What more can be done? Prioritizing the most promising antenatal interventions to improve birth weight.

BACKGROUND: Low birth weight (LBW) is associated with neonatal mortality and sequelae of lifelong health problems; prioritizing the most promising antenatal interventions may guide resource allocation and improve health outcomes. OBJECTIVE: We sought to identify the most promising interventions that are not yet included in the policy recommendations of the World Health Organization (WHO) but could complement antenatal care and reduce the prevalence of LBW and related adverse birth outcomes in low- and middle-income settings. METHODS: We utilized an adapted Child Health and Nutrition Research Initiative (CHNRI) prioritization method. RESULTS: In addition to procedures already recommended by WHO for the prevention of LBW, we identified six promising antenatal interventions that are not currently recommended by WHO with an indication for LBW prevention, namely: (1) provision of multiple micronutrients; (2) low-dose aspirin; (3) high-dose calcium; (4) prophylactic cervical cerclage; (5) psychosocial support for smoking cessation; and (6) other psychosocial support for targeted populations and settings. We also identified seven interventions for further implementation research and six interventions for efficacy research. CONCLUSION: These promising interventions, coupled with increasing coverage of currently recommended antenatal care, could accelerate progress toward the global target of a 30% reduction in the number of LBW infants born in 2025 compared to 2006-10.

Evidence-based antenatal interventions to reduce the incidence of small vulnerable newborns and their associated poor outcomes.

A package of care for all pregnant women within eight scheduled antenatal care contacts is recommended by WHO. Some interventions for reducing and managing the outcomes for small vulnerable newborns (SVNs) exist within the WHO package and need to be more fully implemented, but additional effective measures are needed. We summarise evidence-based antenatal and intrapartum interventions (up to and including clamping the umbilical cord) to prevent vulnerable births or improve outcomes, informed by systematic reviews. We estimate, using the Lives Saved Tool, that eight proven preventive interventions (multiple micronutrient supplementation, balanced protein and energy supplementation, low-dose aspirin, progesterone provided vaginally, education for smoking cessation, malaria prevention, treatment of asymptomatic bacteriuria, and treatment of syphilis), if fully implemented in 81 low-income and middle-income countries, could prevent 5·202 million SVN births (sensitivity bounds 2·398-7·903) and 0·566 million stillbirths (0·208-0·754) per year. These interventions, along with two that can reduce the complications of preterm (<37 weeks' gestation) births (antenatal corticosteroids and delayed cord clamping), could avert 0·476 million neonatal deaths (0·181-0·676) per year. If further research substantiates the preventive effect of three additional interventions (supplementation with omega-3 fatty acids, calcium, and zinc) on SVN births, about 8·369 million SVN births (2·398-13·857) and 0·652 million neonatal deaths (0·181-0·917) could be avoided per year. Scaling up the eight proven interventions and two intrapartum interventions would cost about US$1·1 billion in 2030 and the potential interventions would cost an additional $3·0 billion. Implementation of antenatal care recommendations is urgent and should include all interventions that have proven effects on SVN babies, within the context of access to family planning services and addressing social determinants of health. Attaining high effective coverage with these interventions will be necessary to achieve global targets for the reduction of low birthweight births and neonatal mortality, and long-term benefits on growth and human capital.

Antenatal multiple micronutrient supplements versus iron-folic acid supplements and birth outcomes: Analysis by gestational age assessment method.

Meta-analyses consistently have found that antenatal multiple micronutrient supplementation (MMS) compared with iron and folic acid (IFA) alone reduce adverse birth outcomes. In 2020, the World Health Organization (WHO) placed a conditional recommendation for MMS and requested additional trials using ultrasounds to establish gestational age, because the evidence on low birthweight (LBW), preterm birth and small for gestational age (SGA) was considered inconsistent. We conducted meta-analyses to determine if the effects of MMS on LBW, preterm birth and SGA differed by gestational age assessment method. Using data from the 16 trials in the WHO analyses, we calculated the effect estimates of MMS versus IFA on birth outcomes (generic inverse variance method and random effects model) stratified by method of gestational age assessment: ultrasound, prospective collection of the date of last menstrual period (LMP) and confirmation of pregnancy by urine test and recall of LMP. The effects of MMS versus IFA on birthweight, preterm birth and SGA appeared consistent across subgroups with no evidence of subgroup differences (p > 0.05). When limited to the seven trials that used ultrasound, the beneficial effects of MMS were demonstrated: risk ratios of 0.87 (95% confidence interval [CI] 0.78-0.97) for LBW, 0.90 (95% CI, 0.79-1.03) for preterm birth and 0.9 (95% CI, 0.83-0.99) for SGA. Sensitivity analyses indicated consistency in the results. These results, together with recent analyses demonstrating comparable effects of MMS (vs. IFA) on maternal anaemia outcomes, strengthen the evidence to support a transition from IFA to MMS programmes in low- and middle-income countries.

