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Women and children bear substantial morbidity and mortality as a result of armed conflicts. This Series paper focuses on the direct (due to violence) and indirect health effects of armed conflict on women and children (including adolescents) worldwide. We estimate that nearly 36 million children and 16 million women were displaced in 2017, on the basis of international databases of refugees and internally displaced populations. From geospatial analyses we estimate that the number of non-displaced women and children living dangerously close to armed conflict (within 50 km) increased from 185 million women and 250 million children in 2000, to 265 million women and 368 million children in 2017. Women’s and children’s mortality risk from non-violent causes increases substantially in response to nearby conflict, with more intense and more chronic conflicts leading to greater mortality increases. More than 10 million deaths in children younger than 5 years can be attributed to conflict between 1995 and 2015 globally. Women of reproductive ages living near high intensity conflicts have three times higher mortality than do women in peaceful settings. Current research provides fragmentary evidence about how armed conflict indirectly affects the survival chances of women and children through malnutrition, physical injuries, infectious diseases, poor mental health, and poor sexual and reproductive health, but major systematic evidence is sparse, hampering the design and implementation of essential interventions for mitigating the harms of armed conflicts.

Sleep disordered breathing (SDB) in children is commonly described as a continuum from primary snoring (PS) to obstructive sleep apnea (OSA), based on apnea indices from polysomnography (PSG). This study evaluated the difference in neurocognitive and behavioral parameters, prior to treatment, in symptomatic pre-school children with PSG-diagnosed OSA and PS. All children had positive Pediatric Sleep Questionnaire (PSQ) results and were deemed suitable for adenotonsillectomy by an ENT surgeon. Neurocognitive and behavioral data were analyzed in pre-school children at recruitment for the POSTA study (The Pre-School OSA Tonsillectomy Adenoidectomy Study). Data were compared between PS and OSA groups, with Obstructive Apnea-Hypopnea Index, OAHI

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.

Complications associated with preterm birth (PTB) are the largest contributor to under-five mortality globally. Success in reaching the Sustainable Development Goal target requires identifying potentially modifiable risk factors for PTB, estimating the relative importance of these risk factors, and identifying/implementing effective prevention strategies to address them.We conducted a literature review to define risk relationships and estimate prevalence for established risk factors for spontaneous PTB (sPTB). We then estimated population attributable fractions (PAF) for the sPTB risk factors identified in the review as statistically significant for the 81 low- and middle-income (LMIC) countries included in the Countdown 2030 initiative. We summed country-level findings to produce PAFs for each risk factor and regional estimates for sub-Saharan Africa and South Asia.Forty-four potential sPTB risk factors were identified. and the final analysis included twenty-four risk factors with evidence of significant associations with sPTB. A second model with three additional risk factors with borderline insignificant associations was also run. Taken together, the twenty-four risk factors had a total PAF of 73% for all 81 countries and 77% and 72% of sPTB in sub-Saharan Africa and South Asia, respectively. For all countries, maternal undernutrition had the highest PAF (17.5%), followed by maternal infections (16.6%), environmental exposures (16%) and pregnancy history (8.7%).While multiple risk factors contribute to sPTB, no single risk factor addresses a predominant fraction, and 27% of spontaneous preterm births are not associated with risk factors that we identified. Despite the significant role of preterm birth in child survival, there are major data gaps in LMIC settings. Furthermore, there is a paucity of evidence for effective interventions to prevent preterm birth. Preventing sPTB requires understanding underlying mechanisms leading to sPTB in different populations, and the identification/implementation of effective interventions.

Small for gestational age (SGA) is a public health concern since it is associated with mortality in neonatal and post-neonatal period. Despite the large magnitude of the problem, little is known about the population-attributable risk (PAR) of various risk factors for SGA. This study estimated the relative contribution of risk factors for SGA, as a basis for identifying priority areas for developing and/or implementing interventions to reduce the incidence of SGA births and related mortality and morbidity.We conducted a literature review on 63 potential risk factors for SGA to quantify the risk relationship and estimate the prevalence of risk factors (RFs). We calculated the population-attributable fraction for each of the identified RF for 81 Countdown countries and calculated regional estimates. Twenty-five RFs were included in the final model while extended model included all the 25 RFs from the final model and two additional RFs.In the final and extended models, the RFs included in each model have a total PAF equal to 63.97% and 69.66%, respectively of SGA across the 81 LMICs. In the extended model, maternal nutritional status has the greatest PAF (28.15%), followed by environmental and other exposures during pregnancy (15.82%), pregnancy history (11.01%), and general health issues or morbidity (10.34%). The RFs included in the final and extended model for Sub-Saharan African (SSA) region have a total PAF of 63.28% and 65.72% of SGA, respectively. In SSA, the top three RF categories in the extended model are nutrition (25.05%), environment and other exposure (13.01%), and general health issues or morbidity (10.72%), while in South-Asia's it was nutrition (30.56%), environment and other exposure (15.27%) and pregnancy history (11.68%).The various types of RFs that play a role in SGA births highlight the importance of a multifaceted approach to tackle SGA. Depending on the types of RFs, intervention should be strategically targeted at either individual or household and/or community or policy level. There is also a need to research the mechanisms by which some of the RFs might hinder fetal growth.

The Lives Saved Tool (We updated previousWe did not find new studies demonstrating an effect of improved water source alone on diarrhea morbidity among children under 5 years of age. For improved sanitation, we conducted an updated meta-analysis among 4 studies and found no difference between intervention and control arms (weighted mean difference (WMD) = -5% (95% confidence interval (CI) = -11% to 2%). We identified four trials that assessed the effect of combined interventions targeting improved water, sanitation and hygiene. The weighted mean difference also showed no effect on diarrhea morbidity among children under 5 years of age (WMD = -6%, 95% CI = -15% to 4%). Our updated results for handwashing promotion estimate the effects to results in a 17% reduction in childhood diarrhea morbidity (95% CI = 7% to 27%).Despite widespread acceptance that WASH interventions can improve diarrhea morbidity, the evidence supporting this specifically for children under 5 years of age remains weak. Children interact with the environment in ways that differ from adults and these constant exposures may limit the effect that these WASH interventions can have on diarrhea morbidity.

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.

