A growing body of evidence highlights the importance of a mother's nutrition from preconception through lactation in programming the emerging organ systems and homeostatic pathways of her offspring. ...The developing immune system may be particularly vulnerable. Indeed, examples of nutrition-mediated immune programming can be found in the literature on intra-uterine growth retardation, maternal micronutrient deficiencies, and infant feeding. Current models of immune ontogeny depict a “layered” expansion of increasingly complex defenses, which may be permanently altered by maternal malnutrition. One programming mechanism involves activation of the maternal hypothalamic-pituitary-adrenal axis in response to nutritional stress. Fetal or neonatal exposure to elevated stress hormones is linked in animal studies to permanent changes in neuroendocrine-immune interactions, with diverse manifestations such as an attenuated inflammatory response or reduced resistance to tumor colonization. Maternal malnutrition may also have a direct influence, as evidenced by nutrient-driven epigenetic changes to developing T regulatory cells and subsequent risk of allergy or asthma. A 3rd programming pathway involves placental or breast milk transfer of maternal immune factors with immunomodulatory functions (e.g. cytokines). Maternal malnutrition can directly affect transfer mechanisms or influence the quality or quantity of transferred factors. The public health implications of nutrition-mediated immune programming are of particular importance in the developing world, where prevalent maternal undernutrition is coupled with persistent infectious challenges. However, early alterations to the immune system, resulting from either nutritional deficiencies or excesses, have broad relevance for immune-mediated diseases, such as asthma, and chronic inflammatory conditions like cardiovascular disease.
Linear growth during three distinct stages of life determines attained stature in adulthood: namely, in utero, early postnatal life, and puberty and the adolescent period. Individual host factors, ...genetics, and the environment, including nutrition, influence attained human stature. Each period of physical growth has its specific biological and environmental considerations. Recent epidemiologic investigations reveal a strong influence of prenatal factors on linear size at birth that in turn influence the postnatal growth trajectory. Although average population height changes have been documented in high-income regions, stature as a complex human trait is not well understood or easily modified. This review summarizes the biology of linear growth and its major drivers including nutrition from a life-course perspective, the genetics of programmed growth patterns or height, and gene-environment interactions that determine human stature in toto over the life span. Implications for public health interventions and knowledge gaps are discussed.
Approximately five million children die each year from preventable causes, including respiratory infections, diarrhea, and malaria. Roughly half of those deaths are attributable to undernutrition, ...including micronutrient deficiencies (MNDs). The influence of infection on micronutrient status is well established: The inflammatory response to pathogens triggers anorexia, while pathogens and the immune response can both alter nutrient absorption and cause nutrient losses. We review the roles of vitamin A, vitamin D, iron, zinc, and selenium in the immune system, which act in the regulation of molecular- or cellular-level host defenses, directly affecting pathogens or protecting against oxidative stress or inflammation. We further summarize high-quality evidence regarding the synergistic or antagonistic interactions between MNDs, pathogens, and morbidity or mortality relevant to child health in low- and middle-income countries. We conclude with a discussion of gaps in the literature and future directions for multidisciplinary research on the interactions of MNDs, infection, and inflammation.
Dietary diversity scores and dichotomous indicators derived from them are widely used to assess dietary quality, and specific scoring methods have been recommended for women and 6- to 23-mo-old ...children. However, there is no specific score recommended for older children and the effect of seasonal dietary changes on score performance is not well documented.
We assessed performance of 2 recommended dietary diversity scores as indicators of dietary quality over 3 seasons.
We conducted 7 repeat 24-h dietary recalls among 4- to 8-y-old rural Zambian children (n = 200) over 6 mo. Dietary diversity was assessed using a 7-food group score for assessing infant and young child feeding (DDS-IYCF) and a 10-food group score for use among women of reproductive age (DDS-W). Micronutrient intake adequacy was described by mean probability of adequacy (MPA) over 11 micronutrients. Longitudinal models were fit to test the association between each score and MPA overall and by season. Receiver operating characteristic (ROC) curves were used to describe indicator performance of each score.
Mean ± SE scores were 4.11 ± 0.03 for DDS-IYCF and 4.39 ± 0.03 for DDS-W. Both scores varied by season, but DDS-W better reflected seasonal dietary changes. Across seasons, MPA increased 1–6 percentage points/unit increase in DDS-IYCF or 1–10 percentage points for DDS-W (P < 0.05). Score performance as a predictor of MPA > 0.75 was moderate, with area under the ROC curve values by season ranging from 0.63 to 0.77 for DDS-IYCF and from 0.66 to 0.72 for DDS-W.
DDS-W performed better than DDS-IYCF in characterizing seasonal variability and micronutrient adequacy among rural Zambian children.
