Estimated global and regional causes of deaths from diarrhoea in children younger than 5 years during 2000-21: a systematic review and Bayesian multinomial analysis.

BACKGROUND: Information on the causes of deaths from diarrhoea in children younger than 5 years is needed to design improved preventive and therapeutic approaches. We aimed to conduct a systematic analysis of studies to report estimates of the causes of deaths from diarrhoea in children younger than 5 years at global and regional levels during 2000-21. METHODS: For this systematic review and Bayesian multinomial analysis, we included 12 pathogens with the highest attributable incidence in the Global Enteric Multicenter Study. We searched PubMed, Scopus, Embase, Web of Science, Global Health Index Medicus, Global Health OVID, IndMed, Health Information Platform for the Americas (PLISA), Africa-Wide Information, and Cochrane Collaboration for articles published between Jan 1, 2000, and Dec 31, 2020, using the search terms "child", "hospital", "diarrhea", "diarrhoea", "dysentery", "rotavirus", "Escherichia coli", "salmonella", "shigella", "campylobacter", "Vibrio cholerae", "cryptosporidium", "norovirus", "astrovirus", "sapovirus", and "adenovirus". To be included, studies had to have a patient population of children younger than 5 years who were hospitalised for diarrhoea (at least 90% of study participants), at least a 12-month duration, reported prevalence in diarrhoeal stools of at least two of the 12 pathogens, all patients with diarrhoea being included at the study site or a systematic sample, at least 100 patients with diarrhoea, laboratory tests done on rectal swabs or stool samples, and standard laboratory methods (ie, quantitative PCR [qPCR] or non-qPCR). Studies published in any language were included. Studies were excluded if they were limited to nosocomial, chronic, antibiotic-associated, or outbreak diarrhoea or to a specific population (eg, only children with HIV or AIDS). Each article was independently reviewed by two researchers; a third arbitrated in case of disagreement. If both reviewers identified an exclusion criterion, the study was excluded. Data sought were summary estimates. Data on causes from published studies were adjusted when necessary to account for the poor sensitivity of non-qPCR methods and for attributable fraction based on quantification of pathogens in children who are ill or non-ill. The causes of deaths from diarrhoea were modelled on the causes of hospitalisations for diarrhoea. We separately modelled studies reporting causes of diarrhoea in children who were hospitalised in low-income and middle-income countries (LMICs) and in high-income countries (HICs). FINDINGS: Of 74 282 papers identified in the initial database search, we included 138 studies (91 included data from LMICs and 47 included data from HICs) from 73 countries. We modelled estimates for 194 WHO member states (hereafter referred to as countries), including 42 HICs and 152 LMICs. We could attribute a cause to 1 003 448 (83·8%) of the estimated 1 197 044 global deaths from diarrhoea in children younger than 5 years in 2000 and 360 730 (81·3%) of the estimated 443 833 global deaths from diarrhoea in children younger than 5 years in 2021. The cause with the largest estimated global attribution was rotavirus; in LMICs, the proportion of deaths from diarrhoea due to rotavirus in children younger than 5 years appeared lower in 2021 (108 322 [24·4%] of 443 342, 95% uncertainty interval 21·6-29·5) than in 2000 (316 382 [26·5%] of 1 196 134, 25·7-28·5), but the 95% CIs overlapped. In 2000, the second largest estimated attribution was norovirus GII (95 817 [8·0%] of 1 196 134 in LMICs and 225 [24·7%] of 910 in HICs); in 2021, Shigella sp had the second largest estimated attribution in LMICs (36 082 [8·1%] of 443 342), but norovirus remained with the second largest estimated attribution in HICs (84 [17·1%] of 490). INTERPRETATION: Our results indicate progress in the reduction of deaths from diarrhoea caused by 12 pathogens in children younger than 5 years in the past two decades. There is a need to increase efforts for prevention, including with rotavirus vaccine, and treatment to eliminate further deaths. FUNDING: Bill & Melinda Gates Foundation via Johns Hopkins University and the University of Virginia.

Maternal interventions to decrease stillbirths and neonatal mortality in Tanzania: evidence from the 2017-18 cross-sectional Tanzania verbal and social autopsy study.

