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BackgroundSocio-economic, nutritional, and infectious factors have been associated with impaired infant growth, but how the presence of these factors during infancy affects growth around 5 years is not well understood.MethodsThis secondary analysis of the MAL-ED cohort included 277 children from Pakistan for whom socio-demographic, breastfeeding, complementary foods, illness, nutritional biomarkers, stool pathogens and environmental enteropathy indicators between 0 and 11 months were recorded. We used linear regression models to analyze associations of these indicators with height-for-age (HAZ), weight-for-age (WAZ) and weight-for-height (WLZ) at 54–66 months (~5 years), and Poisson regression with robust standard errors to estimate risk ratios for stunting and underweight ~5 years, controlling for gender, first available weight, and income.ResultsAmong the 237 infants followed longitudinally and evaluated at about 5 years of age, exclusive breastfeeding was short (median = 14 days). Complementary feeding started before 6 months with rice, bread, noodles, or sugary foods. Roots, dairy products, fruits/vegetables, and animal-source foods were provided later than recommended (9–12 months). Anemia (70.9%), deficiencies in iron (22.0%), zinc (80.0%), vitamin A (53.4%) and iodine (13.3%) were common. Most infants (>90%) presented with diarrhea and respiratory infections in their first year. At ~5 years, low WAZ (mean-1.91 ± 0.06) and LAZ (−2.11 ± 0.06) resulted in high prevalence of stunting (55.5%) and underweight (44.4%) but a relatively low rate of wasting (5.5%). While 3.4% had concurrent stunting and wasting ~5 years, 37.8% of children had coexisting stunting and underweight. A higher income and receiving formula or dairy products during infancy were associated with a higher LAZ ~5 years, but infant’s history of hospitalizations and more respiratory infections were associated with lower LAZ and higher risk of stunting ~5 years. Infants’ intake of commercial baby foods and higher serum-transferrin receptors were associated with higher WAZ and lower risk of underweight ~5 years. Presence of Campylobacter and fecal neopterin >6.8 nmol/L in the first year were associated with increased risk of underweight ~5 years.ConclusionGrowth indicators ~5 years were associated with poverty, inappropriate complementary feeding, and infections during the first year of life, which supports the early start of public health interventions for preventing growth delay ~5 years.

Background: \ud The COVID-19 pandemic has caused disruptions to the functioning of societies and their health systems. Prior to the pandemic, health systems in low- and middle-income countries (LMIC) were particularly stretched and vulnerable. The International Society of Global Health (ISoGH) sought to systematically identify priorities for health research that would have the potential to reduce the impact of the COVID-19 pandemic in LMICs.\ud \ud Methods: \ud The Child Health and Nutrition Research Initiative (CHNRI) method was used to identify COVID-19-related research priorities. All ISoGH members were invited to participate. Seventy-nine experts in clinical, translational, and population research contributed 192 research questions for consideration. Fifty-two experts then scored those questions based on five pre-defined criteria that were selected for this exercise: 1) feasibility and answerability; 2) potential for burden reduction; 3) potential for a paradigm shift; 4) potential for translation and implementation; and 5) impact on equity.\ud \ud Results: \ud Among the top 10 research priorities, research questions related to vaccination were prominent: health care system access barriers to equitable uptake of COVID-19 vaccination (ranked 1st), determinants of vaccine hesitancy (4th), development and evaluation of effective interventions to decrease vaccine hesitancy (5th), and vaccination impacts on vulnerable population/s (6th). Health care delivery questions also ranked highly, including: effective strategies to manage COVID-19 globally and in LMICs (2nd) and integrating health care for COVID-19 with other essential health services in LMICs (3rd). Additionally, the assessment of COVID-19 patients’ needs in rural areas of LMICs was ranked 7th, and studying the leading socioeconomic determinants and consequences of the COVID-19 pandemic in LMICs using multi-faceted approaches was ranked 8th. The remaining questions in the top 10 were: clarifying paediatric case-fatality rates (CFR) in LMICs and identifying effective strategies for community engagement against COVID-19 in different LMIC contexts.\ud \ud Interpretation: \ud Health policy and systems research to inform COVID-19 vaccine uptake and equitable access to care are urgently needed, especially for rural, vulnerable, and/or marginalised populations. This research should occur in parallel with studies that will identify approaches to minimise vaccine hesitancy and effectively integrate care for COVID-19 with other essential health services in LMICs. ISoGH calls on the funders of health research in LMICs to consider the urgency and priority of this research during the COVID-19 pandemic and support studies that could make a positive difference for the populations of LMICs.

