A cluster-randomized trial of water, sanitation, handwashing and nutritional interventions on stress and epigenetic programming.

A regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates Foundation, ClinicalTrials.gov NCT01590095) to assess the effects of an integrated nutritional, water, sanitation, and handwashing intervention on child health. We previously reported on the primary outcomes of the trial, linear growth and caregiver-reported diarrhea. Here, we assessed additional prespecified outcomes: physiological stress response, oxidative stress, and DNA methylation (N = 759, ages 1-2 years). Eight neighboring pregnant women were grouped into a study cluster. Eight geographically adjacent clusters were block-randomized into the control or the combined nutrition, water, sanitation, and handwashing (N + WSH) intervention group (receiving nutritional counseling and lipid-based nutrient supplements, chlorinated drinking water, upgraded sanitation, and handwashing with soap). Participants and data collectors were not masked, but analyses were masked. There were 358 children (68 clusters) in the control group and 401 children (63 clusters) in the intervention group. We measured four F2-isoprostanes isomers (iPF(2α)-III; 2,3-dinor-iPF(2α)-III; iPF(2α)-VI; 8,12-iso-iPF(2α)-VI), salivary alpha-amylase and cortisol, and methylation of the glucocorticoid receptor (NR3C1) exon 1F promoter including the NGFI-A binding site. Compared with control, the N + WSH group had lower concentrations of F2-isoprostanes isomers (differences ranging from -0.16 to -0.19 log ng/mg of creatinine, P < 0.01), elevated post-stressor cortisol (0.24 log µg/dl; P < 0.01), higher cortisol residualized gain scores (0.06 µg/dl; P = 0.023), and decreased methylation of the NGFI-A binding site (-0.04; P = 0.037). The N + WSH intervention enhanced adaptive responses of the physiological stress system in early childhood.

The creation of the Global Scales for Early Development (GSED) for children aged 0-3 years: combining subject matter expert judgements with big data.

INTRODUCTION: With the ratification of the Sustainable Development Goals, there is an increased emphasis on early childhood development (ECD) and well-being. The WHO led Global Scales for Early Development (GSED) project aims to provide population and programmatic level measures of ECD for 0-3 years that are valid, reliable and have psychometrically stable performance across geographical, cultural and language contexts. This paper reports on the creation of two measures: (1) the GSED Short Form (GSED-SF)-a caregiver reported measure for population-evaluation-self-administered with no training required and (2) the GSED Long Form (GSED-LF)-a directly administered/observed measure for programmatic evaluation-administered by a trained professional. METHODS: We selected 807 psychometrically best-performing items using a Rasch measurement model from an ECD measurement databank which comprised 66 075 children assessed on 2211 items from 18 ECD measures in 32 countries. From 766 of these items, in-depth subject matter expert judgements were gathered to inform final item selection. Specifically collected were data on (1) conceptual matches between pairs of items originating from different measures, (2) developmental domain(s) measured by each item and (3) perceptions of feasibility of administration of each item in diverse contexts. Prototypes were finalised through a combination of psychometric performance evaluation and expert consensus to optimally identify items. RESULTS: We created the GSED-SF (139 items) and GSED-LF (157 items) for tablet-based and paper-based assessments, with an optimal set of items that fit the Rasch model, met subject matter expert criteria, avoided conceptual overlap, covered multiple domains of child development and were feasible to implement across diverse settings. CONCLUSIONS: State-of-the-art quantitative and qualitative procedures were used to select of theoretically relevant and globally feasible items representing child development for children aged 0-3 years. GSED-SF and GSED-LF will be piloted and validated in children across diverse cultural, demographic, social and language contexts for global use.

Protocol for validation of the Global Scales for Early Development (GSED) for children under 3 years of age in seven countries.

