Identifying neonates at risk for post-discharge mortality in Dar es Salaam, Tanzania, and Monrovia, Liberia: Derivation and internal validation of a novel risk assessment tool.

INTRODUCTION: The immediate period after hospital discharge carries a large burden of childhood mortality in sub-Saharan Africa. Our objective was to derive and internally validate a risk assessment tool to identify neonates discharged from the neonatal ward at risk for 60-day post-discharge mortality. METHODS: We conducted a prospective observational cohort study of neonates discharged from Muhimbili National Hospital in Dar es Salaam, Tanzania, and John F Kennedy Medical Centre in Monrovia, Liberia. Research staff called caregivers to ascertain vital status up to 60 days after discharge. We conducted multivariable logistic regression analyses with best subset selection to identify socioeconomic, demographic, clinical, and anthropometric factors associated with post-discharge mortality. We used adjusted log coefficients to assign points to each variable and internally validated our tool with bootstrap validation with 500 repetitions. RESULTS: There were 2344 neonates discharged and 2310 (98.5%) had post-discharge outcomes available. The median (IQR) age at discharge was 8 (4, 15) days; 1238 (53.6%) were male. In total, 71 (3.1%) died during follow-up (26.8% within 7 days of discharge). Leaving against medical advice (adjusted OR [aOR] 5.62, 95% CI 2.40 to 12.10) and diagnosis of meconium aspiration (aOR 6.98, 95% CI 1.69 to 21.70) conferred the greatest risk for post-discharge mortality. The risk assessment tool included nine variables (total possible score=63) and had an optimism corrected area under the receiver operating characteristic curve of 0.77 (95% CI 0.75 to 0.80). A score of ≥6 was most optimal (sensitivity 68.3% [95% CI 64.8% to 71.5%], specificity 72.1% [95% CI 71.5% to 72.7%]). CONCLUSIONS: A small number of factors predicted all-cause, 60-day mortality after discharge from neonatal wards in Tanzania and Liberia. After external validation, this risk assessment tool may facilitate clinical decision making for eligibility for discharge and the direction of resources to follow-up high risk neonates.

Safe infant feeding in healthcare facilities: Assessment of infection prevention and control conditions and behaviors in India, Malawi, and Tanzania.

Infants need to receive care in environments that limit their exposure to pathogens. Inadequate water, sanitation, and hygiene (WASH) environments and suboptimal infection prevention and control practices in healthcare settings contribute to the burden of healthcare-associated infections, which are particularly high in low-income settings. Specific research is needed to understand infant feeding preparation in healthcare settings, a task involving multiple behaviors that can introduce pathogens and negatively impact health. To understand feeding preparation practices and potential risks, and to inform strategies for improvement, we assessed facility WASH environments and observed infant feeding preparation practices across 12 facilities in India, Malawi, and Tanzania serving newborn infants. Research was embedded within the Low Birthweight Infant Feeding Exploration (LIFE) observational cohort study, which documented feeding practices and growth patterns to inform feeding interventions. We assessed WASH-related environments and feeding policies of all 12 facilities involved in the LIFE study. Additionally, we used a guidance-informed tool to carry out 27 feeding preparation observations across 9 facilities, enabling assessment of 270 total behaviors. All facilities had 'improved' water and sanitation services. Only 50% had written procedures for preparing expressed breastmilk; 50% had written procedures for cleaning, drying, and storage of infant feeding implements; and 33% had written procedures for preparing infant formula. Among 270 behaviors assessed across the 27 feeding preparation observations, 46 (17.0%) practices were carried out sub-optimally, including preparers not handwashing prior to preparation, and cleaning, drying, and storing of feeding implements in ways that do not effectively prevent contamination. While further research is needed to improve assessment tools and to identify specific microbial risks of the suboptimal behaviors identified, the evidence generated is sufficient to justify investment in developing guidance and programing to strengthen infant feeding preparation practices to ensure optimal newborn health.

Association of Sociodemographic Factors and Maternal Educational Attainment with Child Development among Families Living below the Poverty Line in the State of Ceará, Northeastern Brazil.

Maternal educational attainment has been identified as relevant to several child health and development outcomes. This study aimed to evaluate the association of sociodemographic and maternal education factors with child development in families living below the poverty line. A cross-sectional study was conducted through telephone contact from May to July 2021 in Ceará, a state in Northeastern Brazil. The study population comprised families with children up to six years of age participating in the cash transfer program "Mais infância". The families selected to participate in this program must have a monthly per capita income of less than US$16.50. The Ages and Stages Questionnaire version 3 was applied to assess the children's development status. The mothers reported maternal educational attainment as the highest grade and or degree obtained. The final weighted and adjusted model showed that maternal schooling was associated with the risk of delay in all domains except for the fine motor domain. The risk of delay in at least one domain was 2.5-fold higher in mothers with a lower level of schooling (95% CI: 1.6-3.9). The findings of this study suggest that mothers with higher educational attainment have children with better child development outcomes.

A peer-facilitated psychological group intervention for perinatal women living with HIV and depression in Tanzania-Healthy Options: A cluster-randomized controlled trial.