Background: Investments in the survival of older children and adolescents (aged 5-19 years) bring triple dividends for now, their future, and the next generation. However, 1·5 million deaths occurred in this age group globally in 2019, nearly all from preventable causes. To better focus the attention of the global community on improving survival of children and adolescents and to guide effective policy and programmes, sound and timely cause of death data are crucial, but often scarce. Methods: In this systematic analysis, we provide updated time-series for 2000-19 of national, regional, and global cause of death estimates for 5-19-year-olds with age-sex disaggregation. We estimated separately for countries with high versus low mortality, by data availability, and for four age-sex groups (5-9-year-olds [both sexes], 10-14-year-olds [both sexes], 15-19-year-old females, and 15-19-year-old males). Only studies reporting at least two causes of death were included in our analysis. We obtained empirical cause of death data through systematic review, known investigator tracing, and acquisition of known national and subnational cause of death studies. We adapted the Bayesian Least Absolute Shrinkage and Selection Operator approach to address data scarcity, enhance covariate selection, produce more robust estimates, offer increased flexibility, allow country random effects, propagate coherent uncertainty, and improve model stability. We harmonised all-cause mortality estimates with the UN Inter-agency Group for Child Mortality Estimation and systematically integrated single cause estimates as needed from WHO and UNAIDS. Findings: In 2019, the global leading specific causes of death were road traffic injuries (115 843 [95% uncertainty interval 110 672-125 054] deaths; 7·8% [7·5-8·1]); neoplasms (95 401 [90 744-104 812]; 6·4% [6·1-6·8]); malaria (81 516 [72 150-94 477]; 5·5% [4·9-6·2]); drowning (77 460 [72 474-85 952]; 5·2% [4·9-5·5]); and diarrhoea (72 679 [66 599-82 002], 4·9% [4·5-5·3]). The leading causes varied substantially across regions. The contribution of communicable, maternal, perinatal, and nutritional conditions declined with age, whereas the number of deaths associated with injuries increased. The leading causes of death were diarrhoea (51 630 [47 206-56 235] deaths; 10·0% [9·5-10·5]) in 5-9-year-olds; malaria (31 587 [23 940-43 116]; 8·6% [6·6-10·4]) in 10-14-year-olds; self-harm (32 646 [29 530-36 416]; 13·4% [12·6-14·3]) in 15-19-year-old females; and road traffic injuries (48 757 [45 692-52 625]; 13·9% [13·3-14·3]) in 15-19-year-old males. Widespread declines in cause-specific mortality were estimated across age-sex groups and geographies in 2000-19, with few exceptions like collective violence. Interpretation: Child and adolescent survival needs focused attention. To translate the vision into actions, more investments in the health information infrastructure for cause of death and in the related life-saving interventions are needed.

Background Growth faltering in the first 1000 d is associated with lower human capital among adults. The existence of a second window of opportunity for nutritional interventions during adolescence has been postulated. Objectives We aimed to verify the associations between growth from birth to 18 y and intelligence and schooling in a cohort. Methods A total of 5249 hospital-born infants in Pelotas, Brazil, were enrolled during 1993. Follow-up visits to random subsamples took place at 6, 12, and 48 mo and to the full cohort at 11, 15, and 18 y. Weight and length/height were collected in all visits. The Wechsler Adult Intelligence Scale was applied at age 18 y, and primary school completion was recorded. Conditional length/height and conditional BMI were calculated and expressed as z scores according to the WHO Growth Standards. These express the difference between observed and expected size at a given age based on a regression that includes earlier anthropometric measures. Analyses were adjusted for income, parental education, maternal skin color and smoking, and breastfeeding duration. Results In the adjusted analyses, participants with conditional length ≥1 z score at 1 y had mean intelligence quotient (IQ) scores at 18 y 4.50 points (95% CI: 1.08, 7.92) higher than those with conditional length ≤-1 at 1 y. For height-for-age at 4 y, this difference was equal to 3.70 (95% CI: 0.49, 6.90) IQ points. There were no associations between conditional height at 11, 15, or 18 y and IQ. For the same previously mentioned comparison, the prevalence ratio for less than primary schooling was 1.42 (95% CI: 1.12, 1.80) for conditional height at 1 y. There were no consistent associations with conditional BMI. Conclusions Our findings show that adolescent growth is not associated with intelligence and schooling, and are consistent with the literature on the associations between intelligence and schooling and early linear growth.

Background Verbal autopsy is the main method used in countries with weak civil registration systems for estimating community causes of neonatal and 1–59-month-old deaths. However, validation studies of verbal autopsy methods are limited and assessment has been dependent on hospital-based studies, with uncertain implications for its validity in community settings. If the distribution of community deaths by cause was similar to that of facility deaths, or could be adjusted according to related demographic factors, then the causes of facility deaths could be used to estimate population causes. Methods Causes of neonatal and 1–59-month-old deaths from verbal/social autopsy (VASA) surveys in four African countries were estimated using expert algorithms (EAVA) and physician coding (PCVA). Differences between facility and community deaths in individual causes and cause distributions were examined using chi-square and cause-specific mortality fractions (CSMF) accuracy, respectively. Multinomial logistic regression and random forest models including factors from the VASA studies that are commonly available in Demographic and Health Surveys were built to predict population causes from facility deaths. Results Levels of facility and community deaths in the four countries differed for one to four of 10 EAVA or PCVA neonatal causes and zero to three of 12 child causes. CSMF accuracy for facility compared to community deaths in the four countries ranged from 0.74 to 0.87 for neonates and 0.85 to 0.95 for 1–59-month-olds. Crude CSMF accuracy in the prediction models averaged 0.86 to 0.88 for neonates and 0.93 for 1–59-month-olds. Adjusted random forest prediction models increased average CSMF accuracy for neonates to, at most, 0.90, based on small increases in all countries. Conclusions There were few differences in facility and community causes of neonatal and 1–59-month-old deaths in the four countries, and it was possible to project the population CSMF from facility deaths with accuracy greater than the validity of verbal autopsy diagnoses. Confirmation of these findings in additional settings would warrant research into how medical causes of deaths in a representative sample of health facilities can be utilized to estimate the population causes of child death.

Investment in vaccine product development should be guided by up-to-date and transparent global burden of disease estimates, which are also fundamental to policy recommendation and vaccine introduction decisions. For low- and middle-income countries (LMICs), vaccine prioritization is primarily driven by the number of deaths caused by different pathogens. Enteric diseases are known to be a major cause of death in LMICs. The two main modelling groups providing mortality estimates for enteric diseases are the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle and the Maternal Child Epidemiology Estimation (MCEE) group, led by Johns Hopkins Bloomberg School of Public Health. Whilst previous global diarrhoea mortality estimates for under five-year-olds from these two groups were closely aligned, more recent estimates for 2016 have diverged, particularly with respect to numbers of deaths attributable to different enteric pathogens. This has impacted prioritization and investment decisions for vaccines in the development pipeline. The mission of the Product Development for Vaccines Advisory Committee (PDVAC) at the World Health Organisation (WHO) is to accelerate product development of vaccines and technologies that are urgently needed and ensure they are appropriately targeted for use in LMICs. At their 2018 meeting, PDVAC recommended the formation of an independent working group of subject matter experts to explore the reasons for the difference between the IHME and MCEE estimates, and to assess the respective strengths and limitations of the estimation approaches adopted, including a review of the data on which the estimates are based. Here, we report on the proceedings and recommendations from a consultation with the working group of experts, the IHME and MCEE modelling groups, and other key stakeholders. We briefly review the methodological approaches of both groups and provide a series of proposals for investigating the drivers for the differences in enteric disease burden estimates.

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., The specific aim of this research prioritization exercise was to inform the direction of research and investments needed to support the implementation of multiple micronutrient supplementation (MMS) interventions for pregnant women in low‐ and middle‐income countries (LMIC) using the Child Health and Nutrition Research Initiative methodology. This exercise prioritized 35 discrete research questions that merit serious consideration for the potential of MMS during pregnancy to be optimized in LMIC.