INTRODUCTION: Children's early development is affected by caregiving experiences, with lifelong health and well-being implications. Governments and civil societies need population-based measures to monitor children's early development and ensure that children receive the care needed to thrive. To this end, the WHO developed the Global Scales for Early Development (GSED) to measure children's early development up to 3 years of age. The GSED includes three measures for population and programmatic level measurement: (1) short form (SF) (caregiver report), (2) long form (LF) (direct administration) and (3) psychosocial form (PF) (caregiver report). The primary aim of this protocol is to validate the GSED SF and LF. Secondary aims are to create preliminary reference scores for the GSED SF and LF, validate an adaptive testing algorithm and assess the feasibility and preliminary validity of the GSED PF. METHODS AND ANALYSIS: We will conduct the validation in seven countries (Bangladesh, Brazil, Côte d'Ivoire, Pakistan, The Netherlands, People's Republic of China, United Republic of Tanzania), varying in geography, language, culture and income through a 1-year prospective design, combining cross-sectional and longitudinal methods with 1248 children per site, stratified by age and sex. The GSED generates an innovative common metric (Developmental Score: D-score) using the Rasch model and a Development for Age Z-score (DAZ). We will evaluate six psychometric properties of the GSED SF and LF: concurrent validity, predictive validity at 6 months, convergent and discriminant validity, and test-retest and inter-rater reliability. We will evaluate measurement invariance by comparing differential item functioning and differential test functioning across sites. ETHICS AND DISSEMINATION: This study has received ethical approval from the WHO (protocol GSED validation 004583 20.04.2020) and approval in each site. Study results will be disseminated through webinars and publications from WHO, international organisations, academic journals and conference proceedings. REGISTRATION DETAILS: Open Science Framework https://osf.io/ on 19 November 2021 (DOI 10.17605/OSF.IO/KX5T7; identifier: osf-registrations-kx5t7-v1).

Early child stimulation, linear growth and neurodevelopment in low birth weight infants.

BACKGROUND: Children with low birth weight (LBW) are at risk of linear growth faltering and developmental deficits. Evidence suggests that early child stimulation and care reflected as responsive caregiving and opportunities for learning can promote development. The current analysis aimed to measure the extent to which linear growth and early child stimulation modify each other's association with neurodevelopmental outcomes among LBW infants. METHODS: This is a secondary data analyses from a randomized controlled trial on the effect of community-initiated kangaroo mother care in LBW infants on their neurodevelopment at 12 months of corrected age. Bayley Scales of Infant and Toddler Development was used to assess cognitive, motor and language scores. Stimulation at home was assessed by the Pediatric Review of Children's Environmental Support and Stimulation (PROCESS) tool. PROCESS scores were categorized into three groups: < Mean-1SD (low stimulation); Mean ± 1 SD (moderate stimulation) and > mean + 1SD (high stimulation). RESULTS: A total of 516 infants were available for neurodevelopment assessments. Interactions were observed between length for age z-score (LAZ) and PROCESS score categories. In the low stimulation group, the adjusted regression coefficients for the association between LAZ and cognitive, motor and language scores were substantially higher than in the moderate and high stimulation group. Stimulation was positively associated with neurodevelopmental outcomes in both stunted and non-stunted infants; however, the association was twice as strong in stunted than in non-stunted. CONCLUSION: Moderate to high quality stimulation may alleviate the risk of sub-optimal development in LBW infants with linear growth deficits. CLINICAL TRIAL REGISTRATION: The primary trial whose data are analysed is registered at clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT02631343 ).

Telomere length is associated with growth in children in rural Bangladesh.

Background: Previously, we demonstrated that a water, sanitation, handwashing, and nutritional intervention improved linear growth and was unexpectedly associated with shortened childhood telomere length (TL) (Lin et al., 2017). Here, we assessed the association between TL and growth. Methods: We measured relative TL in whole blood from 713 children. We reported differences between the 10th percentile and 90th percentile of TL or change in TL distribution using generalized additive models, adjusted for potential confounders. Results: In cross-sectional analyses, long TL was associated with a higher length-for-age Z score at age 1 year (0.23 SD adjusted difference in length-for-age Z score [95% CI 0.05, 0.42; FDR-corrected p-value = 0.01]). TL was not associated with other outcomes. Conclusions: Consistent with the metabolic telomere attrition hypothesis, our previous trial findings support an adaptive role for telomere attrition, whereby active TL regulation is employed as a strategy to address 'emergency states' with increased energy requirements such as rapid growth during the first year of life. Although short periods of active telomere attrition may be essential to promote growth, this study suggests that a longer overall initial TL setting in the first 2 years of life could signal increased resilience against future telomere erosion events and healthy growth trajectories. Funding: Funded by the Bill and Melinda Gates Foundation. Clinical trial number: NCT01590095.