ContextApproximately 7.3 million births occur annually among adolescents in low- and middle-income countries. Pregnant adolescents constitute a nutritionally vulnerable group that could benefit from intervention to mitigate the mortality and adverse birth outcomes associated with adolescent pregnancy.ObjectiveThe aim of this systematic review and meta-analysis was to assess the following: (1) the effect of multiple-micronutrient (MMN) supplementation vs iron and folic acid (IFA) supplementation among adolescents on maternal morbidity, birth outcomes, and mortality outcomes, (2) the effects of MMN supplementation in adolescents compared with the effects in adult women, and (3) the effect modification, if any, of MMN supplementation by baseline and geographic characteristics of adolescents.Data sourcesMEDLINE and Cochrane databases were searched, along with the reference lists of relevant reviews.Study selectionMultiple-micronutrient supplementation trials in pregnancy that were conducted in a low- or middle-income country and had included at least 100 adolescents (10-19 years of age) were eligible for inclusion. Two independent reviewers assessed study eligibility.Data extractionThirteen randomized controlled trials conducted in Africa and Asia were identified from 1792 reviews and 1578 original trials. Individual-level data was shared by study collaborators and was checked for completeness and extreme values. One- and two-stage individual participant data meta-analyses were conducted using data from randomized controlled trials of MMN supplementation.ResultsA total of 15 283 adolescents and 44 499 adult women with singleton births were included in the individual participant data meta-analyses of MMN supplementation vs IFA supplementation. In adolescents, MMN supplementation reduced low birth weight (1-stage OR = 0.87, 95%CI 0.77-0.97; 2-stage OR = 0.81; 95%CI 0.74-0.88), preterm birth (1-stage OR = 0.88, 95%CI 0.80-0.98; 2-stage OR = 0.86, 95%CI 0.79-0.95), and small-for-gestational-age births (1-stage OR = 0.90, 95%CI 0.81-1.00; 2-stage OR = 0.86, 95%CI 0.79-0.95) when compared with IFA supplementation. The effects of MMN supplementation did not differ between adolescents and older women, although a potentially greater reduction in small-for-gestational-age births was observed among adolescents. Effect modification by baseline characteristics and geographic region was inconclusive.ConclusionsMultiple-micronutrient supplementation can improve birth outcomes among pregnant adolescents in low- and middle-income countries. Policy related to antenatal care in these settings should prioritize MMN supplementation over the currently recommended IFA supplementation for all pregnant women, especially adolescents.

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). publishedVersion

Additional file 6 “Layout”. Example of ward layout for data collection.

Additional file 3 “Key hand-touch sites”. Selection of hand-touch sites.

Additional file 1: Maternal history questions in the FBH and FPH modules (Section II)

Additional file 3. Additional results. 3.1: Maternal characteristics of the births in the five years preceding the survey for five sites. 3.2: Interviewer characteristics of births in the five years preceding the survey for five sites. 3.3: Distribution of missing year or month of pregnancy outcome by FBH+/FPH groups. 3.3: Distribution of missing year or month of pregnancy outcome by FBH+/FPH groups. 3.5A: Distribution of reported gestational age in months by outcome (n=70,973). 3.5B: Distribution of reported gestational age in months by outcome (gestation ≥5 months) (n=66,793). 3.6: Gestational age specific stillbirth, perinatal and early neonatal mortality rates, overall and site specific. 3.7: Summary of reporting of gestational age in weeks for stillbirths. 3.7A: Distribution of reported gestational age in weeks by outcome (n=15,591). 3.7B: Internal consistency of gestational age reported in weeks and months by site and by outcome. 3.8: Birthweight distribution by outcome. 3.9: Heaping indices for birthweight, by outcome (n=6,749). 3.10: Comparison of heaping on multiples of 500g by card and recall by outcome. 3.11: Reported intrapartum monitoring for late gestation stillbirths, by site (n=846). 3.12: Individual-level consistency between intrapartum stillbirth classification, by site. 3.12: Individual-level consistency between intrapartum stillbirth classification, by site. 3.14: Reporting of child’s sex by site and outcome (FPH group only. n=631). 3.14: Reporting of child’s sex by site and outcome (FPH group only. n=631). 3.15: Barriers and enablers to birthweight measurement in surveys for stillbirths by site.

Additional file 8 “ACC breakdown”. Results by categories of ACC.

Additional file 2. Consent form.

Additional file 7 “Sensitivity analyses”. Sensitivity analyses results for microbiological cleanliness.

Additional file 3. Completed CONSORT checklist.

Additional file 1. Framework for factors associated with stillbirths

Additional file 4. Linking between EN-INDEPTH survey and HDSS data.

Additional file 3. STROBE guidelines checklist

Additional file 3: A. Location of Demographic and Health Survey program countries and number of surveys, Phases I-IV. B. Location of Demographic and Health Survey program countries and number of surveys, Phases V-VII

Additional file 7. Primary and secondary outcomes (secondary analyses, excluding “contaminated” control districts).