Effectiveness of Dietary Management for Moderate Wasting among Children > 6 Months of Age-A Systematic Review and Meta-Analysis Exploring Different Types, Quantities, and Durations.

Currently, no World Health Organization guidelines exist for the management of approximately 31.8 million moderately wasted children globally. The objective of this review was to synthesise evidence on the optimal type, quantity, and duration of dietary treatment for moderate wasting. Ten electronic databases were searched until the 23rd of August 2021. Experimental studies comparing interventions for the dietary management of moderate wasting were included. Meta-analyses were conducted and results were presented as risk ratios or mean differences with 95% confidence intervals. Seventeen studies comparing specially formulated foods were included involving 23,005 participants. Findings suggest little or no difference in recovery between Fortified Blended Foods (FBFs) with improved micronutrient and/or milk content (enhanced FBFs) and lipid-based nutrient supplements (LNS), whereas children treated with non-enhanced FBFs (locally produced FBFs or standard corn-soy blend) may have lower recovery rates than those treated with LNS. There was no difference in recovery when ready-to-use therapeutic and ready-to-use supplementary food were compared. Other outcomes mostly aligned with results for recovery. In conclusion, LNSs improve recovery compared to non-enhanced FBFs, but are comparable to enhanced FBFs. Programmatic choice of supplement should consider factors such as cost, cost-effectiveness, and acceptability. Further research is required to determine optimal dosing and duration of supplementation.

Maternal and child nutrition in the Lives Saved Tool: Results of a recent update.

Background: The Lives Saved Tool (LiST) is a mathematical modelling tool for estimating the survival, health, and nutritional impacts of scaling intervention coverage in low- and middle-income countries (LMICs). Various nutrition interventions are included in LiST and are regularly (and independently) reviewed and updated as new data emerge. This manuscript describes our latest in-depth review of nutrition evidence, focusing on intervention efficacy, appropriate population-affected fractions, and new interventions for potential inclusion in the LiST model. Methods: An external advisory group (EAG) was assembled to review evidence from systematic reviews on intervention-outcome (I-O) pairs for women and children under five years of age. GRADE quality was assigned to each pair based on a LiST-specific checklist to facilitate consistent decisions during the consideration. For existing interventions with new information, the EAG was asked to recommend whether to update the default efficacy values and population-affected fractions. For the new interventions, the EAG decided whether there was sufficient evidence of benefit, and in affirmative cases, information on the efficacy and affected fraction values that could be used. Decisions were based on expert group consensus. Results: Overall, the group reviewed 53 nutrition-related I-O pairs, including 25 existing and 28 new ones. Efficacy and population-affected fractions were updated for seven I-O pairs; three pairs were updated for efficacy estimates only, three were updated for population-affected fractions only; and nine new I-O pairs were added to the model, bringing the total of nutrition-related I-O pairs to 34. Included in the new I-O pairs were two new nutrition interventions added to LIST: zinc fortification and neonatal vitamin A supplementation. Conclusions: For modelling tools like LiST to be useful, it is crucial to update interventions, efficacy and population-affected fractions as new evidence becomes available. The present updates will enable LiST users to better estimate the potential health, nutrition, and survival benefits of investing in nutrition.

Effects of Different Doses, Forms, and Frequencies of Zinc Supplementation on Biomarkers of Iron and Zinc Status among Young Children in Dhaka, Bangladesh.

