Effectiveness of nirmatrelvir-ritonavir on severe outcomes of COVID-19 in the era of vaccination and Omicron: An updated meta-analysis.

Nirmatrelvir-ritonavir (NR) was approved to treat SARS-CoV-2 positive outpatients at high risk of progression to severe disease, based on a randomized trial in unvaccinated patients. Effectiveness in vaccinated patients and against Omicron has not yet been confirmed by clinical trial data, but a recent meta-analysis suggested good real-world effectiveness based on 12 studies. We updated this meta-analysis by searching Medline and Embase databases for studies assessing effectiveness of NR on mortality, hospitalization, composite outcome of hospitalization and/or death, and progression to severe disease, published between October 1, 2022 and May 22, 2023. Random effects meta-analysis and subgroup analysis for vaccinated patients was performed. A total of 32 studies were included in the meta-analysis. Pooled RR for the effect of NR on mortality, hospitalization, hospitalization and/or mortality, and progression to severe disease were 0.36 (95% confidence interval [CI]: 0.25-0.52), 0.43 (CI: 0.37-0.51), 0.52 (CI: 0.45-0.61) and 0.54 (CI: 0.41-0.73), respectively. A subgroup analysis on vaccinated patients indicated lower effectiveness of NR on mortality (RR: 0.55, CI: 0.45-0.68), but similar effectiveness for hospitalization, hospitalization and/or mortality, or progression to severe disease (RR: 0.52, 0.58, and 0.66, respectively). This updated meta-analysis robustly confirms the protective effects of NR on severe COVID-19 outcomes.

Neonatal mortality risk of vulnerable newborns by fine stratum of gestational age and birthweight for 230 679 live births in nine low- and middle-income countries, 2000-2017.

OBJECTIVE: To describe the mortality risks by fine strata of gestational age and birthweight among 230 679 live births in nine low- and middle-income countries (LMICs) from 2000 to 2017. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Liveborn infants from 15 population-based cohorts. METHODS: Subnational, population-based studies with high-quality birth outcome data were invited to join the Vulnerable Newborn Measurement Collaboration. All studies included birthweight, gestational age measured by ultrasound or last menstrual period, infant sex and neonatal survival. We defined adequate birthweight as 2500-3999 g (reference category), macrosomia as ≥4000 g, moderate low as 1500-2499 g and very low birthweight as <1500 g. We analysed fine strata classifications of preterm, term and post-term: ≥42+0 , 39+0 -41+6 (reference category), 37+0 -38+6 , 34+0 -36+6 ,34+0 -36+6 ,32+0 -33+6 , 30+0 -31+6 , 28+0 -29+6 and less than 28 weeks. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for neonatal mortality rates (NMR) and relative risks (RR). We also performed meta-analysis for the relative mortality risks with 95% confidence intervals (CIs) by the fine categories, stratified by regional study setting (sub-Saharan Africa and Southern Asia) and study-level NMR (≤25 versus >25 neonatal deaths per 1000 live births). RESULTS: We found a dose-response relationship between lower gestational ages and birthweights with increasing neonatal mortality risks. The highest NMR and RR were among preterm babies born at <28 weeks (median NMR 359.2 per 1000 live births; RR 18.0, 95% CI 8.6-37.6) and very low birthweight (462.8 per 1000 live births; RR 43.4, 95% CI 29.5-63.9). We found no statistically significant neonatal mortality risk for macrosomia (RR 1.1, 95% CI 0.6-3.0) but a statistically significant risk for all preterm babies, post-term babies (RR 1.3, 95% CI 1.1-1.5) and babies born at 370 -386 weeks (RR 1.2, 95% CI 1.0-1.4). There were no statistically significant differences by region or underlying neonatal mortality. CONCLUSIONS: In addition to tracking vulnerable newborn types, monitoring finer categories of birthweight and gestational age will allow for better understanding of the predictors, interventions and health outcomes for vulnerable newborns. It is imperative that all newborns from live births and stillbirths have an accurate recorded weight and gestational age to track maternal and neonatal health and optimise prevention and care of vulnerable newborns.

