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

13 years after the first Lancet Series on maternal and child undernutrition, we reviewed the progress achieved on the basis of global estimates and new analyses of 50 low-income and middle-income countries with national surveys from around 2000 and 2015. The prevalence of childhood stunting has fallen, and linear growth faltering in early life has become less pronounced over time, markedly in middle-income countries but less so in low-income countries. Stunting and wasting remain public health problems in low-income countries, where 4·7% of children are simultaneously affected by both, a condition associated with a 4·8-times increase in mortality. New evidence shows that stunting and wasting might already be present at birth, and that the incidence of both conditions peaks in the first 6 months of life. Global low birthweight prevalence declined slowly at about 1·0% a year. Knowledge has accumulated on the short-term and long-term consequences of child undernutrition and on its adverse effect on adult human capital. Existing data on vitamin A deficiency among children suggest persisting high prevalence in Africa and south Asia. Zinc deficiency affects close to half of all children in the few countries with data. New evidence on the causes of poor growth points towards subclinical inflammation and environmental enteric dysfunction. Among women of reproductive age, the prevalence of low body-mass index has been reduced by half in middle-income countries, but trends in short stature prevalence are less evident. Both conditions are associated with poor outcomes for mothers and their children, whereas data on gestational weight gain are scarce. Data on the micronutrient status of women are conspicuously scarce, which constitutes an unacceptable data gap. Prevalence of anaemia in women remains high and unabated in many countries. Social inequalities are evident for many forms of undernutrition in women and children, suggesting a key role for poverty and low education, and reinforcing the need for multisectoral actions to accelerate progress. Despite little progress in some areas, maternal and child undernutrition remains a major global health concern, particularly as improvements since 2000 might be offset by the COVID-19 pandemic.

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

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.

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.

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.

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.

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 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.

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.

BackgroundSignificant global gains in sexual, reproductive, maternal, newborn, child and adolescent health and nutrition (SRMNCAH&N) will be difficult unless conflict settings are adequately addressed. We aimed to determine the amount, scope and quality of publically available guidance documents, to characterise the process by which agencies develop their guidance and to identify gaps in guidance on SRMNCAH&N promotion in conflicts.MethodsWe identified guidance documents published between 2008 and 2018 through English-language Internet sites of humanitarian response organisations, reviewed them for their scope and assessed their quality with the AGREE II (Appraisal of Guidelines for REsearch and Evaluation II) tool. Additionally, we interviewed 22 key informants on guidance development, dissemination processes, perceived guidance gaps and applicability.FindingsWe identified 105 conflict-relevant guidance documents from 75 organisations. Of these, nine were specific to conflicts, others were applicable also to other humanitarian settings. Fifteen documents were technical normative guidelines, others were operational guides (67), descriptive documents (21) or advice on legal, human rights or ethics questions (2). Nutrition was the most addressed health topic, followed by communicable diseases and violence. The documents rated high quality in their ‘scope and purpose’ and ‘clarity of presentation’ and low for ‘rigour of development’ and ‘editorial independence’. Key informants reported end user need as the primary driver for guideline development and WHO technical guidelines as their main evidence base. Insufficient local contextualisation, lack of inter-agency coordination and lack of systematic implementation were considered problems in guideline development. Several guidance gaps were noted, including abortion care, newborn care, early child development, mental health, adolescent health beyond sexual and reproductive health and non-communicable diseases.InterpretationOrganisations are motivated and actively producing guidance for SRMNCAH&N promotion in humanitarian settings, but few documents address conflicts specifically and there are important guidance gaps. Improved inter-organisation collaboration for guidance on SRMNCAH&N promotion in conflicts and other humanitarian settings is needed.

Despite the high burden of rotavirus diarrhea, uptake of rotavirus vaccines in Asia remains low. This primarily stems from a perception of rotavirus as a non-life-threatening pathogen amidst a background of competing health priorities and limited resources. In the largest pediatric hospital of Bangladesh, where there is a fierce competition for beds, we found that between November 2015 and October 2016, 12% of 23,064 admissions were due to gastrointestinal infections, 54% of which were caused by rotavirus. One in four cases requiring hospitalization, or 5,879 cases, was refused because of unavailability of beds. Most refused cases were of pneumonia (22%), severe perinatal asphyxia (17%), preterm birth complications (7%), and meningitis (2%), all of which bear high risks of death or disability, if not treated timely. When determining vaccine policies and conducting vaccine impact studies, it would be shortsighted to not consider the impact on morbidity and mortality of cases that are refused admission because of the hospitalization of children with a preventable disease as rotavirus diarrhea. In our hospital, routine use of a rotavirus vaccine with 41% efficacy will release 629 beds per year to accommodate previously refused cases. Based on evidence, we make the case that introduction of this vaccine in Bangladesh and the surrounding region will prevent morbidity and mortality, both directly and indirectly, and help us ensure survival and well-being of all children.

