Nutrition, Other Environmental Influences, and Genetics in the Determination of Human Stature.

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.

Interactions of Nutrition and Infection: The Role of Micronutrient Deficiencies in the Immune Response to Pathogens and Implications for Child Health.

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.

An Egg Intervention Improves Ponderal But Not Linear Growth Among Infants 6-12 mo of Age in Rural Bangladesh.

BACKGROUND: Animal source foods are rich in multiple nutrients. Regular egg consumption may improve infant growth in low- and middle-income countries. OBJECTIVES: To assess the impact of daily egg consumption on linear growth among 6-12-mo olds in rural Bangladesh. METHODS: We conducted a 2 × 4 factorial cluster-randomized controlled trial allocating clusters (n = 566) to treatment for enteric pathogens or placebo and a daily egg, protein supplement, isocaloric supplement, or control. All arms received nutrition education. Here, we compare the effect of the egg intervention versus control on linear growth, a prespecified aim of the trial. Infants were enrolled at 3 mo. We measured length and weight at 6 and 12 mo and visited households weekly to distribute eggs and monitor compliance. We used linear regression models to compare 12-mo mean length, weight, and z-scores for length-for-age (LAZ), weight-for-length, and weight-for-age (WAZ), and log-binomial or robust Poisson regression to compare prevalence of stunting, wasting, and underweight between arms. We used generalized estimating equations to account for clustering and adjusted models for baseline measures of outcomes. RESULTS: We enrolled 3051 infants (n = 283 clusters) across arms, with complete 6 and 12 mo anthropometry data from 1228 infants (n = 142 clusters) in the egg arm and 1109 infants (n = 141 clusters) in the control. At baseline, 18.5%, 6.0%, and 16.4% were stunted, wasted, and underweight, respectively. The intervention did not have a statistically significant effect on mean LAZ (ß: 0.05, 95% confidence interval [CI]: -0.01, 0.10) or stunting prevalence (ß: 0.98, 95% CI: 0.89, 1.13) at 12 mo. Mean weight (ß: 0.07 kg, 95% CI: 0.02, 0.11) and WAZ (ß: 0.06, 95% CI: 0.02, 0.11) were significantly higher in the egg compared with control arms. CONCLUSIONS: Provision of a daily egg for 6 mo to infants in rural Bangladesh improved ponderal but not linear growth. TRIAL REGISTRATION NUMBER: NCT03683667, https://clinicaltrials.gov/ct2/show/NCT03683667.

An Egg Intervention Improves Dietary Intakes but Does Not Fill Intake Gaps for Multiple Micronutrients among Infants in Rural Bangladesh.

BACKGROUND: Eggs are nutrient-rich. Strengthening evidence of the impact of egg consumption on dietary quality can inform complementary feeding guidance. OBJECTIVES: We aimed to assess the effect of an egg intervention on dietary intakes among infants aged 6-12 mo in rural Bangladesh. METHODS: We conducted a cluster-randomized controlled trial allocating clusters (n = 566) to enteric pathogen control or placebo treatment, with daily provision of a protein-rich meal, isocaloric meal, egg, or control. Nutrition education was provided to all arms. Our focus here is on the egg and control arms. Infants were enrolled at 3 mo. From 6 mo, we visited households weekly to distribute eggs and measure compliance. A semistructured feeding questionnaire assessed 24-h intake at 6, 9, and 12 mo. Assessments were repeated in ∼10% of subjects 2-29 d later. Using NCI SAS macros, we estimated usual intake distributions for energy, protein, fat, and 18 micronutrients and the proportion meeting intake recommendations. We compared the outcomes between the arms using clustered bootstrapping. RESULTS: Data were available from 757 infants (137 clusters) and 943 infants (141 clusters) in the egg and control arms, respectively. In the egg arm compared with the control arm, the mean usual intakes were higher for energy (610 compared with 602 kcal/d, 9 mo; 669 compared with 658 kcal/d, 12 mo), crude protein (2.2 compared with 1.7 g/(kg·d), 9 mo; 2.4 compared with 1.9 g/(kg·d), 12 mo), available protein (2.0 compared with 1.6 g/(kg·d), 9 mo; 2.1 compared with 1.8 g/(kg·d), 12 mo), and for 13 and 14 micronutrients at 9 and 12 mo, respectively. The proportion meeting intake recommendations for most micronutrients was higher in the egg arm but remained <50% for 15 and 13 micronutrients at 9 and 12 mo, respectively. CONCLUSIONS: Daily egg consumption improved dietary intakes among Bangladeshi infants, but was insufficient to meet multiple micronutrient intake recommendations, demonstrating the need to be coupled with other strategies.