Quality of vital event data for infant mortality estimation in prospective, population-based studies: an analysis of secondary data from Asia, Africa, and Latin America.

INTRODUCTION: Infant and neonatal mortality estimates are typically derived from retrospective birth histories collected through surveys in countries with unreliable civil registration and vital statistics systems. Yet such data are subject to biases, including under-reporting of deaths and age misreporting, which impact mortality estimates. Prospective population-based cohort studies are an underutilized data source for mortality estimation that may offer strengths that avoid biases. METHODS: We conducted a secondary analysis of data from the Child Health Epidemiology Reference Group, including 11 population-based pregnancy or birth cohort studies, to evaluate the appropriateness of vital event data for mortality estimation. Analyses were descriptive, summarizing study designs, populations, protocols, and internal checks to assess their impact on data quality. We calculated infant and neonatal morality rates and compared patterns with Demographic and Health Survey (DHS) data. RESULTS: Studies yielded 71,760 pregnant women and 85,095 live births. Specific field protocols, especially pregnancy enrollment, limited exclusion criteria, and frequent follow-up visits after delivery, led to higher birth outcome ascertainment and fewer missing deaths. Most studies had low follow-up loss in pregnancy and the first month with little evidence of date heaping. Among studies in Asia and Latin America, neonatal mortality rates (NMR) were similar to DHS, while several studies in Sub-Saharan Africa had lower NMRs than DHS. Infant mortality varied by study and region between sources. CONCLUSIONS: Prospective, population-based cohort studies following rigorous protocols can yield high-quality vital event data to improve characterization of detailed mortality patterns of infants in low- and middle-income countries, especially in the early neonatal period where mortality risk is highest and changes rapidly.

Neonatal mortality risk of vulnerable newborns: A descriptive analysis of subnational, population-based birth cohorts for 238 203 live births in low- and middle-income settings from 2000 to 2017.

OBJECTIVE: We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low- and middle-income countries (LMICs). DESIGN: Descriptive multi-country, secondary analysis of individual-level study data of babies born since 2000. SETTING: Sixteen subnational, population-based studies from nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Live birth neonates. METHODS: We categorically defined five vulnerable newborn types based on size (large- or appropriate- or small-for-gestational age [LGA, AGA, SGA]), and term (T) and preterm (PT): T + LGA, T + SGA, PT + LGA, PT + AGA, and PT + SGA, with T + AGA (reference). A 10-type definition included low birthweight (LBW) and non-LBW, and a four-type definition collapsed AGA/LGA into one category. We performed imputation for missing birthweights in 13 of the studies. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for the prevalence, mortality rates and relative mortality risks for the four, six and ten type classification. RESULTS: There were 238 203 live births with known neonatal status. Four of the six types had higher mortality risk: T + SGA (median relative risk [RR] 2.6, interquartile range [IQR] 2.0-2.9), PT + LGA (median RR 7.3, IQR 2.3-10.4), PT + AGA (median RR 6.0, IQR 4.4-13.2) and PT + SGA (median RR 10.4, IQR 8.6-13.9). T + SGA, PT + LGA and PT + AGA babies who were LBW, had higher risk compared with non-LBW babies. CONCLUSIONS: Small and/or preterm babies in LIMCs have a considerably increased mortality risk compared with babies born at term and larger. This classification system may advance the understanding of the social determinants and biomedical risk factors along with improved treatment that is critical for newborn health.

The relationship between wasting and stunting in young children: A systematic review.

In 2014, the Emergency Nutrition Network published a report on the relationship between wasting and stunting. We aim to review evidence generated since that review to better understand the implications for improving child nutrition, health and survival. We conducted a systematic review following PRISMA guidelines, registered with PROSPERO. We identified search terms that describe wasting and stunting and the relationship between the two. We included studies related to children under five from low- and middle-income countries that assessed both ponderal growth/wasting and linear growth/stunting and the association between the two. We included 45 studies. The review found the peak incidence of both wasting and stunting is between birth and 3 months. There is a strong association between the two conditions whereby episodes of wasting contribute to stunting and, to a lesser extent, stunting leads to wasting. Children with multiple anthropometric deficits, including concurrent stunting and wasting, have the highest risk of near-term mortality when compared with children with any one deficit alone. Furthermore, evidence suggests that the use of mid-upper-arm circumference combined with weight-for-age Z score might effectively identify children at most risk of near-term mortality. Wasting and stunting, driven by common factors, frequently occur in the same child, either simultaneously or at different moments through their life course. Evidence of a process of accumulation of nutritional deficits and increased risk of mortality over a child's life demonstrates the pressing need for integrated policy, financing and programmatic approaches to the prevention and treatment of child malnutrition.

