Effects of Vitamin D3 Supplementation During Pregnancy and Lactation on Maternal and Infant Biomarkers of Environmental Enteric Dysfunction, Systemic Inflammation, and Growth: A Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Environmental enteric dysfunction (EED) is an acquired, subclinical state of intestinal inflammation common in children and adults in low- and middle-income countries. Although vitamin D3 supplementation has purported anti-inflammatory properties, its ability to ameliorate biomarkers of EED remains unclear. OBJECTIVE: To examine the effects of maternal vitamin D3 supplementation during pregnancy and lactation on biomarkers of EED, systemic inflammation, and growth in women living with HIV and their infants in Dar es Salaam, Tanzania. METHODS: We conducted subgroup analyses among randomly selected mothers (n=720) and infants (n=365 at six weeks of age, and n=266 at six months of age) that participated in a randomized, triple-blind, placebo-controlled trial of daily maternal 3,000 IU vitamin D3 supplementation from the second trimester of pregnancy until one year postpartum. Biomarkers of EED [soluble CD14 and intestinal fatty acid-binding protein (I-FABP)], systemic inflammation [C-reactive protein and alpha-1-acid glycoprotein (AGP)], and growth factors [insulin-like growth factor-1 (IGF-1) and fibroblast growth factor 21] were measured via the Micronutrient and Environmental Enteric Dysfunction Assessment Tool. Anti-flagellin and anti-lipopolysaccharide immunoglobulins were measured via enzyme-linked immunosorbent assay. Comparisons by randomized treatment arm were performed using ordinary least squared regression models with log2-transformed biomarkers. RESULTS: At 32 weeks gestation, I-FABP (ß: -0.19, p = 0.03) and AGP (ß: -0.11, p = 0.04) were significantly lower in mothers in the vitamin D3 group compared to the placebo group. At six weeks of age, IGF-1 (ß: -0.31, p = 0.03) was significantly lower in infants whose mothers were in the vitamin D3 group compared to the placebo group. CONCLUSIONS: Vitamin D3 supplementation during pregnancy and lactation reduced selected EED and systemic inflammation biomarkers among women living with HIV. While the effects of maternal vitamin D3 supplementation do not appear to extend to infants, there may be an effect on growth factors. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov identifier for parent trial: NCT02305927 (https://clinicaltrials.gov/study/NCT02305927).

Gestational weight gain at the national, regional, and income group levels based on 234 national household surveys from 70 low-income and middle-income countries.

Gestational weight gain (GWG) estimates enable the identification of populations of women at risk for adverse outcomes. We described GWG distribution in low- and middle-income countries (LMICs). Demographic and Health Surveys and other national surveys were used to calculate the average GWG by regressing the weight of pregnant women (15-49 years) at the time of the interview on their gestational age, adjusting for sociodemographic factors. A mixed-effects hierarchical model was built with survey-specific GWG as the dependent variable and restricted cubic splines for survey year, super-region, and country-level covariates (total fertility rate, gross domestic product, and average female body mass index) to predict the national, regional, and income level average GWG in 2020. Uncertainty ranges (UR) were obtained using bootstrap. Estimates were compared with the Institute of Medicine's GWG recommendations for women with normal weight (11.5kg) and underweight (12.5kg). Survey data were available for 70 LMICs (234 data points, 1991-2022). Predicted country-specific GWG for 2020 ranged from 2.6 to 13.5kg. Ten countries presented estimates above the recommendation for women with underweight; nine of which were from Central Europe, Eastern Europe, and Central Asia; apart from one, these were upper-middle income. Regional GWG was estimated at 5.4kg (95%UR 3.1,7.7) in Sub-Saharan Africa; 6.2kg (95%UR 3.4,9.0) in North Africa and the Middle East; 8.6kg (95%UR 6.0,11.3) in South Asia; 9.3kg (95%UR 6.2,12.3) in Southeast Asia, East Asia, and Oceania; 10.0kg (95%UR 7.1,12.9) in Latin America and the Caribbean; and 13.0kg (95%UR 9.0,16.9) in Central and Eastern Europe, and Central Asia. A gradient was observed across income: 5.3kg (95%UR 2.7,7.9) for low-income, 7.6kg (95%UR 5.2,10.1) for lower-middle-income, and 9.8kg (95%UR 7.1,12.5) for upper-middle-income countries. No income group achieved the minimum recommended weight gain. GWG was estimated to be insufficient in almost all LMICs. Improved data and monitoring are crucial for impactful interventions.