Background Environmental enteric dysfunction (EED) is thought to increase the risk of micronutrient deficiencies, but few studies adjust for dietary intakes and systemic inflammation. Objective We tested whether EED is associated with micronutrient deficiency risk independent of diet and systemic inflammation, and whether it mediates the relation between intake and micronutrient status. Methods Using data from 1283 children in the MAL-ED (Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health) birth cohort we evaluated the risk of anemia, low retinol, zinc, and ferritin, and high transferrin receptor (TfR) at 15 mo. We characterized gut inflammation and permeability by myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT) concentrations from asymptomatic fecal samples averaged from 9 to 15 mo, and averaged the lactulose:mannitol ratio z-score (LMZ) at 9 and 15 mo. Nutrient intakes from complementary foods were quantified monthly from 9 to 15 mo and densities were averaged for analyses. α-1-Acid glycoprotein at 15 mo characterized systemic inflammation. Relations between variables were modeled using a Bayesian network. Results A greater risk of anemia was associated with LMZ [1.15 (95% CI: 1.01, 1.31)] and MPO [1.16 (1.01, 1.34)]. A greater risk of low ferritin was associated with AAT [1.19 (1.03, 1.37)] and NEO [1.22 (1.04, 1.44)]. A greater risk of low retinol was associated with LMZ [1.24 (1.08, 1.45)]. However, MPO was associated with a lower risk of high transferrin receptor [0.86 (0.74, 0.98)], NEO with a lower risk of low retinol [0.75 (0.62, 0.89)], and AAT with a lower risk of low plasma zinc [0.83 (0.70, 0.99)]. Greater nutrient intake densities (vitamins A and B6, calcium, protein, and zinc) were negatively associated with EED. Inverse associations between nutrient densities and micronutrient deficiency largely disappeared after adjustment for EED, suggesting that EED mediates these associations. Conclusions EED is independently associated with an increased risk of low ferritin, low retinol, and anemia. Greater nutrient density from complementary foods may reduce EED, and the control of micronutrient deficiencies may require control of EED.

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.

ObjectivePreterm birth can have short-term and long-term complications for a child. Socioeconomic factors and pregnancy-related morbidities may be important to predict and prevent preterm births in low-resource settings. The objective of our study was to find prevalence and predictors of spontaneous preterm birth in rural Nepal.DesignThis is a secondary observational analysis of trial data (registration numberNCT01177111).SettingRural Sarlahi district, Nepal.Participants40 119 pregnant women enrolled from 9 September 2010 to 16 January 2017.Outcome measuresThe outcome variable is spontaneous preterm birth. Generalized Estimating Equations Poisson regression with robust variance was fitted to present effect estimates as risk ratios.ResultThe prevalence of spontaneous preterm birth was 14.5% (0.5% non-spontaneous). Characteristics not varying in pregnancy associated with increased risk of preterm birth were maternal age less than 18 years (adjusted risk ratio=1.13, 95% CI: 1.02 to 1.26); being Muslim (1.53, 1.16 to 2.01); first pregnancy (1.15, 1.04 to 1.28); multiple births (4.91, 4.20 to 5.75) and male child (1.10, 1.02 to 1.17). Those associated with decreased risk were maternal education >5 years (0.81, 0.73 to 0.90); maternal height ≥150 cm (0.89, 0.81 to 0.98) and being from wealthier families (0.83, 0.74 to 0.93). Pregnancy-related morbidities associated with increased risk of preterm birth were vaginal bleeding (1.53, 1.08 to 2.18); swelling (1.37, 1.17 to 1.60); high systolic blood pressure (BP) (1.47, 1.08 to 2.01) and high diastolic BP (1.41, 1.17 to 1.70) in the third trimester. Those associated with decreased risk were respiratory problem in the third trimester (0.86, 0.79 to 0.94); having poor appetite, nausea and vomiting in the second trimester (0.86, 0.80 to 0.92) and third trimester (0.86, 0.79 to 0.94); and higher weight gain from second to third trimester (0.89, 0.87 to 0.90).ConclusionThe prevalence of preterm birth is high in rural Nepal. Interventions that increase maternal education may play a role. Monitoring morbidities during antenatal care to intervene to reduce them through an effective health system may help reduce preterm birth.

Objective : We describe a systematic approach to preparing data in the conduct of Individual Participant Data (IPD) analysis. Study design and setting : A guidance paper proposing methods for preparing individual participant data for meta-analysis from multiple study sources, developed by consultation of relevant guidance and experts in IPD. We present an example of how these steps were applied in checking data for our own IPD meta analysis (IPD-MA). Results : We propose five steps of Processing, Replication, Imputation, Merging, and Evaluation to prepare individual participant data for meta-analysis (PRIME-IPD). Using our own IPD-MA as an exemplar, we found that this approach identified missing variables and potential inconsistencies in the data, facilitated the standardization of indicators across studies, confirmed that the correct data were received from investigators, and resulted in a single, verified dataset for IPD-MA. Conclusion : The PRIME-IPD approach can assist researchers to systematically prepare, manage and conduct important quality checks on IPD from multiple studies for meta-analyses. Further testing of this framework in IPD-MA would be useful to refine these steps.

Objectives We describe a systematic approach to preparing data in the conduct of Individual Participant Data (IPD) analysis. Study design and setting A guidance paper proposing methods for preparing individual participant data for meta-analysis from multiple study sources, developed by consultation of relevant guidance and experts in IPD. We present an example of how these steps were applied in checking data for our own IPD meta analysis (IPD-MA). Results We propose five steps of Processing, Replication, Imputation, Merging, and Evaluation to prepare individual participant data for meta-analysis (PRIME-IPD). Using our own IPD-MA as an exemplar, we found that this approach identified missing variables and potential inconsistencies in the data, facilitated the standardization of indicators across studies, confirmed that the correct data were received from investigators, and resulted in a single, verified dataset for IPD-MA. Conclusion The PRIME-IPD approach can assist researchers to systematically prepare, manage and conduct important quality checks on IPD from multiple studies for meta-analyses. Further testing of this framework in IPD-MA would be useful to refine these steps.

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.

BackgroundWe used the United Nations High Commissioner for Refugees Standardised Expanded Nutrition Survey data to evaluate the effect of a change in food ration on child growth in refugee camps in eastern Chad.MethodsWe compared trends of wasting and stunting prevalence over time and the association between the coexistence of being both stunted and wasted using Pearson’s χ2 test. We analysed the effect of an approximate 50% reduction in the general food distribution, with the introduction of a 20 g daily ration of small quantity lipid-based nutrient supplements given to all children aged 6–23 months, on child growth. This was done using interrupted time-series analysis to observe differences in levels and trends in mean height-for-age z-score (HAZ) and weight-for-height z-score (WHZ) over time and by age group (6–24 months and 24–59 months).ResultsOverall the prevalence of stunting and wasting decreased significantly over time. The odds of being both stunted and wasted was 1.38 higher than having one or the other condition separately (pConclusionsThe dual burden of stunting and wasting is a considerable challenge in refugee camp settings. Changes to the food distribution had adverse effects on child growth for both age groups. Broadening the scope of interventions aimed at children in camps is essential when tackling malnutrition with increased efforts essential during periods of wider food assistance shortages.