BACKGROUND: Reduction of Tanzania's neonatal mortality rate has lagged behind that for all under-fives, and perinatal mortality has remained stagnant over the past two decades. We conducted a national verbal and social autopsy (VASA) study to estimate the causes and social determinants of stillbirths and neonatal deaths with the aim of identifying relevant health care and social interventions. METHODS: A VASA interview was conducted of all stillbirths and neonatal deaths in the prior 5 years identified by the 2015-16 Tanzania Demographic and Health Survey. We evaluated associations of maternal complications with antepartum and intrapartum stillbirth and leading causes of neonatal death; conducted descriptive analyses of antenatal (ANC) and delivery care and mothers' careseeking for complications; and developed logistic regression models to examine factors associated with delivery place and mode. RESULTS: There were 204 stillbirths, with 185 able to be classified as antepartum (88 [47.5%]) or intrapartum (97 [52.5%]), and 228 neonatal deaths. Women with an intrapartum stillbirth were 6.5% (adjusted odds ratio (aOR) = 1.065, 95% confidence interval (CI) 1.002, 1.132) more likely to have a C-section for every additional hour before delivery after reaching the birth attendant. Antepartum hemorrhage (APH), maternal anemia, and premature rupture of membranes (PROM) were significantly positively associated with early neonatal mortality due to preterm delivery, intrapartum-related events and serious infection, respectively. While half to two-thirds of mothers made four or more ANC visits (ANC4+), a third or fewer received quality ANC (Q-ANC). Women with a complication were more likely to deliver at hospital only if they received Q-ANC (neonates: aOR = 4.5, 95% CI 1.6, 12.3) or ANC4+ (stillbirths: aOR = 11.8, 95% CI 3.6, 38.0). Nevertheless, urban residence was the strongest predictor of hospital delivery. CONCLUSIONS: While Q-ANC and ANC4 + boosted hospital delivery among women with a complication, attendance was low and the quality of care is critical. Quality improvement efforts in urban and rural areas should focus on early detection and management of APH, maternal anemia, PROM, and prolonged labor, and on newborn resuscitation.

Estimating the global impact of rotavirus vaccines on child mortality.

OBJECTIVES: We estimated the global impact of rotavirus vaccines on deaths among children under five years old by year. METHODS: We used a proportionate outcomes model with a finely disaggregated age structure to estimate rotavirus deaths prevented by vaccination over the period 2006-2019 in 186 countries. We ran deterministic and probabilistic uncertainty analyses and compared our estimates to surveillance-based estimates in 20 countries. RESULTS: We estimate that rotavirus vaccines prevented 139,000 under-five rotavirus deaths (95% uncertainty interval 98,000-201,000) in the period 2006-2019. In 2019 alone, rotavirus vaccines prevented 15% (95% uncertainty interval 11-21%) of under-five rotavirus deaths (0.5% of child mortality). Assuming global use of rotavirus vaccines and coverage equivalent to other co-administered vaccines could prevent 37% of under-five rotavirus deaths (1.2% of child mortality). Our estimates were sensitive to the choice of rotavirus mortality burden data and several vaccine impact modeling assumptions. The World Health Organization's recommendation to remove age restrictions in 2012 could have prevented up to 17,000 rotavirus deaths in the period 2013-2019. Our modeled estimates of rotavirus vaccine impact were broadly consistent with estimates from post-vaccination surveillance sites. CONCLUSION: Rotavirus vaccines have made a valuable contribution to global public health. Enhanced rotavirus mortality prevention strategies are needed in countries with high mortality in under-5-year-old children.

Systematic Review of Management of Moderate Wasting in Children over 6 Months of Age.

The effective management of the 33 million children with moderate acute malnutrition (MAM) is key to reducing childhood morbidity and mortality. In this review, we aim to evaluate the effectiveness of specially formulated foods (SFFs) compared to non-food-based approaches to manage MAM in children >6 months old. We conducted a search on ten databases until 23 August 2021 and included five studies, covering 3387 participants. Meta-analysis of four studies comparing SFFs to counselling or standard of care showed that SFFs likely increase recovery rate, reduce non-response, and may improve weight-for-height z-score, weight-for-age z-score and time to recovery, but have little or no effect on MUAC gain. One study on a multicomponent intervention (SFFs, antibiotics and counselling provided to high-risk MAM) compared to counselling only was reported narratively. The intervention may increase weight gain after 24 weeks but may have little or no effect on weight gain after 12 weeks and on non-response and mortality after 12 and 24 weeks of enrollment. The effect of this intervention on recovery was uncertain. In conclusion, SFFs may be beneficial for children with moderate wasting in humanitarian contexts. Programmatic recommendations should consider context and cost-effectiveness.

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

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

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

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

Small vulnerable newborns-big potential for impact.