Estimated timing of the first menstrual period and dietary and nutritional correlates of menarche among urban school-going adolescents in four sub-Saharan African sites.

Characterizing the timing of menarche and the factors that are associated with it is important for understanding a population's reproductive health needs and long-term health trajectories. We estimated the age at the menstrual onset among adolescent girls and the association between dietary and nutritional factors and menarche in four sub-Saharan African urban sites. We used cross-sectional school-based data from 2307 female adolescents aged 10-14 years collected by the Africa Research, Implementation Science, and Education (ARISE) Network in Ouagadougou, Burkina Faso; Addis Ababa, Ethiopia; Khartoum, Sudan; and Dar es Salaam, Tanzania. Logit models were used to estimate the median age at menarche at each site. Associations between menarche and BMI-for-age, stunting, dietary quality and food insecurity across settings were assessed using Poisson regression models adjusted for country and school levels. The estimated median age at menarche was 13.1 years (95% confidence interval: 12.7, 13.5) in Ouagadougou; 12.9 (12.6, 13.2) in Addis Ababa; 13.3 (12.7, 13.6) in Khartoum; and 13.2 (12.3, 14.0) in Dar es Salaam. Between 18% and 49% of the girls in each setting had already menstruated. Based on the pooled multivariable models, underweight participants were 42% less likely (adjusted prevalence ratio [PR] 0.58 [0.44, 0.77]) to have experienced menarche in comparison to normal-weight individuals. The likelihood of experiencing menarche increased for overweight [PR 1.47 (1.30,1.66)] and obese [PR 1.57 (1.35,1.82)] in comparison to normal-weight girls. Those stunted were 47% less likely to have experienced menarche [PR 0.53 (0.41, 0.69)] than their nonstunted counterparts. A lower likelihood of menarche among those experiencing moderate/severe hunger when compared to those with no/little hunger was also observed (PR 0.78 [0.63,0.96]). No evidence of association with dietary quality was found. Further research is needed to strengthen the body of evidence and inform evidence-based initiatives in low- and middle-income settings.

School health and nutrition environments: A multicountry survey in five countries of sub-Saharan Africa region-Burkina Faso, Ethiopia, South Africa, Sudan, and Tanzania.

Schools are increasingly regarded as a key setting for promoting the health, well-being, and development of children and adolescents. In this multicountry cross-sectional survey, we describe the health, nutrition, and food environments of public primary schools in five urban settings in Africa region: Ouagadougou, Burkina Faso; Addis Ababa, Ethiopia; Durban; South Africa, Khartoum, Sudan; and, Dar es Salaam, Tanzania. We evaluated the school health and nutrition (SHN) environments in three main areas: (1) the availability of health-related policies, guidelines, and school curricula, (2) the provision of health, nutrition, and water, sanitation, and hygiene (WASH) services in schools, and (3) the school food environments and eating habits of adolescents. We used stratified random sampling to recruit 79 schools from five countries. Trained fieldworkers collected standardized questionnaire data from 79 school administrators, 765 food vendors, and 4999 in-school adolescents aged 10-15 years. In our study, 24 out of 79 school administrators were aware of their school's health-related policies and guidelines while 30 schools had a specific SHN curriculum. In general, health, nutrition, and WASH services were inadequate. Possibly due to a lack of school kitchens, 14.4% of students bought snacks and unhealthy foods from food vendors. Our study indicates that schools' food and nutrition environments are insufficient to improve adolescent health and nutrition in the African region, including limited coverage of SHN policies, suboptimal facilities and nutrition services, and unregulated food environments. Schools in sub-Saharan Africa need to improve their health and nutrition environments.

Emotional and cognitive influences on alcohol consumption in middle-aged and elderly Tanzanians: a population-based study.

Alcohol consumption in Tanzania exceeds the global average. While sociodemographic difference in alcohol consumption in Tanzania have been studied, the relationship between psycho-cognitive phenomena and alcohol consumption has garnered little attention. Our study examines how depressive symptoms and cognitive performance affect alcohol consumption, considering sociodemographic variations. We interviewed 2299 Tanzanian adults, with an average age of 53 years, to assess their alcohol consumption, depressive symptoms, cognitive performance, and sociodemographic characteristics using a zero-inflated negative binomial regression model. The logistic portion of our model revealed that the likelihood alcohol consumption increased by 8.4% (95% confidence interval [CI] 3.6%, 13.1%, p < 0.001) as depressive symptom severity increased. Conversely, the count portion of the model indicated that with each one-unit increase in the severity of depressive symptoms, the estimated number of drinks decreased by 2.3% (95% CI [0.4%, 4.0%], p = .016). Additionally, the number of drinks consumed decreased by 4.7% (95% CI [1.2%, 8.1%], p = .010) for each increased cognitive score. Men exhibited higher alcohol consumption than women, and Christians tended to consume more than Muslims. These findings suggest that middle-aged and elderly adults in Tanzania tend to consume alcohol when they feel depressed but moderate their drinking habits by leveraging their cognitive abilities.