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 Documentation of the demographic and geographical details of changes in cause-specific neonatal (younger than 1 month) and 1–59-month mortality in India can guide further progress in reduction of child mortality. In this study we report the changes in cause-specific child mortality between 2000 and 2015 in India. Methods Since 2001, the Registrar General of India has implemented the Million Death Study (MDS) in 1·3 million homes in more than 7000 randomly selected areas of India. About 900 non-medical surveyors do structured verbal autopsies for deaths recorded in these homes. Each field report is assigned randomly to two of 404 trained physicians to classify the cause of death, with a standard process for resolution of disagreements. We combined the proportions of child deaths according to the MDS for 2001–13 with annual UN estimates of national births and deaths (partitioned across India's states and rural or urban areas) for 2000–15. We calculated the annual percentage change in sex-specific and cause-specific mortality between 2000 and 2015 for neonates and 1–59-month-old children. Findings The MDS captured 52 252 deaths in neonates and 42 057 deaths at 1–59 months. Examining specific causes, the neonatal mortality rate from infection fell by 66% from 11·9 per 1000 livebirths in 2000 to 4·0 per 1000 livebirths in 2015 and the rate from birth asphyxia or trauma fell by 76% from 9·0 per 1000 livebirths in 2000 to 2·2 per 1000 livebirths in 2015. At 1–59 months, the mortality rate from pneumonia fell by 63% from 11·2 per 1000 livebirths in 2000 to 4·2 per 1000 livebirths in 2015 and the rate from diarrhoea fell by 66% from 9·4 per 1000 livebirths in 2000 to 3·2 per 1000 livebirths in 2015 (with narrowing girl–boy gaps). The neonatal tetanus mortality rate fell from 1·6 per 1000 livebirths in 2000 to less than 0·1 per 1000 livebirths in 2015 and the 1–59-month measles mortality rate fell from 3·3 per 1000 livebirths in 2000 to 0·3 per 1000 livebirths in 2015. By contrast, mortality rates for prematurity or low birthweight rose from 12·3 per 1000 livebirths in 2000 to 14·3 per 1000 livebirths in 2015, driven mostly by increases in term births with low birthweight in poorer states and rural areas. 29 million cumulative child deaths occurred from 2000 to 2015. The average annual decline in mortality rates from 2000 to 2015 was 3·3% for neonates and 5·4% for children aged 1–59 months. Annual declines from 2005 to 2015 (3·4% decline for neonatal mortality and 5·9% decline in 1–59-month mortality) were faster than were annual declines from 2000 to 2005 (3·2% decline for neonatal mortality and 4·5% decline in 1–59-month mortality). These faster declines indicate that India avoided about 1 million child deaths compared with continuation of the 2000–05 declines. Interpretation To meet the 2030 Sustainable Development Goals for child mortality, India will need to maintain the current trajectory of 1–59-month mortality and accelerate declines in neonatal mortality (to >5% annually) from 2015 onwards. Continued progress in reduction of child mortality due to pneumonia, diarrhoea, malaria, and measles at 1–59 months is feasible. Additional attention to low birthweight is required. Funding National Institutes of Health, Disease Control Priorities Network, Maternal and Child Epidemiology Estimation Group, and University of Toronto.

Objective To evaluate the effect of zinc as an adjuvant therapy in radiologically confirmed pneumonia in children 2-24 months of age. Patients and methods We analyzed data of 212 children with pneumonia for whom chest X-ray films were available at enrollment and at least two radiologists agreed on the diagnosis of pneumonia. We compared the time to recovery in the two groups (n = 121, zinc group and n = 91, placebo group) using a Cox proportional hazards regression model. Results Time to recovery was similar in both groups [median interquartile range: zinc, 84 h (64, 140 h); placebo, 85 h (65, 140 h)]. The absolute risk reduction for treatment failure was 5.2% (95% confidence interval: -4.8, 15.1) with zinc supplementation. Conclusion There was no significant beneficial effect of zinc on the duration of recovery or risk of treatment failure in children with radiologically confirmed pneumonia.

Adolescent nutritional behaviors are assuming considerable importance in nutrition interventions given their important relationships with medium- and long-term outcomes. This is the period when young people undergo major anatomical and physiological maturational changes in preparation for adulthood. Nutritional requirements during puberty are higher during adolescence than during the prepubertal stage and during adulthood. A significant proportion of adolescents also become parents, and hence the importance of their health and nutritional status before as well as during pregnancy has its impact on their own health, fetal well-being, and newborn health. In this paper, we describe the evidence-based nutrition recommendations and the current global guidance for nutrition actions for adolescents. Despite the limitations of available information, we believe that a range of interventions are feasible to address outcomes in this age group, although some would need to start earlier in childhood. We propose packages of preventive care and management comprising nutrition-specific and nutrition-sensitive interventions to address adolescent undernutrition, overnutrition, and micronutrient deficiencies. We discuss potential delivery platforms and strategies relevant to low- and middle-income countries. Beyond the evidence synthesis, there is a clear need to translate evidence into policy and for implementation of key recommendations and addressing knowledge gaps through prioritized research.

As part of Disease Control Priorities 3rd Edition, the World Bank will publish a volume on Reproductive, Maternal, Newborn, and Child Health that identifies essential cost-effective health interventions that can be scaled up to reduce maternal, newborn, and child deaths, and stillbirths. This Review summarises the volume's key findings and estimates the effect and cost of expanded implementation of these interventions. Recognising that a continuum of care from the adolescent girl, woman, or mother to child is needed, the volume includes details of preventive and therapeutic health interventions in integrated packages: Maternal and Newborn Health and Child Health (along with folic acid supplementation, a key reproductive health intervention). Scaling up all interventions in these packages from coverage in 2015 to hypothetically immediately achieve 90% coverage would avert 149 000 maternal deaths, 849 000 stillbirths, 1 498 000 neonatal deaths, and 1 515 000 additional child deaths. In alternative calculations that consider only the effects of reducing the number of pregnancies by provision of contraceptive services as part of a Reproductive Health package, meeting 90% of the unmet need for contraception would reduce global births by almost 28 million and consequently avert deaths that could have occurred at 2015 rates of fertility and mortality. Thus, 67 000 maternal deaths, 440 000 neonatal deaths, 473 000 child deaths, and 564 000 stillbirths could be averted from avoided pregnancies. Particularly effective interventions in the Maternal and Newborn Health and Child Health packages would be management of labour and delivery, care of preterm births, and treatment of serious infectious diseases and acute malnutrition. Nearly all of these essential interventions can be delivered by health workers in the community or in primary health centres, which can increase population access to needed services. The annual incremental cost of immediately scaling up these essential interventions would be US$6·2 billion in low-income countries, $12·4 billion in lower-middle-income countries, and $8·0 billion in upper-middle-income countries. With the additional funding, greater focus on high-effect integrated interventions and innovations in service delivery, such as task shifting to other groups of health workers and supply and demand incentives, can help rectify major gaps in accessibility and quality of care. In recent decades, reduction of avoidable maternal and child deaths has been a global priority. With continued priority and expansion of essential reproductive, maternal, newborn, and child health interventions to high coverage, equity, and quality, as well as interventions to address underlying problems such as women's low status in society and violence against women, these deaths and substantial morbidity can be largely eliminated in another generation.