Intestinal parasites affect millions of children globally. We aimed to assess effects of deworming children on nutritional and cognitive outcomes across potential effect modifiers using individual participant data (IPD). We searched multiple databases to 27 March 2018, grey literature, and other sources. We included randomised and quasi randomised trials of deworming compared to placebo or other nutritional interventions with data on baseline infection. We used a random-effects network meta-analysis with IPD and assessed overall quality, following a pre-specified protocol. We received IPD from 19 trials of STH deworming. Overall risk of bias was low. There were no statistically significant subgroup effects across age, sex, nutritional status or infection intensity for each type of STH. These analyses showed that children with moderate or heavy intensity infections, deworming for STH may increase weight gain (very low certainty). The added value of this review is an exploration of effects on growth and cognition in children with moderate to heavy infections as well as replicating prior systematic review results of small effects at the population level. Policy implications are that complementary public health strategies need to be assessed and considered to achieve growth and cognition benefits for children in helminth endemic areas.

Background: \ud India accounts for a disproportionate burden of global childhood illnesses. To inform policies and measure progress towards achieving child health targets, we estimated the annual national and state-specific childhood mortality and morbidity attributable to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) between 2000 and 2015.\ud \ud Methods: \ud In this modelling study, we used vaccine clinical trial data to estimate the proportion of pneumonia deaths attributable to pneumococcus and Hib. The proportion of meningitis deaths attributable to each pathogen was derived from pathogen-specific meningitis case fatality and bacterial meningitis case data from surveillance studies. We applied these proportions to modelled state-specific pneumonia and meningitis deaths from 2000 to 2015 prepared by the WHO Maternal and Child Epidemiology Estimation collaboration (WHO/MCEE) on the basis of verbal autopsy studies from India. The burden of clinical and severe pneumonia cases attributable to pneumococcus and Hib was ascertained with vaccine clinical trial data and state-specific all-cause pneumonia case estimates prepared by WHO/MCEE by use of risk factor prevalence data from India. Pathogen-specific meningitis cases were derived from state-level modelled pathogen-specific meningitis deaths and state-level meningitis case fatality estimates. Pneumococcal and Hib morbidity due to non-pneumonia, non-meningitis (NPNM) invasive syndromes were derived by applying the ratio of pathogen-specific NPNM cases to pathogen-specific meningitis cases to the state-level pathogen-specific meningitis cases. Mortality due to pathogen-specific NPNM was calculated with the ratio of pneumococcal and Hib meningitis case fatality to pneumococcal and Hib meningitis NPNM case fatality. Census data from India provided the population at risk.\ud \ud Findings: \ud Between 2000 and 2015, estimates of pneumococcal deaths in Indian children aged 1–59 months fell from 166 000 (uncertainty range [UR] 110 000–198 000) to 68 700 (44 600–86 000), while Hib deaths fell from 82 600 (52 300–112 000) to 15 600 (9800–21 500), representing a 58% (UR 22–78) decline in pneumococcal deaths and an 81% (59–91) decline in Hib deaths. In 2015, national mortality rates in children aged 1–59 months were 56 (UR 37–71) per 100 000 for pneumococcal infection and 13 (UR 8–18) per 100 000 for Hib. Uttar Pradesh (18 900 [UR 12 300–23 600]) and Bihar (8600 [5600–10 700]) had the highest numbers of pneumococcal deaths in 2015. Uttar Pradesh (9300 [UR 5900–12 700]) and Odisha (1100 [700–1500]) had the highest numbers of Hib deaths in 2015. Less conservative assumptions related to the proportion of pneumonia deaths attributable to pneumococcus indicate that as many as 118 000 (UR 69 000–140 000) total pneumococcal deaths could have occurred in 2015 in India.\ud \ud Interpretation: \ud Pneumococcal and Hib mortality have declined in children aged 1–59 months in India since 2000, even before nationwide implementation of conjugate vaccines. Introduction of the Hib vaccine in several states corresponded with a more rapid reduction in morbidity and mortality associated with Hib infection. Rapid scale-up and widespread use of the pneumococcal conjugate vaccine and sustained use of the Hib vaccine could help accelerate achievement of child survival targets in India.\ud \ud Funding: \ud Bill & Melinda Gates Foundation.

Summary Background India had the largest number of under-5 deaths of all countries in 2015, with substantial subnational disparities. We estimated national and subnational all-cause and cause-specific mortality among children younger than 5 years annually in 2000–15 in India to understand progress made and to consider implications for achieving the Sustainable Development Goal (SDG) child survival targets. Methods We used a multicause model to estimate cause-specific mortality proportions in neonates and children aged 1–59 months at the state level, with causes of death grouped into pneumonia, diarrhoea, meningitis, injury, measles, congenital abnormalities, preterm birth complications, intrapartum-related events, and other causes. AIDS and malaria were estimated separately. The model was based on verbal autopsy studies representing more than 100 000 neonatal deaths globally and 16 962 deaths among children aged 1–59 months at the subnational level in India. By applying these proportions to all-cause deaths by state, we estimated cause-specific numbers of deaths and mortality rates at the state, regional, and national levels. Findings In 2015, there were 25·121 million livebirths in India and 1·201 million under-5 deaths (under-5 mortality rate 47·81 per 1000 livebirths). 0·696 million (57·9%) of these deaths occurred in neonates. There were disparities in child mortality across states (from 9·7 deaths [Goa] to 73·1 deaths [Assam] per 1000 livebirths) and regions (from 29·7 deaths [the south] to 63·8 deaths [the northeast] per 1000 livebirths). Overall, the leading causes of under-5 deaths were preterm birth complications (0·330 million [95% uncertainty range 0·279–0·367]; 27·5% of under-5 deaths), pneumonia (0·191 million [0·168–0·219]; 15·9%), and intrapartum-related events (0·139 million [0·116–0·165]; 11·6%), with cause-of-death distributions varying across states and regions. In states with very high under-5 mortality, infectious-disease-related causes (pneumonia and diarrhoea) were among the three leading causes, whereas the three leading causes were all non-communicable in states with very low mortality. Most states had a slower decline in neonatal mortality than in mortality among children aged 1–59 months. Ten major states must accelerate progress to achieve the SDG under-5 mortality target, while 17 are not on track to meet the neonatal mortality target. Interpretation Efforts to reduce vaccine-preventable deaths and to reduce geographical disparities should continue to maintain progress achieved in 2000–15. Enhanced policies and programmes are needed to accelerate mortality reduction in high-burden states and among neonates to achieve the SDG child survival targets in India by 2030. Funding Bill & Melinda Gates Foundation.