Fetal, neonatal, and infant death among offspring of pregnant women living with HIV in Tanzania.

OBJECTIVE: Assess the risk of death for offspring of pregnant women living with HIV (PWLHIV) and the association with sociodemographic, pregnancy, HIV-related, and birth factors. DESIGN: We conducted a prospective cohort study of PWLHIV on antiretroviral therapy (ART) and their offspring in urban Tanzania who were enrolled in a vitamin D trial conducted from June 2015 to October 2019. METHODS: We described rates of fetal, neonatal, and infant death and assessed risk factors for these outcomes with generalized estimating equations. We also estimated population-attributable risk percentages for the contribution of prematurity and small-for-gestational age (SGA) to neonatal and infant mortality. RESULTS: Among 2,299 PWLHIV, there were a total of 136 fetal deaths (5.6%) and the stillbirth rate was 42.0 per 1,000 total births. Among 2,167 livebirths, there were 57 neonatal deaths (26.3 per 1,000 livebirths) and 114 infant deaths (52.6 per 1,000 livebirths). Twin birth was associated with neonatal death, while maternal CD4 T-cell count <350 cells/µL in pregnancy was associated with infant death (p-values < 0.05). As compared to term-appropriate-for-gestational age (AGA) births, the relative risks for neonatal mortality for term-SGA, preterm-AGA, and preterm-SGA infants were 2.07 (95% CI: 1.00-4.28), 2.87 (95% CI 1.54-5.35) and 7.15 (95% CI: 2.11-24.30), respectively. We estimated that 42.7% of neonatal and 29.4% of infant deaths were attributable to prematurity and SGA in the cohort. CONCLUSIONS: The risk of death is high for offspring of PWLHIV in Tanzania and the combination of prematurity and fetal growth restriction may account for nearly half of neonatal deaths.

Meals, Education, and Gardens for In-School Adolescents: A Cluster Randomized Trial of an Adolescent Nutrition Intervention Package in Tanzania.

PURPOSE: This study aimed to implement and evaluate integrated, school-based nutrition intervention packages for adolescents in Dodoma, Tanzania. METHODS: A cluster randomized controlled trial was conducted among six secondary schools in Dodoma, Tanzania. Two schools received the full-intervention package of school meals, nutrition education, school gardens, and community workshops. Two schools received the partial-intervention package without the school meals component. Two schools served as the controls and did not receive any intervention. The intervention was implemented over one academic year. The analytical sample included 534 adolescents aged 14 to 17 at baseline and 286 parents. Outcomes included nutrition knowledge, food preferences, diet quality, food insecurity, physical activity, growth, and anemia. Linear models were used to estimate mean differences, and logistic regression models were used to estimate odds ratios (ORs). RESULTS: Compared to the control, both the partial (OR: 0.59; 95% confidence interval [CI]: 0.35, 1.00) and full (OR: 0.49; 95% CI: 0.40, 0.59) interventions were associated with lower odds of poor diet quality among adolescents. Among the parents, both the partial (OR: 0.28; 95% CI: 0.20, 0.40) and full (OR: 0.28; 95% CI: 0.13, 0.58) interventions were associated with lower odds of poor diet quality. The partial (OR: 0.29; 95% CI: 0.18, 0.47) and full (OR: 0.47; 95% CI: 0.30, 0.72) interventions were associated with lower odds of adolescent overweight or obesity. DISCUSSION: School-based nutritional intervention packages incorporating multiple actions may improve the diet quality of adolescents and their household members and reduce the double burden of adolescent malnutrition.

Anemia and Iron Supplementation in Relation to Viral Load and Mortality among 70,442 People Living with Human Immunodeficiency Virus in Tanzania.