Measuring and understanding the effects of a performance based financing scheme applied to nutrition services in Burundi-a mixed method impact evaluation design.

BACKGROUND: Malnutrition is a huge problem in Burundi. In order to improve the provision of services at hospital, health centre and community levels, the Ministry of Health is piloting the introduction of malnutrition prevention and care indicators within its performance based financing (PBF) scheme. Paying for units of services and for qualitative indicators is expected to enhance provision and quality of these nutrition services, as PBF has done, in Burundi and elsewhere, for several other services. METHODS: This paper presents the protocol for the impact evaluation of the PBF scheme applied to malnutrition. The research design consists in a mixed methods model adopting a sequential explanatory design. The quantitative component is a cluster-randomized controlled evaluation design: among the 90 health centres selected for the study, half receive payment related to their results in malnutrition activities, while the other half get a budget allocation. Qualitative research will be carried out both during the intervention period and at the end of the quantitative evaluation. Data are collected from 1) baseline and follow-up surveys of 90 health centres and 6,480 households with children aged 6 to 23 months, 2) logbooks filled in weekly in health centres, and 3) in-depth interviews and focus group discussions. The evaluation aims to provide the best estimate of the impact of the project on malnutrition outcomes in the community as well as outputs at the health centre level (malnutrition care outputs) and to describe quantitatively and qualitatively the changes that took place (or did not take place) within health centres as a result of the program. DISCUSSION: Although PBF schemes are blooming in low in-come countries, there is still a need for evidence, especially on the impact of revising the list of remunerated indicators. It is expected that this impact evaluation will be helpful for the national policy dialogue in Burundi, but it will also provide key evidence for countries with an existing PBF scheme and confronted with malnutrition problems on the appropriateness to extend the strategy to nutrition services. TRIAL REGISTRATION: ClinicalTrials.gov PRS Identifier: NCT02721160; registered March 2016.

Risk of dietary exposure to aflatoxins and fumonisins in infants less than 6 months of age in Rombo, Northern Tanzania.

Infants less than 6 months of age receiving foods other than breast milk are at a high risk of exposure to mycotoxins. We surveyed food intake and estimated the risk of exposures to aflatoxin and fumonisin mycotoxins for infants less than 6 months of age in Northern Tanzania. A total of 143 infants were progressively recruited and three follow-up visits were made at 1, 3 and 5 months of age. A 24-h dietary recall technique was used to estimate flour intake of infants who had been introduced to maize foods. Aflatoxins and fumonisins in the flours were analysed using high-performance liquid chromatography technique. Exposure to aflatoxins or fumonisins was estimated using the deterministic approach. By the age of 3 months, 98 infants had started taking food; 67 of them, maize flours at levels ranging from 0.57 to 37.50 g per infant per day (average 8 g per infant per day). Fifty-eight per cent of 67 maize flour samples contained detectable aflatoxins (range 0.33-69.47 µg kg(-1) ; median 6 µg kg(-1) ) and 31% contained detectable fumonisins (range 48-1224 µg kg(-1) ; median 124 µg kg(-1) ). For infants who consumed contaminated flours, aflatoxin exposure ranged from 0.14 to 120 ng kg(-1) body weight (BW) per day (all above the health concern level of 0.017 ng kg(-1) BW per day as recommended by the European Food Safety Agency) and fumonisin exposure ranged from 0.005 to 0.88 µg kg(-1) BW per day. Insignificant association was observed between exposure to fumonisins or aflatoxins and stunting or underweight. Reducing aflatoxin and fumonisin contamination of maize and dietary diversification can prevent infants and the public, in general, from exposure to the toxins.

