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.

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).

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.

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.

Factors associated with anemia among school-going adolescents aged 10-17 years in Zanzibar, Tanzania: a cross sectional study.

BACKGROUND: Anemia among adolescents (ages 10-19 years) is a leading cause of morbidity and mortality in low- and middle-income countries and carries long-term health and economic consequences. To address the issue, policymakers and programmers require evidence of the burden of anemia among adolescents in specific contexts, as well as an understanding of the factors associated with anemia in this population. METHODS: We conducted a cross-sectional survey as a baseline assessment to determine the prevalence and factors associated with anemia in secondary school students, as part of a cluster-randomized effectiveness trial testing different micronutrient supplementation strategies in addressing anemia among adolescents in Zanzibar. Between March 7th to 25th, 2022 the survey was conducted on 2,479 school-going adolescents aged 10-17 years from 42 schools on the island of Zanzibar, Tanzania. Hemoglobin concentration was measured along with the collection of socio-demographics, health, food frequency, and water, sanitation and hygiene data. RESULTS: Based on the World Health Organization cutoffs for anemia, 53.3% of the sample had anemia (mild, moderate, or severe). Using chi-square tests and logistic regressions, we determined that females had higher odds of anemia than males (Adjusted OR = 1.47; 95% CI: 1.24, 1.74), those in the highest wealth quintile had lower odds of anemia than those in the lowest wealth quintile (Adjusted OR = 0.7; CI: 0.54, 0.91), stunted adolescents had higher odds of anemia than non-stunted students (Adjusted OR = 1.38; 95% CI: 1.06,1.81), and those who used shared toilets had higher odds of moderate or severe anemia than those with private toilet access (Adjusted OR = 1.68; CI: 1.07, 2.64). CONCLUSIONS: The high prevalence of anemia in this sample indicates an urgent need to address anemia among adolescents in Zanzibar, and the factors associated with anemia point to the importance of water, sanitation, and hygiene interventions in addition to dietary and nutritional support. TRIAL REGISTRATION: NCT05104554, registered 03/11/2021.

School-based supplementation with iron-folic acid or multiple micronutrient tablets to address anemia among adolescents in Burkina Faso: a cluster-randomized trial.

BACKGROUND: Iron-deficiency anemia is a leading cause of morbidity among adolescents (aged 10-19 y), especially in low- and middle-income settings. Few policies and programs have targeted adolescent health. OBJECTIVES: This study aimed to evaluate the effectiveness of school-based supplementation with iron-folic acid (IFA) or multiple micronutrient supplements (MMSs) in addressing anemia among adolescents in Burkina Faso. METHODS: In this cluster-randomized trial, 3123 secondary school students aged 10 to 18 y in Burkina Faso were either supplemented with weekly IFA, daily MMSs, or received standard nutrition education as controls. Supplementation occurred between April 2021 and April 2022 over 2 supplementation periods (10 wk, then 16 wk) separated by a gap of 20 wk without supplementation. Hemoglobin was evaluated 4 times: at baseline prior to each supplementation period and at the end of each period. Anemia was categorized by the World Health Organization hemoglobin level cutoffs as none, mild, moderate, or severe. Associations between treatment arm and anemia or continuous hemoglobin (g/dL) were assessed using multilevel mixed effects generalized linear models with schools as a random effect, controlling for baseline hemoglobin or anemia status. RESULTS: Baseline anemia prevalence was similar across study arms, with 32.7% in IFA, 31.2% in MMS, and 29.5% in the control arm. Over the full study period, adolescents provided IFA had hemoglobin levels higher than those in the control arm (adjusted ß: 0.32; 95% CI: 0.02, 0.62). No significant associations were observed for MMS or for anemia outcomes; however, the direction and magnitude of nonsignificant associations indicate potential protective effects of IFA and MMSs on anemia. CONCLUSIONS: The results do not provide strong evidence that weekly IFA or daily MMS alone is effective, but supplementation may play a role in addressing adolescent anemia if combined with cointerventions. Additional research is required to determine the best strategy to address anemia. This trial was registered at clinicaltrials.gov as NCT04657640.