Household animal ownership is associated with infant animal source food consumption in Bangladesh.

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.

Within-person, between-person and seasonal variance in nutrient intakes among 4- to 8-year-old rural Zambian children.

Estimates of the components of nutrient intake variation are needed for modelling distributions of usual intake or predicting the usual intake of individuals. Season is a potential source of variation in nutrient intakes in addition to within- and between-person variation, particularly in low- or middle-income countries. We aimed to describe seasonal variation in nutrient intakes and estimate within-person, between-person and other major components of intake variance among Zambian children. Children from rural villages and peri-urban towns in Mkushi District, Zambia aged 4-8 years were enrolled in the non-intervened arm of a randomised controlled trial of pro-vitamin A carotenoid biofortified maize (n 200). Up to seven 24-h dietary recalls per child were obtained at monthly intervals over a 6-month period covering the late post-harvest (August-October), early lean (November-January) and late lean (February-April) seasons (2012-2013). Nutrient intakes varied significantly by season. For energy and most nutrients, intakes were highest in the early lean season and lower in the late post-harvest and late lean seasons. Season and recall on a market day had the strongest effects on nutrient intakes among covariates examined. Unadjusted within- to between-person variance ratios ranged from 4·5 to 31·3. In components of variance models, season accounted for 3-20 % of nutrient intake variance. Particularly in rural settings in low- and middle-income countries, where availability of locally grown, nutrient-rich foods may vary seasonally, studies should include replicates across seasons to more precisely estimate long-term usual intakes.

Relative Contributions of Malaria, Inflammation, and Deficiencies of Iron and Vitamin A to the Burden of Anemia during Low and High Malaria Seasons in Rural Zambian Children.

OBJECTIVE: To estimate the burden of anemia attributable to malaria, inflammation, and deficiency of iron or vitamin A during low and high malaria seasons among Zambian children. STUDY DESIGN: From a cohort of children (n = 820), 4-8 years of age participating in a randomized controlled trial of pro-vitamin A, we estimated attributable fractions for anemia (hemoglobin of <110 or 115 g/L, by age) owing to current malaria or inflammation (C-reactive protein of >5 mg/L, or α-1 acid glycoprotein of >1 g/L, or both), and current or prior iron deficiency (ID; defined as low ferritin [<12 or 15 µg/L for age <5 or >5 years] or functional ID [soluble transferrin receptor of >8.3 mg/L] or both) and vitamin A deficiency (retinol of <0.7 µmol/L), during low and high malaria seasons, using multivariate logistic regression. Serum ferritin, soluble transferrin receptor, and retinol were adjusted for inflammation. RESULTS: The burden of anemia independently associated with current malaria, inflammation, ID, and vitamin A deficiency in the low malaria season were 12% (P < .001), 6% (P = .005), 14% (P = .001), and 2% (P = .07), respectively, and 32% (P < .001), 15% (P < .001), 10% (P = .06), and 2% (P = .06), respectively, in the high malaria season. In both seasons, functional ID was independently associated with more anemia (approximately 11%) than low ferritin (approximately 4%). Anemia and ID in the low malaria season, accounted for 20% (P < .001) and 4% (P = .095) of the anemia in the subsequent high malaria season. CONCLUSIONS: Anemia in this population is strongly linked to malaria, inflammation, and functional ID, and to a lesser extent, low iron stores. Integrated control strategies are needed.