Improved tuberculosis (TB) prevention and control depend critically on the development of a simple, readily accessible rapid triage test to stratify TB risk. We hypothesized that a blood protein-based host response signature for active TB (ATB) could distinguish it from other TB-like disease (OTD) in adult patients with persistent cough, thereby providing a foundation for a point-of-care (POC) triage test for ATB. Three adult cohorts consisting of ATB suspects were recruited. A bead-based immunoassay and machine learning algorithms identified a panel of four host blood proteins, interleukin-6 (IL-6), IL-8, IL-18, and vascular endothelial growth factor (VEGF), that distinguished ATB from OTD. An ultrasensitive POC-amenable single-molecule array (Simoa) panel was configured, and the ATB diagnostic algorithm underwent blind validation in an independent, multinational cohort in which ATB was distinguished from OTD with receiver operator characteristic-area under the curve (ROC-AUC) of 0.80 [95% confidence interval (CI), 0.75 to 0.85], 80% sensitivity (95% CI, 73 to 85%), and 65% specificity (95% CI, 57 to 71%). When host antibodies against TB antigen Ag85B were added to the panel, performance improved to 86% sensitivity and 69% specificity. A blood-based host response panel consisting of four proteins and antibodies to one TB antigen can help to differentiate ATB from other causes of persistent cough in patients with and without HIV infection from Africa, Asia, and South America. Performance characteristics approach World Health Organization (WHO) target product profile accuracy requirements and may provide the foundation for an urgently needed blood-based POC TB triage test.

Supplemental Digital Content is available in the text, Objectives: There is a lack of consensus on how to measure diarrheal severity. Within the context of a multisite, prospective cohort study, we evaluated the performance of a modified Vesikari score (MAL-ED), 2 previously published scores (Clark and CODA [a diarrheal severity score (Community DiarrheA) published by Lee et al]), and a modified definition of moderate-to-severe diarrhea (MSD) based on dysentery and health care worker diagnosed dehydration. Methods: Scores were built using maternally reported symptoms or fieldworker-reported clinical signs obtained during the first 7 days of a diarrheal episode. The association between these and the risk of hospitalization were tested using receiver operating characteristic analysis. Severity scores were also related to illness etiology, and the likelihood of the episode subsequently becoming prolonged or persistent. Results: Of 10,159 episodes from 1681 children, 143 (4.0%) resulted in hospitalization. The area under the curve of each score as a predictor of hospitalization was 0.84 (95% confidence interval: 0.81, 0.87) (Clark), 0.85 (0.82, 0.88) (MAL-ED), and 0.87 (0.84, 0.89) (CODA). Severity was also associated with etiology and episode duration. Although families were more likely to seek care for severe diarrhea, approximately half of severe cases never reached the health system. Conclusions: Community-based diarrheal severity scores are predictive of relevant child health outcomes. Because they require no assumptions about health care access or utilization, they are useful in refining estimates of the burden of diarrheal disease, in estimating the effect of disease control interventions, and in triaging children for referral in low- and middle-income countries in which the rates of morbidity and mortality after diarrhea remain high.

Neonatal infections are estimated to account for a quarter of the 2·8 million annual neonatal deaths, as well as approximately 3% of all disability-adjusted life-years. Despite this burden, few data are available on incidence, aetiology, and outcomes, particularly regarding impairment. We aimed to develop guidelines for improved scientific reporting of observational neonatal infection studies, to increase comparability and to strengthen research in this area. This checklist, Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE- NI), is an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement. STROBE-NI was developed following systematic reviews of published literature (1996-2015), compilation of more than 130 potential reporting recommendations, and circulation of a survey to relevant professionals worldwide, eliciting responses from 147 professionals from 37 countries. An international consensus meeting of 18 participants (with expertise in infectious diseases, neonatology, microbiology, epidemiology, and statistics) identified priority recommendations for reporting, additional to the STROBE statement. Implementation of these STROBE-NI recommendations, and linked checklist, aims to improve scientific reporting of neonatal infection studies, increasing data utility and allowing meta-analyses and pathogen-specific burden estimates to inform global policy and new interventions, including maternal vaccines.

Rotavirus is the leading cause of vaccine-preventable diarrhea among children under 5 globally. Rotavirus vaccination has been shown to prevent severe rotavirus infections with varying efficacy and effectiveness by region.We sought to generate updated region-specific estimates of rotavirus vaccine efficacy and effectiveness. We systematically reviewed published vaccine efficacy and effectiveness studies to assess the region-specific effect of rotavirus vaccination on select diarrheal morbidity and mortality outcomes in children under 5 years of age. We employed meta-analytic methods to generate pooled effect sizes by Millennium Development Goal region.Rotavirus vaccination was both efficacious and effective in preventing rotavirus diarrhea, severe rotavirus diarrhea and rotavirus hospitalizations among children under 5 across all regions represented by the 48 included studies. Efficacy against severe rotavirus diarrhea ranged from 90.6% [95% confidence interval (CI): 82.3-95.0] in the developed region to 88.4% (95% CI: 67.1-95.9) in Eastern/Southeastern Asia, 79.6% (95% CI: 71.3-85.5) in Latin America and the Caribbean, 50.0% (95% CI: 34.4-61.9) in Southern Asia and 46.1% (95% CI: 29.1-59.1) in sub-Saharan Africa. Region-specific effectiveness followed a similar pattern. There was also evidence of vaccine efficacy against severe diarrhea and diarrheal hospitalizations.Our findings confirm the protective efficacy and effectiveness of rotavirus vaccination against rotavirus diarrheal outcomes among children under 5 globally.

Purpose To research the origins of the 2500 g cutoff for low birth weight and the evolution of indicators to identify newborns at high mortality risk. Description Early research concluded "prematurity", measured mainly through birth weight, was responsible for increased health risks. The World Health Organization's original prematurity definition was birth weight ≤2500 g. 1960s research clarified the difference between gestational age and birth weight leading to questions of the causal role of birth weight for health outcomes. Focus turned to two etiologies of low birth weight, preterm births and intrauterine growth restriction, which were both causally associated with morbidity and mortality but through different pathways; a standard cutoff based on gestational age or customized cutoff was debated. Assessment While low birth weight can be due to preterm or intrauterine growth restriction (or both), the historic 2500 g cutoff remains the standard by which the majority of policy makers define low birth weight and use it to predict perinatal and infant adverse outcomes. Conclusion Current efforts to refocus research on preterm births and poor intrauterine growth are important to understanding the direct causes of mortality rather than low birth weight as a convenient surrogate. Such distinctions also allow researchers and practitioners to test and target interventions outcomes more effectively.