Vitamin D and Zinc Supplementation to Improve Treatment Outcomes among COVID-19 Patients in India: Results from a Double-Blind Randomized Placebo-Controlled Trial.

Background: There remains a need to identify low-cost interventions to improve coronavirus disease 2019 (COVID-19) outcomes. Vitamin D and zinc play a role in respiratory infections and could hold value as part of therapeutic regimens. Objectives: To determine the effect of vitamin D or zinc supplementation on recovery from COVID-19. Methods: We conducted a double-blind, randomly assigned 2 x 2 factorial placebo-controlled trial with 1:1:1:1 allocation ratio, enrolling nonpregnant adults with COVID-19 from hospitals in Mumbai and Pune, India (NCT04641195). Participants (N = 181) were randomly assigned to vitamin D3 (180,000 IU bolus, then 2000 IU daily), zinc (40 mg daily), vitamin D3 and zinc, or placebo, for 8 wk. Participants were followed until 8 wk. The primary outcome was time to resolution of fever, cough, and shortness of breath. Secondary outcomes were duration of individual symptoms; need for assisted ventilation; duration of hospital stay; all-cause mortality; and blood biomarkers, including nutritional, inflammatory, and immunological markers. Results: We observed no effect of vitamin D or zinc supplementation on time to resolution of all 3 symptoms [vitamin D hazard ratio (HR): 0.92; 95% confidence interval (95% CI): 0.66, 1.30; P = 0.650; zinc HR: 0.94; 95% CI: 0.67, 1.33; P = 0.745)]. Neither vitamin D nor zinc supplementation was associated with secondary outcomes, except for increased endline serum vitamin D with vitamin D supplementation [median (interquartile range) difference between endline and baseline for vitamin D: 5.3 ng/mL (-2.3 to 13.7); for no vitamin D: -1.4 ng/mL (-5.6 to 3.9); P = 0.003]. We observed nonsignificant increases in serum zinc at endline following zinc supplementation. There was no evidence of interaction between vitamin D and zinc supplementation, no effect of either on hypercalcemia, and no adverse events. Conclusions: Results suggest that neither vitamin D nor zinc supplementation improves COVID-19 treatment outcomes in this population. However, much larger-scale evidence, particularly from populations with vitamin D or zinc deficiency and severe infection, is required to corroborate our findings. This trial was registered at ClinicalTrials.gov and the Clinical Trials Registry of India as NCT04641195 and CTRI/2021/04/032593 respectively.

Antenatal depression and adverse birth outcomes among pregnant women living with HIV in Dar es Salaam, Tanzania.

BACKGROUND: Women who experience antenatal depression may be at increased risk of adverse birth outcomes. Few studies have examined this association among women living with HIV (WHIV). METHODS: We conducted a prospective cohort study of 2298 pregnant WHIV on antiretroviral therapy (ART) in Dar es Salaam, Tanzania, who were participants in a randomized trial of vitamin D3 supplementation. Depressive symptoms were assessed at 12-27 weeks gestation using the Hopkins Symptoms Checklist (HSCL-25). Generalized estimating equations to account for twins were used to assess the relative risks of adverse birth outcomes. RESULTS: Approximately 67 % of the women in our study population reported symptoms consistent with depression. We observed a 4.0 % prevalence of stillbirth and a 25.1 % prevalence of preterm birth. We found that low social support, higher education, and more recent initiation of ART were associated with a greater risk of antenatal depression. There was no association of antenatal depression with risk of fetal loss, stillbirth, low birth weight, birth weight, preterm birth, gestational age at delivery, or small-for-gestational age. LIMITATIONS: Depression was self-reported and only collected at one timepoint in pregnancy. Our findings may not be generalizable to all WHIV. CONCLUSIONS: Our findings illustrate the high risk of both depression and adverse birth outcomes among WHIV and underscore the need for interventions to improve their mental health and the health of their infants; however, the relationship between depression and birth outcomes remains unclear. Further research on this topic is merited, particularly examining the chronicity and timing of depression in pregnancy.