Validation of the Infant and Young Child Development (IYCD) Indicators in Three Countries: Brazil, Malawi and Pakistan.

BACKGROUND: The early childhood years provide an important window of opportunity to build strong foundations for future development. One impediment to global progress is a lack of population-based measurement tools to provide reliable estimates of developmental status. We aimed to field test and validate a newly created tool for this purpose. METHODS: We assessed attainment of 121 Infant and Young Child Development (IYCD) items in 269 children aged 0-3 from Pakistan, Malawi and Brazil alongside socioeconomic status (SES), maternal educational, Family Care Indicators and anthropometry. Children born premature, malnourished or with neurodevelopmental problems were excluded. We assessed inter-rater and test-retest reliability as well as understandability of items. Each item was analyzed using logistic regression taking SES, anthropometry, gender and FCI as covariates. Consensus choice of final items depended on developmental trajectory, age of attainment, invariance, reliability and acceptability between countries. RESULTS: The IYCD has 100 developmental items (40 gross/fine motor, 30 expressive/receptive language/cognitive, 20 socio-emotional and 10 behavior). Items were acceptable, performed well in cognitive testing, had good developmental trajectories and high reliability across countries. Development for Age (DAZ) scores showed very good known-groups validity. CONCLUSIONS: The IYCD is a simple-to-use caregiver report tool enabling population level assessment of child development for children aged 0-3 years which performs well across three countries on three continents to provide reliable estimates of young children's developmental status.

Community initiated kangaroo mother care and early child development in low birth weight infants in India-a randomized controlled trial.

BACKGROUND: In a randomized controlled trial (RCT) with 8402 stable low birthweight (LBW) infants, majority being late preterm or term small for gestational age, community-initiated KMC (ciKMC) showed a significant improvement in survival. However, the effect of ciKMC on neurodevelopment is unclear. This is important to elucidate as children born with low birth weight are at high risk of neurodevelopmental deficits. In the first 552 stable LBW infants enrolled in the above trial, we evaluated the effect of ciKMC on neurodevelopmental outcomes during infancy. METHOD: This RCT was conducted among 552 stable LBW infants, majorly late preterm or term small for gestational age infants without any problems at birth and weighing 1500-2250 g at birth. The intervention comprised of promotion of skin-to-skin contact and exclusive breastfeeding by trained intervention delivery team through home visits. The intervention group mother-infant-dyads were supported to practice ciKMC till day 28 after birth or until the baby wriggled-out. All infants in the intervention and control groups received Home Based Post Natal Care (HBPNC) visits by government health workers. Cognitive, language, motor and socio-emotional outcomes were assessed at infant-ages 6- and 12-months using Bayley Scale of Infant Development (BSID-III). Other outcomes measured were infant temperament, maternal depression, maternal sense of competence, mother-infant bonding and home-environment. We performed post-hoc equivalence testing using two one-sided tests of equivalence (TOST) to provide evidence that ciKMC does not do harm in terms of neurodevelopment. RESULTS: In the intervention arm, the median (IQR) time to initiate ciKMC was 48 (48 to 72) hours after birth. The mean (SD) duration of skin-to-skin-contact was 27.9 (3.9) days with a mean (SD) of 8.7 (3.5) hours per day. We did not find significant effect of ciKMC on any of the child developmental outcomes during infancy. The TOST analysis demonstrated that composite scores for cognitive, language and motor domains at 12 months among the study arms were statistically equivalent. CONCLUSION: Our study was unable to capture any effect of ciKMC on neurodevelopment during infancy in this sample of stable late preterm or term small for gestational age infants. Long term follow-up may provide meaningful insights. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov NCT02631343 dated February 17, 2016; Retrospectively registered.

Association between Malaria Infection and Early Childhood Development Mediated by Anemia in Rural Kenya.