The lysosomal-autophagic pathway is activated by starvation and plays an important role in both cellular clearance and lipid catabolism. However, the transcriptional regulation of this pathway in ...response to metabolic cues is uncharacterized. Here we show that the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is induced by starvation through an autoregulatory feedback loop and exerts a global transcriptional control on lipid catabolism via Ppargc1α and Ppar1α. Thus, during starvation a transcriptional mechanism links the autophagic pathway to cellular energy metabolism. The conservation of this mechanism in Caenorhabditis elegans suggests a fundamental role for TFEB in the evolution of the adaptive response to food deprivation. Viral delivery of TFEB to the liver prevented weight gain and metabolic syndrome in both diet-induced and genetic mouse models of obesity, suggesting a new therapeutic strategy for disorders of lipid metabolism.
Approximately 62,000 Zambian children are living with HIV. HIV care and treatment is generally more limited in rural areas, where a heavy reliance on rain-fed subsistence agriculture also places ...households at risk of food and water insecurity. We nested a mixed methods study with an explanatory sequential design in a clinical cohort of children and adolescents living with HIV (CHIV) in rural Zambia. We used validated questionnaires to assess household food and water insecurity and examined associations between indicators derived from those scales, household characteristics, and HIV treatment adherence and outcomes using log-binomial regression. We identified caregivers and older CHIV from food insecure households for in-depth interviews. Of 186 participants completing assessments, 72% lived in moderately or severely food insecure households and 2% in water insecure households. Food insecurity was more prevalent in households of lower socioeconomic status (80% vs. 59% for higher scores; p = 0.02) and where caregivers had completed primary (79%) vs. secondary school or higher (62%; p = 0.01). No other characteristics or outcomes were associated with food insecurity. Parents limited both the quality and quantity of foods they consumed to ensure food availability for their CHIV. Coping strategies included taking on piecework or gathering wild foods; livestock ownership was a potential buffer. Accessing sufficient clean water was less of a concern. During periods of drought or service interruption, participants travelled further for drinking water and accessed water for other purposes from alternative sources or reduced water use. Community contributions afforded some protection against service interruptions. Overall, while food insecurity was prevalent, strategies used by parents may have protected children from a measurable impact on HIV care or treatment outcomes. Reinforcing social protection programs by integrating livestock ownership and strengthening water infrastructure may further protect CHIV in the case of more extreme food or water system shocks.
Replacement of conventional staples with biofortified or industrially fortified staples in household diets may increase maternal breast milk retinol content and vitamin A intakes from complementary ...foods, improving infant total body stores (TBS) of vitamin A.
To determine whether biofortified or industrially fortified maize consumption by Zambian women and their breastfeeding infants could improve milk retinol concentration and infant TBS.
We randomly assigned 255 lactating women and their 9-mo-old infants to a 90-d intervention providing 0 µg retinol equivalents (RE)/d as conventional maize or ∼315 µg RE/d to mothers and ∼55 µg RE/d to infants as provitamin A carotenoid-biofortified maize or retinyl palmitate–fortified maize. Outcomes were TBS, measured by retinol isotope dilution in infants (primary), and breast milk retinol, measured by HPLC in women (secondary).
The intervention groups were comparable at baseline. Loss to follow-up was 10% (n = 230 mother-infant pairs). Women consumed 92% of the intended 287 g/d and infants consumed 82% of the intended 50 g/d maize. The baseline geometric mean (GM) milk retinol concentration was 1.57 μmol/L (95% CI: 1.45, 1.69 μmol/L), and 24% of women had milk retinol <1.05 μmol/L. While mean milk retinol did not change in the biofortified arm (β: 0.11; 95% CI: −0.02, 0.24), the intervention reduced low milk retinol (RR: 0.42; 95% CI: 0.21, 0.85). Fortified maize increased mean milk retinol (β: 0.17; 95% CI: 0.04, 0.30) and reduced the prevalence of low milk retinol (RR: 0.46; 95% CI: 0.25, 0.82). The baseline GM TBS was 178 μmol (95% CI: 166, 191 μmol). This increased by 24 µmol (± 136) over the 90-d intervention period, irrespective of treatment group.
Both biofortified and fortified maize consumption improved milk retinol concentration. This did not translate into greater infant TBS, most likely due to adequate TBS at baseline. This trial was registered at clinicaltrials.gov as NCT02804490.