Associations of Diet Quality, Socioeconomic Factors, and Nutritional Status with Gestational Weight Gain among Pregnant Women in Dar es Salaam, Tanzania.

Background: Gestational weight gain (GWG) is a modifiable factor associated with maternal and child health outcomes, but the relationship between diet quality and GWG has not been evaluated using metrics validated for low-income and middle-income countries (LMICs). Objective: This study aimed to investigate relationships between diet quality, socioeconomic characteristics, and GWG adequacy using the novel Global Diet Quality Score (GDQS), the first diet quality indicator validated for use across LMIC. Methods: Weights of pregnant women enrolled between 12 and 27 wk of gestation (N = 7577) were recorded in Dar es Salaam, Tanzania, from 2001 to 2005 during a prenatal micronutrient supplementation trial. GWG adequacy was the ratio of measured GWG to Institute of Medicine-recommended GWG, categorized into severely inadequate (<70%), inadequate (70 to <90%), adequate (90 to <125%), or excessive (≥125%). Dietary data were collected using 24-h recalls. Multinomial logit models were used to estimate relationships between GDQS tercile, macronutrient intake, nutritional status, and socioeconomic characteristics and GWG. Results: GDQS scores in the second [relative risk (RR): 0.82; 95% confidence interval (CI): 0.70, 0.97] tercile were associated with lower risk of inadequate weight gain than those in the first tercile. Increased protein intake was associated with higher risk of severely inadequate GWG (RR: 1.06; 95% CI: 1.02, 1.09). Nutritional status and socioeconomic factors were associated with GWG: underweight prepregnancy BMI (in kg/m2) with a higher risk of severely inadequate GWG (RR: 1.49; 95% CI: 1.12, 1.99), overweight or obese BMI with a higher risk of excessive GWG (RR: 6.80; 95% CI: 5.34, 8.66), and a higher education (RR: 0.61; 95% CI: 0.42, 0.89), wealth (RR: 0.68; 95% CI: 0.48, 0.80), and height (RR: 0.96; 95% CI: 0.95, 0.98) with a lower risk of severely inadequate GWG. Conclusions: Dietary indicators showed few associations with GWG. However, stronger relationships were revealed between GWG, nutritional status, and several socioeconomic factors.This trial was registered at clinicaltrials.gov as NCT00197548.

Dietary Iron Intake and HIV-Related Outcomes Among Adults Initiating Antiretroviral Therapy in Tanzania.

OBJECTIVE: Anemia is highly prevalent among people living with HIV (PLWHIV) and is often due to iron deficiency. This study evaluated the relationship of dietary iron intake levels and sources with mortality and clinical outcomes among adults initiating HAART. DESIGN: We conducted a secondary analysis of a multivitamin supplementation trial among 2293 PLWHIV initiating HAART in Dar es Salaam, Tanzania. METHODS: Dietary iron intake was assessed with a food frequency questionnaire at HAART initiation, and participants followed until death or censoring. Total, animal-, and plant-sourced iron were categorized into quartiles. Intake of food groups was categorized into 0-1, 2-3, and ≥4 servings/wk. Cox proportional hazards models estimated hazard ratios for mortality and incident clinical outcomes. RESULTS: There were 175 deaths (8%). Red meat intake was associated with a lower risk of all-cause mortality (HR: 0.54; 95% CI: 0.35 to 0.83), AIDS-related mortality (HR: 0.49; 95% CI: 0.28 to 0.85), and severe anemia (HR: 0.57; 95% CI: 0.35 to 0.91), when intake ≥4 servings/wk, compared with 0-1 servings/wk. Legume intake was a lower risk of associated with all-cause mortality (HR: 0.49; 95% CI: 0.31 to 0.77) and AIDS-related mortality (HR: 0.37; 95% CI: 0.23 to 0.61), when intake ≥4 servings/wk, compared with 0-1 servings/wk. Although total dietary iron and overall plant-sourced iron intake were not associated with the risk of mortality or HIV-related outcomes, the highest quartile of animal-sourced iron intake was associated with a lower risk of all-cause mortality (HR: 0.56; 95% CI: 0.35 to 0.90) and a lower risk of AIDS-related mortality (HR: 0.50; 95% CI: 0.30 to 0.90), compared with the lowest quartile. CONCLUSION: Intake of iron-rich food groups may be associated with a lower risk of mortality and critical HIV-related outcomes among adults initiating HAART. TRIAL REGISTRATION: The parent trial was registered at Clinicaltrials.gov . Identifier: NCT00383669.