Malaria is a leading cause of morbidity and mortality among children under five years of age, with most cases occurring in Sub-Saharan Africa. Children in this age group in Africa are at greatest risk worldwide for developmental deficits. There are research gaps in quantifying the risks of mild malaria cases, understanding the pathways linking malaria infection and poor child development, and evaluating the impact of malaria on the development of children under five years. We analyzed the association between malaria infection and gross motor, communication, and personal social development in 592 children age 24 months in rural, western Kenya as part of the WASH Benefits environmental enteric dysfunction sub-study. Eighteen percent of children had malaria, 20% were at risk for gross motor delay, 21% were at risk for communication delay, and 23% were at risk for personal social delay. Having a positive malaria test was associated with increased risk for gross motor, communication, and personal social delay while adjusting for child characteristics, household demographics, study cluster, and intervention treatment arm. Mediation analyses suggested that anemia was a significant mediator in the pathway between malaria infection and risk for gross motor, communication, and personal social development delays. The proportion of the total effect of malaria on the risk of developmental delay that is mediated by anemia across the subscales was small (ranging from 9% of the effect on gross motor development to 16% of the effect on communication development mediated by anemia). Overall, malaria may be associated with short-term developmental delays during a vulnerable period of early life. Therefore, preventative malaria measures and immediate treatment are imperative for children's optimal development, particularly in light of projections of continued high malaria transmission in Kenya and Africa.

Multilingual assessment of early child development: Analyses from repeated observations of children in Kenya.

In many low- and middle-income countries, young children learn a mother tongue or indigenous language at home before entering the formal education system where they will need to understand and speak a country's official language(s). Thus, assessments of children before school age, conducted in a nation's official language, may not fully reflect a child's development, underscoring the importance of test translation and adaptation. To examine differences in vocabulary development by language of assessment, we adapted and validated instruments to measure developmental outcomes, including expressive and receptive vocabulary. We assessed 505 2-to-6-year-old children in rural communities in Western Kenya with comparable vocabulary tests in three languages: Luo (the local language or mother tongue), Swahili, and English (official languages) at two time points, 5-6 weeks apart, between September 2015 and October 2016. Younger children responded to the expressive vocabulary measure exclusively in Luo (44%-59% of 2-to-4-year-olds) much more frequently than did older children (20%-21% of 5-to-6-year-olds). Baseline receptive vocabulary scores in Luo (ß = 0.26, SE = 0.05, p < 0.001) and Swahili (ß = 0.10, SE = 0.05, p = 0.032) were strongly associated with receptive vocabulary in English at follow-up, even after controlling for English vocabulary at baseline. Parental Luo literacy at baseline (ß = 0.11, SE = 0.05, p = 0.045) was associated with child English vocabulary at follow-up, while parental English literacy at baseline was not. Our findings suggest that multilingual testing is essential to understanding the developmental environment and cognitive growth of multilingual children.

Creation of the WHO Indicators of Infant and Young Child Development (IYCD): metadata synthesis across 10 countries.

BACKGROUND: Renewed global commitment to the improvement of early child development outcomes, as evidenced by the focus of the United Nations Sustainable Development Goal 4, highlights an increased need for reliable and valid measures to evaluate preventive and interventional efforts designed to affect change. Our objective was to create a new tool, applicable across multicultures, to measure development from 0 to 3 years through metadata synthesis. METHODS: Fourteen cross-sectional data sets were contributed on 21 083 children from 10 low/middle-income countries (LMIC), assessed using seven different tools (caregiver reported or directly assessed). Item groups, measuring similar developmental skills, were identified by item mapping across tools. Logistic regression curves displayed developmental trajectories for item groups across countries and age. Following expert consensus to identify well-performing items across developmental domains, a second mapping exercise was conducted to fill any gaps across the age range. The first version of the tool was constructed. Item response analysis validated our approach by putting all data sets onto a common scale. RESULTS: 789 individual items were identified across tools in the first mapping and 129 item groups selected for analysis. 70 item groups were then selected through consensus, based on statistical performance and perceived importance, with a further 50 items identified at second mapping. A tool comprising 120 items (23 fine motor, 23 gross motor, 20 receptive language, 24 expressive language, 30 socioemotional) was created. The linked data sets on a common scale showed a curvilinear trajectory of child development, highlighting the validity of our approach through excellent coverage by age and consistency of measurement across contributed tools, a novel finding in itself. CONCLUSIONS: We have created the first version of a prototype tool for measuring children in the early years, developed using novel easy to apply methodology; now it needs to be feasibility tested and piloted across several LMICs.

Effect of water quality, sanitation, hand washing, and nutritional interventions on child development in rural Bangladesh (WASH Benefits Bangladesh): a cluster-randomised controlled trial.