A 10-Food Group Dietary Diversity Score Outperforms a 7-Food Group Score in Characterizing Seasonal Variability and Micronutrient Adequacy in Rural Zambian Children.

Background: 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. Objective: We assessed performance of 2 recommended dietary diversity scores as indicators of dietary quality over 3 seasons. Methods: 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. Results: 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. Conclusions: DDS-W performed better than DDS-IYCF in characterizing seasonal variability and micronutrient adequacy among rural Zambian children.

Nutritional Status Measures Are Correlated with Pupillary Responsiveness in Zambian Children.

Background: Impairments in visual function have been well characterized in vitamin A deficiency. However, eye function may also be sensitive to other nutrient deficiencies. Objective: We examined associations between visual function-characterized by pupillary threshold or pupillary responsiveness-and nutritional status in Zambian children. Methods: We used digital pupillometry to measure visual responses to calibrated light stimuli (-2.9 to 0.1 log cd/m2) among dark-adapted children aged 4-8 y (n = 542). We defined pupillary threshold as the first light stimulus at which pupil diameter decreased by ≥10% and considered a pupillary threshold ≥-0.9 log cd/m2 as impaired. Pupillary responsiveness was defined by absolute percentage of change in pupil diameter from pre- to poststimulus. We tested associations between these measures and serum concentrations of retinol, ß-carotene, ferritin, soluble transferrin receptor, and hemoglobin (Hb <11.0 or 11.5 g/dL were used to define anemia, depending on age), as well as anthropometric indexes, with the use multilevel mixed-effects models. Results: Pupillary threshold was correlated only with serum retinol (r = 0.12, P < 0.05). The strongest correlates of pupillary responsiveness were Hb (r = -0.16, P < 0.01), height-for-age z score (r = 0.14, P < 0.05), weight-for-age z score (r = 0.14, P < 0.05), and soluble transferrin receptor (r = 0.12, P < 0.05). In multivariate models, anemia was positively associated with pupillary responsiveness (ß = 2.99; 95% CI: 1.26, 4.72). Conclusions: In this marginally nourished population, we found positive correlations between vitamin A status, iron status, or anthropometric indexes and visual function. Hb was negatively associated with visual function, with greater pupillary responsiveness among anemic children. We posit that this may signal altered parasympathetic activity, possibly driven by infection. Future studies should consider a broader range of indicators to better characterize the relation between nutrition and visual function. This trial was registered at clinicaltrials.gov as NCT01695148.

Malaria exacerbates inflammation-associated elevation in ferritin and soluble transferrin receptor with only modest effects on iron deficiency and iron deficiency anaemia among rural Zambian children.

OBJECTIVE: In 4- to 8-year-old Zambian children (n = 744), we evaluated the effects of adjusting for inflammation (α1-acid glycoprotein >1 g/l), with or without additional adjustment for malaria, on prevalence estimates of iron deficiency (ID) and iron deficiency anaemia (IDA) during low malaria (LowM) and high malaria (HighM) transmission seasons. METHODS: To estimate adjustment factors, children were classified as: (i) reference (malaria negative without inflammation), (ii) inflammation without malaria (I), (iii) malaria without inflammation (M) and (iv) inflammation with malaria (IM). We estimated the unadjusted ID or IDA prevalence, and then adjusted for inflammation alone (IDI or IDAI ) or inflammation and malaria (IDIM or IDAIM ). RESULTS: Mean ferritin was 38 (reference), 45 (I), 43 (M) and 54 µg/l (IM) in LowM, increasing to 44, 56, 96 and 167 µg/l, respectively, in HighM. Corresponding mean sTfR was 6.4, 6.9, 7.9 and 8.4 mg/l in LowM, increasing to 8.2, 9.2. 8.7 and 9.7 mg/l in HighM. Ferritin-based ID, IDI and IDIM were 7.8%, 8.7% or 9.1%, respectively, in LowM and 4.6%, 10.0% or 11.7%, respectively, in HighM. Corresponding soluble transferrin receptor (sTfR)-based estimates were 27.0%, 24.1% and 19.1%, respectively, in LowM, increasing to 53.6%, 46.5% and 45.3%, respectively, in HighM. Additional adjustment for malaria resulted in a ~1- to 2-percentage point change in IDA, depending on biomarker and season. CONCLUSIONS: In this population, malaria substantially increased ferritin and sTfR concentrations, with modest effects on ID and IDA prevalence estimates.