Assessing environmental enteric dysfunction via multiplex assay and its relation to growth and development among HIV-exposed uninfected Tanzanian infants.

BACKGROUND: Environmental enteric dysfunction (EED) may contribute to poor growth and development in young children. While validated EED biomarkers are currently lacking, multiplex assays are able to capture multiple domains of the condition. The purpose of this exploratory study was to examine the relationship between biomarkers of EED and subsequent growth and development among Tanzanian HIV-exposed uninfected (HEU) infants. METHODOLOGY: We enrolled 467 infants of mothers living with HIV who had participated in a trial of vitamin D3 supplementation during pregnancy. Infant serum samples collected at 6 weeks (n = 365) and 6 months (n = 266) were analyzed for anti-flagellin and anti-lipopolysaccharide (LPS) IgA and IgG via ELISA as well as the 11-plex Micronutrient and EED Assessment Tool (MEEDAT), which incorporates two biomarkers of EED [intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14)]. Outcomes were 12-month growth [length-for-age z-score (LAZ), weight-for-length z-score (WLZ), and weight-for-age z-score (WAZ)] and development [Caregiver Reported Early Development Instruments (CREDI) z-scores] and were assessed using linear regression. FINDINGS: In primary analyses, higher quartiles of 6-month anti-LPS IgG concentrations were significantly associated with lower LAZ at 12 months (ptrend = 0.040). In secondary analyses, higher log2-transformed 6-week anti-flagellin IgA and 6-month anti-LPS IgA concentrations were significantly associated with lower LAZ at 12 months. No associations were observed between I-FABP or sCD14 and infant growth. However, higher log2-transformed 6-week sCD14 concentrations were significantly associated with lower overall CREDI z-scores, while higher log2-transformed 6-month I-FABP concentrations were significantly associated with higher overall CREDI z-scores. CONCLUSIONS: Unlike anti-flagellin and anti-LPS Igs, MEEDAT's biomarkers of EED (I-FABP and sCD14) were not associated with subsequent linear growth among HEU infants in Tanzania. The relationship between EED and infant development warrants further study.

Oral iron supplementation and anaemia in children according to schedule, duration, dose and cosupplementation: a systematic review and meta-analysis of 129 randomised trials.

INTRODUCTION: WHO guidelines on iron supplementation among children call for further research to identify the optimal schedule, duration, dose and cosupplementation regimen. METHODS: A systematic review and meta-analysis of randomised controlled trials was undertaken. Randomised controlled trials providing ≥30 days of oral iron supplementation versus placebo or control to children and adolescents aged <20 years were eligible. Random-effects meta-analysis was used to summarise the potential benefits and harms of iron supplementation. Meta-regression was used to estimate iron effect heterogeneity. RESULTS: 129 trials with 201 intervention arms randomised 34 564 children. Frequent (3-7/week) and intermittent (1-2/week) iron regimens were similarly effective at decreasing anaemia, iron deficiency and iron deficiency anaemia (p heterogeneity >0.05), although serum ferritin levels and (after adjustment for baseline anaemia) haemoglobin levels increased more with frequent supplementation. Shorter (1-3 months) versus longer (7+ months) durations of supplementation generally showed similar benefits after controlling for baseline anaemia status, except for ferritin which increased more with longer duration of supplementation (p=0.04). Moderate-dose and high-dose supplements were more effective than low-dose supplements at improving haemoglobin (p=0.004), ferritin (p=0.008) and iron deficiency anaemia (p=0.02), but had similar effects to low-dose supplements for overall anaemia. Iron supplementation provided similar benefits when administered alone or in combination with zinc or vitamin A, except for an attenuated effect on overall anaemia when iron was cosupplemented with zinc (p=0.048). CONCLUSIONS: Weekly and shorter duration iron supplementation at moderate or high doses might be optimal approaches for children and adolescents at risk of deficiency. TRIAL REGISTRATION NUMBER: CRD42016039948.