BACKGROUND: Perinatal women living with HIV (PWLH) have a greater risk of depression compared to other women; however, there are limited specialized mental health services available to them. We aimed to determine whether a stepped-care intervention facilitated by trained lay providers can improve mental health outcomes postpartum for PWLH. METHODS AND FINDINGS: Healthy Options is a cluster-randomized controlled study conducted in 16 government-managed antenatal care clinics that provided HIV care for pregnant women in urban Tanzania. Recruitment occurred from May 2015 through April 2016, with the final round of data collection completed in October 2017. Participants included a consecutive sample of pregnant women under 30 weeks of gestation, living with HIV and depression, and attending the study clinics. Control sites received enhanced usual care for depression (EUDC). Intervention sites received EUDC plus the Healthy Options intervention, which includes prenatal group sessions of problem-solving therapy (PST) plus cognitive behavioral therapy (CBT) sessions for individuals showing depressive symptoms at 6 weeks postdelivery. We assessed depressive symptoms comparable to major depressive disorder (MDD) using the Patient Health Questionnaire-9 (PHQ-9) with a locally validated cutoff at 9 months and 6 weeks postpartum. The primary time point is 9 months postpartum. We examined differences in outcomes using an intent-to-treat analysis with a complete case approach, meaning those with data at the relevant time point were included in the analysis. We used generalized estimating equations accounting for clustering. Of 818 women screened using the PHQ-9, 742 were determined eligible and enrolled (395 intervention; 347 control); 649 women (87.5%) participated in the first follow-up and 641 women (86.4%) in the second. A majority (270, 74.6%) of women in the intervention arm attended 5 or more PST sessions. Women enrolled in Healthy Options demonstrated a 67% (RR 0.33; 95% CI: 0.22, 0.51; p-value: <0.001; corresponding to a 25.7% difference in absolute risk) lower likelihood of depressive symptoms than women in control clusters at 6 weeks postpartum. At 9 months postpartum, women enrolled in Healthy Options demonstrated a nonsignificant 26% (RR 0.74; 95% CI: 0.42, 1.3; p-value: 0.281; corresponding to a 3.2% difference in absolute risk) lower likelihood of depressive symptoms than women in control clusters. Study limitations include not using diagnostic interviews to measure depression and not blinding data collectors to intervention status during follow-up. CONCLUSIONS: The Healthy Options intervention did not demonstrate reduction in depressive symptoms at 9 months postpartum, the primary outcome. Significant reductions were seen in depression symptoms at 6 weeks postpartum, the secondary outcome. Stepped-care interventions may be relevant for improving outcomes in the critical early postpartum window. TRIAL REGISTRATION: Clinical Trial registration number (closed to new participants) NCT02039973.

Re-evaluating the health impact and cost-effectiveness of tuberculosis preventive treatment for modern HIV cohorts on antiretroviral therapy: a modelling analysis using data from Tanzania.

BACKGROUND: Isoniazid preventive therapy (IPT) can prevent tuberculosis among people receiving antiretroviral therapy (ART). HIV programmes are now initiating patients on ART with higher average CD4 cell counts and lower tuberculosis risks under test-and-treat guidelines. We aimed to investigate how this change has affected the health impact and cost-effectiveness of IPT. METHODS: We constructed a tuberculosis-HIV microsimulation model parameterised using data from a large HIV treatment programme in Dar es Salaam, Tanzania. We simulated long-term health and cost outcomes for the 211 748 individuals initiating ART between Jan 1, 2014, and Dec 31, 2020, under three scenarios: no IPT access; observed levels of IPT access (75%) and completion (71%); and full (100%) IPT access and completion. We stratified results by ART initiation year and starting CD4 cell count. FINDINGS: Observed levels of IPT access were estimated to have averted 12 800 (95% uncertainty interval 7300 to 21 600) disability-adjusted life-years (DALYs) and saved US$23 000 (-2 268 000 to 1 388 000). Full IPT access would have averted 24 500 (15 100 to 38 300) DALYs and cost $825 000 (-1 594 000 to 4 751 000), equivalent to $23·4 per DALY averted. Lifetime health benefits of IPT were estimated to be greater for more recent ART cohorts, while lifetime costs were stable. In subgroup analyses, a higher CD4 cell count at ART initiation was associated with greater health gains from IPT (15 900 [10 300 to 22 500] DALYs averted by full IPT per 100 000 patients for CD4 count >500 cells per µL at ART initiation, versus 7400 [4500 to 11 600] for CD4 count <100 cells per µL) and lower incremental lifetime costs. INTERPRETATION: IPT remains highly cost-effective or cost-saving for recent ART cohorts. The health impact and cost-effectiveness of IPT are estimated to improve as patients initiate ART earlier in the course of infection. FUNDING: US National Institutes of Health.

Priority setting in early childhood development: an analytical framework for economic evaluation of interventions.