Summary Background Climate change threatens to undermine recent progress in reducing global deaths from diarrhoeal disease in children. However, the scarcity of evidence about how individual environmental factors affect transmission of specific pathogens makes prediction of trends under different climate scenarios challenging. We aimed to model associations between daily estimates of a suite of hydrometeorological variables and rotavirus infection status ascertained through community-based surveillance. Methods For this analysis of multisite cohort data, rotavirus infection status was ascertained through community-based surveillance of infants in the eight-site MAL-ED cohort study, and matched by date with earth observation estimates of nine hydrometeorological variables from the Global Land Data Assimilation System: daily total precipitation volume (mm), daily total surface runoff (mm), surface pressure (mbar), wind speed (m/s), relative humidity (%), soil moisture (%), solar radiation (W/m 2 ), specific humidity (kg/kg), and average daily temperatures (°C). Lag relationships, independent effects, and interactions were characterised by use of modified Poisson models and compared with and without adjustment for seasonality and between-site variation. Final models were created with stepwise selection of main effects and interactions and their validity assessed by excluding each site in turn and calculating Tjur's Coefficients of Determination. Findings All nine hydrometeorological variables were significantly associated with rotavirus infection after adjusting for seasonality and between-site variation over multiple consecutive or non-consecutive lags, showing complex, often non-linear associations that differed by symptom status and showed considerable mutual interaction. The final models explained 5·9% to 6·2% of the variability in rotavirus infection in the pooled data and their predictions explained between 0·0% and 14·1% of the variability at individual study sites. Interpretation These results suggest that the effect of climate on rotavirus transmission was mediated by four independent mechanisms: waterborne dispersal, airborne dispersal, virus survival on soil and surfaces, and host factors. Earth observation data products available at a global scale and at subdaily resolution can be combined with longitudinal surveillance data to test hypotheses about routes and drivers of transmission but showed little potential for making predictions in this setting. Funding Bill & Melinda Gates Foundation; Foundation for the National Institutes of Health, National Institutes of Health, Fogarty International Center; Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases, Johns Hopkins School of Medicine; and NASA's Group on Earth Observations Work Programme.

Background: The complementary feeding (CF) period accompanies a critical window of vulnerability. During this time, failure to consume adequate energy, protein, vitamins and minerals is a significant concern and can lead to poor growth outcomes, increased susceptibility to infections, allergies, and diseases, and lower developmental potential. It is therefore of utmost importance to determine the most optimal time to start CF. The objective of this review is to assess the impact of early and late of introduction of CF on infant health, nutrition and developmental outcomes.Methods: We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We will search MEDLINE, Embase, CINAHL, CENTRAL, Web of Science, and other databases and key organizational websites using terms related to complementary feeding and infants. We will also search clinicaltrials.gov for ongoing trials. We will include experimental (randomized trials (individually or cluster) and quasi-randomized trials) and observational studies with a concurrent comparison group (cohort (prospective and retrospective), controlled before-after studies and nested case control studies). We will only include studies that enroll infants, living in low, middle- or high-income countries. Outcomes will be assessed for the following two comparisons:1. Early introduction of CF (before 5 months of age) compared to introduction at 5 to 6.9 months of age2. Late introduction of CF (after 7 months) compared to introduction at 5 to 6.9 months of age All the included studies will be screened on Covidence software and analyzed on Review Manager (version 5.4.1) software.Discussion: There are inconsistencies in the existing recommendations for the introduction of CF, as the recommended age for introducing CF ranges between four and six months of age in various international guidelines. It is imperative to evaluate of consequences of both early and late introduction of complementary foods since optimal timing of introduction may have potential beneficial short- and long-term health effects. Systematic review registration: PROSPERO CRD42020218517

Background: Child wasting is highly prevalent, with around 49.5 million children under five years affected globally. More evidence is needed to inform the scale up of effective treatment of wasted children worldwide. The aim of this study was to identify and prioritise the main outstanding research questions relating to the treatment of wasting to inform future research agendas. Methods: A research prioritisation exercise was undertaken using the Child Health and Nutrition Research Initiative method. Research gaps were identified from multiple sources, grouped in themes and condensed into a list of 53 research areas by a group of experts. An online survey was developed and circulated globally to individuals working in the global nutrition sector. Participants evaluated each research area according to four agreed criteria. Research areas were then ranked according to an overall research priority score. Results: A total of 394 individuals from 63 countries participated in the survey. Research areas prioritised by the group focused on the effective detection and diagnosis of ‘high risk’ wasted children in the community; provision of a continuum of care; and early life course interventions. The group also prioritised evidence to inform guidance on the impatient management of wasted children with diarrhoea; prevention of post-treatment relapse and mortality; and the optimisation of ready-to-use therapeutic foods in treatment programmes. Conclusions: Critical gaps in our understanding of the treatment of wasting must be filled to inform guidance, policy and programming to ensure that all wasted children receive the treatment services that they need. A coordinated research agenda across treatment and prevention is urgently needed to maximise the impact of funding investments towards the meeting of global targets to reduce child wasting.

Progress has been made globally in improving the coverage of key maternal, newborn, and early childhood interventions in low-income and middle-income countries, which has contributed to a decrease in child mortality and morbidity. However, inequities remain, and many children and adolescents are still not covered by life-saving and nurturing care interventions, despite their relatively low costs and high cost-effectiveness. This Series paper builds on a large body of work from the past two decades on evidence-based interventions and packages of care for survival, strategies for delivery, and platforms to reach the most vulnerable. We review the current evidence base on the effectiveness of a variety of essential and emerging interventions that can be delivered from before conception until age 20 years to help children and adolescents not only survive into adulthood, but also to grow and develop optimally, support their wellbeing, and help them reach their full developmental potential. Although scaling up evidence-based interventions in children younger than 5 years might have the greatest effect on reducing child mortality rates, we highlight interventions and evidence gaps for school-age children (5-9 years) and the transition from childhood to adolescence (10-19 years), including interventions to support mental health and positive development, and address unintentional injuries, neglected tropical diseases, and non-communicable diseases.

This article is accessible at the following link: https://doi.org/10.1016/s0140-6736(21)00133-1, Existing global guidance for addressing women's and children's health and nutrition in humanitarian crises is not sufficiently contextualised for conflict settings specifically, reflecting the still-limited evidence that is available from such settings. As a preliminary step towards filling this guidance gap, we propose a conflict-specific framework that aims to guide decision makers focused on the health and nutrition of women and children affected by conflict to prioritise interventions that would address the major causes of mortality and morbidity among women and children in their particular settings and that could also be feasibly delivered in those settings. Assessing local needs, identifying relevant interventions from among those already recommended for humanitarian settings or universally, and assessing the contextual feasibility of delivery for each candidate intervention are key steps in the framework. We illustratively apply the proposed decision making framework to show what a framework-guided selection of priority interventions might look like in three hypothetical conflict contexts that differ in terms of levels of insecurity and patterns of population displacement. In doing so, we aim to catalyse further iteration and eventual field-testing of such a decision making framework by local, national, and international organisations and agencies involved in the humanitarian health response for women and children affected by conflict.