Scaling-up high-impact micronutrient supplementation interventions to improve adolescents' nutrition and health in Burkina Faso and Tanzania: protocol for a cluster-randomised controlled trial.

INTRODUCTION: Adolescence is a critical time for growth and development, but this age group is often neglected in research and development of nutrition interventions. Despite recommendations from the WHO to provide nutrient supplements to adolescents, evidence remains scarce on the most effective supplementation strategy. This study aims to compare weekly iron and folic acid (IFA) supplementation with daily multiple micronutrient supplements (MMSs) in prevention of anaemia and improvement of school outcomes among adolescents in Burkina Faso and Tanzania. METHODS AND ANALYSIS: A three-arm cluster-randomised, school-based supplementation trial will be conducted among 84 schools (42 schools per site) and roughly 4500 students aged 10-17. Schools will be matched on three characteristics: number of students, school ranking profile, distance to main road (Tanzania) or distance to city council (Burkina Faso). Each school will be randomised to receive either weekly IFA, daily MMSs or serve as a control. Supplements will be delivered to students by teachers, who will provide monitoring data to the study team. Baseline and endline surveys will be conducted prior to and after each supplementation cycle (12 weeks in Burkina Faso; 1 year in Tanzania) to assess haemoglobin, anthropometry and sociodemographic variables. The primary outcome of haemoglobin will be analysed continuously using linear regression, and anaemia status will be analysed using logistic or multinomial regression, depending on categorisation level of the outcome. Secondary analyses of school performance indicators will also be conducted with either logistic or linear regression. ETHICS AND DISSEMINATION: This protocol has been approved by the Institutional Review Board of the Harvard TH Chan School of Public Health (IRB20-1108) and the Research Ethics Committees for the Ministries of Health in Tanzania (Zanzibar) and Burkina Faso. Results will be disseminated during meetings with the Ministries of Health and the participating communities as well as through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04657640; NCT05104554.

The effect of iron supplementation on maternal iron deficiency anemia does not differ by baseline anemia type among Tanzanian pregnant women without severe iron deficiency anemia.

PURPOSE: Whether anemia type modifies the risk of pregnancy and newborn outcomes and the effectiveness of iron supplementation is unclear. We examined the association of iron deficiency anemia (IDA) and non-iron deficiency anemia (NIDA) on the risks of these outcomes and the extent to which anemia type modifies the impact of prenatal iron supplementation. METHODS: This was a secondary analysis of a placebo-controlled trial of iron supplementation among 1450 HIV-negative women in Tanzania. Eligibility criteria included gestational age < 27 weeks, hemoglobin > 85 g/L, and ferritin > 12 µg/L. Individuals were categorized as non-anemia, IDA or NIDA using hemoglobin, ferritin and CRP. Analyses were conducted using regression models and likelihood ratio tests. RESULTS: Compared to the non-anemia group, delivery hemoglobin was lower by 15 g/L (95% CI 10.9, 19.3) in the baseline IDA group, and 7.3 g/L (95% CI 3.1, 11.5) in the baseline NIDA group. The RRs of anemia severity, iron deficiency, placental malaria, stillbirths, perinatal mortality, birthweight, and preterm birth were not different among women in the baseline NIDA group (vs. non-anemia) compared to the baseline IDA group (vs. non-anemia). The difference in the mean delivery hemoglobin for iron supplementation and placebo arms was 8 g/L (95% CI 6, 11) in the non-anemia group, 7 g/L (95% CI 2, 13) in the NIDA group, and 16 g/L (95% CI 10, 22) in the IDA group. CONCLUSION: Iron supplementation is effective even among pregnant women with NIDA. TRIAL REGISTRATION: NCT01119612 (May 7, 2010).