BACKGROUND: Anemia may be associated with poor clinical outcomes among people living with human immunodeficiency virus (HIV) (PLHIV) despite highly active antiretroviral therapy (HAART). There are concerns that iron supplementation may be unsafe to prevent and treat anemia among PLHIV. OBJECTIVE: The objective of the study was to evaluate the associations of anemia and iron supplementation with mortality and viral load among PLHIV in Tanzania. METHODS: We analyzed data from a cohort of 70,442 nonpregnant adult PLHIV in Tanzania conducted between 2015 and 2019. Regression models evaluated the relationships between anemia severity and iron supplement use with mortality and unsuppressed HIV-1 viral load among all participants and stratified by whether participants were initiating or continuing HAART. RESULTS: Anemia was associated with an increased risk of mortality and unsuppressed viral load for participants who initiated or continued HAART. Iron supplement use was associated with reduced mortality risk but also had a greater risk of an unsuppressed viral load among participants continuing HAART. There was no association of iron supplement use with mortality, and unsuppressed viral load among PLHIV that were initiating HAART. There was a stronger negative association between iron supplement use and the risk of having an unsuppressed viral load among participants with stage III/IV disease compared with stage I/II disease. CONCLUSIONS: Anemia is associated with increased risk of mortality and unsuppressed viral load, but the benefits and safety of iron supplements appear to differ for those initiating compared with continuing ART as well as by HIV disease severity.

Targeting strategies of antenatal balanced energy and protein supplementation in Addis Ababa, Ethiopia: study protocol for a randomized effectiveness study.

BACKGROUND: Antenatal balanced energy and protein (BEP) supplements have well-documented benefits for pregnancy outcomes. However, considerable practical gaps remain in the effective and cost-effective delivery of antenatal BEP supplements at scale in low- and middle-income countries. METHODS: A randomized effectiveness study will be conducted in two sub-cities of Addis Ababa, Ethiopia, to evaluate the effectiveness, cost-effectiveness, and implementation of different targeting strategies of antenatal BEP supplements. Pregnant women aged 18 to 49, with a gestational age of 24 weeks or less, and attending antenatal visits in one of the nine study health facilities are eligible for enrollment. In six of the health facilities, participants will be randomized to one of three study arms: control (Arm 1), targeted BEP provision based on baseline nutritional status (Arm 2), and targeted BEP supplementation based on baseline nutritional status and monthly gestational weight gain (GWG) monitoring (Arm 3). In the remaining three facilities, participants will be assigned to universal BEP provision (Arm 4). Participants in Arms 2 and 3 will receive BEP supplements if they have undernutrition at enrollment, as defined by a baseline body mass index less than 18.5 kg/m2 or mid-upper arm circumference less than 23 cm. In Arm 3, in addition to targeting based on baseline undernutrition, regular weight measurements will be used to identify insufficient GWG and inform the initiation of additional BEP supplements. Participants in Arm 4 will receive BEP supplements until the end of pregnancy, regardless of baseline nutritional status or GWG. All participants will receive standard antenatal care, including iron and folic acid supplementation. A total of 5400 pregnant women will be enrolled, with 1350 participants in each arm. Participants will be followed up monthly during their visits to the antenatal facilities until delivery. Maternal and infant health status will be evaluated within 72 h after delivery and at 6 weeks postpartum. The effectiveness and cost-effectiveness of the different BEP targeting strategies in preventing adverse pregnancy outcomes will be compared across arms. Qualitative data will be analyzed to assess the feasibility, acceptability, and implementation of different supplementation strategies. DISCUSSION: This study will inform global recommendations and operational guidelines for the effective and cost-effective delivery of antenatal BEP supplements. The targeted approaches have the potential for broader scale-up in Ethiopia and other low-resource settings with a high burden of undernutrition among pregnant women. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT06125860. Registered November 9, 2023.

The effects of prenatal and postnatal high-dose vitamin B-12 supplementation on human milk vitamin B-12: a randomized, double-blind, placebo-controlled trial in Tanzania.