BACKGROUND: Early childhood development (ECD) sets the foundation for healthy and successful lives with important ramifications for education, labour market outcomes and other domains of well-being. Even though a large number of interventions that promote ECD have been implemented and evaluated globally, there is currently no standardised framework that allows a comparison of the relative cost-effectiveness of these interventions. METHODS: We first reviewed the existing literature to document the main approaches that have been used to assess the relative effectiveness of interventions that promote ECD, including early parenting and at-home psychosocial stimulation interventions. We then present an economic evaluation framework that builds on these reviewed approaches and focuses on the immediate impact of interventions on motor, cognitive, language and socioemotional skills. Last, we apply our framework to compute the relative cost-effectiveness of interventions for which recent effectiveness and costing data were published. For this last part, we relied on a recently published review to obtain effect sizes documented in a consistent manner across interventions. FINDINGS: Our framework enables direct value-for-money comparison of interventions across settings. Cost-effectiveness estimates, expressed in $ per units of improvement in ECD outcomes, vary greatly across interventions. Given that estimated costs vary by orders of magnitude across interventions while impacts are relatively similar, cost-effectiveness rankings are dominated by implementation costs and the interventions with higher value for money are generally those with a lower implementation cost (eg, psychosocial interventions involving limited staff). CONCLUSIONS: With increasing attention and investment into ECD programmes, consistent assessments of the relative cost-effectiveness of available interventions are urgently needed. This paper presents a unified analytical framework to address this need and highlights the rather remarkable range in both costs and cost-effectiveness across currently available intervention strategies.

Anemia Etiology in Ethiopia: Assessment of Nutritional, Infectious Disease, and Other Risk Factors in a Population-Based Cross-Sectional Survey of Women, Men, and Children.

BACKGROUND: While the causes of anemia at an individual level (such as certain nutritional deficiencies, infections, and genetic disorders) are well defined, there is limited understanding of the relative burden of anemia attributable to each cause within populations. OBJECTIVES: We sought to estimate the proportion of anemia cases attributable to nutrition, infectious diseases, and other risk factors among women, men, and children in 6 regions of Ethiopia. METHODS: A population-based cross-sectional study was conducted. Data were obtained from 2520 women of reproductive age (15-49 y), 1044 adult men (15-49 y), and 1528 children (6-59 mo). Participants provided venous blood samples for assessment of their hemoglobin concentration; ferritin, folate, vitamin B12, and C-reactive protein levels; and the presence of malaria infection. Stool samples were collected to ascertain the helminth infection status. Sociodemographic questionnaires and a 24-h diet recall were administered. Population-weighted prevalences of anemia and risk factors were calculated. Multivariable-adjusted associations of risk factors with anemia and partial population attributable risk percentages were estimated using generalized linear models. RESULTS: The anemia prevalences were 17% (95% CI: 13%-21%) among women, 8% (95% CI: 6%-12%) among men, and 22% (95% CI: 19%-26%) among children. Low serum ferritin contributed to 11% (95% CI: -1% to 23%) of anemia cases among women, 9% (95% CI: 0%-17%) among men, and 21% (95% CI: 4%-34%) among children. The proportions of anemia attributable to low serum folate were estimated at 25% (95% CI: 5%-41%) among women and 29% (95% CI: 11%-43%) among men. Dietary iron intake was adequate for nearly all participants, while inadequacy was common for folate and vitamin B12. Inflammation and malaria were responsible for less than 1 in 10 anemia cases. CONCLUSIONS: Folate deficiency, iron deficiency, and inflammation appear to be important contributors to anemia in Ethiopia. Folic acid food fortification, targeted iron interventions, and strategies to reduce infections may be considered as potential public health interventions to reduce anemia in Ethiopia.

Associations between women's empowerment and child development, growth, and nurturing care practices in sub-Saharan Africa: A cross-sectional analysis of demographic and health survey data.

BACKGROUND: Approximately 40% of children 3 to 4 years of age in low- and middle-income countries have suboptimal development and growth. Women's empowerment may help provide inputs of nurturing care for early development and growth by building caregiver capacity and family support. We examined the associations between women's empowerment and child development, growth, early learning, and nutrition in sub-Saharan Africa (SSA). METHODS AND FINDINGS: We pooled data on married women (15 to 49 years) and their children (36 to 59 months) from Demographic and Health Surveys that collected data on child development (2011 to 2018) in 9 SSA countries (N = 21,434): Benin, Burundi, Cameroon, Chad, Congo, Rwanda, Senegal, Togo, and Uganda. We constructed a women's empowerment score using factor analysis and assigned women to country-specific quintile categories. The child outcomes included cognitive, socioemotional, literacy-numeracy, and physical development (Early Childhood Development Index), linear growth (height-for-age Z-score (HAZ) and stunting (HAZ <-2). Early learning outcomes were number of parental stimulation activities (range 0 to 6) and learning resources (range 0 to 4). The nutrition outcome was child dietary diversity score (DDS, range 0 to 7). We assessed the relationship between women's empowerment and child development, growth, early learning, and nutrition using multivariate generalized linear models. On average, households in our sample were large (8.5 ± 5.7 members) and primarily living in rural areas (71%). Women were 31 ± 6.6 years on average, 54% had no education, and 31% had completed primary education. Children were 47 ± 7 months old and 49% were female. About 23% of children had suboptimal cognitive development, 31% had suboptimal socioemotional development, and 90% had suboptimal literacy-numeracy development. Only 9% of children had suboptimal physical development, but 35% were stunted. Approximately 14% of mothers and 3% of fathers provided ≥4 stimulation activities. Relative to the lowest quintile category, children of women in the highest empowerment quintile category were less likely to have suboptimal cognitive development (relative risk (RR) 0.89; 95% confidence interval (CI) 0.80, 0.99), had higher HAZ (mean difference (MD) 0.09; 95% CI 0.02, 0.16), lower risk of stunting (RR 0.93; 95% CI 0.87, 1.00), higher DDS (MD 0.17; 95% CI 0.06, 0.29), had 0.07 (95% CI 0.01, 0.13) additional learning resources, and received 0.16 (95% CI 0.06, 0.25) additional stimulation activities from their mothers and 0.23 (95% CI 0.17 to 0.29) additional activities from their fathers. We found no evidence that women's empowerment was associated with socioemotional, literacy-numeracy, or physical development. Study limitations include the possibility of reverse causality and suboptimal assessments of the outcomes and exposure. CONCLUSIONS: Women's empowerment was positively associated with early child cognitive development, child growth, early learning, and nutrition outcomes in SSA. Efforts to improve child development and growth should consider women's empowerment as a potential strategy.