Despite major achievements in child survival, the burden of neonatal mortality has remained high and even increased in some countries since 1990. Currently, most neonatal deaths are attributable to being born preterm, small for gestational age (SGA), or with low birthweight (LBW). Besides neonatal mortality, these conditions are associated with stillbirth and multiple morbidities, with short-term and long-term adverse consequences for the newborn, their families, and society, resulting in a major loss of human capital. Prevention of preterm birth, SGA, and LBW is thus critical for global child health and broader societal development. Progress has, however, been slow, largely because of the global community's failure to agree on the definition and magnitude of newborn vulnerability and best ways to address it, to frame the problem attractively, and to build a broad coalition of actors and a suitable governance structure to implement a change. We propose a new definition and a conceptual framework, bringing preterm birth, SGA, and LBW together under a broader umbrella term of the small vulnerable newborn (SVN). Adoption of the framework and the unified definition can facilitate improved problem definition and improved programming for SVN prevention. Interventions aiming at SVN prevention would result in a healthier start for live-born infants, while also reducing the number of stillbirths, improving maternal health, and contributing to a positive economic and social development in the society.

Small babies, big risks: global estimates of prevalence and mortality for vulnerable newborns to accelerate change and improve counting.

Small newborns are vulnerable to mortality and lifelong loss of human capital. Measures of vulnerability previously focused on liveborn low-birthweight (LBW) babies, yet LBW reduction targets are off-track. There are two pathways to LBW, preterm birth and fetal growth restriction (FGR), with the FGR pathway resulting in the baby being small for gestational age (SGA). Data on LBW babies are available from 158 (81%) of 194 WHO member states and the occupied Palestinian territory, including east Jerusalem, with 113 (58%) having national administrative data, whereas data on preterm births are available from 103 (53%) of 195 countries and areas, with only 64 (33%) providing national administrative data. National administrative data on SGA are available for only eight countries. Global estimates for 2020 suggest 13·4 million livebirths were preterm, with rates over the past decade remaining static, and 23·4 million were SGA. In this Series paper, we estimated prevalence in 2020 for three mutually exclusive types of small vulnerable newborns (SVNs; preterm non-SGA, term SGA, and preterm SGA) using individual-level data (2010-20) from 23 national datasets (∼110 million livebirths) and 31 studies in 18 countries (∼0·4 million livebirths). We found 11·9 million (50% credible interval [Crl] 9·1-12·2 million; 8·8%, 50% Crl 6·8-9·0%) of global livebirths were preterm non-SGA, 21·9 million (50% Crl 20·1-25·5 million; 16·3%, 14·9-18·9%) were term SGA, and 1·5 million (50% Crl 1·2-4·2 million; 1·1%, 50% Crl 0·9-3·1%) were preterm SGA. Over half (55·3%) of the 2·4 million neonatal deaths worldwide in 2020 were attributed to one of the SVN types, of which 73·4% were preterm and the remainder were term SGA. Analyses from 12 of the 23 countries with national data (0·6 million stillbirths at ≥22 weeks gestation) showed around 74% of stillbirths were preterm, including 16·0% preterm SGA and approximately one-fifth of term stillbirths were SGA. There are an estimated 1·9 million stillbirths per year associated with similar vulnerability pathways; hence integrating stillbirths to burden assessments and relevant indicators is crucial. Data can be improved by counting, weighing, and assessing the gestational age of every newborn, whether liveborn or stillborn, and classifying small newborns by the three vulnerability types. The use of these more specific types could accelerate prevention and help target care for the most vulnerable babies.

Completeness and Factors Affecting Community Workers' Reporting of Births and Deaths in the Countrywide Mortality Surveillance for Action in Mozambique.

Since March 2018, the Countrywide Mortality Surveillance for Action project, implemented as a national sample registration system by the Mozambique Instituto Nacional de Saude and the Instituto Nacional de Estatistica in 700 geographic clusters randomly distributed across the 11 provinces, has trained and deployed community surveillance agents (CSAs) to report births and deaths in each cluster prospectively. An independent, retrospective data collection was conducted to assess the completeness of surveillance data. Record linkage procedures were used to match households and vital events reported in the two data sources. We calculated birth and death reporting rates and used a regression model to determine factors associated with the likelihood of vital events being reported by the CSAs. Between March 2018 and December 2019, CSAs reported 54% of births (8,787/16,421) and 45% of deaths (1,726/3,867). Births of smaller cluster sizes (< 1,000 people) were more likely to be reported (adjusted odds ratio [aOR] = 1.45; 95% CI = 1.15-1.83) compared with those of larger cluster sizes (> 1,500 people). Deaths of rural clusters were more likely to be reported (aOR = 1.41; 95% CI = 1.07-1.85) than those of urban clusters. Adult deaths were more likely to be reported (aOR = 1.49; 95% CI = 1.10-2.02) than child deaths. Our findings suggest that a fully functioning sample vital registration system must adopt a dual system with high-quality surveys or other ways to estimate underregistration periodically, consider a smaller cluster size manageable by a community worker, and pay special attention to urban clusters as underreporting is larger.