Systematic reviews have highlighted that repeated severe wasting after receiving treatment is likely to be common, but standardised measurement is needed urgently. The Council of Research & Technical Advice for Acute Malnutrition (CORTASAM) released recommendations on standard measurement of relapse (wasting within 6 months after exiting treatment as per recommended discharge criteria), regression (wasting within 6 months after exiting treatment before reaching recommended discharge criteria) and reoccurrence (wasting after 6 months of exit from treatment as per recommended discharge criteria). We provide a theoretical framework of post-treatment relapse and regression to severe wasting to guide discussions, risk factor analyses, and development and evaluations of interventions. This framework highlights that there are factors that may impact risk of relapse and regression in addition to the impact of contextual factors associated with incidence and reoccurrence of severe wasting more generally. Factors hypothesised to be associated with relapse and regression relate specifically to the nutrition and health status of the child on admission to, during and exit from treatment and treatment interventions, platforms and approaches as well as type of exit from treatment (e.g., before reaching recommended criteria). These factors influence whether children reach full recovery, and poorer nutritional and immunological status at exit from treatment are more proximate determinants of risk of severe wasting after treatment, although post-treatment interventions may modify risks. The evidence base for many of these factors is weak. Our framework can guide research to improve our understanding of risks of relapse and regression and how to prevent them and inform programmes on what data to collect to evaluate relapse. Implementation research is needed to operationalise results in programmes and reduce post-treatment severe wasting at scale. publishedVersion

Background: Stunting during childhood has long-term consequences on human capital, including decreased physical growth, and lower educational attainment, cognition, workforce productivity and wages. Literature has quantified the costs of stunting to national economies however few studies have focused on the private sector which employs nearly 90% of the workforce in many low- and middle-income countries (LMICs). We aimed to examine i) the impact of childhood stunting on income loss of private sector workforce in LMICs; ii) to quantify losses in sales to private firms in LMICs due to childhood stunting; and iii) to estimate potential gains (benefit-cost ratios) if stunting levels are reduced in select high prevalence countries Methods: This multiple-methods study engaged multi-disciplinary technical advisers, executed several literature reviews, used innovative statistical methods, and implemented health and labor economic models. We analyzed data from seven longitudinal datasets (up to 30+ years of follow-up), 109 private firm datasets, and many global datasets including Joint Malnutrition Estimates, and World Development Indicators to produce estimates for 120+ LMICs. We studied the impact of childhood stunting on adult cognition, education and height as pathways to wages/productivity in adulthood. We employed cloud-based artificial intelligence (AI) platforms, and conducted comparative analyses using three analytic approaches: traditional frequentist statistics, Bayesian inferential statistics and machine learning. We employed labour and health economic models to estimate wage losses to the private sector worker and firm revenue losses due to stunting. We also estimated benefit-cost ratios for countries investing in nutrition-specific interventions to prevent stunting. Findings: Across 95 LMICs, childhood stunting costs the private sector at least US$135.4 billion in sales annually. Firms from countries in Latin America and the Caribbean and East Asia and Pacific regions had the greatest losses. Totals sales losses to the private sector accumulated to 0.01% to 1.2% of national GDP across countries. Sectors most affected by childhood stunting were manufacturing (non-metallic mineral, fabricated metal, other), garments and food sectors. Sale losses were highest for larger size private firms. Across regions (representing 123 LMICs), US$700 million (Middle East and North Africa) to US$16.5 billion (East Asia and Pacific) monthly income was lost among private sector workers. Investing in stunting reduction interventions yields gains from US$2 to US$81 per $1 invested annually (or 100% to 8000% across countries). Across sectors, the highest returns were in elementary occupations (US$46) and the lowest were among agricultural workers (US$8). By gender, women incurred a higher income penalty from childhood stunting and earned less than men; due to their relatively higher earnings, the returns for investing in stunting reduction were consistently higher for men across most countries studied. Interpretation: Childhood stunting costs the private sector in LMICs billions of dollars in sales and earnings for the workforce annually. Returns to nutrition interventions show that there is an economic case to be made for investing in improvements to childhood nutrition, alongside a moral one. This research could be used to motivate the private sector to invest in childhood undernutrition for both short- and long-term gains. Funding Information: The Power of Nutrition (UK); Patrick J McGovern Foundation (USA). Declaration of Interests: We declare no competing interests.

The COVID-19-related economic crisis and food- and health-system disruptions threaten to exacerbate undernutrition in low- and middle-income countries (LMIC). We used three modelling tools (MIRAGRODEP, Lives Saved Tool, and Optima Nutrition Tool) to estimate impacts on child stunting, wasting, and mortality, maternal anemia, children born to low BMI women, and future productivity losses for three scenarios across 2020–2022 (n = 118 LMICs). We also estimated the additional cost of mitigation for six nutrition interventions to maximize non-stunted and alive children. By 2022 COVID-19 could result in an additional 9.3 million wasted and 2.6 million stunted children, 168,000 additional child-deaths 2.1 million maternal anemia cases, 2.1 million children born to low BMI women and US$29.7 billion future productivity losses due to excess stunting and child mortality. An additional $1.2 billion per year is needed to mitigate these effects. Governments and donors must maintain nutrition as a priority, continue to support resilient systems, and ensure efficient use of new and existing resources.

Background Tanzania has decreased its child mortality rate by more than 70 percent in the last three decades and is striving to develop a nationally-representative sample registration system with verbal autopsy to help focus health policies and programs toward further reduction. As an interim measure, a verbal and social autopsy study was conducted to provide vital information on the causes and social determinants of neonatal and child deaths. Methods Causes of neonatal and 1-59 month-old deaths identified by the 2015-16 Tanzania Demographic and Health Survey were assessed using the expert algorithm verbal autopsy method. The social autopsy examined prevalence of key household, community and health system indicators of preventive and curative care provided along the continuum of care and Pathway to Survival models. Careseeking for neonates and 1-59 month-olds was compared, and tests of associations of age and cause of death to careseeking indicators and place of death were conducted. Results The most common causes of death of 228 neonates and 351 1-59 month-olds, respectively, were severe infection, intrapartum related events and preterm delivery, and pneumonia, diarrhea and malaria. Coverage of early initiation of breastfeeding (24%), hygienic cord care (29%), and full immunization of 12-59 month-olds (33%) was problematic. Most (88.8%) neonates died in the first week, including 44.3% in their birth facility before leaving. Formal care was sought for just 41.9% of newborns whose illness started at home and was delayed by 5.3 days for 1-59 month-olds who sought informal care. Care was less likely to be sought for the youngest neonates and infants and severely ill children. Although 70.3% of 233 under-5 year-olds were moderately or severely ill on discharge from their first provider, only 29.0%-31.2% were referred. Conclusions The study highlights needed actions to complete Tanzania's child survival agenda. Low levels of some preventive interventions need to be addressed. The high rate of facility births and neonatal deaths requires strengthening of institutionally-based interventions targeting maternal labor and delivery complications and neonatal causes of death. Scale-up of Integrated Community Case Management should be considered to strengthen careseeking for the youngest newborns, infants and severely ill children and referral practices at first level facilities.

Introduction Adenotonsillectomy forms part of first-line management for pediatric obstructive sleep apnea (OSA). In nonrandomized studies of preschool-aged children, it is associated with postoperative weight gain. Being overweight or obese in childhood is a predictor of cardiovascular and metabolic disease in later life. Using longitudinal data from a multicenter randomised controlled trial, we assessed the impact of adenotonsillectomy on growth trajectory in preschool-aged children with mild-moderate OSA. Secondary aims were to assess the influence of social factors and baseline polysomnography parameters on growth trajectory. Methods A total of 190 children (aged 3–5 years) with obstructive apnea hypopnea index ≤10 were randomly assigned to early (within 2 months) or routine (12-month wait) adenotonsillectomy. Anthropometry and polysomnography were performed at baseline, 12-month and 24-month timepoints for 126 children. Social risk factors were recorded using a questionnaire. Baseline characteristics were compared using a Mann-Whitney or t-test for continuous variables, and Fisher’s exact test for categorical variables. Data were analyzed using linear mixed modelling. Results Demographic and polysomnographic parameters were similar between groups at baseline. Baseline body mass index (BMI) z-score was 0.52 for both groups. For BMI z-score, there was a significant increase in the early surgery group between 0 and 12 months (0.4, 95%CI 0.1–0.8) but not from 12–24 months. For the routine surgery group, there was a significant BMI z-score increase following surgery between 12 and 24 months (0.45, 95%CI 0.1–0.8), but not from 0–12 months. Final BMI z-score was similar between the two groups. Findings for weight-for-age z-score were similar to the abovementioned findings for BMI z-score. Height-for-age z-score was not significantly different between different timepoints or intervention groups. Children with an unemployed primary income earner had a higher BMI z-score than those with a full-time employed income earner. No other social risk or polysomnography parameters were statistically significant. Conclusion This study provides randomized controlled trial evidence of notable weight increase in preschool children with milder spectrum OSA that occurs in the months immediately following adenotonsillectomy. For children undergoing adenotonsillectomy, counselling regarding nutritional intake and exercise alongside weight monitoring should be considered, especially for those already at risk of becoming overweight or obese. Support (if any)