Usual nutrient intake adequacy among young, rural Zambian children.

Inadequate nutrient intakes put children at risk for impaired growth and development. We described diet, usual intakes of energy and macro- and micronutrients and prevalence of nutrient intake adequacies among 4-8-year-old Zambian children. Children not yet in school and living in Mkushi District, Central Province, Zambia were enrolled into an efficacy trial of pro-vitamin A biofortified maize. Children in the non-intervened arm were included in this analysis (n 202). Dietary intake data were collected by tablet-based 24-h recall on a monthly basis over the 6-month trial. Observed nutrient intakes were derived from reported food quantities, standard recipes and food composition tables. Usual nutrient intake distributions were modelled based on observed intakes. Prevalence of inadequacy was estimated by comparing the usual nutrient intake distribution to the nutrient requirement distribution. Frequency and quantity of consumption of commonly reported foods were described and key sources of energy and nutrients were identified. Median usual energy intake was 6422 kJ/d (1535 kcal/d). Most childrens' macronutrient intakes fell within recommended ranges (74-98 %). Estimated prevalences of inadequate intakes of Fe, folate, vitamin B12 and Ca were 25, 57, 76 and >99 %, respectively. Estimated prevalences of inadequacy for other micronutrients were low (0·1-2·2 %). Commonly consumed foods included maize, vegetable oil, tomatoes, rape leaves and small fish (>0·6 servings/d), whereas meat, eggs or dairy were rarely eaten (<0·2 servings/d). These findings suggest that the heavily plant-based diet of rural Zambian children provides inadequate Ca, folate, vitamin B12 and Fe to meet recommended nutrient intakes.

High Iron Stores in the Low Malaria Season Increase Malaria Risk in the High Transmission Season in a Prospective Cohort of Rural Zambian Children.

Background: Higher iron stores, defined by serum ferritin (SF) concentration, may increase malaria risk.Objective: We evaluated the association between SF assessed during low malaria season and the risk of malaria during high malaria season, controlling for inflammation.Methods: Data for this prospective study were collected from children aged 4-8 y (n = 745) participating in a biofortified maize efficacy trial in rural Zambia. All malaria cases were treated at baseline (September 2012). We used baseline SF and malaria status indicated by positive microscopy at endline (March 2013) to define exposure and outcome, respectively. Iron status was defined as deficient (corrected or uncorrected SF <12 or <15 µg/L, depending on age <5 or ≥5 y, respectively), moderate (<75 µg/L, excluding deficient), or high (≥75 µg/L). We used a modified Poisson regression to model the risk of malaria in the high transmission seasons (endline) as a function of iron status assessed in the low malaria seasons (baseline).Results: We observed an age-dependent, positive dose-response association between ferritin in the low malaria season and malaria incidence during the high malaria season in younger children. In children aged <6 y (but not older children), we observed a relative increase in malaria risk in the moderate iron status [incidence rate ratio (IRR) with SF: 1.56; 95% CI: 0.64, 3.86; IRR with inflammation-corrected SF: 1.92; 95% CI: 0.75, 4.93] and high iron status (IRR with SF: 2.66; 95% CI: 1.10, 6.43; or IRR with corrected SF: 2.93; 95% CI: 1.17, 7.33) categories compared with the deficient iron status category. The relative increase in malaria risk for children with high iron status was statistically significant only among those with a concurrently normal serum soluble transferrin receptor concentration (<8.3 mg/L; IRR: 1.97; 95% CI: 1.20, 7.37).Conclusions: Iron adequacy in 4- to 8-y-old children in rural Zambia was associated with increased malaria risk. Our findings underscore the need to integrate iron interventions with malaria control programs. This trial was registered at clinicaltrials.gov as NCT01695148.