Countrywide Mortality Surveillance for Action in Mozambique: Results from a National Sample-Based Vital Statistics System for Mortality and Cause of Death.

Sub-Saharan Africa lacks timely, reliable, and accurate national data on mortality and causes of death (CODs). In 2018 Mozambique launched a sample registration system (Countrywide Mortality Surveillance for Action [COMSA]-Mozambique), which collects continuous birth, death, and COD data from 700 randomly selected clusters, a nationally representative population of 828,663 persons. Verbal and social autopsy interviews are conducted for COD determination. We analyzed data collected in 2019-2020 to report mortality rates and cause-specific fractions. Cause-specific results were generated using computer-coded verbal autopsy (CCVA) algorithms for deaths among those age 5 years and older. For under-five deaths, the accuracy of CCVA results was increased through calibration with data from minimally invasive tissue sampling. Neonatal and under-five mortality rates were, respectively, 23 (95% CI: 18-28) and 80 (95% CI: 69-91) deaths per 1,000 live births. Mortality rates per 1,000 were 18 (95% CI: 14-21) among age 5-14 years, 26 (95% CI: 20-31) among age 15-24 years, 258 (95% CI: 230-287) among age 25-59 years, and 531 (95% CI: 490-572) among age 60+ years. Urban areas had lower mortality rates than rural areas among children under 15 but not among adults. Deaths due to infections were substantial across all ages. Other predominant causes by age group were prematurity and intrapartum-related events among neonates; diarrhea, malaria, and lower respiratory infections among children 1-59 months; injury, malaria, and diarrhea among children 5-14 years; HIV, injury, and cancer among those age 15-59 years; and cancer and cardiovascular disease at age 60+ years. The COMSA-Mozambique platform offers a rich and unique system for mortality and COD determination and monitoring and an opportunity to build a comprehensive surveillance system.

Optimal timing of introduction of complementary feeding: a systematic review and meta-analysis.

CONTEXT: The timing of introducing complementary feeding (CF) is crucial because premature or delayed CF can be associated with adverse health outcomes in childhood and adulthood. OBJECTIVE: This systematic review aims to evaluate the impact of the timing of CF introduction on health, nutrition, and developmental outcomes among normal-term infants. DATA SOURCES: Electronic databases and trial registries were searched, along with the reference lists of the included studies and relevant systematic reviews. DATA EXTRACTION: Two investigators independently extracted data from the included studies on a standardized data-extraction form. DATA ANALYSIS: Data were meta-analyzed separately for randomized controlled trials (RCTs) and observational studies on the basis of early introduction of CF (< 3 months, < 4 months, < 6 months of age) or late introduction of CF (> 6 months, > 8 months of age). Evidence was summarized according to GRADE criteria. In total, 268 documents were included in the review, of which 7 were RCTs (from 24 articles) and 217 were observational studies (from 244 articles). Evidence from RCTs did not suggest an impact of early introduction, while low-certainty evidence from observational studies suggested that early introduction of CF (< 6 months) might increase body mass index (BMI) z score and overweight/obesity. Early introduction at < 3 months might increase BMI and odds of lower respiratory tract infection (LRTI), and early introduction at < 4 months might increase height, LRTI, and systolic and diastolic blood pressure (BP). For late introduction of CF, there was a lack of evidence from RCTs, but low-certainty evidence from observational studies suggests that late introduction of CF (> 6 months) might decrease height, BMI, and systolic and diastolic BP and might increase odds of intestinal helminth infection, while late introduction of CF (> 8 months) might increase height-for-age z score. CONCLUSION: Insufficient evidence does suggest increased adiposity with early introduction of CF. Hence, the current recommendation of introduction of CF should stand, though more robust studies, especially from low- and middle-income settings, are needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42020218517.

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

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

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

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

Anthropometric criteria for best-identifying children at high risk of mortality: a pooled analysis of twelve cohorts.