Objective To examine the current partnerships to improve the childhood immunisation programme in the Democratic Peoples' Republic of Korea (DPRK) in the context of the political determinants of health equity. Methods A literature search was conducted to identify public health collaborations with the DPRK government. Based on the amount of publicly accessible data and a shared approach in health system strengthening among the partners in immunisation programmes, the search focused on these partnerships. Results The efforts by WHO, UNICEF, GAVI and IVI with the DPRK government improved the delivery of childhood vaccines (e.g. pentavalent vaccines, inactivated polio vaccine, two-dose measles vaccine and Japanese encephalitis vaccine) and strengthened the DPRK health system by equipping health centres, and training all levels of public health personnel for VPD surveillance and immunisation service delivery. Conclusion The VPD-focused programmatic activities in the DPRK have improved the delivery of childhood immunisation and have created dialogue and contact with the people of the DPRK. These efforts are likely to ameliorate the political isolation of the people of the DPRK and potentially improve global health equity.

We conducted a cluster randomized trial of the effects of the integrated community case management of childhood illness (iCCM) strategy on careseeking for and coverage of correct treatment of suspected pneumonia, diarrhea, and malaria, and mortality among children aged 2–59 months in 31 districts of the Oromia region of Ethiopia. We conducted baseline and endline coverage and mortality surveys approximately 2 years apart, and assessed program strength after about 1 year of implementation. Results showed strong iCCM implementation, with iCCM-trained workers providing generally good quality of care. However, few sick children were taken to iCCM providers (average 16 per month). Difference in differences analyses revealed that careseeking for childhood illness was low and similar in both study arms at baseline and endline, and increased only marginally in intervention (22.9–25.7%) and comparison (23.3–29.3%) areas over the study period (P = 0.77). Mortality declined at similar rates in both study arms. Ethiopia's iCCM program did not generate levels of demand and utilization sufficient to achieve significant increases in intervention coverage and a resulting acceleration in reductions in child mortality. This evaluation has allowed Ethiopia to strengthen its strategic approaches to increasing population demand and use of iCCM services.

Results: Village doctors' knowledge on the assessment and management of childhood illnesses improved significantly after training; knowledge of danger signs of pneumonia and severe pneumonia increased from 39% to 78% (P < 0.0001) and from 17% to 47% (P < 0.0001) respectively. Knowledge on the correct management of severe pneumonia increased from 62% to 84% (P < 0.0001), and diarrhoea management improved from 65% to 82% (P = 0.0005). Village doctors retained this knowledge over three years except for home management of pneumonia. No significant differences were observed in prescribing practices for diarrhoea and pneumonia management between trained and untrained village doctors. Village doctors were accessible to communities; 76% had cell phones; almost all attended home calls, and did not charge consultation fees. Nearly all (91%) received incentives from pharmaceutical representatives.Conclusions: Village doctors have the capacity to learn and retain knowledge on the appropriate management of under-five illnesses. Training alone did not improve inappropriate antibiotic prescription practices. Intensive monitoring and efforts to target key actors including pharmaceutical companies, which influence village doctors dispensing practices, and implementation of mechanisms to track and regulate these providers are necessary for future engagement in management of under-five childhood illnesses.Background: Informal health care providers particularly "village doctors" are the first point of care for under-five childhood illnesses in rural Bangladesh. We engaged village doctors as part of the Multi-Country Evaluation (MCE) of Integrated Management of Childhood Illness (IMCI) and assessed their management of sick under-five children before and after a modified IMCI training, supplemented with ongoing monitoring and supportive supervision.Methods: In 2003-2004, 144 village doctors across 131 IMCI intervention villages in Matlab Bangladesh participated in a two-day IMCI training; 135 of which completed pre- and post-training evaluation tests. In 2007, 38 IMCI-trained village doctors completed an end-of-project knowledge retention test. Village doctor prescription practices for sick under-five children were examined through household surveys, and routine monitoring visits. In-depth interviews were done with mothers seeking care from village doctors.

Background: Mass deworming affects millions of children afflicted by intestinal parasites.We aimed to assess differences in effects of deworming on nutritional and cognitive outcomes across potential effect modifiers. Methods: For this systematic review and network meta-analysis of individual participant data (IPD), we searched MEDLINE, CINAHL, LILACS, EMBASE, the Cochrane Library, Econlit, Internet Documents in Economics Access Service, Public Affairs Information Service, Social Services Abstracts, Global Health CABI and CAB Abstracts to March 27, 2018. We searched grey literature, contacted authors and screened reviews. We included randomized and quasi randomized trials of deworming children compared to placebo or other nutritional or deworming interventions with data on baseline infection. We used a frequentist approach for random-effects network meta-analysis with IPD using General Linear Mixed Models, assessed Cochrane Risk of Bias and GRADE for overall quality, following a pre-specified protocol. The main outcomes were weight, height, haemoglobin and cognition. Findings: We received IPD from 19 RCTs of STH deworming with 31,945 participants. For deworming for schistosomiasis alone, we received too few studies. Overall risk of bias was low. STH deworming vs. placebo effect on weight was 0.01 kg (95%CI: -0.08 to 0.11), height 0.09 cm (95%CI: -0.08, to 0.27) (moderate certainty), and haemoglobin 0.32 g/L (95%CI: -0.63 to 1.26) (low certainty). No study showed important effects on cognition (low certainty). There were no statistically significant subgroup effects across age, sex, nutritional status or infection intensity. Confidence limits included important effects on weight and haemoglobin for children with higher intensity infections. Interpretation: Deworming for STH alone is insufficient to improve child nutrition and cognition at population level in areas with light intensity infections. Funding Statement: Bill and Melinda Gates Foundation Declaration of Interests: Dr. Friis reports grants from ARLA Food for Health Center, grants from Danish Dairy Research Foundation, grants from Nutriset, outside the submitted work. Dr. Elliott reports grants from Wellcome Trust, during the conduct of the study. Dr. King reports grants from World Health Organization for work included in the study. Dr. LIU reports grants from International Initiative for Impact Evaluation, grants from National Natural Science Foundation of China, during the conduct of the study. All other authors state they have nothing to disclose. Ethics Approval Statement: This study was approved by the Bruyere Research Institute and SickKids research ethics boards.