Short-Term Daily Consumption of Provitamin A Carotenoid-Biofortified Maize Has Limited Impact on Breast Milk Retinol Concentrations in Zambian Women Enrolled in a Randomized Controlled Feeding Trial.

BACKGROUND: Provitamin A carotenoid-biofortified maize is a conventionally bred staple crop designed to help prevent vitamin A deficiency. Lactating women are a potential target group, because regularly eating biofortified maize may increase vitamin A in breast milk-a critical source of vitamin A for breastfeeding infants. OBJECTIVE: We assessed whether daily consumption of biofortified orange maize would increase the retinol concentration in the breast milk of Zambian women. METHODS: Lactating women (n = 149) were randomly assigned to receive orange maize delivering 600 µg retinol equivalents (REs)/d as carotenoid plus placebo (OM), low-carotenoid white maize plus 600 µg REs/d as retinyl palmitate (VA), or white maize plus placebo (WM). Boiled maize (287 g dry weight/d) was served as 2 meals/d, 6 d/wk for 3 wk. We measured initial and final breast milk plasma retinol and ß-carotene concentrations, and plasma inflammatory protein concentrations. RESULTS: Groups were comparable at enrollment, with an overall geometric mean milk retinol concentration of 0.95 µmol/L (95% CI: 0.86, 1.05 µmol/L); 56% of samples had milk retinol <1.05 µmol/L. Median capsule and maize intake was 97% and 258 g dry weight/d, respectively. Final milk ß-carotene did not vary across groups (P = 0.76). Geometric mean (95% CI) milk retinol concentration tended to be higher in the OM [1.15 µmol/L (0.96, 1.39 µmol/L)] and VA [1.17 µmol/L (0.99, 1.38 µmol/L)] groups than in the WM group [0.91 µmol/L (0.72, 1.14 µmol/L); P = 0.13], and the proportion of women with milk retinol <1.05 µmol/L was 52.1%, 42.9%, and 36.7% in the WM, OM, and VA groups, respectively (P-trend = 0.16). CONCLUSIONS: Daily biofortified maize consumption did not increase mean milk retinol concentration in lactating Zambian women; however, there was a plausible downward trend in the risk of low milk retinol across intervention groups. This trial was registered at clinicaltrials.gov as NCT01922713.

Provitamin A Carotenoid-Biofortified Maize Consumption Increases Pupillary Responsiveness among Zambian Children in a Randomized Controlled Trial.

BACKGROUND: 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. OBJECTIVE: We tested the impact of provitamin A carotenoid-biofortified maize consumption (∼15 µg ß-carotene/g) on dark adaptation in Zambian children. METHODS: 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/m2) in a dark-adapted state. RESULTS: 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/m2), 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. CONCLUSIONS: 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.

A novel device for assessing dark adaptation in field settings.