Evaluating implementation of LEAPS, a youth-led early childhood care and education intervention in rural Pakistan: protocol for a stepped wedge cluster-randomized trial.

BACKGROUND: The Sustainable Development Goals (SDGs) highlight the importance of investments in early childhood care and education (ECCE) and youth development. Given Pakistan's large young population, and gender and urban-rural inequalities in access to education, training, and employment, such investments offer opportunities. LEAPS is a youth-led ECCE program that trains female youth, 18-24 years, as Community Youth Leaders (CYLs) to deliver high-quality ECCE for children, 3.5-5.5 years, in rural Sindh, Pakistan. METHODS: We use a stepped wedge cluster-randomized trial to evaluate implementation of LEAPS. Ninety-nine clusters will be randomized to receive the intervention in one of three 7-month steps (33 clusters/step). The primary outcome is children's school readiness (indexed by the total score on the International Development and Early Learning Assessment (IDELA)). Secondary child outcomes are children's IDELA domain scores and executive functions. Data are collected in cross-sectional surveys of 1089 children (11 children/cluster from 99 clusters) aged 4.5-5.5 years at four timepoints (baseline and at the end of each step). Additionally, we will enroll three non-randomized youth participant open cohorts, one per step (33 CYLs: 66 comparison youth per cohort; 99:198 in total). Youth cohorts will be assessed at enrollment and every 7 months thereafter to measure secondary outcomes of youth personal and professional development, depressive symptoms, and executive functions. A non-randomized school cohort of 330 LEAPS students (10 students/cluster from 33 clusters) will also be enrolled and assessed during Step 1 after intervention rollout and at endline. The quality of the learning environment will be assessed in each LEAPS ECCE center and in a comparison center at two timepoints midway following rollout and at endline. A concurrent mixed-methods implementation evaluation will assess program fidelity and quality, and the extent to which a technical support strategy is successful in strengthening systems for program expansion. A cost evaluation will assess cost per beneficiary. Data collection for implementation and cost evaluations will occur in Step 3. DISCUSSION: Youth-led models for ECCE offer a promising approach to support young children and youth. This study will contribute to the evidence as a means to promote sustainable human development across multiple SDG targets. TRIAL REGISTRATION: ClinicalTrials.gov NCT03764436 . Registered on December 5, 2018.

Coronavirus disease 2019, food security and maternal mental health in Ceará, Brazil: a repeated cross-sectional survey.

OBJECTIVE: To quantify the change in the risk of food insecurity and maternal mental disorder (MMD) before and during the coronavirus disease 2019 (COVID-19) pandemic. DESIGN: Repeated cross-sectional survey. Between 17 July and 10 September 2020, mother-child pairs who were enrolled in a population-based survey in 2017 were re-contacted by telephone for consent and to complete a telephonic COVID-19 survey. We used the Brazilian Food Insecurity Scale to assess food security and the Self Reporting Questionnaire-20 to assess MMD. McNemar's test for paired data that also accounted for clustering was used. Logistic regression was used to assess the relationship of unemployment and receipt of government assistance with food insecurity and MMD in 2020. SETTING: Ceará, Brazil. PARTICIPANTS: Five hundred and seventy-seven mother-child pairs completed the 2017 and 2020 surveys. At the time of the 2020 interview, the child cohort was 36-108 months of age. RESULTS: The proportion of mothers reporting food insecurity was 15·5 % higher (95 % CI 5·9, 25·1, P value < 0·001) during the pandemic in July-August 2020 as compared with November 2017, while the prevalence of MMD was 40·2 % higher during the pandemic (95 % CI 32·6, 47·8, P value < 0·001). Loss of formal employment was associated with increased risk of food insecurity, but not with the risk of MMD. CONCLUSIONS: The risk of food insecurity and MMD in Ceará increased during the COVID-19 pandemic. These findings highlight the need for policies and interventions to reduce the impact of the COVID-19 pandemic on maternal and child health, nutrition and well-being in Brazil.