Summary Background The absolute number of pneumonia deaths in India has declined substantially since 2000. However, pneumonia remains a major cause of morbidity in children in the country. We used a risk factor-based model to estimate pneumonia and severe pneumonia morbidity in Indian states in 2000 and 2015. Methods In this modelling study, we estimated the burden of pneumonia and severe pneumonia in children younger than 5 years using a risk factor-based model. We did a systematic literature review to identify published data on the incidence of pneumonia from community-based longitudinal studies and calculated summary estimates. We estimated state-specific incidence rates for WHO-defined clinical pneumonia between 2000 and 2015 using Poisson regression and the prevalence of risk factors in each state was obtained from National Family Health Surveys. From clinical pneumonia studies, we identified studies reporting the proportion of clinical pneumonia cases with lower chest wall indrawing to estimate WHO-defined severe pneumonia cases. We used the estimate of the proportion of cases with lower chest wall indrawing to estimate WHO-defined severe pneumonia cases for each state. Findings Between 2000 and 2015, the estimated number of pneumonia cases in Indian HIV-uninfected children younger than 5 years decreased from 83·8 million cases (95% uncertainty interval [UI] 14·0–300·8) to 49·8 million cases (9·1–174·2), representing a 41% reduction in pneumonia cases. The incidence of pneumonia in children younger than 5 years in India was 657 cases per 1000 children (95% UI 110–2357) in 2000 and 403 cases per 1000 children (74–1408) in 2015. The estimated national pneumonia case fatality rate in 2015 was 0·38% (95% UI 0·11–2·10). In 2015, the estimated number of severe pneumonia cases was 8·4 million (95% UI 1·2–31·7), with an incidence of 68 cases per 1000 children (9–257) and a case fatality ratio of 2·26% (0·60–16·30). In 2015, the estimated number of pneumonia cases in HIV-uninfected children was highest in Uttar Pradesh (12·4 million [95% UI 2·1–45·0]), Bihar (7·3 million [1·3–26·1]), and Madhya Pradesh (4·6 million [0·7–17·0]). Between 2000 and 2015, the greatest reduction in pneumonia cases was observed in Kerala (82% reduction). In 2015, pneumonia incidence was greater than 500 cases per 1000 children in two states: Uttar Pradesh (565 cases per 1000 children [95% UI 94–2047]) and Madhya Pradesh (563 cases per 1000 children [88–2084]). Interpretation The estimated number of pneumonia and severe pneumonia cases among children younger than 5 years in India decreased between 2000 and 2015. Improvements in socioeconomic indicators and specific government initiatives are likely to have contributed to declines in the prevalence of pneumonia risk factors in many states. However, pneumonia incidence in many states remains high. The introduction of new vaccines that target pneumonia pathogens and reduce risk factors will help further reduce the burden of pneumonia in the country. Funding Bill & Melinda Gates Foundation.

Background Nigeria is the largest country in sub-Saharan Africa, with one of the highest neonatal mortality rates and the second highest number of neonatal deaths in the world. There is broad international consensus on which interventions can most effectively reduce neonatal mortality, however, there is little direct evidence on what interventions are effective in the Nigerian setting. Methods We used the 2013 Nigeria Demographic and Health Survey (NDHS) and the follow-up 2014 Verbal and Social Autopsy study of neonatal deaths to estimate the association between neonatal survival and mothers’ and neonates’ receipt of 18 resources and interventions along the continuum of care with information available in the NDHS. We formed propensity scores to predict the probability of receiving the intervention or resource and then weighted the observations by the inverse of the propensity score to estimate the association with mortality. We examined all-cause mortality as well as mortality due to infectious causes and intrapartum related events. Results Among 19,685 livebirths and 538 neonatal deaths, we achieved adequate balance for population characteristics and maternal and neonatal health care received for 10 of 18 resources and interventions, although inference for most antenatal interventions was not possible. Of ten resources and interventions that met our criteria for balance of potential confounders, only early breastfeeding was related to decreased all-cause neonatal mortality (relative risk 0.42, 95% CI 0.32–0.52, p Conclusion Access to immediate postnatal care and women’s autonomous decision-making have been among the most effective interventions for reducing neonatal mortality in Nigeria. As neonatal mortality increases relative to overall child mortality, accessible interventions are necessary to make further progress for neonatal survival in Nigeria and other low resource settings.

We described prenatal care quality for four indicators over a 12-years period among puerperae living in Southern Brazil. Five surveys including all women giving birth between 01/01 to 31/12 in 2007, 2010, 2013, 2016, and 2019 were conducted in Rio Grande, Rio Grande do Sul state, Brazil. A single standardized questionnaire was applied within 48 h after delivery in all the city's maternity hospitals. Outcomes included the followings proportion of pregnant women who started prenatal care in the first trimester and performed at least six medical visits, completed at least two HIV, two syphilis and two qualitative urine tests. These indicators were stratified according to quartiles of household income. Absolute and relative measures of inequalities were calculated. A total of 12,645 (98% of the total) of the 12,914 mothers eligible in the five surveys were successfully interviewed. Coverage for all indicators increased substantially, especially in the poorest quartile for six prenatal care visits starting in the first trimester, and for HIV and qualitative urine tests. The slope index (SII) and the concentration index (CIX) of inequality showed clear disadvantage among the poorest for prenatal visits starting in the first trimester and performing two or more urine tests. There was a substantial increase in coverage for all variables studied in the period. The reduced inequity, mainly for the beginning of the first trimester and for visits and urine tests, was due to the higher coverage achieved in the poorest quartile.

Addressing malnutrition requires strategies that are comprehensive and multi‐sectoral. Within a multi‐sectoral approach, the health system is essential to deliver 10 nutrition‐specific interventions, which, if scaled up, could substantially reduce under‐5 deaths in high‐burden countries through improving maternal and child undernutrition. This study identifies the health system components required for the effective delivery of these interventions, highlighting opportunities and challenges for nutrition programmes and policies. We reviewed implementation guidance for each nutrition‐specific intervention, mapping the delivery process for each intervention and determining the health system components required for their delivery. We integrated the components into a single health systems framework for nutrition, illustrating the pathways by which health system components influence household‐level determinants of nutrition and individual‐level health outcomes. Nutrition‐specific interventions are typically delivered in one of four ways: (i) when nutrition interventions are intentionally sought out, (ii) when care is sought for other, unrelated interventions, (iii) at a health facility after active community case finding and referral, and (iv) in the community after active community case finding. A health system enables these processes by providing health services and facilitating care seeking for services, which together require a skilled and motivated health workforce, an effective supply chain, demand for services and access to services. The nutrition community should consider the processes by which nutrition‐specific interventions are delivered and the health system components required for their success. Programmes should encourage the delivery of nutrition interventions at every client–provider interaction and should actively generate demand for services—in general, and for nutrition services specifically.