Effect of Oral Iron Supplementation on Cognitive Function among Children and Adolescents in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.

BACKGROUND: There is abundant evidence showing that iron deficiency is closely linked with delayed brain development, worse school performance, and behavioral abnormalities. However, evidence on the impact of iron supplementation among children and adolescents in low- and middle-income countries (LMICs) has been inconsistent. This study aims to examine the effect of oral iron supplementation on cognitive function among children and adolescents in LMICs. METHODS: A systematic review and meta-analysis was conducted to examine the impact of iron supplementation on cognitive function (including intelligence, attention, short-term memory, long-term memory, and school performance) among children and adolescents aged 5 to 19. We searched PubMed, Embase, Web of Science, CINAHL, and references of related articles published from the inception of the databases to 1 May 2022. Random-effects pooled standardized mean difference (SMD) with 95% confidence intervals (CIs) were calculated to estimate the effect of iron supplementation on cognitive function. We also investigated the heterogeneity of the effects using subgroup and meta-regression analyses. This review was registered with PROSPERO (CRD42020179064). RESULTS: Nine studies with 1196 individual participants from five countries were identified and included. Iron had a positive impact on intelligence test scores among children and adolescents (SMD = 0.47, 95% confidence interval [CI]: 0.10, 0.83). Meta-regression showed that the intelligence test scores improved with increasing the iron supplement dose (odds ratio [CI] = 1.02, 95% CI: 1.00, 1.04). There were no significant effects on attention, short-term memory, long-term memory, or school performance. CONCLUSIONS: Oral iron intake can improve the intelligence test scores of children and adolescents in LMICs and should be considered for future nutritional interventions.

Association of Exposure to Intimate Partner Violence With Maternal Depressive Symptoms and Early Childhood Socioemotional Development Among Mothers and Children in Rural Tanzania.

Importance: Approximately 1 in 4 women experience intimate partner violence (IPV) or nonpartner sexual violence during their lifetime. Mothers exposed to IPV are more likely to experience depressive symptoms and to discipline their children harshly, which may affect their children's socioemotional development; however, there is limited evidence on these outcomes. Objective: To examine the association between IPV, maternal depressive symptoms, harsh child discipline, and child stimulation with child socioemotional development. Design, Setting, and Participants: This study used cross-sectional follow-up data collected from February 19 to October 10, 2014, from a birth cohort of children aged 18 to 36 months who were enrolled in a randomized, double-blind, placebo-controlled trial of neonatal vitamin A supplementation in the Morogoro region of Tanzania. Data analysis occurred between September 10, 2019, and January 20, 2020. Exposures: Lifetime experience of IPV was assessed using an abbreviated module of the Tanzania Demographic and Health Survey, maternal depressive symptoms were assessed with the Patient Health Questionnaire, and data on harsh child discipline and maternal stimulation of their children were collected using modules of the United Nations Children's Fund Multiple Indicator Cluster Survey. Main Outcomes and Measures: Child socioemotional development was measured by the Caregiver-Reported Early Childhood Development Instruments. Results: A total of 981 mother-child dyads were included in the analytic sample; 388 children (39.6%) were between ages 18 and 24 (mean [SD] age, 27.06 [6.08]) months, and 515 (52.5%) were male children. A negative association was observed between maternal report of physical IPV only (mean difference, -0.022; 95% CI, -0.045 to -0.006) and physical and sexual IPV (mean difference, -0.045; 95% CI, -0.077 to -0.013) with child socioemotional scores, but neither was statistically significant after including depressive symptoms in the model, which is consistent with mediation. Furthermore, a negative association was observed between maternal mild to severe depressive symptoms and child socioemotional development, including adjustment for IPV (mean difference, -0.073; 95% CI, -0.103 to -0.043). Harsh disciplinary practices and stimulation were not associated with child socioemotional development after adjusting for IPV, maternal depressive symptoms, and other factors. Conclusions and Relevance: The findings of this study suggest that maternal depressive symptoms may explain the negative association between IPV and child socioemotional development.