The age of opportunity: prevalence of key risk factors among adolescents 10-19 years of age in nine communities in sub-Saharan Africa.

OBJECTIVE: To measure health-related behaviours and risk factors among sub-Saharan African adolescents. METHODS: Cross-sectional study in nine communities in Burkina Faso, Ethiopia, Eswatini, Ghana, Nigeria, Tanzania and Uganda between 2015 and 2017. Community-representative samples of males and females 10-19 years of age were selected. All communities used a uniform questionnaire that was adapted from the WHO Global School-based Student Health Survey. Weighted prevalence estimates and 95% confidence intervals were calculated for each indicator and stratified by age and sex using SAS version 9.4. All prevalence estimates were pooled across communities through random-effects meta-analyses in Stata version 14. RESULTS: A total of 8075 adolescents participated in the study. We observed a high prevalence of inadequate fruit consumption (57-63%) and low physical activity (82-90%); a moderate prevalence of inadequate vegetable consumption (21-31%), unprotected last sex (38-45%), age at first sex <15 years (21-28%) and bullying and physical fighting (12-35%); and a low prevalence of mental health risk factors (1-11%) and alcohol and substance use risk factors (0-6%). We observed a moderate to high prevalence of daily soft drink consumption (21-31%) for all adolescents. Among sexually active adolescents 15-19 years, 37% of females reported ever being pregnant and 8% of males reported to have ever made someone pregnant. Bullying (23%) and physical fighting (35%) were more common among younger male adolescents . The prevalence of low mood was generally higher among older (15-19 years) than younger adolescents (10-14 years). The proportion of adolescents reporting alcohol, drug or cigarette use was very small, with the exception of khat use in Ethiopia. CONCLUSION: Overall, diet and physical activity, violence, sexual and reproductive health, and depression are important risk factors for these sub-Saharan African communities. These findings suggest that more evidence is needed including novel efforts for the collection of sensitive information, as well as a need to move towards community-tailored interventions to reach adolescent populations with varying needs.

OBJECTIF: Mesurer les comportements liés à la santé et les facteurs de risque chez les adolescents africains subsahariens. MÉTHODES: Etude transversale dans neuf communautés au Burkina Faso, en Ethiopie, à Eswatini, au Ghana, au Nigéria, en Tanzanie et en Ouganda entre 2015 et 2017. Des échantillons représentatifs de la communauté composés d'hommes et de femmes âgés de 10 à 19 ans ont été sélectionnés. Toutes les communautés ont utilisé un questionnaire uniforme adapté de l'Enquête Mondiale sur la Santé des Elèves de l'OMS. Les estimations de prévalence pondérée et les intervalles de confiance à 95% ont été calculés pour chaque indicateur et stratifiées par âge et sexe à l'aide de la version 9.4 de SAS. Toutes les estimations de prévalence ont été poolées dans les communautés via des méta-analyses à effets aléatoires dans Stata, version 14. RÉSULTATS: 8.075 adolescents ont participé à l'étude. Nous avons observé une prévalence élevée de consommation insuffisante de fruits (57-63%) et de faible activité physique (82-90%); une prévalence modérée de consommation insuffisante de légumes (21-31%), du dernier rapport sexuel non protégé (38-45%), du premier rapport sexuel à moins de 15 ans (21-28%) et de l'intimidation et des combats physiques (12-35%), une faible prévalence de facteurs de risque pour la santé mentale (1-11%) et de facteurs de risque pour la consommation d'alcool et de substances (0-6%). Nous avons observé une prévalence modérée à élevée de consommation quotidienne de boissons gazeuses (21-31%) chez tous les adolescents. Parmi les adolescents sexuellement actifs âgées de 15 à 19 ans, 37,0% des femmes ont déclaré avoir déjà été enceintes et 8,0% des hommes ont rapporté avoir déjà enceinté une femme. L'intimidation (23%) et les combats physiques étaient plus fréquents chez les adolescents plus jeunes (35%). La prévalence de la mauvaise humeur était généralement plus élevée chez les adolescents d'âge plus élevé (de 15 à 19 ans) que chez les plus jeunes (de 10 à 14 ans). La proportion d'adolescents déclarant avoir consommé de l'alcool, des drogues ou des cigarettes était très faible, à l'exception de la consommation de khat en Ethiopie. CONCLUSION: Dans l'ensemble, le régime alimentaire et l'activité physique, la violence, la santé sexuelle et reproductive et la dépression sont des facteurs de risque importants pour ces communautés d'Afrique subsaharienne. Ces résultats suggèrent que davantage de données sont nécessaires, notamment de nouveaux efforts pour la collecte d'informations sensibles, ainsi que la nécessité de passer à des interventions adaptées aux communautés pour atteindre les populations adolescentes avec des besoins variés.

Effect of a community health worker delivered health, nutrition and responsive stimulation package and conditional cash transfers on child development and growth in rural Tanzania: protocol for a cluster-randomized trial.