Zinc is essential to supporting growth in young children especially for tissues undergoing rapid cellular differentiation and turnover, such as those in the immune system and gastrointestinal tract. Therapeutic zinc supplementation has been initiated in low-income countries as part of diarrhea treatment programs to support these needs for young children, but the effects of preventive supplemental zinc as a tablet or as a multiple micronutrient powder (MNP) on child growth and diarrheal disease are mixed and pose programmatic uncertainties. Thus, a randomized, double-blind community-based efficacy trial of five different doses, forms, and frequencies of preventive zinc supplementation vs. a placebo was designed for a study in children aged 9–11 months in an urban community in Dhaka, Bangladesh. The primary outcomes of this 24-week study are incidence of diarrheal disease and linear growth. Study workers will conduct in-home morbidity checks twice weekly; anthropometry will be measured at baseline, 12 weeks and 24 weeks. Serum zinc and other related biomarkers will be measured in a subsample along with an estimate of the exchangeable zinc pool size using stable isotope techniques in a subgroup. Therapeutic zinc will be provided as part of diarrhea treatment, in accordance with Bangladesh’s national policy. Therefore, the proposed study will determine the additional benefit of a preventive zinc supplementation intervention. The protocol has been approved by the Institutional Review Boards (IRBs) of icddr,b and Children’s Hospital Oakland Research Institute (CHORI). The IRB review process is underway at the University of Colorado Denver as well.

Increased diarrheal episode severity has been linked to better 2-week recall and improved care-seeking and treatment among caregivers of children under five. Using cross-sectional data from three Indian states, we sought to assess the relationship between episode severity and the recall, care-seeking, and treatment of childhood diarrhea. Recall error was higher for episodes with onset 8–14 days (31.2%) versus 1–7 days (4.8%) before the survey, and logistic regression analysis showed a trend toward increased severity of less recent compared with more recent episodes. This finding indicates that data collection with 2-week recall underestimates diarrhea prevalence while overestimating the proportion of severe episodes. There was a strong correlation between care-seeking and dehydration, fever, vomiting, and increased stool frequency and duration. Treatment with oral rehydration salts was associated with dehydration, vomiting, and higher stool frequency, and trends were established between therapeutic zinc supplementation and increased duration and stool frequency. However, state and care-seeking sector were stronger determinants of treatment than episode severity, illustrating the need to address disparities in treatment quality across regions and delivery channels. Our findings are of importance to researchers and diarrhea management program evaluators aiming to produce accurate estimates of diarrheal outcomes and program impact in low- and middle-income countries.

BACKGROUND: The etiology of >90% of cases of suspected neonatal infection remains unknown. We conducted community-based surveillance in conjunction with hospital-based surveillance in a rural region in Bangladesh from June 2006 to September 2007 to assess the incidence and etiology of community-acquired viral infections among neonates. METHODS: Community health workers (CHWs) assessed neonates at home on days 0 2 5 and 8 after birth and referred cases of suspected illness to the hospital (CHW surveillance). Among neonates with clinically suspected upper respiratory tract infection (URTI) pneumonia sepsis and/or meningitis virus identification studies were conducted on nasal wash cerebrospinal fluid and/or blood specimens. In the hospital-based surveillance similar screening was conducted among all neonates (referred by CHWs and self-referred) who were admitted to the hospital. RESULTS: CHW surveillance found an incidence rate of 15.6 neonatal viral infections per 1000 live births with 30% of infections identified on the day of birth. Among neonates with suspected sepsis a viral etiology was identified in 36% of cases with enterovirus accounting for two-thirds of those infections. Respiratory syncytial virus was the most common etiologic agent among those with viral pneumonia (91%) and URTI (68%). There was a low incidence (1.2%) of influenza in this rural population. CONCLUSION: Viral infections are commonly associated with acute newborn illness even in the early neonatal period. The estimated incidence was 5-fold greater than reported previously for bacterial infections. Low-cost preventive measures for neonatal viral infections are urgently needed.

Training public-sector providers to treat diarrhea in children with low-osmolarity oral rehydration salts and zinc appeared to be effective. Among private providers, drug-detailing visits by pharmaceutical representatives seemed less effective, particularly in improving knowledge of the correct dosage and duration of zinc treatment. Consistent supplies and sufficient attention to training all health care cadres, especially community health workers who may be new to diarrhea treatment and informal-sector providers who are typically excluded from formal training, are critical to improving knowledge and prescribing behaviors., Diarrhea remains a leading cause of morbidity and mortality among children under 5 years of age in low- and middle-income countries. In 2006, the Indian government formally endorsed the World Health Organization guidelines that introduced zinc supplementation and low-osmolarity oral rehydration salts (ORS) for the treatment of diarrhea. Despite this, zinc is rarely prescribed and has not been available in the public sector in India until very recently. The Diarrhea Alleviation Through Zinc and ORS Treatment (DAZT) project was implemented in Gujarat between 2011 and 2013 to accelerate the uptake of zinc and ORS among public and private providers in 6 rural districts. As part of an external evaluation of DAZT, we interviewed 619 randomly selected facility- and community-based public and private providers 2–3 months after a 1-day training event had been completed (or, in the case of private providers, after at least 1 drug-detailing visit by a pharmaceutical representative had occurred) and supplies were in place. The purpose of the interviews was to assess providers’ knowledge of appropriate treatment for diarrhea in children, reported treatment practices, and availability of drugs in stock. More than 80% of all providers interviewed reported they had received training or a drug-detailing visit on diarrheal treatment in the past 6 months. Most providers in all cadres (range, 68% to 100%) correctly described how to prepare ORS and nearly all (range, 90% to 100%) reported routinely prescribing it to treat diarrhea in children. Reported routine prescription of zinc was lower, ranging from 62% among private providers to 96% among auxiliary nurse-midwives. Among providers who reported ever not recommending zinc (n = 242), the 2 most frequently reported reasons for not doing so were not completely understanding zinc for diarrhea treatment and not having zinc in stock at the time of contact with the patient. In a multiple logistic regression analysis, recent training or drug-detailing visits and having zinc in stock were associated with reported zinc prescribing (P