BACKGROUND: Vitamin B-12 status in human milk (HM) has critical implications for infant growth and development. Few studies have separately evaluated the effects of prenatal and postnatal maternal high-dose vitamin B-12 supplementation on HM vitamin B-12 concentration. OBJECTIVES: This randomized controlled trial aimed to assess the effects of prenatal and postnatal vitamin B-12 supplementation on HM vitamin B-12 at 6 wk and 7 mo postpartum. METHODS: Pregnant women were enrolled in Dar es Salaam, Tanzania, between 2001 and 2004. From recruitment (12-27 weeks of gestation) through 6 wk postpartum, participants were randomly assigned to daily oral multiple micronutrient supplementation or placebo. From 6 wk to 18 mo postpartum, a subset of participants was randomly assigned to a postnatal supplement or placebo. The supplement included 50 µg/d of vitamin B-12 and various other vitamins. HM vitamin B-12 concentrations were analyzed at 6 wk and 7 mo postpartum for 412 participants. RESULTS: The prevalence of HM vitamin B-12 of <310 pmol/L was 73.3% and 68.4% at 6 wk and 7 mo postpartum, respectively. Prenatal supplementation increased HM vitamin B-12 concentration (percent difference: 34.4; 95% CI: 17.0, 54.5; P < 0.001) at 6 wk; this effect was not present at 7 mo. Postnatal supplementation increased HM vitamin B-12 concentration (percent difference: 15.9; 95% CI: 1.91, 31.9; P = 0.025) at 7 mo. Effect modification between prenatal and postnatal supplementation on HM vitamin B-12 status at 7 mo was found, with the effects of prenatal and postnatal supplements more pronounced among those receiving control during the other period; the prenatal supplement had a greater effect with postnatal control, and the postnatal supplement had a greater effect with prenatal control. CONCLUSIONS: Prenatal maternal vitamin B-12 supplementation has benefits on short-term HM status, and postnatal maternal vitamin B-12 supplementation has benefits on long-term HM status. This trial was registered at clinicaltrials.gov as NCT00197548. https://clinicaltrials.gov/ct2/show/NCT00197548.

The Impact of Excluding Adverse Neonatal Outcomes on the Creation of Gestational Weight Gain Charts Among Women from Low- and Middle-income Countries with Normal and Overweight BMI.

BACKGROUND: Existing gestational weight gain (GWG) charts vary considerably in their choice of exclusion/inclusion criteria, and it is unclear to what extent these criteria create differences in the charts' percentile values. OBJECTIVES: We aimed to establish the impact of including/excluding pregnancies with adverse neonatal outcomes when constructing GWG charts. METHODS: This is an individual participant data analysis from 31 studies from low- and middle-income countries. We created a dataset that included all participants and a dataset restricted to those with no adverse neonatal outcomes: preterm < 37 wk, small or large for gestational age, low birth weight < 2500 g, or macrosomia > 4000 g. Quantile regression models were used to create GWG curves from 9 to 40 wk, stratified by prepregnancy BMI, in each dataset. RESULTS: The dataset without the exclusion criteria applied included 14,685 individuals with normal weight and 4831 with overweight. After removing adverse neonatal outcomes, 10,479 individuals with normal weight and 3466 individuals with overweight remained. GWG distributions at 13, 27, and 40 wk were virtually identical between the datasets with and without the exclusion criteria, except at 40 wk for normal weight and 27 wk for overweight. For the 10th and 90th percentiles, the differences between the estimated GWG were larger for overweight (∼1.5 kg) compared with normal weight (<1 kg). Removal of adverse neonatal outcomes had minimal impact on GWG trajectories of normal weight. For overweight, the percentiles estimated in the dataset without the criteria were slightly higher than those in the dataset with the criteria applied. Nevertheless, differences were <1 kg and virtually nonexistent at the end of pregnancy. CONCLUSIONS: Removing pregnancies with adverse neonatal outcomes has little or no influence on the GWG trajectories of individuals with normal and overweight.

Community-based interventions targeting multiple forms of malnutrition among adolescents in low-income and middle-income countries: protocol for a scoping review.

BACKGROUND: Adolescent malnutrition is a significant public health challenge in low-income and middle-income countries (LMICs), with long-term consequences for health and development. Community-based interventions have the potential to address multiple forms of malnutrition and improve the health outcomes of adolescents. However, there is a limited understanding of the content, implementation and effectiveness of these interventions. This scoping review aims to synthesise evidence on community-based interventions targeting multiple forms of malnutrition among adolescents in LMICs and describe their effects on nutrition and health. METHODS AND ANALYSIS: A comprehensive search strategy will be implemented in multiple databases including MEDLINE (through PubMed), Embase, CENTRAL (through Cochrane Library) and grey literature, covering the period from 1 January 2000 to 14 July 2023. We will follow the Participants, Concept and Context model to design the search strategy. The inclusion criteria encompass randomised controlled trials and quasi-experimental studies focusing on adolescents aged 10-19 years. Various types of interventions, such as micronutrient supplementation, nutrition education, feeding interventions, physical activity and community environment interventions, will be considered. Two reviewers will perform data extraction independently, and, where relevant, risk of bias assessment will be conducted using standard Cochrane risk-of-bias tools. We will follow the PRISMA Extension for Scoping Reviews checklist while reporting results. ETHICS AND DISSEMINATION: The scope of this scoping review is restricted to publicly accessible databases that do not require prior ethical approval for access. The findings of this review will be shared through publications in peer-reviewed journals, and presentations at international and regional conferences and stakeholder meetings in LMICs. SCOPING REVIEW REGISTRATION: The final protocol was registered prospectively with the Open Science Framework on 19 July 2023 (https://osf.io/t2d78).