BACKGROUND: Child health, nutrition, and responsive stimulation interventions have been developed to improve child survival, growth and development outcomes in low- and middle-income countries. Nevertheless, research on integrated implementation approaches to deliver and promote uptake of these interventions is needed, particularly in sub-Saharan Africa. METHODS/DESIGN: We will conduct a cluster-randomized controlled trial of a supply-side community health worker (CHW) delivered child health, nutrition, and responsive stimulation intervention alone and in combination with a demand-side conditional cash transfer (CCT) intervention to promote antenatal care and child growth monitoring attendance in rural Morogoro region, Tanzania. Twelve village clusters will be randomly assigned to one of the three trial arms: (1) CHW, (2) CHW + CCT, or (3) Control. Mothers (or another primary caregiver) residing in study villages are eligible for trial enrollment if they are currently pregnant or have a child < 1 year of age at the time of enrollment. For the duration of the trial, CHWs will visit households once every 4-6 weeks to deliver the intervention package and CCTs will be provided for documented antenatal care and routine child health and growth monitoring clinic visits. Participants will be followed-up at 9 months (midline) and 18 months (endline) post-randomization. The primary outcomes of the trial are child development assessed by the Bayley Scales of Infant and Toddler Development (BSID-III) and child height-for-age z-score. Secondary outcomes include a range of maternal, child and household outcomes. DISCUSSION: This trial will provide evidence on the effect of CHWs and conditional cash transfers on child growth and development. The results of the trial may be generalizable to similar settings in sub-Saharan Africa. TRIAL REGISTRATION: ISRCTN10323949 , Retrospectively registered on October 3, 2017.

Lifetime economic impact of the burden of childhood stunting attributable to maternal psychosocial risk factors in 137 low/middle-income countries.

INTRODUCTION: The first 1000 days of life is a period of great potential and vulnerability. In particular, physical growth of children can be affected by the lack of access to basic needs as well as psychosocial factors, such as maternal depression. The objectives of the present study are to: (1) quantify the burden of childhood stunting in low/middle-income countries attributable to psychosocial risk factors; and (2) estimate the related lifetime economic costs. METHODS: A comparative risk assessment analysis was performed with data from 137 low/middle-income countries throughout Asia, Latin America and the Caribbean, North Africa and the Middle East, and sub-Saharan Africa. The proportion of stunting prevalence, defined as <-2 SDs from the median height for age according to the WHO Child Growth Standards, and the number of cases attributable to low maternal education, intimate partner violence (IPV), maternal depression and orphanhood were calculated. The joint effect of psychosocial risk factors on stunting was estimated. The economic impact, as reflected in the total future income losses per birth cohort, was examined. RESULTS: Approximately 7.2 million cases of stunting in low/middle-income countries were attributable to psychosocial factors. The leading risk factor was maternal depression with 3.2 million cases attributable. Maternal depression also demonstrated the greatest economic cost at $14.5 billion, followed by low maternal education ($10.0 billion) and IPV ($8.5 billion). The joint cost of these risk factors was $29.3 billion per birth cohort. CONCLUSION: The cost of neglecting these psychosocial risk factors is significant. Improving access to formal secondary school education for girls may offset the risk of maternal depression, IPV and orphanhood. Focusing on maternal depression may play a key role in reducing the burden of stunting. Overall, addressing psychosocial factors among perinatal women can have a significant impact on child growth and well-being in the developing world.

Sociodemographic Determinants of Preterm Birth and Small for Gestational Age in Rural West Bengal, India.

Preterm birth and small for gestational age (SGA) are major contributors to neonatal mortality in India. However, social determinates of preterm births and SGA are poorly characterized. We use population-based data from a health and demographic surveillance system (HDSS) in rural West Bengal, India, to examine risk factors for preterm birth and SGA. HDSS pregnancy cohort data for 2430 pregnant women were used in this analysis. Of 2430 pregnancies, 16% were preterm births and 38.2% were SGA. Results from logistic regression reveal that higher maternal education (≥11 years) was associated with reduced risk of preterm births and SGA. Greater wealth quintile was also associated with decreased risk of preterm births and SGA (p-value for trend: <0.05). In light of the findings, ensuring effective coverage of preterm and SGA interventions among women of low socioeconomic status will be essential to mitigate the large burden of preterm births and SGA.

Determinants of delayed or incomplete diphtheria-tetanus-pertussis vaccination in parallel urban and rural birth cohorts of 30,956 infants in Tanzania.