Background Child stunting and linear growth faltering have declined over the past few decades and several countries have made exemplary progress. Objectives To synthesize findings from mixed methods studies of exemplar countries to provide guidance on how to accelerate reduction in child stunting. Methods We did a qualitative and quantitative synthesis of findings from existing literature and 5 exemplar country studies (Nepal, Ethiopia, Peru, Kyrgyz Republic, Senegal). Methodology included 4 broad research activities: 1) a series of descriptive analyses of cross-sectional data from demographic and health surveys and multiple indicator cluster surveys; 2) multivariable analysis of quantitative drivers of change in linear growth; 3) interviews and focus groups with national experts and community stakeholders and mothers; and 4) a review of policy and program evolution related to nutrition. Results Several countries have dramatically reduced child stunting prevalence, with or without closing geographical, economic, and other population inequalities. Countries made progress through interventions from within and outside the health sector, and despite significant heterogeneity and differences in context, contributions were comparable from health and nutrition sectors (40% of change) and other sectors (50%), previously called nutrition-specific and -sensitive strategies. Improvements in maternal education, maternal nutrition, maternal and newborn care, and reductions in fertility/reduced interpregnancy intervals were strong contributors to change. A roadmap to reducing child stunting at scale includes several steps related to diagnostics, stakeholder consultations, and implementing direct and indirect nutrition interventions related to the health sector and nonhealth sector . Conclusions Our results show that child stunting reduction is possible even in diverse and challenging contexts. We propose that our framework of organizing nutrition interventions as direct/indirect and inside/outside the health sector should be considered when mapping causal pathways of child stunting and planning interventions and strategies to accelerate stunting reduction to achieve the 2030 Sustainable Development Goals.

Salt iodization is the main public health policy to prevent and control iodine deficiency disorders. The National Salt Iodization Impact Assessment Survey (PNAISAL) was conducted to measure iodine concentration among Brazilian schoolchildren. A survey including 6&ndash, 14-year-old schoolchildren from public and private schools from all 26 Brazilian states and the Federal District was carried out in the biennia 2008&ndash, 2009 and 2013&ndash, 2014. Municipalities, schools, and students were randomly selected. Students were interviewed at school using a standard questionnaire, which included the collection of demographic, educational, weight, height, and 10 mL non-fasting urine collection information. The analyses were weighted according to the population of students per federative unit. The median urinary iodine concentration (MUIC) for the entire sample by region, federative unit per school, and student characteristics, was described from the cutoff points defined by the World Health Organization (severe disability: &lt, 20 &micro, g/L, moderate: 20&ndash, 49 &micro, g/L, mild: 50&ndash, 99 &micro, g/L, adequate: 100&ndash, 199 &micro, g/L, more than adequate: 200&ndash, 299 &micro, g/L, and excessive: &gt, 300 &micro, g/L). In total, 18,864 students (95.9% of the total) from 818 schools in 477 municipalities from all federative units were included in this study. Almost 70% were brown skin color, nine-years-old or older, studied in urban schools, and were enrolled in elementary school. The prevalence of overweight/obesity, as measured by body mass index (BMI) for age, was about twice as high compared to nutritional deficits (17.3% versus 9.6%). The MUIC arrived at 276.7 &micro, g/L (25th percentile = 175.5 &micro, g/L and 75th percentile = 399.71 &micro, g/L). In Brazil as a whole, the prevalence of mild, moderate, and severe deficit was 6.9%, 2.6%, and 0.6%, respectively. About one-fifth of the students (20.7%) had adequate iodine concentration, while 24.9% and 44.2% had more than adequate or excessive concentration, respectively. The prevalence of iodine deficits was significantly higher among younger female students from municipal public schools living in rural areas with the lowest BMI. The median urine iodine concentration showed that Brazilian students have an adequate nutritional intake, with a significant proportion of them evidencing overconsumption of this micronutrient.

Background: Policy and programming to improve maternal and child nutrition has become a mainstay of most countries because of the direct implications of nutrition on population health, economic development, and human capital. Since the 2013 Lancet Nutrition series, more evidence on the set of 10 recommended interventions has emerged, along with evidence for newer interventions. This paper primarily aims to determine what works in the current low and middle-income country (LMIC) context to improve maternal and child undernutrition. Methods: We undertook ten new systematic reviews that examined the impact of direct and indirect nutrition interventions on maternal, newborn, child, and adolescent health and nutrition with a focus on LMICs. We used the PICO methodology to construct our search strategies; appropriate syntax was applied to key words and MeSH terms/key words were combined with Boolean operators. Searches were run in all relevant databases, which varied depending on the research question, and grey literature searches were conducted in Google, Google Scholar, and within websites of key nutrition organizations. Review updates were also undertaken. Results from our reviews and review updates were triangulated with other, high-quality published evidence of intervention effects. Findings: The updated evidence underscores the effectiveness of the ten interventions recommended in the 2013 Lancet Nutrition Series including periconceptional folic acid supplementation or fortification, maternal balanced energy protein supplementation, maternal calcium supplementation, maternal multiple micronutrient supplementation, promotion of breast feeding, appropriate complementary feeding, vitamin A and preventive zinc supplementation in children 6-59 months of age, and management of severe- and moderate-acute malnutrition. The evidence for antenatal multiple micronutrient supplementation has strengthened, with greater effects on stillbirths and babies born preterm, small for gestational age and with low birthweight compared to iron-folic acid supplementation. Emerging interventions with evidence of effects on child growth outcomes include small-quantity lipid-nutrient supplements for children 6-23 months of age and kangaroo mother care for healthy term and late preterm neonates through facility and community-based approaches. Evidence supports the provision of supplementary food to pregnant women and children residing in food-insecure settings, and community-based approaches to manage children with acute malnutrition with locally produced supplementary and therapeutic food. Indirect nutrition strategies, such as malaria prevention, preconception care, and water, sanitation, and hygiene, may provide nutritional benefits in some settings. Interpretation: Evidence continues to support the direct nutrition interventions and the indirect health and nutrition interventions recommended in 2013. Additionally, small-quantity lipid-nutrient supplements and kangaroo mother care should be considered for scale up in LMICs to improve growth and micronutrient status. The coverage of priority interventions remains low, especially in contexts where they are needed most. Hence, greater focus and effort are required to improve the reach of these interventions, especially for the most vulnerable populations. There is also a need to develop evidence-based strategies to address undernutrition in school-age children and adolescents. Funding Statement: This study was funded by the Bill & Melinda Gates Foundation with additional support from the Centre for Global Child Health, the Hospital for Sick Children, Toronto and the Center of Excellence in Women and Child Health, the Aga Khan University, Karachi, Pakistan. Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: Not required.

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.