Co-occurrence of and factors associated with health risk behaviors among adolescents: a multi-center study in sub-Saharan Africa, China, and India.

Background: Despite lifelong and detrimental effects, the co-occurrence of health risk behaviors (HRBs) during adolescence remains understudied in low- and middle-income countries. This study examines the co-occurrence of HRBs and its correlates among adolescents in sub-Saharan Africa, China, and India. Methods: A multi-country cross-sectional study was conducted in 2021-2022, involving 9697 adolescents (aged 10-19 years) from eight countries, namely Burkina Faso, China, Ethiopia, India, Ghana, Nigeria, Tanzania, and Uganda. A standardized questionnaire was administered to examine five types of HRBs - physical inactivity, poor dietary habits, smoking, alcohol consumption, and risky sexual behavior. Latent class analysis was employed to identify clustering patterns among the behaviors, and logistic regression was used to identify the correlates of these patterns. Findings: Three clusters of HRBs were identified, with Cluster 1 (27.73%) characterized by the absence of any specific risky behavior, Cluster 2 (68.16%) characterized by co-occurrence of physical inactivity and poor dietary habits, and Cluster 3 (4.11%) characterized by engagement in smoking, alcohol consumption, and risky sexual behavior. Relative to Cluster 1, being in Cluster 2 was associated with being female (aOR 1.20, 95% CI 1.09-1.32), not enrolled in education (aOR 0.84, 95% CI 0.71-0.99), and not engaged in paid work (aOR 1.23, 95% CI 1.08-1.41). Compared with those Cluster 1, adolescents in Cluster 3 were less likely to be female (aOR 0.41, 95% CI 0.32-0.54), be engaged in paid work (aOR 0.54, 95% CI 0.41-0.71), more likely to be older (aOR 7.56, 95% CI 5.18-11.03), not be enrolled in educational institution (aOR 1.74, 95% CI 1.27-2.38), and more likely to live with guardians other than parents (aOR 1.56, 95% CI 1.19-2.05). Interpretation: The significant clustering patterns of HRBs among adolescents in sub-Saharan Africa, China, and India highlights the urgent need for convergent approaches to improve adolescent health behaviors. Early life and school-based programs aimed at promoting healthy behaviors and preventing risky and unhealthy behaviors should be prioritized to equip adolescents with the tools and skills for lifelong well-being. Funding: Fondation Botnar (Grant #INV-037672) and Harvard T.H. Chan School of Public Health, partially funded this study.

Neonatal mortality risk of vulnerable newborns by fine stratum of gestational age and birthweight for 230 679 live births in nine low- and middle-income countries, 2000-2017.