OBJECTIVE: To understand which anthropometric diagnostic criteria best discriminate higher from lower risk of death in children and explore programme implications. DESIGN: A multiple cohort individual data meta-analysis of mortality risk (within 6 months of measurement) by anthropometric case definitions. Sensitivity, specificity, informedness and inclusivity in predicting mortality, face validity and compatibility with current standards and practice were assessed and operational consequences were modelled. SETTING: Community-based cohort studies in twelve low-income countries between 1977 and 2013 in settings where treatment of wasting was not widespread. PARTICIPANTS: Children aged 6 to 59 months. RESULTS: Of the twelve anthropometric case definitions examined, four (weight-for-age Z-score (WAZ) <-2), (mid-upper arm circumference (MUAC) <125 mm), (MUAC < 115 mm or WAZ < -3) and (WAZ < -3) had the highest informedness in predicting mortality. A combined case definition (MUAC < 115 mm or WAZ < -3) was better at predicting deaths associated with weight-for-height Z-score <-3 and concurrent wasting and stunting (WaSt) than the single WAZ < -3 case definition. After the assessment of all criteria, the combined case definition performed best. The simulated workload for programmes admitting based on MUAC < 115 mm or WAZ < -3, when adjusted with a proxy for required intensity and/or duration of treatment, was 1·87 times larger than programmes admitting on MUAC < 115 mm alone. CONCLUSIONS: A combined case definition detects nearly all deaths associated with severe anthropometric deficits suggesting that therapeutic feeding programmes may achieve higher impact (prevent mortality and improve coverage) by using it. There remain operational questions to examine further before wide-scale adoption can be recommended.

Prognostic value of different anthropometric indices over different measurement intervals to predict mortality in 6-59-month-old children.

OBJECTIVE: To compare the prognostic value of mid-upper arm circumference (MUAC), weight-for-height Z-score (WHZ) and weight-for-age Z-score (WAZ) for predicting death over periods of 1, 3 and 6 months follow-up in children. DESIGN: Pooled analysis of twelve prospective studies examining survival after anthropometric assessment. Sensitivity and false-positive ratios to predict death within 1, 3 and 6 months were compared for three individual anthropometric indices and their combinations. SETTING: Community-based, prospective studies from twelve countries in Africa and Asia. PARTICIPANTS: Children aged 6-59 months living in the study areas. RESULTS: For all anthropometric indices, the receiver operating characteristic curves were higher for shorter than for longer durations of follow-up. Sensitivity was higher for death with 1-month follow-up compared with 6 months by 49 % (95 % CI (30, 69)) for MUAC < 115 mm (P < 0·001), 48 % (95 % CI (9·4, 87)) for WHZ < -3 (P < 0·01) and 28 % (95 % CI (7·6, 42)) for WAZ < -3 (P < 0·005). This was accompanied by an increase in false positives of only 3 % or less. For all durations of follow-up, WAZ < -3 identified more children who died and were not identified by WHZ < -3 or by MUAC < 115 mm, 120 mm or 125 mm, but the use of WAZ < -3 led to an increased false-positive ratio up to 16·4 % (95 % CI (12·0, 20·9)) compared with 3·5 % (95 % CI (0·4, 6·5)) for MUAC < 115 mm alone. CONCLUSIONS: Frequent anthropometric measurements significantly improve the identification of malnourished children with a high risk of death without markedly increasing false positives. Combining two indices increases sensitivity but also increases false positives among children meeting case definitions.

How do children with severe underweight and wasting respond to treatment? A pooled secondary data analysis to inform future intervention studies.

Children with weight-for-age z-score (WAZ) <-3 have a high risk of death, yet this indicator is not widely used in nutrition treatment programming. This pooled secondary data analysis of children aged 6-59 months aimed to examine the prevalence, treatment outcomes, and growth trajectories of children with WAZ <-3 versus children with WAZ ≥-3 receiving outpatient treatment for wasting and/or nutritional oedema, to inform future protocols. Binary treatment outcomes between WAZ <-3 and WAZ ≥-3 admissions were compared using logistic regression. Recovery was defined as attaining mid-upper-arm circumference ≥12.5 cm and weight-for-height z-score ≥-2, without oedema, within a period of 17 weeks of admission. Data from 24,829 children from 9 countries drawn from 13 datasets were included. 55% of wasted children had WAZ <-3. Children admitted with WAZ <-3 compared to those with WAZ ≥-3 had lower recovery rates (28.3% vs. 48.7%), higher risk of death (1.8% vs. 0.7%), and higher risk of transfer to inpatient care (6.2% vs. 3.8%). Growth trajectories showed that children with WAZ <-3 had markedly lower anthropometry at the start and end of care, however, their patterns of anthropometric gains were very similar to those with WAZ ≥-3. If moderately wasted children with WAZ <-3 were treated in therapeutic programmes alongside severely wasted children, we estimate caseloads would increase by 32%. Our findings suggest that wasted children with WAZ <-3 are an especially vulnerable group and those with moderate wasting and WAZ <-3 likely require a higher intensity of nutritional support than is currently recommended. Longer or improved treatment may be necessary, and the timeline and definition of recovery likely need review.