ObjectiveMuch is known about national trends in child undernutrition, but there is little information on how socio-economic inequalities are evolving over time. We aimed to assess socio-economic inequalities in stunting prevalence over time.DesignWe selected nationally representative surveys carried out since the mid-1990s for which information was available on asset indices and on child anthropometry. We identified twenty-five countries that had at least two surveys over an interval of 10 years or more, totalling eighty-seven surveys. Stunting prevalence was calculated according to wealth quintiles. Absolute and relative inequalities were calculated and time trends were obtained by regression.SettingNationally representative household surveys from twenty-five low- and middle-income countries.SubjectsChildren ResultsNational prevalence declined significantly in twenty-two of the twenty-five countries. In eighteen out of twenty-five countries, relative reductions were higher among the rich than among the poor. Overall, there was no indication that inequalities improved. Striking examples are Nepal, with a 17·0 percentage points decline in stunting per decade, but where inequalities increased sharply; and Brazil, where stunting fell by 6·7 percentage points and inequalities were all but eliminated.ConclusionsGlobal progress in reducing stunting has not been accompanied by improved equity, but countries varied markedly in how successful they were in reducing prevalence among the poorest children. It is important to document how some countries were able to reduce inequalities, so that these lessons can be used to foster global progress, particularly in light of the increased importance of within-country inequalities in the post-2015 agenda.

Background Measles vaccination effectiveness studies showed dramatic decreases in all-cause mortality in excess of what would be expected from the prevention of measles disease alone. This invited speculation that measles infection may increase the risk of diarrhea morbidity and mortality subsequent to the acute phase of the disease. The aim of the present systematic review is to summarize the existing evidence in the publically available literature pertaining to the putative causal link between measles and diarrhea in the period 4–26 weeks following measles rash onset. Methods We searched the PubMed, Embase, Open Grey and Grey Literature Report databases for relevant literature using broad search terms. Prospective, retrospective and case-control studies in low- and middle-income countries involving children under five wherein relevant evidence were presented were included. Data were extracted from the articles and summarized. Results Fifty abstracts retrieved through the database searches met the initial screening criteria. Twelve additional documents were identified by review of the references of the documents found in the initial searches. Six documents representing five unique studies that presented evidence relevant to the research question were found. Four of the included studies took place in Bangladesh. One of the included studies took place in Sudan. Some measles vaccine effectiveness studies show lower diarrhea morbidity and mortality among the vaccinated. However, children who received vaccine may have differed in important ways from children who did not, such as health service utilization. Additionally, cohort studies following unvaccinated children showed no difference in diarrhea morbidity and mortality between cases and controls more than 4 weeks after measles rash onset. One study showed some evidence that severe measles may predispose children to gastroenteritis, but was not able to show a corresponding increase in the risk of diarrhea mortality. Conclusions The available evidence suggests that the risk of measles-associated diarrhea mortality is largely limited to the 5-week period 1 week prior to and 4 weeks after measles rash onset, and that there is no increased risk of diarrhea mortality in the longer-term caused by measles.

Background The Lives Saved Tool (LiST) is a widely used resource for evidence-based decision-making regarding health program scale-up in low- and middle-income countries. LiST estimates the impact of specified changes in intervention coverage on mortality and stunting among children under 5 years of age. We aimed to improve the estimates of the parameters in LiST that determine the rate at which the effects of interventions to prevent stunting attenuate as children get older. Methods We identified datasets with serial measurements of children’s lengths or heights and used random effects models and restricted cubic splines to model the growth trajectories of children with at least six serial length/height measurements. We applied WHO growth standards to both measured and modelled (smoothed) lengths/heights to determine children’s stunting status at multiple ages (1, 6, 12, 24 months). We then calculated the odds ratios for the association of stunting at one age point with stunting at the next (“stunting-to-stunting ORs”) using both measured and smoothed data points. We ran analyses in LiST to compare the impact on intervention effect attenuation of using smoothed rather than measured stunting-to-stunting ORs. Results A total of 21,786 children with 178,786 length/height measurements between them contributed to our analysis. The odds of stunting at a given age were strongly related to whether a child is stunted at an earlier age, using both measured and smoothed lengths/heights, although the relationship was stronger for smoothed than measured lengths/heights. Using smoothed lengths/heights, we estimated that children stunted at 1 month have 45 times the odds of being stunted at 6 months, with corresponding odds ratios of 362 for the period 6 to 12 months and 175 for the period 12 to 24 months. Using the odds ratios derived from the smoothed data in LiST resulted in a somewhat slower attenuation of intervention effects over time, but substantial attenuation was still observed in the LiST outputs. For example, in Mali the effect of effectively eliminating SGA births reduced prevalence of stunting at age 59 months from 44.4% to 43.7% when using odds ratios derived from measured lengths/heights and from 44.4% to 41.9% when using odds ratios derived from smoothed lengths/heights. Conclusions Smoothing of children’s measured lengths/heights increased the strength of the association between stunting at a given age and stunting at an earlier age. Using odds ratios based on smoothed lengths/heights in LiST resulted in a small reduction in the attenuation of intervention effects with age and thus some increase in the estimated benefits, and may better reflect the true benefits of early nutritional interventions. Electronic supplementary material The online version of this article (10.1186/s12889-017-4744-3) contains supplementary material, which is available to authorized users.