Scaling up prenatal nutrition could reduce the global burden of noncommunicable diseases in the next generation: a modeling analysis.

BACKGROUND: Nutritional conditions during pregnancy may influence the epigenetic development of an individual and consequently their later-life risk of noncommunicable disease (NCD). Improving nutrition for pregnant females may therefore serve the dual purpose of directly improving pregnancy outcomes and preventing NCDs in the next generation. OBJECTIVES: We estimated the impact of prenatal supplementation with iron and folic acid (IFA), multiple micronutrients (MMS), or calcium at 50%, 75%, or 90% coverage on future NCDs by age and sex in 2015. METHODS: We used secondary data sources from 132 countries to quantify the cases of diabetes and hypertension and the deaths from selected NCDs that could be averted or delayed by scaling up prenatal micronutrient supplementation. RESULTS: Globally, >51,000 NCD deaths, 6 million cases of hypertension, and 3 million cases of diabetes could be prevented per offspring birth cohort if mothers were prenatally supplemented with MMS at 90% coverage. For IFA these numbers would be roughly half. Calcium supplementation at 90% could delay 51,000 deaths per birth cohort. Our model suggests that substantial numbers of NCD deaths and cases of hypertension and diabetes could be prevented in future generations by scaling up micronutrient supplementation for mothers during pregnancy. CONCLUSIONS: Highlighting the additional benefits of proven nutrition interventions is critical in ensuring adequate and sustained investments, and programmatic integration. As the double burden of disease continues to grow, population-wide efforts to scale up micronutrient supplementation to pregnant females could help prevent both undernutrition and chronic disease.

Effects of prenatal nutritional supplements on gestational weight gain in low- and middle-income countries: a meta-analysis of individual participant data.

BACKGROUND: Gestational weight gain (GWG) below or above the Institute of Medicine (IOM) recommendations has been associated with adverse perinatal outcomes. Few studies have examined the effect of prenatal nutrient supplementations on GWG in low- and middle-income countries (LMICs). OBJECTIVES: We aimed to investigate the effects of multiple micronutrient supplements (MMSs) and small-quantity lipid-based nutrient supplements (LNSs) on GWG in LMICs. METHODS: A 2-stage meta-analysis of individual participant data was conducted to examine the effects of MMSs (45,507 women from 14 trials) and small-quantity LNSs (6237 women from 4 trials) on GWG compared with iron and folic acid supplements only. Percentage adequacy of GWG and total weight gain at delivery were calculated according to the IOM 2009 guidelines. Binary outcomes included severely inadequate (percentage adequacy <70%), inadequate (<90%), and excessive (>125%) GWG. Results from individual trials were pooled using fixed-effects inverse-variance models. Heterogeneity was examined using I2, stratified analysis, and meta-regression. RESULTS: MMSs resulted in a greater percentage adequacy of GWG [weighted mean difference (WMD): 0.86%; 95% CI: 0.28%, 1.44%; P < 0.01] and higher GWG at delivery (WMD: 209 g; 95% CI: 139, 280 g; P < 0.01) than among those in the control arm. Women who received MMSs had a 2.9% reduced risk of severely inadequate GWG (RR: 0.971; 95% CI: 0.956, 0.987; P < 0.01). No association was found between small-quantity LNSs and GWG percentage adequacy (WMD: 1.51%; 95% CI: -0.38%, 3.40%; P = 0.21). Neither MMSs nor small-quantity LNSs were associated with excessive GWG. CONCLUSIONS: Maternal MMSs were associated with greater GWG percentage adequacy and total GWG at delivery than was iron and folic acid only. This finding is consistent with previous results on birth outcomes and will inform policy development and local recommendations of switching routine prenatal iron and folic acid supplements to MMSs.