BACKGROUND: Poor nutrition and hygiene make children vulnerable to delays in growth and development. We aimed to assess the effects of water quality, sanitation, handwashing, and nutritional interventions individually or in combination on the cognitive, motor, and language development of children in rural Bangladesh. METHODS: In this cluster-randomised controlled trial, we enrolled pregnant women in their first or second trimester from rural villages of Gazipur, Kishoreganj, Mymensingh, and Tangail districts of central Bangladesh, with an average of eight women per cluster. Groups of eight geographically adjacent clusters were block-randomised, using a random number generator, into six intervention groups (all of which received weekly visits from a community health promoter for the first 6 months and every 2 weeks for the next 18 months) and a double-sized control group (no intervention or health promoter visit). The six intervention groups were: chlorinated drinking water; improved sanitation; handwashing with soap; combined water, sanitation, and handwashing; improved nutrition through counselling and provision of lipid-based nutrient supplements; and combined water, sanitation, handwashing, and nutrition. Here, we report on the prespecified secondary child development outcomes: gross motor milestone achievement assessed with the WHO module at age 1 year, and communication, gross motor, personal social, and combined scores measured by the Extended Ages and Stages Questionnaire (EASQ) at age 2 years. Masking of participants was not possible. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01590095. FINDINGS: Between May 31, 2012, and July 7, 2013, 5551 pregnant women residing in 720 clusters were enrolled. Index children of 928 (17%) enrolled women were lost to follow-up in year 1 and an additional 201 (3%) in year 2. 4757 children were assessed at 1 year and 4403 at 2 years. At year 1, compared with the control group, the combined water, sanitation, handwashing, and nutrition group had a higher rate of attaining the standing alone milestone (hazard ratio 1·19, 95% CI 1·01-1 ·40), and the nutrition group had a higher rate of attaining the walking alone milestone (1·32, 95% CI 1·07-1·62). The combined water, sanitation, handwashing, and nutrition group had a higher rate of attaining the walking alone milestone than those in the water, sanitation, and handwashing group (1·29, 1·01-1·65). At 2 years, we noted beneficial effects in the combined EASQ score in all intervention groups, with effect sizes smallest in the water treatment group (difference 0·15, 95% CI 0·04 to 0·26 vs control) and largest in the combined water, sanitation, handwashing, and nutrition treatment group (0·37, 0·27-0·46). INTERPRETATION: Improvements in water quality, handwashing, sanitation, or nutrition supported by intensive interpersonal communication, when delivered either individually or in combination, contributed to improvements in child development. A crucial next step is to establish whether similar effects can be achieved with reduced intensity of promoter contacts that could be supported in large-scale interventions. FUNDING: Bill & Melinda Gates Foundation.

Effects of water quality, sanitation, handwashing, and nutritional interventions on child development in rural Kenya (WASH Benefits Kenya): a cluster-randomised controlled trial.

BACKGROUND: Poor nutrition and infectious diseases can prevent children from reaching their developmental potential. We aimed to assess the effects of improvements in water, sanitation, handwashing, and nutrition on early child development in rural Kenya. METHODS: In this cluster-randomised controlled trial, we enrolled pregnant women in their second or third trimester from three counties (Kakamega, Bungoma, and Vihiga) in Kenya's western region, with an average of 12 households per cluster. Groups of nine geographically adjacent clusters were block-randomised, using a random number generator, into the six intervention groups (including monthly visits to promote target behaviours), a passive control group (no visits), or a double-sized active control group (monthly household visits to measure child mid-upper arm circumference). The six intervention groups were: chlorinated drinking water; improved sanitation; handwashing with soap; combined water, sanitation, and handwashing; improved nutrition through counselling and provision of lipid-based nutrient supplements; and combined water, sanitation, handwashing, and nutrition. Here we report on the prespecified secondary child development outcomes: gross motor milestone achievement assessed with the WHO module at year 1, and communication, gross motor, personal social, and combined scores measured by the Extended Ages and Stages Questionnaire (EASQ) at year 2. Masking of participants was not possible, but data assessors were masked. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01704105. FINDINGS: Between Nov 27, 2012, and May 21, 2014, 8246 women residing in 702 clusters were enrolled. No clusters were lost to follow-up, but 2212 households with 2279 children were lost to follow-up by year 2. 5791 (69%) children were measured at year 1 and 6107 (73%) at year 2. At year 1, compared with the active control group, the combined water, sanitation, handwashing, and nutrition group had greater rates of attaining the standing with assistance milestone (hazard ratio 1·23, 95% CI 1·09-1·40) and the walking with assistance milestone (1·32, 1·17-1·50), and the handwashing group had a greater rate of attaining the standing alone milestone (1·15, 1·01-1·31). There were no differences when comparing the other intervention groups with the active control group on any of the motor milestone measures at year 1. At year 2, there were no differences among groups for the communication, gross motor, personal social, or combined EASQ scores. INTERPRETATION: The handwashing and combined water, sanitation, handwashing, and nutrition interventions might have improved child motor development after 1 year, although after 2 years there were no other differences between groups. Future research should examine ways to make community health and nutrition programmes more effective at supporting child development. FUNDING: Bill & Melinda Gates Foundation.