Introduction To estimate and monitor national incidence of Juvenile onset Recurrent Respiratory Papillomatosis (JoRRP) in Australia following the extensive quadrivalent HPV vaccine catch up program (females aged 12–26 years in 2007–2009, which included women of child bearing age) and to assess demographics and risk factors of incident cases. Methods The Australian Paediatric Surveillance Unit (APSU) undertakes surveillance of rare paediatric diseases by contacting practitioners monthly to report cases. We utilised this well established methodology to undertake prospective population based surveillance of JoRRP by enrolment in APSU of paediatric ENT surgeons, designing a JoRRP case reporting form, and offering clinicians HPV typing of incident cases. Surveillance commenced Oct 2011 and we report here findings for the five-year period to end 2016. Results Using Australian Bureau of Statistics population estimates for children 0–15 years, the average annual incidence rate over the period was 0.12 per 1 00 000. The largest number of cases was reported in the first year, with a decreasing frequency each year thereafter. The rate declined from 0.3 per 1 00 000 in 2012 to 0.04 per 1 00 000 in 2016. Among incident cases, no mothers had been vaccinated prior to pregnancy, 20% had a past history of genital warts, 60% of cases were male, and 60% were first born. The majority were born by vaginal delivery. Four incident cases were genotyped; all were positive for HPV6 (n=1) or HPV11 (n=3). Conclusion To our knowledge this is the first report internationally documenting a decline in JoRRP incidence in a population of children following the introduction of a quadrivalent HPV vaccination program. Support : I Professor Suzanne Garland, have received Grants to my institution from Commonwealth Department of Health for HPV genoprevalance surveillance post vaccination, Merck and GSK (GlaxoSmithKline) to perform phase 3 clinical vaccine trials: Merck to evaluate HPV in RRP post vaccination programme, CSL for HPV in cervical cancer study, and VCA (Victoria Cancer Agency) for a study on effectiveness of public health HPV vaccine study plus a study on associations of early onset cancers. I have received speaking fees from MSD and SPMSD for work performed in my personal time. Merck paid for travel and accommodation to present at HPV Advisory board meetings.

Background: IQ deficits are linked to even mild obstructive sleep apnoea (OSA) in children. Although OSA is commonly first diagnosed in the pre-school age group, a randomised trial is still needed to assess IQ outcomes after adenotonsillectomy in the pre-school age-group. This randomised control trial (RCT) will primarily determine whether adenotonsillectomy improves IQ compared to no adenotonsillectomy after 12months, in preschool (3-5 year-old) children with mild to moderate OSA. Methods: This protocol is for an ongoing multi-centred RCT with a recruitment target of 210 subjects (105 in each arm). Children age 3-5 years with symptoms of OSA, are recruited through doctor referral, at the point of referral to the Ear Nose and Throat (ENT) services. Screening is initially with a questionnaire (Paediatric Sleep Questionnaire, PSQ) for symptoms of obstructive sleep apnoea (OSA). Where questionnaires are positive (suggestive of OSA) and ENT surgeons recommend them for adenotonsillectomy, they are invited to participate in POSTA. Baseline testing includes neurocognitive testing (IQ and psychometric evaluation with the neuropsychologist blinded to randomisation) and overnight polysomnography (PSG). Where the Obstructive Apnoea-Hypopnea Index (OAHI) from the PSG is

Objectives To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21st birth weight standard.Design Secondary analysis of data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up. Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21st birth weight standard. Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level. With available national level data, prevalence of small for gestational age and population attributable fractions of neonatal mortality attributable to small for gestational age were estimated.Setting CHERG birth cohorts from 14 population based sites in low and middle income countries.Main outcome measures In low and middle income countries in the year 2012, the number and proportion of infants born small for gestational age; number and proportion of neonatal deaths attributable to small for gestational age; the number and proportion of neonatal deaths that could be prevented by reducing the prevalence of small for gestational age to 10%.Results In 2012, an estimated 23.3 million infants (uncertainty range 17.6 to 31.9; 19.3% of live births) were born small for gestational age in low and middle income countries. Among these, 11.2 million (0.8 to 15.8) were term and not low birth weight (≥2500 g), 10.7 million (7.6 to 15.0) were term and low birth weight (Conclusions In low and middle income countries, about one in five infants are born small for gestational age, and one in four neonatal deaths are among such infants. Increased efforts are required to improve the quality of care for and survival of these high risk infants in low and middle income countries.

The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study communities in Peru are located in Loreto province, in a rural area 15 km from the city of Iquitos. This riverine population of approximately 5000 individuals is fairly representative of Loreto. The province lags behind the rest of the country in access to water and sanitation, per capita income, and key health indicators including infant mortality (43.0 vs 16.0 per 1000 nationwide) and under-5 mortality (60.6 vs 21.0 per 1000). Total fertility rates are higher than elsewhere in the country (4.3 vs 2.6). Nationwide, the prevalence of human immunodeficiency virus is estimated at 0.45%, the prevalence of tuberculosis is 117 per 100 000, and the incidence of malaria is 258 per 100 000. Stunting in this community is high, whereas acute undernutrition is relatively uncommon. The population suffers from high rates of diarrheal disease. Prevalent enteric pathogens include Ascaris, Giardia, enterotoxigenic Escherichia coli, Shigella, and Campylobacter.

Diarrhea and linear growth faltering continue to burden low-income countries and are among the most important contributors to poor health during early childhood. Diarrhea is thought to adversely affect linear growth, but catch-up growth can occur if no additional insults are experienced. We sought to characterize catch-up growth in relation to diarrhea burden in a multisite dataset of 1007 children. Using longitudinal anthropometry and diarrheal surveillance data from 7 cohort studies in 4 countries, we examined the relation between diarrhea prevalence and growth in 3- to 6-mo periods using linear mixed-effect models. Growth during each period was calculated as a function of age using linear splines. We incorporated the longitudinal prevalence of diarrhea in both current and previous periods into the model. Diarrhea during the current period was associated with slower linear and ponderal growth. Faster (catch-up) growth in length was observed in children with no diarrhea in age groups immediately after an age group in which diarrhea was experienced [age group >6-12 mo: 0.03 mm/mo for each percentage diarrhea prevalence in the previous period (95% CI: 0.007, 0.06) relative to 11.3 mm/mo mean growth rate; age group >12-18 mo: 0.04 mm/mo (95% CI: 0.02, 0.06) relative to 8.9 mm/mo mean growth rate; age group >18-24 mo: 0.04 mm/mo (95% CI: 0.003, 0.09) relative to 7.9 mm/mo mean growth rate]. The associations were stronger in boys than in girls when separate models were run. Similar results were observed when weight was the outcome variable. When diarrheal episodes are followed by diarrhea-free periods in the first 2 y of life, catch-up growth is observed that may allow children to regain their original trajectories. The finding of a greater effect of diarrhea on linear growth in boys than in girls was unexpected and requires additional study. Diarrhea burdens are high throughout the first 2 y of life in these study sites, therefore reducing the likelihood of catch-up growth. Extending diarrhea-free periods may increase the likelihood of catch-up growth and decrease the prevalence of stunting.