BACKGROUND: Aberrant dark adaptation is common to many ocular diseases and pathophysiological conditions, including vitamin A deficiency, cardiopulmonary diseases, and hypoxia. Scotopic vision and pupillary responsiveness have typically been measured using subjective, time-consuming methods. Existing techniques are particularly challenging for use in developing country settings, where vitamin A deficiency remains a major public health problem. Our aim was design a compact, low cost, and easily operated device to assess dark adaptation in the field. METHODS: The Portable Field Dark Adaptometer (PFDA) incorporates a digital camera, a retinal bleaching flash, and a Ganzfeld light source inside a pair of light-obscuring goggles. After a ~10 min period of dark adaption, the infrared camera digitally records afferent pupillary responses to graded light stimuli (-2.9 to 0.1 log cd/m(2)). We tested this device in a variety of field settings to assess: a) ease of use and b) whether test data could clearly and accurately depict the well-known dose-response relationship between light intensity and pupil contraction. A total of 822 videos were collected. We used an open source video analysis software to measure pupil size in pixel units. Pupillary responsiveness was expressed as the percent change in pupil size from pre- to post-light exposure. Box plots, t test, and multi-level mixed effects linear regression modeling were used to characterize the relationship between light intensity and pupillary response. RESULTS: The PFDA was employed with only minor technical challenges in Bangladesh, Kenya, Zambia, and Peru. Our data show a clear linear increase in pupillary constriction with increasing log light intensity. Light intensity was a strong predictor of pupillary response, regardless of baseline pupil size. CONCLUSIONS: The consistent physiological response demonstrated here supports the use of the PFDA as a reliable tool to measure dark adaptation. As a next step, PFDA measurements will be validated against biochemical indicators of vitamin A status and hypoxemia. Ultimately, this new technology may provide a novel approach for nutritional assessment, with potential clinical applications.

Assessing Child Nutrient Intakes Using a Tablet-Based 24-Hour Recall Tool in Rural Zambia.

BACKGROUND: Detailed dietary intake data in low-income populations are needed for research and program evaluation. However, collection of such data by paper-based 24-hour recall imposes substantial demands for staff time and expertise, training, materials, and data entry. OBJECTIVE: To describe our development and use of a tablet-based 24-hour recall tool for conducting dietary intake surveys in remote settings. METHODS: We designed a 24-hour recall tool using Open Data Kit software on an Android tablet platform. The tool contains a list of local foods, questions on portion size, cooking method, ingredients, and food source and prompts to guide interviewers. We used this tool to interview caregivers on dietary intakes of children participating in an efficacy trial of provitamin A-biofortified maize conducted in Mkushi, a rural district in central Zambia. Participants were children aged 4 to 8 years not yet enrolled in school (n = 938). Dietary intake data were converted to nutrient intakes using local food composition and recipe tables. RESULTS: We developed a tablet-based 24-hour recall tool and used it to collect dietary data among 928 children. The majority of foods consumed were maize, leafy vegetable, or small fish dishes. Median daily energy intake was 6416 kJ (1469 kcal). CONCLUSIONS: Food and nutrient intakes assessed using the tablet-based tool were consistent with those reported in prior research. The tool was easily used by interviewers without prior nutrition training or computing experience. Challenges remain to improve programming, but the tool is an innovation that enables efficient collection of 24-hour recall data in remote settings.

Food and water insecurity in households of children and adolescents living with HIV and receiving care in a rural Zambian hospital: A mixed-methods study.

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.

Prelacteal feeding is not associated with infant size at 3 months in rural Bangladesh: a prospective cohort study.

BACKGROUND: Early and exclusive breastfeeding may reduce neonatal and post-neonatal mortality in low-resource settings. However, prelacteal feeding (PLF), the practice of giving food or liquid before breastfeeding is established, is still a barrier to optimal breastfeeding practices in many South Asian countries. We used a prospective cohort study to assess the association between feeding non-breastmilk food or liquid in the first three days of life and infant size at 3-5 months of age. METHODS: The analysis used data from 3,332 mother-infant pairs enrolled in a randomized controlled trial in northwestern rural Bangladesh conducted from 2018 to 2019. Trained interviewers visited women in their households during pregnancy to collect sociodemographic data. Project staff were notified of a birth by telephone and interviewers visited the home within approximately three days and three months post-partum. At each visit, interviewers collected data on breastfeeding practices and anthropometric measures. Infant length and weight measurements were used to produce length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) Z-scores. We used multiple linear regression to assess the association between anthropometric indices and PLF practices, controlling for household wealth, maternal age, weight, education, occupation, and infant age, sex, and neonatal sizes. RESULTS: The prevalence of PLF was 23%. Compared to infants who did not receive PLF, infants who received PLF may have a higher LAZ (Mean difference (MD) = 0.02 [95% CI: -0.04, 0.08]) score, a lower WLZ (MD=-0.06 [95% CI: -0.15, 0.03]) score, and a lower WAZ (MD=-0.02 [95% CI: -0.08, 0.05]) score at 3-5 months of age, but none of the differences were statistically significant. In the adjusted model, female sex, larger size during the neonatal period, higher maternal education, and wealthier households were associated with larger infant size. CONCLUSION: PLF was a common practice in this setting. Although no association between PLF and infant growth was identified, we cannot ignore the potential harm posed by PLF. Future studies could assess infant size at an earlier time point, such as 1-month postpartum, or use longitudinal data to assess more subtle differences in growth trajectories with PLF. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03683667 and NCT02909179.

