromycin and nitazoxanide) and/or 2) nicotinamide, a niacin vitamer, on attained length at 18 months. Mother/infant dyads were enrolled within 14 days of the infant’s birth from September 2017 to September 2018, with the follow-up to be completed in February 2020. Here, we describe the baseline characteristics of the study cohort, risk factors for low enrollment weight, and neonatal adverse events (AEs). Risk factors for a low enrollment weight included being a firstborn child (−0.54 difference in weight-for-age z-score [WAZ] versus other children, 95% CI: −0.71, −0.37), lower socioeconomic status (−0.28, 95% CI: −0.43, −0.12 difference in WAZ), and birth during the preharvest season (November to March) (−0.22, 95% CI: −0.33, −0.11 difference in WAZ). The most common neonatal serious AEs were respiratory tract infections and neonatal sepsis (2.2 and 1.4 events per 100 child-months, respectively). The study cohort represents a high-risk population for whom interventions to improve child growth and development are urgently needed. Further analyses are needed to understand the persistent impacts of seasonal malnutrition and the interactions between seasonality, socioeconomic status, and the study interventions.

Cultural competency is a required standard for American medical students, but it can be challenging to effectively engage students with this topic. Because nutrition and culture are inherently intertwined in patient care, classroom role-play with nutrition-focused case scenarios enables students to practice strategies for navigating cultural barriers with patients.

Initiating breastfeeding within the first hour of life confers an important benefit in terms of child mortality and severe morbidity. Intestinal permeability to ingested macromolecules and immunoglobulins is limited to the first days of human life. These exchanges cease in the very early post‐partum period but may increase beyond the neonatal period in response to local inflammation or introduction of a weaning food. From animal‐ and limited human‐based observations, compelling evidence points out to breastmilk cells also trafficking from mother to infant mucosal tissues and participating to the maternal microchimerism. The precise nature of breastmilk cells that are involved is presently not known but likely includes progenitor/stem cells—representing up to 6% of breastmilk cells—with possible contribution of mature immune cells. Stem cell microchimerism may induce tolerance to non‐inherited maternal antigens (NIMAs), breastfeeding generating regulatory T cells (T_reg) that suppress antimaternal immunity. Therefore, in complement to pregnancy‐induced microchimerism, breastfeeding‐induced microchimerism may be pivotal in infant immune development, intestinal tissue repair/growth and protection against infectious diseases. As a continuum of the gestational period, the neonatal gut may be considered as a temporary, but important developmental extension of the role played by the placenta during intrauterine life; breastmilk playing the role of maternal blood by delivering maternal soluble factors (macromolecules, Ig, cytokines) and immunologically active milk cells. A better understanding of breastfeeding‐induced maternal microchimerism would provide further evidence in support of public health messages that reinforce the importance of early initiation of breastfeeding.