Seasonality modifies the effect of a lipid-based nutrient supplement for pregnant rural women on birth length.

BACKGROUND: Maternal nutritional status is a major determinant of low birth weight and fluctuates across seasons. Seasonality may influence the outcome of prenatal nutrition interventions that aim to enhance fetal growth. OBJECTIVE: This study investigated seasonal modifications of the efficacy of a randomized controlled prenatal nutrition intervention trial in pregnant women to improve fetal growth in rural Burkina Faso. METHODS: The second Micronutriments et Santé de la Mère et de l'Enfant study compared a lipid-based nutrient supplement (LNS) fortified with multiple micronutrients (MMNs) to an MMN supplement. Truncated Fourier series were used to characterize seasonality in birth outcomes. Models that included the Fourier series and newborn and maternal characteristics were used to assess seasonal effect modifications of prenatal supplementation on birth outcomes. RESULTS: Birth weight, birth length, small for gestational age as a proxy for intrauterine growth retardation, and preterm birth were significantly related to date of birth and showed important seasonal variations. LNSs, which supply energy in addition to MMNs, resulted in a significant increase in birth length (+13.5 mm, 95% CI: 6.5, 20.5 mm) at the transition from rain to dry season (September to November) compared to MMNs alone. CONCLUSIONS: The climatologic and agricultural seasonal patterns in Burkina Faso affect the efficacy of prenatal LNSs on birth length. In this context, prenatal MMN supplementation programs should be complemented by energy supplementation during the annual rain season to promote fetal growth. This trial was registered at clinicaltrials.gov as NCT00909974.

Short Maternal Stature Increases Risk of Small-for-Gestational-Age and Preterm Births in Low- and Middle-Income Countries: Individual Participant Data Meta-Analysis and Population Attributable Fraction.

BACKGROUND: Small-for-gestational-age (SGA) and preterm births are associated with adverse health consequences, including neonatal and infant mortality, childhood undernutrition, and adulthood chronic disease. OBJECTIVES: The specific aims of this study were to estimate the association between short maternal stature and outcomes of SGA alone, preterm birth alone, or both, and to calculate the population attributable fraction of SGA and preterm birth associated with short maternal stature. METHODS: We conducted an individual participant data meta-analysis with the use of data sets from 12 population-based cohort studies and the WHO Global Survey on Maternal and Perinatal Health (13 of 24 available data sets used) from low- and middle-income countries (LMIC). We included those with weight taken within 72 h of birth, gestational age, and maternal height data (n = 177,000). For each of these studies, we individually calculated RRs between height exposure categories of < 145 cm, 145 to < 150 cm, and 150 to < 155 cm (reference: ≥ 155 cm) and outcomes of SGA, preterm birth, and their combination categories. SGA was defined with the use of both the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) birth weight standard and the 1991 US birth weight reference. The associations were then meta-analyzed. RESULTS: All short stature categories were statistically significantly associated with term SGA, preterm appropriate-for-gestational-age (AGA), and preterm SGA births (reference: term AGA). When using the INTERGROWTH-21st standard to define SGA, women < 145 cm had the highest adjusted risk ratios (aRRs) (term SGA-aRR: 2.03; 95% CI: 1.76, 2.35; preterm AGA-aRR: 1.45; 95% CI: 1.26, 1.66; preterm SGA-aRR: 2.13; 95% CI: 1.42, 3.21). Similar associations were seen for SGA defined by the US reference. Annually, 5.5 million term SGA (18.6% of the global total), 550,800 preterm AGA (5.0% of the global total), and 458,000 preterm SGA (16.5% of the global total) births may be associated with maternal short stature. CONCLUSIONS: Approximately 6.5 million SGA and/or preterm births in LMIC may be associated with short maternal stature annually. A reduction in this burden requires primary prevention of SGA, improvement in postnatal growth through early childhood, and possibly further intervention in late childhood and adolescence. It is vital for researchers to broaden the evidence base for addressing chronic malnutrition through multiple life stages, and for program implementers to explore effective, sustainable ways of reaching the most vulnerable populations.