Evolution of the child health day strategy for the integrated delivery of child health and nutrition services.

BACKGROUND: In efforts to meet the Millennium Development Goal for mortality among children under 5 years of age, countries require strategies for covering hard-to-reach and older children who are often missed by routine, fixed-site health services. OBJECTIVE: To document the evolution of Child Health Days (CHDs), designed as regular events for the delivery of health and nutrition services to children under the age of five. METHODS: We extracted information on service delivery strategies and codelivered interventions for the period 1999 to 2010from global monitoring databases for vitamin A and immunization. RESULTS: Our data illustrate a dramatic rise in CHDs over the decade: only two countries held CHDs in 1999; in 2010, 96 CHDs were conducted in 51 countries. Reliance on CHDs has been particularly marked in sub-Saharan Africa, where they are increasingly used to deliver five or more_services per event. Whereas early CHDs were largely defined by codelivery of vitamin A, immunizations, and deworming, they have since evolved into diverse packages including services such as water purification tablets and screening for severe malnutrition. CONCLUSIONS: The scale-up of CHDs is helping countries to achieve high and equitable coverage of essential health and nutrition services. Future research should consider whether the increasingly diverse services delivered via CHDs are guided by epidemiologic considerations, and whether the rising number of codelivered interventions is affecting coverage performance or service quality. Guidance is also needed to ensure that CHDs are implemented as part of systematic efforts to improve health systems.

The use and interpretation of serum retinol distributions in evaluating the public health impact of vitamin A programmes.

OBJECTIVE: Developing countries have adopted universal, high-potency vitamin A (VA) supplementation and food fortification as major strategies to control deficiency, prevent nutritional blindness and reduce child mortality. Yet questions persist regarding how best to measure impact and when to phase out supplementation. The present paper provides guidance on the use and interpretation of serum retinol (SROL) distributions as indicators of both programme impact and adequate VA intake in a population. DESIGN: We reviewed extant data on SROL's response to high-potency VA supplementation and VA-fortified foods in children. RESULTS: Supplementation virtually eliminates xerophthalmia and reduces child mortality; however, it shifts the SROL distribution only transiently (<2 months). Regular consumption of VA-fortified foods prevents xerophthalmia, lowers mortality and sustainably improves SROL distributions, from which both compliance and public health impact can be inferred. CONCLUSIONS: Given SROL's limited responsiveness to high-potency VA supplementation, target population coverage remains the preferred performance indicator. However, periodic SROL surveys do reflect underlying dietary risk and can guide programming: low or marginal SROL distributions in areas with high supplementation coverage do not signify programme failure, but rather suggest the need to continue supplementation while working to effectively raise dietary VA intakes. We propose that a sustained rise in the SROL distribution, defined as ≤5 % prevalence of SROL < 0·70 µmol/l among vulnerable population groups in at least two consecutive surveys (≥1 year apart), be used as an indicator of stable and adequate dietary VA intake and status in a population, at which point programmes may re-evaluate the need for continued universal supplementation.