Young children in resource-constrained settings are susceptible to zinc deficiency and its deleterious health effects. The objective of this secondary analysis was to evaluate the effects of the following six interventions on biomarkers of iron and zinc status among a subgroup of young children in Dhaka, Bangladesh, who participated in the Zinc in Powders Trial (ZiPT): (1) standard micronutrient powders (MNPs) containing 4.1 mg zinc and 10 mg iron, daily; (2) high-zinc (10 mg) and low-iron (6 mg) (HiZn LoFe) MNP, daily; (3) HiZn (10 mg) and LoFe (6 mg)/HiZn (10 mg) and no-iron MNPs on alternating days; (4) dispersible zinc tablet (10 mg), daily; (5) dispersible zinc tablet (10 mg), daily for 2 weeks at enrollment and at 12 weeks; (6) placebo powder, daily. At the end of the 24 week intervention period, children in the daily dispersible zinc tablet group exhibited a mean serum zinc concentration (SZC) of 92.5 µg/dL, which was significantly higher than all other groups except the HiZn LoFe MNP alternating group (81.3 µg/dL). MNPs containing 10 mg and 6 mg of iron had a similar impact on biomarkers of iron status, with no evidence of an adverse interaction with zinc.

Effect of multiple micronutrient supplements vs iron and folic acid supplements on neonatal mortality: a reanalysis by iron dose.

OBJECTIVE: Antenatal multiple micronutrient supplements (MMS) are a cost-effective intervention to reduce adverse pregnancy and birth outcomes. However, the current WHO recommendation on the use of antenatal MMS is conditional, partly due to concerns about the effect on neonatal mortality in a subgroup of studies comparing MMS with iron and folic acid supplements (IFA) containing 60 mg of iron. We aimed to assess the effect of MMS vs IFA on neonatal mortality stratified by iron dose in each supplement. METHODS: We updated the neonatal mortality analysis of the 2020 WHO guidelines using the generic inverse variance method and applied the random effects model to calculate the effect estimates of MMS vs. IFA on neonatal mortality in subgroups of trials (n=13) providing the same or different amounts of iron, i.e. MMS with 60 mg of iron vs IFA with 60 mg of iron; MMS with 30 mg of iron vs IFA with 30 mg of iron; MMS with 30 mg of iron vs IFA with 60 mg of iron; and MMS with 20 mg of iron vs IFA with 60 mg of iron. RESULTS: There were no statistically significant differences in neonatal mortality between MMS and IFA within any of the subgroups of trials. Analysis of MMS with 30 mg vs IFA with 60 mg of iron (7 trials, 14,114 participants), yielded a nonsignificant Risk Ratio (RR) of 1.12 (95% CI 0.83 to 1.50). CONCLUSION: Neonatal mortality did not differ between MMS and IFA regardless of iron dose in either supplement.

Exchangeable Zinc Pool Size Reflects Form of Zinc Supplementation in Young Children and Is Not Associated with Markers of Inflammation.

A sensitive and reliable biomarker of zinc status has yet to be identified, but observational research suggests that the exchangeable zinc pool (EZP) size may be a possible biomarker. This randomized, placebo-controlled trial aimed to compare the change in EZP size from baseline to endline in 174 children who were preventatively supplemented with 10 mg of zinc as part of a multiple micronutrient power (MNP) or as a standalone dispersible tablet for 24 weeks versus a placebo powder. The effects of systemic inflammation on EZP size were also evaluated. Zinc stable isotopes were administered intravenously to children at baseline and endline, and the EZP was measured by the urine extrapolation method. A total of 156 children completed the study with the zinc dispersible tablet group having the greatest increase in EZP (14.1 mg) over 24 weeks when compared with the MNP group (6.8 mg) (p < 0.01) or placebo group (2.0 mg) (p < 0.001). Median EZP size was not different between children with normal or elevated serum inflammatory markers. EZP size was responsive to longitudinal zinc supplementation and reflected the expected difference in bioavailability for two forms of supplementation. The apparent absence of an effect of inflammation on EZP size may offer an advantage for use as a biomarker for group comparisons between different interventions.

Characteristics and birth outcomes of pregnant adolescents compared to older women: An analysis of individual level data from 140,000 mothers from 20 RCTs.