BACKGROUND: Substantial progress in reducing the child mortality rate has been made globally in the last two decades. However, for China, the number of children dying from preventable diseases is still very large. It is important to have regularly updated information on the distribution of causes of death (COD) in children to inform policy and research. In this study, we aim to estimate the COD spectrum in children younger than five years old from 2009 to 2015 with a focus on the year 2015 and to provide an updated COD prediction model for China.METHODS: Updated data of under-five mortality rates (U5MRs) and the number of live births at national and provincial levels were obtained from United Nation's Inter-agency Group for Child Mortality Estimation (UN IGME), Institute for Health Metrics and Evaluation (IHME), and United Nations Population Division (UNPD). Then, we conducted a systematic review across four Chinese and English bibliographic databases and identified high-quality community-based longitudinal studies of COD in children younger than five years in China. We developed a number of single-cause models to predict the number of child death for main COD in different age groups at both national and provincial levels. The jackknife procedure was applied to construct the 95% Uncertainty Ranges (URs).RESULTS: From 2009 to 2015, the under-five mortality rates have declined by 37.1%. The leading causes of death in 2015 were preterm birth complications (17.4%), birth asphyxia (15.2%), congenital abnormalities (14.1%), accidents (13.5%) and pneumonia (12.4%) for children under five years old. The COD spectrum varied substantially across Chinese provinces with different development levels. The leading cause in children under five years in the wealthier provinces (with lower U5MRs) was congenital abnormalities (up to 18.9%), while in the poorer provinces (with higher U5MRs), pneumonia was the dominant COD (up to 23.4%).CONCLUSIONS: This study updates and validates the accuracy of the findings of our previous COD study and proposes a new modelling method to predict proportions for the most common causes of child death in China. These updated COD estimates suggest that current strategies to reduce child mortality should prioritise action on neonatal deaths and target interventions against the top COD according to the local COD spectrum. Special attention should also be given to reducing differences between Chinese provinces and regions with differing development levels.

Aligned with the Sustainable Development Goals, the Global Strategy for Women’s, Children’s and Adolescents’ Health (2016–2030) represents an essential shift in prioritisation for actions designed to help families live healthy, secure lives and fulfil their economic potential.1 The reproductive, maternal, newborn, child and adolescent health and nutrition (RMNCAH-N) agenda is now both broader and more complex than was the case during the Millennium Development Goal era, creating a need for new data. To contribute to this need, Countdown to 2030 for Women’s, Children’s and Adolescents’ Health (Countdown), a multi-institutional network of academics from institutions around the world and representatives from United Nations agencies and civil society, aims to enhance monitoring and measurement of women’s, children’s and adolescents’ health globally and in countries.2 In 2018, Countdown organised a measurement conference in Stellenbosch, South Africa, that brought together 100 experts in multiple areas of RMNCAH-N, which resulted in the six papers in this supplement and an overall research agenda. The manuscripts in this collection represent the first developments of Countdown’s work to enhance measurement. They identify some of the persistent measurement and monitoring gaps in RMNCAH-N, for example, by reviewing the evidence on methods for generating effective coverage estimates and presenting actionable analytical methods to identify inequalities within and between countries. The collection also considers measurement advances for early childhood development and for nutrition. Further, it expands to analyse new priority issues, including using national surveys to analyse the impact of armed conflicts on RMNCAH-N;3 and describing the new data needed to better understand the social, political and contextual complexity of health system governance. Countdown will continue to extend this measurement improvement agenda. In some aspects, however, the measurement and monitoring of RMNCAH-N is more advanced than other health areas, such as infectious diseases, non-communicable diseases, injuries and mental …

This article in the Global Health series assesses international progress toward achieving the Millennium Development Goals for the health of women and children. With less than 3 years to go, many countries are failing to reach targets set for maternal and child mortality.

Background. Human noroviruses are among the most common enteropathogens globally, and are a leading cause of infant diarrhea in developing countries. However, data measuring the impact of norovirus at the community level are sparse. Methods. We followed a birth cohort of children to estimate norovirus infection and diarrhea incidence in a Peruvian community. Stool samples from diarrheal episodes and randomly selected nondiarrheal samples were tested by polymerase chain reaction for norovirus genogroup and genotype. Excretion duration and rotavirus coinfection were evaluated in a subset of episodes. Results. Two hundred twenty and 189 children were followed to 1 and 2 years of age, respectively. By 1 year, 80% (95% confidence interval [CI], 75%–85%) experienced at least 1 norovirus infection and by 2 years, 71% (95% CI, 65%–77%) had at least 1 episode of norovirus-associated diarrhea. Genogroup II (GII) infections were 3 times more frequent than genogroup 1 (GI) infections. Eighteen genotypes were found; GII genotype 4 accounted for 41%. Median excretion duration was 34.5 days for GII vs 8.5 days for GI infection (P = .0006). Repeat infections by the same genogroup were common, but repeat infections by the same genotype were rare. Mean length-for-age z score at 12 months was lower among children with prior norovirus infection compared to uninfected children (coefficient: −0.33 [95% CI, −.65 to −.01]; P = .04); the effect persisted at 24 months. Conclusions. Norovirus infection occurs early in life and children experience serial infections with multiple genotypes, suggesting genotype-specific immunity. An effective vaccine would have a substantial impact on morbidity, but may need to target multiple genotypes.