Inconsistent diagnosis of acute malnutrition by weight-for-height and mid-upper arm circumference: contributors in 16 cross-sectional surveys from South Sudan, the Philippines, Chad, and Bangladesh.

BACKGROUND: The two anthropometric indicators of acute malnutrition in children under 5 years, i.e. a Mid-Upper Arm Circumference < 125 mm (MUAC125) or a Weight-for-Height Z-score<-2 (WHZ-2), correlate poorly. We aimed at assessing the contribution of age, sex, stunting (Height-for-Age HAZ<-2), and low sitting-standing height ratio Z-score (SSRZ in the 1st tertile of the study population, called hereafter 'longer legs') to this diagnosis discrepancy. METHODS: Data from 16 cross-sectional nutritional surveys carried out by Action Against Hunger International in South Sudan, the Philippines, Chad, and Bangladesh fed multilevel, multivariate regression models, with either WHZ-2 or MUAC125 as the dependent variable and age, sex, stunting, and 'longer legs' as the independent ones. We also compared how the performance of MUAC125 and WHZ-2 to detect slim children, i.e. children with a low Weight-for-Age (WAZ<-2) but no linear growth retardation (HAZ≥-2), was modified by the contributors. RESULTS: Overall 23.1% of the 14,409 children were identified as acutely malnourished by either WHZ-2 or MUAC125, but only 28.5% of those (949/3,328) were identified by both indicators. Being stunted (+17.8%; 95 % CI: 14.8%; 22.8%), being a female (+16.5%; 95 % CI: 13.5%; 19.5%) and being younger than 24 months (+33.6%; 95 % CI: 30.4%; 36.7%) were factors strongly associated with being detected as malnourished by MUAC125 and not by WHZ-2, whereas having 'longer legs' moderately increased the diagnosis by WHZ-2 (+4.2%; 95 % CI: 0.7%; 7.6%). The sensitivity to detect slim children by MUAC125 was 31.0% (95 % CI: 26.8%; 35.2%) whereas it was 70.6% (95 % CI: 65.4%; 75.9%) for WHZ-2. The sensitivity of MUAC125 was particularly affected by age (57.4% vs. 18.1% in children aged < 24 months vs. ≥ 24 months). Specificity was high for both indicators. CONCLUSIONS: MUAC125 should not be used as a stand-alone criterion of acute malnutrition given its strong association with age, sex and stunting, and its low sensitivity to detect slim children. Having 'longer legs' moderately increases the diagnosis of acute malnutrition by WHZ-2. Prospective studies are urgently needed to elucidate the clinical and physiological outcomes of the various anthropometric indicators of malnutrition.

A decade of nutrition research in Africa: assessment of the evidence base and academic collaboration.

OBJECTIVE: Malnutrition in Africa has not improved compared with other regions in the world. Investment in the build-up of a strong African research workforce is essential to provide contextual solutions to the nutritional problems of Africa. To orientate this process, we reviewed nutrition research carried out in Africa and published during the last decade. DESIGN: We assessed nutrition research from Africa published between 2000 and 2010 from MEDLINE and EMBASE and analysed the study design and type of intervention for studies indexed with major MeSH terms for vitamin A deficiency, protein-energy malnutrition, obesity, breast-feeding, nutritional status and food security. Affiliations of first authors were visualised as a network and power of affiliations was assessed using centrality metrics. SETTING: Africa. SUBJECTS: Africans, all age groups. RESULTS: Most research on the topics was conducted in Southern (36%) and Western Africa (34%). The intervention studies (9%; n 95) mainly tested technological and curative approaches to the nutritional problems. Only for papers on protein-energy malnutrition and obesity did lead authorship from Africa exceed that from non-African affiliations. The 10% most powerfully connected affiliations were situated mainly outside Africa for publications on vitamin A deficiency, breast-feeding, nutritional status and food security. CONCLUSIONS: The development of the evidence base for nutrition research in Africa is focused on treatment and the potential for cross-African networks to publish nutrition research from Africa remains grossly underutilised. Efforts to build capacity for effective nutrition action in Africa will require forging a true academic partnership between African and non-African research institutions.

Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis.

BACKGROUND: Babies with low birthweight (<2500 g) are at increased risk of early mortality. However, low birthweight includes babies born preterm and with fetal growth restriction, and not all these infants have a birthweight less than 2500 g. We estimated the neonatal and infant mortality associated with these two characteristics in low-income and middle-income countries. METHODS: For this pooled analysis, we searched all available studies and identified 20 cohorts (providing data for 2,015,019 livebirths) from Asia, Africa, and Latin America that recorded data for birthweight, gestational age, and vital statistics through 28 days of life. Study dates ranged from 1982 through to 2010. We calculated relative risks (RR) and risk differences (RD) for mortality associated with preterm birth (<32 weeks, 32 weeks to <34 weeks, 34 weeks to <37 weeks), small-for-gestational-age (SGA; babies with birthweight in the lowest third percentile and between the third and tenth percentile of a US reference population), and preterm and SGA combinations. FINDINGS: Pooled overall RRs for preterm were 6·82 (95% CI 3·56-13·07) for neonatal mortality and 2·50 (1·48-4·22) for post-neonatal mortality. Pooled RRs for babies who were SGA (with birthweight in the lowest tenth percentile of the reference population) were 1·83 (95% CI 1·34-2·50) for neonatal mortality and 1·90 (1·32-2·73) for post-neonatal mortality. The neonatal mortality risk of babies who were both preterm and SGA was higher than that of babies with either characteristic alone (15·42; 9·11-26·12). INTERPRETATION: Many babies in low-income and middle-income countries are SGA. Preterm birth affects a smaller number of neonates than does SGA, but is associated with a higher mortality risk. The mortality risks associated with both characteristics extend beyond the neonatal period. Differentiation of the burden and risk of babies born preterm and SGA rather than with low birthweight could guide prevention and management strategies to speed progress towards Millennium Development Goal 4--the reduction of child mortality. FUNDING: Bill & Melinda Gates Foundation.

A school-based intervention improves physical fitness in Ecuadorian adolescents: a cluster-randomized controlled trial.

BACKGROUND: Effective lifestyle interventions are needed to prevent noncommunicable diseases in low- and middle-income countries. We analyzed the effects of a school-based health promotion intervention on physical fitness after 28 months and explored if the effect varied with important school characteristics. We also assessed effects on screen time, physical activity and BMI. METHODS AND RESULTS: We performed a cluster-randomized pair matched trial in schools in urban Ecuador. The intervention included an individual and environmental component tailored to the local context and resources. Primary outcomes were physical fitness (EUROFIT battery), screen time (questionnaires) and physical activity (accelerometers). Change in BMI was a secondary outcome. A total of 1440 grade 8 and 9 adolescents (intervention: n = 700, 48.6%) and 20 schools (intervention: n = 10, 50%) participated. Data of 1083 adolescents (intervention: n = 550, 50.8%) from 20 schools were analyzed. CONCLUSIONS: A school-based intervention with an individual and environment component can improve physical fitness and can minimize the decline in physical activity levels from childhood into adolescence in urban Ecuador. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01004367.

Clinical and biochemical responses to treatment of uncomplicated severe acute malnutrition: a multicenter observational cohort from the OptiDiag study.