BACKGROUND: Adolescence is a critical period of maturation when nutrient needs are high, especially among adolescents entering pregnancy. Using individual-level data from 140,000 participants, we examined socioeconomic, nutrition, and pregnancy and birth outcomes for adolescent mothers (10-19 years) compared to older mothers in low and middle-income countries. METHODS: This study was conducted between March 16, 2018 and May 25, 2021. Data were obtained from 20 randomised controlled trials of micronutrient supplementation in pregnancy. Stratified analyses were conducted by age (10-14 years, 15-17 years, 18-19 years, 20-29 years, 30-39 years, 40+ years) and geographical region (Africa, Asia). Crude and confounder-adjusted means, prevalence and relative risks of pregnancy, nutrition and birth outcomes were estimated using multivariable linear and log-binomial regression models with 95% confidence intervals. FINDINGS: Adolescent mothers comprised 31.6% of our data. Preterm birth, small-for-gestational age (SGA), low birthweight (LBW) and newborn mortality followed a U-shaped trend in which prevalence was highest among the youngest mothers (10-14 years) and then reduced gradually, but increased again for older mothers (40+ years). When compared to mothers aged 20-29 years, there was a 23% increased risk of preterm birth, a 60% increased risk of perinatal mortality, a 63% increased risk of neonatal mortality, a 28% increased risk of LBW, and a 22% increased risk of SGA among mothers 10-14 years. Mothers 40+ years experienced a 22% increased risk of preterm birth and a 103% increased risk of stillbirth when compared to the 20-29 year group. INTERPRETATION: The youngest and oldest mothers suffer most from adverse pregnancy and birth outcomes. Policy and programming agendas should consider both biological and socioeconomic/environmental factors when targeting these populations. FUNDING: Bill and Melinda Gates Foundation (Grant No: OP1137750).

Multiple micronutrient supplements versus iron-folic acid supplements and maternal anemia outcomes: an iron dose analysis.

Antenatal multiple micronutrient supplements (MMS) are more effective than iron and folic acid (IFA) supplements in reducing adverse pregnancy outcomes. Questions remain, however, about the ability of MMS to prevent anemia as effectively as IFA, especially at a lower dose of daily iron and in areas of high anemia prevalence. Analyzing data from 11 trials from a recent Cochrane review, we compared MMS to IFA, delivering either 30 or 60 mg of iron, in sustaining hemoglobin and preventing third trimester anemia and iron deficiency anemia (IDA), accounting for daily iron dose, total supplemental iron intake, and baseline prevalence of anemia. There were no differences between MMS and IFA in third trimester hemoglobin concentration or risks of anemia or IDA by iron dose or total supplemental iron consumed. MMS providing 30 mg of iron was comparable to IFA with 60 mg of iron: mean hemoglobin difference of -0.26 g/L (95% CI: -1.41 to 0.89), risk ratios of 0.99 (95% CI: 0.92-1.07) for anemia, and 1.31 (95% CI: 0.66-2.60) for IDA. Baseline prevalence of anemia did not explain heterogeneity in findings. Compared to IFA, MMS results in comparable hemoglobin concentration and protection against anemia during pregnancy, independently of iron dose.

Different Doses, Forms, and Frequencies of Zinc Supplementation for the Prevention of Diarrhea and Promotion of Linear Growth among Young Bangladeshi Children: A Six-Arm, Randomized, Community-Based Efficacy Trial.