The use of clozapine requires monitoring the absolute neutrophil count because of the risk of agranulocytosis, but other potentially fatal adverse events associated with clozapine (specifically, ...myocarditis and cardiomyopathy) do not have mandatory procedures. We performed a systematic review of English-language articles to synthesize an evidence-based approach for myocarditis and cardiomyopathy monitoring. Articles published from January 1988 through February 2017 were identified through a search of Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Google Scholar. Selected articles were required to relate to myocarditis or cardiomyopathy in humans from exposure to clozapine. A total of 144 articles were included. Recommendations varied widely. Some authors recommended baseline laboratory monitoring, with or without follow-up testing, for C-reactive protein, creatine kinase MB, and troponin. Electrocardiography was commonly recommended, and echocardiography was less commonly recommended. The expense of monitoring was a consideration. A unanimous recommendation was to stop the use of clozapine and seek a cardiovascular consultation if myocarditis or cardiomyopathy is suspected. Although there is general agreement on which tests to perform for confirming myocarditis and cardiomyopathy, preemptive screening for these clozapine-induced conditions is controversial, and cost and barriers for the use of clozapine are concerns. For asymptomatic patients receiving clozapine, testing could include baseline electrocardiography, echocardiography as part of a cardiac consultation if patients have cardiac disease or risk factors, and monitoring of C-reactive protein and troponin as indicated.
Context‐specific research is needed on the relationship between household animal production and nutrition outcomes to inform programmes intervening in small‐scale animal production. We examined ...associations between household animal/fishpond ownership and animal source food (ASF) consumption among 6‐ to 12‐month‐old infants enroled in the control arm of a cluster‐randomised controlled trial in rural Bangladesh. We measured ASF consumption using a 7‐day food frequency questionnaire at 6, 9 and 12 months and assessed household animal/fishpond ownership at 12 months. We developed negative binomial regression models with random intercepts for infant and cluster, controlling for infant age and sex, maternal age, socioeconomic status and season. Models were stratified by a dichotomised maternal decision‐making score. Compared with infants in households without each animal type, those with 4–10 and ≥11 poultry consumed eggs 1.3 (95% confidence interval CI: 1.1, 1.6) and 1.6 (95% CI: 1.3, 2.0) times more, respectively; 2–3 and ≥4 dairy‐producing animals consumed dairy 1.9 (95% CI: 1.3, 2.7) and 2.0 (95% CI: 1.3, 3.1) times more, respectively; and ≥12 meat‐producing animals consumed meat 1.4 (95% CI: 1.0, 1.8) times more. It was unclear whether there was an association between fishpond ownership and fish consumption. Our results did not suggest that maternal decision‐making power was a modifier in the relationship between animal/fishpond ownership and ASF consumption. In this South Asian context, strategies intervening in household animal production may increase infant consumption of eggs, dairy and meat, but not necessarily fish. Research is needed on the role of market access and other dimensions of women's empowerment.
Key messages
Household ownership of poultry and dairy‐ and meat‐producing animals was associated with higher infant intakes of eggs, dairy and meat, respectively. There was not a clear association between household fishpond ownership and infant fish consumption.
While we found no significant differences in these relationships by maternal decision‐making power, future research in this setting should consider the relative importance of other dimensions of women's empowerment or other contextual factors, such as market access.
In Bangladesh and similar rural South Asian settings, programmes aiming to impact infant and child diet through agricultural interventions must assess the factors constraining both production and consumption.
Impaired dark adaptation is an early functional indicator of vitamin A deficiency that may be prevented by regular dietary intake of foods containing provitamin A carotenoids.
We tested the impact of ...provitamin A carotenoid-biofortified maize consumption (∼15 μg β-carotene/g) on dark adaptation in Zambian children.
We used a cluster-randomized trial of children aged 4-8 y (n = 1024) in Mkushi District, Zambia, and compared the regular consumption (2 meals/d, 6 d/wk for 6 mo) of biofortified orange maize (OM) to white maize (WM). The primary outcome was the serum retinol response. In a random sample (n = 542), we used a digital pupillometer to test pre- and postintervention responses to graded light stimuli (-2.9 to 0.1 log cd/m
) in a dark-adapted state.
At baseline, 11.7% of the children had serum retinol <0.7 μmol/L, 14.4% had impaired dark adaptation (pupillary threshold ≥ -1.11 log cd/m
), and 2.3% had night blindness. The mean ± SD pupillary responsiveness to light stimuli was poorer at baseline in the OM group (16.1% ± 6.6%) than the WM group (18.1% ± 6.4%) (P = 0.02) but did not differ at follow-up (OM: 17.6% ± 6.5%; WM: 18.3% ± 6.5%). Among children with serum retinol <1.05 μmol/L at baseline, there was greater improvement in pupillary responsiveness in the OM group (2.2%; 95% CI: 0.1%, 4.3%) than the WM group (0.2%; 95% CI: -1.1%, 1.5%; P = 0.01), but there were no differences in children with adequate baseline status. We found no effect of treatment on pupillary threshold or night blindness.
The regular consumption of provitamin A carotenoid-biofortified maize increased pupillary responsiveness among children with marginal or deficient vitamin A status, providing evidence of a functional benefit to consuming this biofortified crop. This trial was registered at clinicaltrials.gov as NCT01695148.
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