BACKGROUND: Delayed vaccination increases the time infants are at risk for acquiring vaccine-preventable diseases. Factors associated with incomplete vaccination are relatively well characterized in resource-limited settings; however, few studies have assessed immunization timeliness. METHODS: We conducted a prospective cohort study examining Diphtheria-Tetanus-Pertussis (DTP) vaccination timing among newborns enrolled in a Neonatal Vitamin A supplementation trial (NEOVITA) conducted in urban Dar es Salaam (n = 11,189) and rural Morogoro Region (n = 19,767), Tanzania. We used log-binomial models to assess the relationship of demographic, socioeconomic, healthcare access, and birth characteristics with late or incomplete DTP1 and DTP3 immunization. RESULTS: The proportion of infants with either delayed or incomplete vaccination was similar in Dar es Salaam (DTP1 11.5% and DTP3 16.0%) and Morogoro (DTP1 9.2% and DTP3 17.3%); however, the determinants of delayed or incomplete vaccination as well as their magnitude of association differed by setting. Both maternal and paternal education were more strongly associated with vaccination status in rural Morogoro region as compared to Dar es Salaam (p-values for heterogeneity < 0.05). Infants in Morogoro who had fathers and mothers with no education had 36% (95% CI: 22-52%) and 22% (95% CI: 10-34%) increased risk of delayed or incomplete DTP3 vaccination as compared to those with primary school education, respectively. In Dar es Salaam, mothers who attended their first antenatal care (ANC) visit in the 3rd trimester had 1.55 (95% CI: 1.36-1.78) times the risk of delayed or not received vaccination as compared to those with a 2nd trimester booking, while there was no relationship in Morogoro. In rural Morogoro, infants born at home had 17% (95% CI: 8-27%) increased risk for delayed or no receipt of DTP3 vaccination. In both settings, younger maternal age and poorer households were at increased risk for delayed or incomplete vaccination. CONCLUSION: We found some risk factors for delayed and incomplete vaccination were shared between urban and rural Tanzania; however, we found several context-specific risk factors as well as determinants that differed in their magnitude of risk between contexts. Immunization programs should be tailored to address context-specific barriers and enablers to improve timely and complete vaccination.

Nutritional, Socioeconomic, and Delivery Characteristics Are Associated with Neurodevelopment in Tanzanian Children.

OBJECTIVES: To evaluate the hypothesis that various maternal, socioeconomic, delivery, and infant nutritional characteristics are associated with early childhood development in young Tanzanian children. STUDY DESIGN: We performed a prospective cohort study among 206 HIV-exposed, uninfected and 247 HIV-unexposed Tanzanian infants who had been enrolled in 2 separate micronutrient trials (NCT00197730 and NCT00421668). Trained nurses administered culturally modified Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III), to evaluate cognitive, motor, and language development at 15 months of age. This analysis explored predictors of BSID-III z-scores using multivariable linear regression. RESULTS: Among maternal determinants, we found that low maternal height predicted all BSID-III domains in HIV-unexposed children; low maternal education predicted lower cognitive (standardized mean difference, -0.41; 95% CI, -0.74 to -0.08) and lower gross motor scores (standardized mean difference, -0.32; 95% CI, -0.61 to -0.04) in HIV-exposed children. Among delivery characteristics, facility delivery predicted higher cognitive scores (standardized mean difference, 1.36; 95% CI, 0.26-2.46); and oxytocin administration predicted lower fine motor scores (standardized mean difference, -0.48; 95% CI, -0.87 to -0.09) in HIV-exposed children. Higher length-for-age z-scores at 6 weeks of age predicted better cognitive (standardized mean difference, 0.15; 95% CI, 0.01-0.29) and expressive language scores (standardized mean difference, 0.16; 95% CI, 0.02-0.29) at 15 months in HIV-exposed infants. CONCLUSIONS: This hypothesis-generating study found significant associations between nutritional status and health of the mother and child, and maternal educational attainment, with direct measures of early childhood development at 15 months of age. In addition, several aspects of delivery (facility birth and oxytocin administration) were associated with early childhood development. Future intervention trials should focus on modifiable maternal, infant, and obstetric factors to strengthen the evidence base concerning early childhood development. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00197730 and NCT00421668.

Risk Factors for Childhood Stunting in 137 Developing Countries: A Comparative Risk Assessment Analysis at Global, Regional, and Country Levels.

BACKGROUND: Stunting affects one-third of children under 5 y old in developing countries, and 14% of childhood deaths are attributable to it. A large number of risk factors for stunting have been identified in epidemiological studies. However, the relative contribution of these risk factors to stunting has not been examined across countries. We estimated the number of stunting cases among children aged 24-35 mo (i.e., at the end of the 1,000 days' period of vulnerability) that are attributable to 18 risk factors in 137 developing countries. METHODS AND FINDINGS: We classified risk factors into five clusters: maternal nutrition and infection, teenage motherhood and short birth intervals, fetal growth restriction (FGR) and preterm birth, child nutrition and infection, and environmental factors. We combined published estimates and individual-level data from population-based surveys to derive risk factor prevalence in each country in 2010 and identified the most recent meta-analysis or conducted de novo reviews to derive effect sizes. We estimated the prevalence of stunting and the number of stunting cases that were attributable to each risk factor and cluster of risk factors by country and region. The leading risk worldwide was FGR, defined as being term and small for gestational age, and 10.8 million cases (95% CI 9.1 million-12.6 million) of stunting (out of 44.1 million) were attributable to it, followed by unimproved sanitation, with 7.2 million (95% CI 6.3 million-8.2 million), and diarrhea with 5.8 million (95% CI 2.4 million-9.2 million). FGR and preterm birth was the leading risk factor cluster in all regions. Environmental risks had the second largest estimated impact on stunting globally and in the South Asia, sub-Saharan Africa, and East Asia and Pacific regions, whereas child nutrition and infection was the second leading cluster of risk factors in other regions. Although extensive, our analysis is limited to risk factors for which effect sizes and country-level exposure data were available. The global nature of the study required approximations (e.g., using exposures estimated among women of reproductive age as a proxy for maternal exposures, or estimating the impact of risk factors on stunting through a mediator rather than directly on stunting). Finally, as is standard in global risk factor analyses, we used the effect size of risk factors on stunting from meta-analyses of epidemiological studies and assumed that proportional effects were fairly similar across countries. CONCLUSIONS: FGR and unimproved sanitation are the leading risk factors for stunting in developing countries. Reducing the burden of stunting requires a paradigm shift from interventions focusing solely on children and infants to those that reach mothers and families and improve their living environment and nutrition.