BACKGROUND: Children in resource-limited settings remain vulnerable to zinc deficiency and its consequences. OBJECTIVES: To evaluate the effects of different doses, durations, and frequencies of zinc supplementation on the incidence of diarrhea and change in linear growth among young children. METHODS: We conducted a randomized, partially double-blind, controlled, 6-arm, community-based efficacy trial in Dhaka, Bangladesh. Children aged 9-11 mo were randomly assigned to receive 1 of the following interventions for 24 wk: 1) standard micronutrient powder (MNP) containing 4.1 mg zinc and 10 mg iron, daily; 2) high-zinc (10 mg), low-iron (6 mg) (HiZn LoFe) MNP, daily; 3) HiZn (10 mg) LoFe (6 mg)/HiZn (10 mg), no-iron MNPs on alternating days; 4) dispersible zinc tablet (10 mg), daily; 5) dispersible zinc tablet (10 mg), daily for 2 wk at enrollment and 12 wk; 6) placebo powder, daily. Primary outcomes were incidence of diarrhea and change in length-for-age z-score (LAZ) over the 24-wk intervention period. Home visits were conducted twice weekly to assess diarrhea and other morbidity. Incidence and prevalence outcomes were compared among groups with Poisson regression; continuous outcomes were compared using ANCOVA. RESULTS: A total of 2886 children were enrolled between February 2018 and July 2019. The mean incidence and prevalence of diarrhea among all participants was 1.21 episodes per 100 d and 3.76 d per 100 d, respectively. There were no differences in the incidence or prevalence of diarrhea across intervention groups. The decline in LAZ was slightly smaller among children in the daily HiZn LoFe MNP group compared with the placebo powder group (P < 0.05). CONCLUSIONS: The dose of zinc in MNPs as well as the duration and frequency of supplementation evaluated in this trial were not effective in reducing diarrhea; however, the daily HiZn LoFe MNP formulation offered modest improvements in linear growth among young children. This trial was registered at clinicaltrials.gov as NCT03406793.

Zinc Supplementation and the Prevention and Treatment of Sepsis in Young Infants: A Systematic Review and Meta-Analysis.

BACKGROUND: Prematurity and low birth weight are major risk factors for neonatal sepsis. Zinc supplements have been previously shown to be beneficial in pregnancy and small for gestational age birth outcomes. There is sparse information, however, on the potential benefits of zinc supplementation to prevent or treat serious infections in this age group. OBJECTIVE: The aim of this study was to assess the efficacy of preventive and therapeutic zinc supplementation in young infant (<4 months) sepsis. METHODS: MEDLINE, Cochrane CENTRAL, and other databases were searched from inception until 18 June 2021. Studies assessing preventive and therapeutic zinc supplementation in young infants in relation to incidence and outcomes of suspected sepsis were included. Meta-analyses of pooled effects were calculated for sepsis-related outcomes. RESULTS: Nine randomized controlled trials involving 2,553 infants were included. Six studies reported therapeutic efficacy, whereas 3 evaluated preventive benefits of zinc supplementation. Preventive studies suggest a protective effect of zinc supplementation on neonatal mortality rate (NMR) (risk ratio (RR) 0.28; 95% CI 0.12-0.67, LOW certainty), but with no effect on the incidence of sepsis, both in preterm neonates. Among young infants, therapeutic zinc was associated with significant reductions in treatment failure (RR 0.61; 95% CI 0.44-0.85; MODERATE certainty) and further subgroup analysis showing significant reduction in infant mortality rate with 3 mg/kg/twice a day dosage only (RR 0.49; 95% CI 0.27-0.87, LOW certainty). Therapeutic zinc supplementation in neonates did not show any effect on hospital stay or NMR. CONCLUSION: Zinc supplementation could potentially reduce mortality and treatment failure in young infants but has no noteworthy influence on hospital stay and in the prevention of sepsis. Further studies with larger sample sizes are needed to confirm the direction and magnitude of effects if any.

Zinc Supplementation with or without Additional Micronutrients Does Not Affect Peripheral Blood Gene Expression or Serum Cytokine Level in Bangladeshi Children.

Preventive zinc supplementation provided as a stand-alone dispersible tablet, or via home fortification as multiple micronutrient powders (MNPs), has been considered a potential strategy to prevent zinc deficiency and improve health (including immune) outcomes among children in low- and middle-income countries. However, the impact of zinc supplementation on immune profiles has not been well characterized. We sought to define the effect of zinc supplementation on peripheral blood gene expression and cytokine levels among young children in Dhaka, Bangladesh. In a sub-study of a large randomized, controlled, community-based efficacy trial where children 9-11 months of age received one of the following interventions on a daily basis for 24 weeks: (1) MNPs containing 10 mg of zinc; (2) dispersible tablet containing 10 mg zinc; or (3) placebo powder, we used RNA sequencing to profile the peripheral blood gene expression, as well as highly sensitive multiplex assays to detect cytokine profiles. We profiled samples from 100 children enrolled in the parent trial (zinc MNPs 28, zinc tablets 39, placebo 33). We did not detect an effect from either zinc intervention on differential peripheral blood gene expression at the end of the intervention, or an effect from the intervention on changes in gene expression from baseline. We also did not detect an effect from either intervention on cytokine concentrations. Exploratory analysis did not identify an association between undernutrition (defined as stunting, underweight or wasting) and peripheral blood gene expression. Zinc interventions in children did not produce a gene expression or cytokine signature in the peripheral blood. However, this study demonstrates a proof of principle that sensitive multi-omic techniques can be applied to samples collected in field studies.