Additional file 7. Results: Additional details. 7.1: Gestational age capture in weeks in the EN-INDEPTH survey. 7.1A: Logit estimates of adjusted ORs and 95% confidence interval of responding to GA in weeks. 7.1B: Matching of GA months with GA weeks, EN-INDEPTH survey. 7.1C: Gestational age distribution by religion, Matlab site, EN-INDEPTH survey in last five years. 7.2: Comparison of GA weeks between survey, HDSS and early pregnancy ultrasound, Matlab site. 7.2A: GA weeks in last five years by HDSS, early pregnancy ultrasound and five years prior to EN-INDEPTH survey. 7.2B: GA weeks for livebirths by HDSS, early pregnancy ultrasound and EN-INDEPTH survey in last five years. 7.2C: Early pregnancy ultrasound versus EN-INDEPTH survey and HDSS data in last five years by ultrasound timing. 7.2D: Adjusted relative risk ratios for over- and under-reporting of GA weeks, survey and HDSS versus ultrasound. 7.3: Community perceptions, practices and barriers to reporting GA, EN-INDEPTH study (five sites). 7.4: Comparison of preterm birth rates in EN-INDEPTH study to external data sources.

Additional file 2. Definition of other reported outcomes.

Additional file 4. Additional results. Additional file 4.1: Don’t know and missing responses by pregnancy outcomes for selected DHS-7 standard pregnancy and postnatal care questions. Additional file 4.2: Data errors in timing of postnatal care questions. Additional file 4.3: Comparison of selected maternal care indicators by outcome. Additional file 4.4: Distribution of age at first antenatal care visit by outcome. Additional file 4.4A: Distribution of age at first ANC reported in weeks by outcome (n=501). Additional file 4.4B: Distribution of age at first ANC reported in months by outcome (n=13,400). Additional file 4.5: Distribution of post-delivery length of stay in facility in days. Additional file 4.6: Distribution of age at first postnatal care visit in hours

Additional file 4. Ethical approval of local Institutional Review Boards.

Additional file 5: DHS surveys with Full Birth History modules by DHS phase

Additional file 5 “Tablet façade”. Visual of data collection tool.

Additional file 4. Actual roll-out of the IeDA intervention with step dates and number (N) of children aged 2–59 months observed at each step in each district.

Additional file 8. Proposed revised questions to capture gestational age.

Additional file 5. Comparison of HCWs’ performance with and without use of IMCI paper-forms in the control arm. (DOCX 18 kb)

Additional file 5. Ethical approval of local Institutional Review Boards

Additional file 2. Selection of women with a livebirth surviving the neonatal period, EN-INDEPTH survey.

Additional file 5. Calculation of survey weights. 5.1: Methods for calculation of survey weights. 5.2: Weighted numbers of livebirths by HDSS sites.

Additional file 1 “ToC and Assumptions". Details of the Theory of Change.

Additional file 3. Overview of gestational age data collection in Matlab and Bandim HDSS sites.

Additional file 1. Additional methods. 1.1: Background overview of the five HDSS sites. 1.2: Details of selection of women with a livebirth surviving the neonatal period. 1.3: Details of qualitative methods for FGD in EN-INDEPTH study.

Additional file 1. STROBE guidelines checklist.

Additional file 9 “Sensitivity and Specificity”. Sensitivity and specificity calculations.

Additional file 2. Additional methods. Additional file 2.1: Background overview of the five HDSS sites. Additional file 2.2: Details of selection of women with a livebirth surviving the neonatal period. Additional file 2.3: Questions on stillbirths and maternity care asked in EN-INDEPTH survey. Additional file 2.3A: Questions on stillbirths asked in EN-INDEPTH survey1. Additional file 2.3B: Questions on maternity care asked in EN-INDEPTH survey. Additional file 2.4: Calculation of survey weights.

Additional file 10 “Champions breakdown”. Details of champions selected.

Additional file 9. Ethical approval of local Institutional Review Boards.

Additional file 1. SPIRIT check-list.

Additional file 6. Qualitative methods for Focus Group Discussions in the EN-INDEPTH study.

Additional file 2 “SQUIRE guidelines”. SQUIRE checklist.

Additional file 4: DHS surveys with Full Pregnancy History modules by DHS phase

Additional file 6. Agreement between HCWs and validation nurses’ children measurements. 6b: Agreement between HCWs and validation nurses’ RDT results and caretakers’ answers.