BACKGROUND: Severe acute malnutrition (SAM) can be diagnosed using weight-for-height Z-score (WHZ) and/or mid-upper arm circumference (MUAC). Although some favor using MUAC alone, valuing its presumed ability to identify children at greatest need for nutritional care, the functional severity and physiological responses to treatment in children with varying deficits in WHZ and MUAC remain inadequately characterized. OBJECTIVE: We aimed to compare clinical and biochemical responses to treatment in children with 1) both low MUAC and low WHZ, 2) low MUAC-only, and 3) low WHZ-only. METHODS: A multicenter, observational cohort study was conducted in children aged 6-59 mo with nonedematous, uncomplicated SAM in Bangladesh, Burkina Faso, and Liberia. Anthropometric measurements and critical indicators were collected 3 times during treatment; metrics included clinical status, nutritional status, viability, and serum leptin, a biomarker of mortality risk in SAM. RESULTS: Children with combined MUAC and WHZ deficits had greater increases in leptin levels during treatment than those with low MUAC alone, showing a 34.4% greater increase on the second visit (95% confidence interval [CI]: 7.6%, 43.6%; P = 0.02) and a 34.3% greater increase on the third visit (95% CI: 13.2%, 50.3%; P = 0.01). Similarly, weight gain velocity was higher by 1.56 g/kg/d in the combined deficit group (95% CI: 0.38, 2.75; P = 0.03) compared with children with low MUAC-only. Children with combined deficits had higher rates of iron deficiency and wasting while those with low WHZ alone and combined deficits had higher rates of tachypnea and pneumonia during treatment. CONCLUSIONS: Given the comparable treatment responses of children with low WHZ alone and those with low MUAC alone, and the greater vulnerability at admission and during treatment in those with combined deficits, our findings support retaining WHZ as an independent diagnostic and admission criterion of SAM, alongside MUAC. This trial was registered at www. CLINICALTRIALS: gov/study/NCT03400930 as NCT03400930.

Diet and physical activity for the prevention of noncommunicable diseases in low- and middle-income countries: a systematic policy review.

BACKGROUND: Diet-related noncommunicable diseases (NCDs) are increasing rapidly in low- and middle-income countries (LMICs) and constitute a leading cause of mortality. Although a call for global action has been resonating for years, the progress in national policy development in LMICs has not been assessed. This review of strategies to prevent NCDs in LMICs provides a benchmark against which policy response can be tracked over time. METHODS AND FINDINGS: We reviewed how government policies in LMICs outline actions that address salt consumption, fat consumption, fruit and vegetable intake, or physical activity. A structured content analysis of national nutrition, NCDs, and health policies published between 1 January 2004 and 1 January 2013 by 140 LMIC members of the World Health Organization (WHO) was carried out. We assessed availability of policies in 83% (116/140) of the countries. NCD strategies were found in 47% (54/116) of LMICs reviewed, but only a minority proposed actions to promote healthier diets and physical activity. The coverage of policies that specifically targeted at least one of the risk factors reviewed was lower in Africa, Europe, the Americas, and the Eastern Mediterranean compared to the other two World Health Organization regions, South-East Asia and Western Pacific. Of the countries reviewed, only 12% (14/116) proposed a policy that addressed all four risk factors, and 25% (29/116) addressed only one of the risk factors reviewed. Strategies targeting the private sector were less frequently encountered than strategies targeting the general public or policy makers. CONCLUSIONS: This review indicates the disconnection between the burden of NCDs and national policy responses in LMICs. Policy makers urgently need to develop comprehensive and multi-stakeholder policies to improve dietary quality and physical activity.

Treatment of severe acute malnutrition in infants aged <6 months in Niger.

OBJECTIVE: To report a nutritional rehabilitation program in Niger for the management of severe acute malnutrition in infants aged <6 months. STUDY DESIGN: This is a presentation of a case series (n = 632) of young infants who were admitted to a nutrition rehabilitation program in 2010-2011. The main characteristics of the inpatient treatment protocol where the use of diluted F-100 milk via a supplementary suckling technique until exclusive breastfeeding was reinitialized, coaching of mothers on infant feeding, and intensive antibiotic therapy as indicated during the stabilization phase. Semistructured interviews were conducted with 103 mothers. RESULTS: Rates of recovery, mortality, and default were 85% (537 of 632), 6% (37 of 632), and 9% (55 of 632), respectively. The majority of infants had an infectious disease at study entry (81%), particularly acute watery diarrhea and respiratory tract infections. Infection on admission was a predictor of death during treatment (OR, 3.9; 95% CI, 1.6-9.2). Anorexia at entry was a risk factor for treatment failure (OR, 4.4; 95% CI, 1.71-11.1). Interviews revealed a very low rate of exclusive breastfeeding (3%), with delayed initiation in 68% of cases. Traditional beliefs, perceived insufficiency of breast milk, and psychological problems played important roles in feeding choices. CONCLUSION: Severe acute malnutrition in infants aged <6 months can be successfully treated by managing cases as inpatients with an adapted protocol, intensive clinical supervision, and intensive drug treatment if indicated. Whether similar outcomes are achievable in community-based programs remains to be verified. Effective interventions for improving breastfeeding practices are needed.