Enablers and Barriers of Zinc Fortification; Experience from 10 Low- and Middle-Income Countries with Mandatory Large-Scale Food Fortification.

Adequate zinc nutrition is important for child growth, neurodevelopment, immune function, and normal pregnancy outcomes. Seventeen percent of the global population is estimated to be at risk for inadequate zinc intake. However, zinc is not included in the fortification standards of several low- and middle-income countries with mandatory fortification programs, despite data suggesting a zinc deficiency public health problem. To guide policy decisions, we investigated the factors enabling and impeding the inclusion of zinc as a fortificant by conducting in-depth interviews with 17 key informants from 10 countries. Findings revealed the decision to include zinc was influenced by guidance from international development partners and enabled by the assessment of zinc deficiency, mandatory regional food fortification standards which included zinc, the World Health Organization (WHO) guidelines for zinc fortification, and the low cost of zinc compound commonly used. Barriers included the absence of zinc from regional fortification standards, limited available data on the efficacy and effectiveness of zinc fortification, and the absence of national objectives related to the prevention of zinc deficiency. To promote zinc fortification there is a need to put the prevention of zinc deficiency higher on the international nutrition agenda and to promote large-scale food fortification as a key deficiency mitigation strategy.

Effects of Foods Fortified with Zinc, Alone or Cofortified with Multiple Micronutrients, on Health and Functional Outcomes: A Systematic Review and Meta-Analysis.

Seventeen per cent of the world's population is estimated to be at risk of inadequate zinc intake, which could in part be addressed by zinc fortification of widely consumed foods. We conducted a review of efficacy and effectiveness studies to ascertain the effect of zinc fortification [postharvest fortification of an industrially produced food or beverage; alone or with multiple micronutrients (MMN)] on a range of health outcomes. Previous reviews have required that the effect of zinc be isolated; because zinc is always cofortified with MMN in existing fortification programs, we did not impose this condition. Outcomes assessed were zinc-related biomarkers (plasma or serum, hair or urine zinc concentrations, comet assay, plasma fatty acid concentrations, and the proportion of and total zinc absorbed in the intestine from the diet), child anthropometry, morbidity, mortality, cognition, plasma or serum iron and copper concentrations, and for observational studies, a change in consumption of the food vehicle. Fifty-nine studies were included in the review; 54 in meta-analyses, totaling 73 comparisons. Zinc fortification with and without MMN increased plasma zinc concentrations (efficacy, n = 27: 4.68 µg/dL; 95% CI: 2.62-6.75; effectiveness, n = 13: 6.28 µg/dL; 95% CI: 5.03-7.77 µg/dL) and reduced the prevalence of zinc deficiency (efficacy, n = 11: OR: 0.76, 95% CI: 0.60-0.96; effectiveness, n = 10: OR: 0.45, 95% CI: 0.31-0.64). There were statistically significant increases in child weight (efficacy, n = 11: 0.43 kg, 95% CI: 0.11-0.75 kg), improvements in short-term auditory memory (efficacy, n = 3: 0.32 point, 95% CI: 0.13-0.50 point), and decreased incidence of diarrhea (efficacy, n = 3: RR: 0.79, 95% CI: 0.68-0.92) and fever (efficacy, n = 2: RR: 0.85, 95% CI: 0.74-0.97). However, these effects cannot be solely attributed to zinc. Our review found that zinc fortification with or without MMN reduced the prevalence of zinc deficiency and may provide health and functional benefits, including a reduced incidence of diarrhea.

Effective interventions to address maternal and child malnutrition: an update of the evidence.