Schooling and wage income losses due to early-childhood growth faltering in developing countries: national, regional, and global estimates.

BACKGROUND: The growth of >300 million children <5 y old was mildly, moderately, or severely stunted worldwide in 2010. However, national estimates of the human capital and financial losses due to growth faltering in early childhood are not available. OBJECTIVE: We quantified the economic cost of growth faltering in developing countries. DESIGN: We combined the most recent country-level estimates of linear growth delays from the Nutrition Impact Model Study with estimates of returns to education in developing countries to estimate the impact of early-life growth faltering on educational attainment and future incomes. Primary outcomes were total years of educational attainment lost as well as the net present value of future wage earnings lost per child and birth cohort due to growth faltering in 137 developing countries. Bootstrapped standard errors were computed to account for uncertainty in modeling inputs. RESULTS: Our estimates suggest that early-life growth faltering in developing countries caused a total loss of 69.4 million y of educational attainment (95% CI: 41.7 million, 92.6 million y) per birth cohort. Educational attainment losses were largest in South Asia (27.6 million y; 95% CI: 20.0 million, 35.8 million y) as well as in Eastern (10.3 million y; 95% CI: 7.2 million, 12.9 million y) and Western sub-Saharan Africa (8.8 million y; 95% CI: 6.4 million, 11.5 million y). Globally, growth faltering in developing countries caused a total economic cost of $176.8 billion (95% CI: $100.9 billion, $262.6 billion)/birth cohort at nominal exchange rates, and $616.5 billion (95% CI: $365.3 billion, $898.9 billion) at purchasing power parity-adjusted exchange rates. At the regional level, economic costs were largest in South Asia ($46.6 billion; 95% CI: $33.3 billion, $61.1 billion), followed by Latin America ($44.7 billion; 95% CI: $19.2 billion, $74.6 billion) and sub-Saharan Africa ($34.2 billion; 95% CI: $24.4 billion, $45.3 billion). CONCLUSIONS: Our results indicate that the annual cost of early-childhood growth faltering is substantial. Further investment in scaling up effective interventions in this area is urgently needed and likely to yield long run benefits of $3 for every $1 invested.

Early Childhood Developmental Status in Low- and Middle-Income Countries: National, Regional, and Global Prevalence Estimates Using Predictive Modeling.

BACKGROUND: The development of cognitive and socioemotional skills early in life influences later health and well-being. Existing estimates of unmet developmental potential in low- and middle-income countries (LMICs) are based on either measures of physical growth or proxy measures such as poverty. In this paper we aim to directly estimate the number of children in LMICs who would be reported by their caregivers to show low cognitive and/or socioemotional development. METHODS AND FINDINGS: The present paper uses Early Childhood Development Index (ECDI) data collected between 2005 and 2015 from 99,222 3- and 4-y-old children living in 35 LMICs as part of the Multiple Indicator Cluster Survey (MICS) and Demographic and Health Surveys (DHS) programs. First, we estimate the prevalence of low cognitive and/or socioemotional ECDI scores within our MICS/DHS sample. Next, we test a series of ordinary least squares regression models predicting low ECDI scores across our MICS/DHS sample countries based on country-level data from the Human Development Index (HDI) and the Nutrition Impact Model Study. We use cross-validation to select the model with the best predictive validity. We then apply this model to all LMICs to generate country-level estimates of the prevalence of low ECDI scores globally, as well as confidence intervals around these estimates. In the pooled MICS and DHS sample, 14.6% of children had low ECDI scores in the cognitive domain, 26.2% had low socioemotional scores, and 36.8% performed poorly in either or both domains. Country-level prevalence of low cognitive and/or socioemotional scores on the ECDI was best represented by a model using the HDI as a predictor. Applying this model to all LMICs, we estimate that 80.8 million children ages 3 and 4 y (95% CI 48.1 million, 113.6 million) in LMICs experienced low cognitive and/or socioemotional development in 2010, with the largest number of affected children in sub-Saharan Africa (29.4.1 million; 43.8% of children ages 3 and 4 y), followed by South Asia (27.7 million; 37.7%) and the East Asia and Pacific region (15.1 million; 25.9%). Positive associations were found between low development scores and stunting, poverty, male sex, rural residence, and lack of cognitive stimulation. Additional research using more detailed developmental assessments across a larger number of LMICs is needed to address the limitations of the present study. CONCLUSIONS: The number of children globally failing to reach their developmental potential remains large. Additional research is needed to identify the specific causes of poor developmental outcomes in diverse settings, as well as potential context-specific interventions that might promote children's early cognitive and socioemotional well-being.