OBJECTIVE: To describe the mortality risks by fine strata of gestational age and birthweight among 230 679 live births in nine low- and middle-income countries (LMICs) from 2000 to 2017. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Liveborn infants from 15 population-based cohorts. METHODS: Subnational, population-based studies with high-quality birth outcome data were invited to join the Vulnerable Newborn Measurement Collaboration. All studies included birthweight, gestational age measured by ultrasound or last menstrual period, infant sex and neonatal survival. We defined adequate birthweight as 2500-3999 g (reference category), macrosomia as ≥4000 g, moderate low as 1500-2499 g and very low birthweight as <1500 g. We analysed fine strata classifications of preterm, term and post-term: ≥42+0 , 39+0 -41+6 (reference category), 37+0 -38+6 , 34+0 -36+6 ,34+0 -36+6 ,32+0 -33+6 , 30+0 -31+6 , 28+0 -29+6 and less than 28 weeks. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for neonatal mortality rates (NMR) and relative risks (RR). We also performed meta-analysis for the relative mortality risks with 95% confidence intervals (CIs) by the fine categories, stratified by regional study setting (sub-Saharan Africa and Southern Asia) and study-level NMR (≤25 versus >25 neonatal deaths per 1000 live births). RESULTS: We found a dose-response relationship between lower gestational ages and birthweights with increasing neonatal mortality risks. The highest NMR and RR were among preterm babies born at <28 weeks (median NMR 359.2 per 1000 live births; RR 18.0, 95% CI 8.6-37.6) and very low birthweight (462.8 per 1000 live births; RR 43.4, 95% CI 29.5-63.9). We found no statistically significant neonatal mortality risk for macrosomia (RR 1.1, 95% CI 0.6-3.0) but a statistically significant risk for all preterm babies, post-term babies (RR 1.3, 95% CI 1.1-1.5) and babies born at 370 -386 weeks (RR 1.2, 95% CI 1.0-1.4). There were no statistically significant differences by region or underlying neonatal mortality. CONCLUSIONS: In addition to tracking vulnerable newborn types, monitoring finer categories of birthweight and gestational age will allow for better understanding of the predictors, interventions and health outcomes for vulnerable newborns. It is imperative that all newborns from live births and stillbirths have an accurate recorded weight and gestational age to track maternal and neonatal health and optimise prevention and care of vulnerable newborns.

Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy.

BACKGROUND: The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers. METHODS: We conducted two independent randomized trials of calcium supplementation, in India and Tanzania, to assess the noninferiority of a 500-mg daily dose to a 1500-mg daily dose of calcium supplementation. In each trial, the two primary outcomes were preeclampsia and preterm birth, and the noninferiority margins for the relative risks were 1.54 and 1.16, respectively. RESULTS: A total of 11,000 nulliparous pregnant women were included in each trial. The cumulative incidence of preeclampsia was 3.0% in the 500-mg group and 3.6% in the 1500-mg group in the India trial (relative risk, 0.84; 95% confidence interval [CI], 0.68 to 1.03) and 3.0% and 2.7%, respectively, in the Tanzania trial (relative risk, 1.10; 95% CI, 0.88 to 1.36) - findings consistent with the noninferiority of the lower dose in both trials. The percentage of live births that were preterm was 11.4% in the 500-mg group and 12.8% in the 1500-mg group in the India trial (relative risk, 0.89; 95% CI, 0.80 to 0.98), which was within the noninferiority margin of 1.16; in the Tanzania trial, the respective percentages were 10.4% and 9.7% (relative risk, 1.07; 95% CI, 0.95 to 1.21), which exceeded the noninferiority margin. CONCLUSIONS: In these two trials, low-dose calcium supplementation was noninferior to high-dose calcium supplementation with respect to the risk of preeclampsia. It was noninferior with respect to the risk of preterm live birth in the trial in India but not in the trial in Tanzania. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT03350516; Clinical Trials Registry-India number, CTRI/2018/02/012119; and Tanzania Medicines and Medical Devices Authority Trials Registry number, TFDA0018/CTR/0010/5).

Effects of Zinc Supplementation on Metabolomic Profiles in Tanzanian Infants: A Randomized Trial.

BACKGROUND: Provision of zinc supplementation to young children has been associated with reduced infectious morbidity and better growth outcomes. However, the metabolic pathways underlying these outcomes are unclear, and metabolomic data from humans undergoing zinc supplementation, particularly infants, are generally lacking. OBJECTIVES: This study aimed to examine the effect of zinc supplementation on metabolic profiles in Tanzanian infants aged 6 wk and 6 mo. METHODS: Blood samples were collected at age 6 wk and 6 mo from 50 Tanzanian infants who were enrolled in a randomized placebo-controlled trial of zinc supplementation (5 mg oral daily). Metabolomic analysis using an ultrahigh-performance liquid chromatography/tandem mass spectroscopy platform was performed to identify potential metabolomic profiles and biomarkers associated with zinc supplementation. Principal component analysis (PCA) was used to summarize metabolomic data from all samples. Two-way repeated measures analysis of variance with compound symmetry covariance structures were used to compare metabolome levels over time between infants in the 2 treatment arms. RESULTS: In PCA, the samples tended to be more separated by child age (6 wk compared with 6 mo) than by zinc supplementation status. We found that zinc supplementation affected a variety of metabolites associated with amino acid, lipid, nucleotide, and xenobiotic metabolism, including indoleacetate in the tryptophan metabolism pathway; 3-methoxytrosine and 4-hydrxoyphenylphruvate in the tyrosine pathway; eicosanedioate, 2-aminooctanoate, and N-acetyl-2-aminooctanoate in the fatty acid pathway; and N6-succinyladenosine in the purine metabolism pathway. Compared to the relatively small number of metabolites associated with zinc supplements, many infant metabolites changed significantly from age 6 wk to 6 mo. CONCLUSIONS: Zinc supplementation, despite having overall clinical benefits, appears to induce limited metabolomic changes in blood metabolites in young infants. Future larger studies may be warranted to further examine metabolic pathways associated with zinc supplementation. The parent trial was registered at clinicaltrials.gov as NCT00421668.