BACKGROUND: Despite remarkable progress in the improvement of child survival between 1990 and 2015, the Millennium Development Goal (MDG) 4 target of a two-thirds reduction of under-5 mortality rate (U5MR) was not achieved globally. In this paper, we updated our annual estimates of child mortality by cause to 2000-15 to reflect on progress toward the MDG 4 and consider implications for the Sustainable Development Goals (SDG) target for child survival. METHODS: We increased the estimation input data for causes of deaths by 43% among neonates and 23% among 1-59-month-olds, respectively. We used adequate vital registration (VR) data where available, and modelled cause-specific mortality fractions applying multinomial logistic regressions using adequate VR for low U5MR countries and verbal autopsy data for high U5MR countries. We updated the estimation to use Plasmodium falciparum parasite rate in place of malaria index in the modelling of malaria deaths; to use adjusted empirical estimates instead of modelled estimates for China; and to consider the effects of pneumococcal conjugate vaccine and rotavirus vaccine in the estimation. FINDINGS: In 2015, among the 5·9 million under-5 deaths, 2·7 million occurred in the neonatal period. The leading under-5 causes were preterm birth complications (1·055 million [95% uncertainty range (UR) 0·935-1·179]), pneumonia (0·921 million [0·812 -1·117]), and intrapartum-related events (0·691 million [0·598 -0·778]). In the two MDG regions with the most under-5 deaths, the leading cause was pneumonia in sub-Saharan Africa and preterm birth complications in southern Asia. Reductions in mortality rates for pneumonia, diarrhoea, neonatal intrapartum-related events, malaria, and measles were responsible for 61% of the total reduction of 35 per 1000 livebirths in U5MR in 2000-15. Stratified by U5MR, pneumonia was the leading cause in countries with very high U5MR. Preterm birth complications and pneumonia were both important in high, medium high, and medium child mortality countries; whereas congenital abnormalities was the most important cause in countries with low and very low U5MR. INTERPRETATION: In the SDG era, countries are advised to prioritise child survival policy and programmes based on their child cause-of-death composition. Continued and enhanced efforts to scale up proven life-saving interventions are needed to achieve the SDG child survival target. FUNDING: Bill & Melinda Gates Foundation, WHO.

A comparison of LAZ/HAZ scores based on measured and fitted lengths/heights for children aged 1, 6, 12, and 24 months. (DOCX 433 kb)

Distribution of measured lengths/heights against transformed age for 21786 children. (DOCX 1363 kb)

A comparison of LAZ/HAZ scores based on measured and fitted lengths/heights for children aged 1, 6, 12, and 24 months. (DOCX 433 kb)

A randomized trial reported by Alassane Dicko and colleagues shows that intermittent preventive treatment for malaria in children who are protected from mosquitoes by insecticide-treated bednets provides substantial protection from malaria., Background Previous studies have shown that in areas of seasonal malaria transmission, intermittent preventive treatment of malaria in children (IPTc), targeting the transmission season, reduces the incidence of clinical malaria. However, these studies were conducted in communities with low coverage with insecticide-treated nets (ITNs). Whether IPTc provides additional protection to children sleeping under an ITN has not been established. Methods and Findings To assess whether IPTc provides additional protection to children sleeping under an ITN, we conducted a randomised, double-blind, placebo-controlled trial of IPTc with sulphadoxine pyrimethamine (SP) plus amodiaquine (AQ) in three localities in Kati, Mali. After screening, eligible children aged 3–59 mo were given a long-lasting insecticide-treated net (LLIN) and randomised to receive three rounds of active drugs or placebos. Treatments were administered under observation at monthly intervals during the high malaria transmission season in August, September, and October 2008. Adverse events were monitored immediately after the administration of each course of IPTc and throughout the follow-up period. The primary endpoint was clinical episodes of malaria recorded through passive surveillance by study clinicians available at all times during the follow-up. Cross-sectional surveys were conducted in 150 randomly selected children weekly and in all children at the end of the malaria transmission season to assess usage of ITNs and the impact of IPTc on the prevalence of malaria, anaemia, and malnutrition. Cox regression was used to compare incidence rates between intervention and control arms. The effects of IPTc on the prevalence of malaria infection and anaemia were estimated using logistic regression. 3,065 children were screened and 3,017 (1,508 in the control and 1,509 in the intervention arm) were enrolled in the study. 1,485 children (98.5%) in the control arm and 1,481 (98.1%) in the intervention arm completed follow-up. During the intervention period, the proportion of children reported to have slept under an ITN was 99.7% in the control and 99.3% in intervention arm (p = 0.45). A total of 672 episodes of clinical malaria defined as fever or a history of fever and the presence of at least 5,000 asexual forms of Plasmodium falciparum per microlitre (incidence rate of 1.90; 95% confidence interval [CI] 1.76–2.05 episodes per person year) were observed in the control arm versus 126 (incidence rate of 0.34; 95% CI 0.29–0.41 episodes per person year) in the intervention arm, indicating a protective effect (PE) of 82% (95% CI 78%–85%) (p, Editors' Summary Background Malaria accounts for one in five of all childhood deaths in Africa and of the one million annual malarial deaths world-wide, over 75% occur in African children

Additional file 1. SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents.

Additional file 2. aSCRIP definition.