Malnutrition-consisting of undernutrition, overweight and obesity, and micronutrient deficiencies-continues to afflict millions of women and children, particularly in low-income and middle-income countries (LMICs). Since the 2013 Lancet Series on maternal and child nutrition, evidence on the ten recommended interventions has increased, along with evidence of newer interventions. Evidence on the effectiveness of antenatal multiple micronutrient supplementation in reducing the risk of stillbirths, low birthweight, and babies born small-for-gestational age has strengthened. Evidence continues to support the provision of supplementary food in food-insecure settings and community-based approaches with the use of locally produced supplementary and therapeutic food to manage children with acute malnutrition. Some emerging interventions, such as preventive small-quantity lipid-based nutrient supplements for children aged 6-23 months, have shown positive effects on child growth. For the prevention and management of childhood obesity, integrated interventions (eg, diet, exercise, and behavioural therapy) are most effective, although there is little evidence from LMICs. Lastly, indirect nutrition strategies, such as malaria prevention, preconception care, water, sanitation, and hygiene promotion, delivered inside and outside the health-care sector also provide important nutritional benefits. Looking forward, greater effort is required to improve intervention coverage, especially for the most vulnerable, and there is a crucial need to address the growing double burden of malnutrition (undernutrition, and overweight and obesity) in LMICs.

Setting research priorities on multiple micronutrient supplementation in pregnancy.

Prenatal micronutrient deficiencies are associated with negative maternal and birth outcomes. Multiple micronutrient supplementation (MMS) during pregnancy is a cost-effective intervention to reduce these adverse outcomes. However, important knowledge gaps remain in the implementation of MMS interventions. The Child Health and Nutrition Research Initiative (CHNRI) methodology was applied to inform the direction of research and investments needed to support the implementation of MMS interventions for pregnant women in low- and middle-income countries (LMIC). Following CHNRI methodology guidelines, a group of international experts in nutrition and maternal health provided and ranked the research questions that most urgently need to be resolved for prenatal MMS interventions to be successfully implemented. Seventy-three research questions were received, analyzed, and reorganized, resulting in 35 consolidated research questions. These were scored against four criteria, yielding a priority ranking where the top 10 research options focused on strategies to increase antenatal care attendance and MMS adherence, methods needed to identify populations more likely to benefit from MMS interventions and some discovery issues (e.g., potential benefit of extending MMS through lactation). This exercise prioritized 35 discrete research questions that merit serious consideration for the potential of MMS during pregnancy to be optimized in LMIC.

Factors associated with the decline in under-five diarrhea mortality in India: a LiST analysis.

BACKGROUND: India has achieved 86% reduction in the number of under-five diarrheal deaths from 1980 to 2015. Nonetheless diarrhea is still among the leading causes of under-five deaths. The aim of this analysis was to study the contribution of factors that led to decline in diarrheal deaths in the country and the effect of scaling up of intervention packages to address the remaining diarrheal deaths. METHODS: We assessed the attribution of different factors and intervention packages such as direct diarrhea case management interventions, nutritional factors and WASH interventions which contributed to diarrhea specific under-five mortality reduction (DSMR) during 1980 to 2015 using the Lives Saved Tool (LiST). The potential impact of scaling up different packages of interventions to achieve universal coverage levels by year 2030 on reducing the number of remaining diarrheal deaths were estimated. RESULTS: The major factors associated with DSMR reduction in under-fives during 1980 to 2015, were increase in ORS use, reduction in stunting prevalence, improved sanitation, changes in age appropriate breastfeeding practices, increase in the vitamin-A supplementation and persistent diarrhea treatment. ORS use and reduction in stunting were the two key interventions, each accounting for around 32% of the lives saved during this period. Scaling up the direct diarrhea case management interventions from the current coverage levels in 2015 to achieve universal coverage levels by 2030 can save around 82 000 additional lives. If the universal targets for nutritional factors and WASH interventions can be achieved, an additional 23 675 lives can potentially be saved. CONCLUSIONS: While it is crucial to improve the coverage and equity in ORS use, an integrated approach to promote nutrition, WASH and direct diarrhea interventions is likely to yield the highest impact on reducing the remaining diarrheal deaths in under-five children.