Women's input and decision-making in agriculture are associated with diet quality in rural Tanzania.

Background: Women's empowerment is one critical pathway through which agriculture can impact women's nutrition; however, empirical evidence is still limited. We evaluated the associations of women's participation, input, and decision-making in key agricultural and household activities with women's diet quality. Methods: We analyzed data from a cross-sectional study of 870 women engaged in homestead agriculture. We used food frequency questionnaires to assess women's diets and computed women's diet quality using the Prime Diet Quality Score (PDQS) (range 0-42), which captures healthy and unhealthy foods. We evaluated women's decision-making in 8 activities, food crop farming, cash crop farming, livestock raising, non-farm economic activities, wage/salary employment, fishing, major household expenditures, and minor household expenditures. Generalized estimating equations (GEE) linear models were used to evaluate associations between (a) women's participation, (b) decision-making, (c) adequate input, (d) adequate extent of independence in decision-making in agriculture, and (e) adequate input in use of agricultural income with their PDQS. Adequate input was defined as input into some, most or all decisions compared to input into few decisions or none. Adequate extent of independence was defined as input to a medium or high extent compared to input to a small extent or none. Findings: Median PDQS was 19 (IQR: 16-21). Women's adequate input in decision-making on wage and salary employment (estimate: 4.19, 95% CI: 2.80, 5.57) and minor expenditures were associated with higher PDQS vs. inadequate input. Women with independence in decision-making on livestock production (estimate: 0.97, 95% CI: 0.05, 1.90) and minor household expenditures, and women with adequate decision-making in the use of income from wages/salaries (estimate: 3.16, 95% CI: 2.44, 3.87) had higher PDQS. Participation in agricultural activities was positively associated with PDQS. Conclusions: Women's participation and input in decision-making in wage and salary employment, livestock production, and minor household expenditures were strongly associated with the consumption of better-quality diets. Women participating in multiple farm activities were also likely to have better diet quality. This study adds to the growing evidence on the pathways through which women's empowerment may influence women's nutrition in rural Tanzania.

Depressive symptoms among adolescents in six sub-Saharan African countries: A pooled analysis of associated factors.

There is a need to identify risk factors, including nutrition-related factors, for depressive disorders among sub-Saharan African (SSA) adolescents. We examined the association of multiple measures with depressive symptoms among adolescents living across six SSA countries. Building on previous analyses, we used data from a cross-sectional study conducted from 2015 to 2017 among adolescents aged 10-19 years in six SSA countries (N = 7512). Depressive symptoms were defined as highest tertile of the 6-item Kutcher Adolescent Depression Scale score. Using mixed-effects Poisson regression models, we pooled data across sites and examined the association of sociodemographic, nutrition, and other indices with depressive symptoms. We additionally assessed effect modification by sex, age, and school-going status. We observed higher risk of depressive symptoms among girls (adjusted risk ratio [RR]: 1.29, 95 % confidence interval [95 % CI]: 1.05-1.58, P = 0.016), older adolescents (RR for 18-19 years: 1.59, 95 % CI: 1.44-1.76, P < 0.001), and adolescents experiencing bullying (RR: 1.43, 95 % CI: 1.26-1.62, P < 0.001) or violence (RR: 1.34, 95 % CI: 1.24-1.45, P < 0.001). Adolescents experiencing food insecurity also had a higher risk of depressive symptoms (RR: 1.90, 95 % CI: 1.64-2.19, P < 0.001) along with those consuming ≥ 5 servings of fruit and vegetables per day (RR: 1.18, 95 % CI: 1.03-1.34, P = 0.015); conversely, those who consumed grains, roots and tubers in the past day were at decreased risk (RR: 0.73, 95 % CI: 0.69-0.77, P < 0.001). There was no strong evidence of effect modification of associations. This study reinforces the potential role of multiple sociodemographic and nutrition-related measures on risk of depressive symptoms in these populations.