Anthropometric deficits and the associated risk of death by age and sex in children aged 6-59 months: A meta-analysis.

Risk of death from undernutrition is thought to be higher in younger than in older children, but evidence is mixed. Research also demonstrates sex differences whereby boys have a higher prevalence of undernutrition than girls. This analysis described mortality risk associated with anthropometric deficits (wasting, underweight and stunting) in children 6-59 months by age and sex. We categorised children into younger (6-23 months) and older (24-59 months) age groups. Age and sex variations in near-term (within 6 months) mortality risk, associated with individual anthropometric deficits were assessed in a secondary analysis of multi-country cohort data. A random effects meta-analysis was performed. Data from seven low-or-middle-income-countries collected between 1977 and 2013 were analysed. One thousand twenty deaths were recorded for children with anthropometric deficits. Pooled meta-analysis estimates showed no differences by age in absolute mortality risk for wasting (RR 1.08, p = 0.826 for MUAC < 125 mm; RR 1.35, p = 0.272 for WHZ < -2). For underweight and stunting, absolute risk of death was higher in younger (RR 2.57, p < 0.001) compared with older children (RR 2.83, p < 0.001). For all deficits, there were no differences in mortality risk for girls compared with boys. There were no differences in the risk of mortality between younger and older wasted children, supporting continued inclusion of all children under-five in wasting treatment programmes. The risk of mortality associated with underweight and stunting was higher among younger children, suggesting that prevention programmes might be justified in focusing on younger children where resources are limited. There were no sex differences by age in mortality risk for all deficits.

Prevalence and predictors of spontaneous preterm births in Nepal: findings from a prospective, population-based pregnancy cohort in rural Nepal-a secondary data analysis.

OBJECTIVE: Preterm birth can have short-term and long-term complications for a child. Socioeconomic factors and pregnancy-related morbidities may be important to predict and prevent preterm births in low-resource settings. The objective of our study was to find prevalence and predictors of spontaneous preterm birth in rural Nepal. DESIGN: This is a secondary observational analysis of trial data (registration number NCT01177111). SETTING: Rural Sarlahi district, Nepal. PARTICIPANTS: 40 119 pregnant women enrolled from 9 September 2010 to 16 January 2017. OUTCOME MEASURES: The outcome variable is spontaneous preterm birth. Generalized Estimating Equations Poisson regression with robust variance was fitted to present effect estimates as risk ratios. RESULT: The prevalence of spontaneous preterm birth was 14.5% (0.5% non-spontaneous). Characteristics not varying in pregnancy associated with increased risk of preterm birth were maternal age less than 18 years (adjusted risk ratio=1.13, 95% CI: 1.02 to 1.26); being Muslim (1.53, 1.16 to 2.01); first pregnancy (1.15, 1.04 to 1.28); multiple births (4.91, 4.20 to 5.75) and male child (1.10, 1.02 to 1.17). Those associated with decreased risk were maternal education >5 years (0.81, 0.73 to 0.90); maternal height ≥150 cm (0.89, 0.81 to 0.98) and being from wealthier families (0.83, 0.74 to 0.93). Pregnancy-related morbidities associated with increased risk of preterm birth were vaginal bleeding (1.53, 1.08 to 2.18); swelling (1.37, 1.17 to 1.60); high systolic blood pressure (BP) (1.47, 1.08 to 2.01) and high diastolic BP (1.41, 1.17 to 1.70) in the third trimester. Those associated with decreased risk were respiratory problem in the third trimester (0.86, 0.79 to 0.94); having poor appetite, nausea and vomiting in the second trimester (0.86, 0.80 to 0.92) and third trimester (0.86, 0.79 to 0.94); and higher weight gain from second to third trimester (0.89, 0.87 to 0.90). CONCLUSION: The prevalence of preterm birth is high in rural Nepal. Interventions that increase maternal education may play a role. Monitoring morbidities during antenatal care to intervene to reduce them through an effective health system may help reduce preterm birth.