Prenatal lipid-based nutrient supplements increase cord leptin concentration in pregnant women from rural Burkina Faso.

In developing countries, prenatal lipid-based nutrient supplements (LNSs) were shown to increase birth size; however, the mechanism of this effect remains unknown. Cord blood hormone concentrations are strongly associated with birth size. Therefore, we hypothesize that LNSs increase birth size through a change in the endocrine regulation of fetal development. We compared the effect of daily prenatal LNSs with multiple micronutrient tablets on cord blood hormone concentrations using a randomized, controlled design including 197 pregnant women from rural Burkina Faso. Insulin-like growth factors (IGF) I and II, their binding proteins IGFBP-1 and IGFBP-3, leptin, cortisol, and insulin were quantified in cord sera using immunoassays. LNS was associated with higher cord blood leptin mainly in primigravidae (+57%; P = 0.02) and women from the highest tertile of BMI at study inclusion (+41%; P = 0.02). We did not find any significant LNS effects on other measured cord hormones. The observed increase in cord leptin was associated with a significantly higher birth weight. Cord sera from small-for-gestational age newborns had lower median IGF-I (-9 µg/L; P = 0.003), IGF-II (-79 µg/L; P = 0.003), IGFBP-3 (-0.7 µg/L; P = 0.007), and leptin (-1.0 µg/L; P = 0.016) concentrations but higher median cortisol (+18 µg/L; P = 0.037) concentrations compared with normally grown newborns. Prenatal LNS resulted in increased cord leptin concentrations in primigravidae and mothers with higher BMI at study inclusion. The elevated leptin concentrations could point toward a higher neonatal fat mass.

The associations of parity and maternal age with small-for-gestational-age, preterm, and neonatal and infant mortality: a meta-analysis.

BACKGROUND: Previous studies have reported on adverse neonatal outcomes associated with parity and maternal age. Many of these studies have relied on cross-sectional data, from which drawing causal inference is complex. We explore the associations between parity/maternal age and adverse neonatal outcomes using data from cohort studies conducted in low- and middle-income countries (LMIC). METHODS: Data from 14 cohort studies were included. Parity (nulliparous, parity 1-2, parity ≥ 3) and maternal age (<18 years, 18-<35 years, ≥ 35 years) categories were matched with each other to create exposure categories, with those who are parity 1-2 and age 18-<35 years as the reference. Outcomes included small-for-gestational-age (SGA), preterm, neonatal and infant mortality. Adjusted odds ratios (aOR) were calculated per study and meta-analyzed. RESULTS: Nulliparous, age <18 year women, compared with women who were parity 1-2 and age 18-<35 years had the highest odds of SGA (pooled adjusted OR: 1.80), preterm (pooled aOR: 1.52), neonatal mortality (pooled aOR: 2.07), and infant mortality (pooled aOR: 1.49). Increased odds were also noted for SGA and neonatal mortality for nulliparous/age 18-<35 years, preterm, neonatal, and infant mortality for parity ≥ 3/age 18-<35 years, and preterm and neonatal mortality for parity ≥ 3/≥ 35 years. CONCLUSIONS: Nulliparous women <18 years of age have the highest odds of adverse neonatal outcomes. Family planning has traditionally been the least successful in addressing young age as a risk factor; a renewed focus must be placed on finding effective interventions that delay age at first birth. Higher odds of adverse outcomes are also seen among parity ≥ 3 / age ≥ 35 mothers, suggesting that reproductive health interventions need to address the entirety of a woman's reproductive period. FUNDING: Funding was provided by the Bill & Melinda Gates Foundation (810-2054) by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group.