Effects of water quality, sanitation, handwashing, and nutritional interventions on diarrhoea and child growth in rural Kenya: a cluster-randomised controlled trial.

BACKGROUND: Poor nutrition and exposure to faecal contamination are associated with diarrhoea and growth faltering, both of which have long-term consequences for child health. We aimed to assess whether water, sanitation, handwashing, and nutrition interventions reduced diarrhoea or growth faltering. METHODS: The WASH Benefits cluster-randomised trial enrolled pregnant women from villages in rural Kenya and evaluated outcomes at 1 year and 2 years of follow-up. Geographically-adjacent clusters were block-randomised to active control (household visits to measure mid-upper-arm circumference), passive control (data collection only), or compound-level interventions including household visits to promote target behaviours: drinking chlorinated water (water); safe sanitation consisting of disposing faeces in an improved latrine (sanitation); handwashing with soap (handwashing); combined water, sanitation, and handwashing; counselling on appropriate maternal, infant, and young child feeding plus small-quantity lipid-based nutrient supplements from 6-24 months (nutrition); and combined water, sanitation, handwashing, and nutrition. Primary outcomes were caregiver-reported diarrhoea in the past 7 days and length-for-age Z score at year 2 in index children born to the enrolled pregnant women. Masking was not possible for data collection, but analyses were masked. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01704105. FINDINGS: Between Nov 27, 2012, and May 21, 2014, 8246 women in 702 clusters were enrolled and randomly assigned an intervention or control group. 1919 women were assigned to the active control group; 938 to passive control; 904 to water; 892 to sanitation; 917 to handwashing; 912 to combined water, sanitation, and handwashing; 843 to nutrition; and 921 to combined water, sanitation, handwashing, and nutrition. Data on diarrhoea at year 1 or year 2 were available for 6494 children and data on length-for-age Z score in year 2 were available for 6583 children (86% of living children were measured at year 2). Adherence indicators for sanitation, handwashing, and nutrition were more than 70% at year 1, handwashing fell to less than 25% at year 2, and for water was less than 45% at year 1 and less than 25% at year 2; combined groups were comparable to single groups. None of the interventions reduced diarrhoea prevalence compared with the active control. Compared with active control (length-for-age Z score -1·54) children in nutrition and combined water, sanitation, handwashing, and nutrition were taller by year 2 (mean difference 0·13 [95% CI 0·01-0·25] in the nutrition group; 0·16 [0·05-0·27] in the combined water, sanitation, handwashing, and nutrition group). The individual water, sanitation, and handwashing groups, and combined water, sanitation, and handwashing group had no effect on linear growth. INTERPRETATION: Behaviour change messaging combined with technologically simple interventions such as water treatment, household sanitation upgrades from unimproved to improved latrines, and handwashing stations did not reduce childhood diarrhoea or improve growth, even when adherence was at least as high as has been achieved by other programmes. Counselling and supplementation in the nutrition group and combined water, sanitation, handwashing, and nutrition interventions led to small growth benefits, but there was no advantage to integrating water, sanitation, and handwashing with nutrition. The interventions might have been more efficacious with higher adherence or in an environment with lower baseline sanitation coverage, especially in this context of high diarrhoea prevalence. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development.

Improving child nutrition and development through community-based childcare centres in Malawi - The NEEP-IE study: study protocol for a randomised controlled trial.

BACKGROUND: The Nutrition Embedded Evaluation Programme Impact Evaluation (NEEP-IE) study is a cluster randomised controlled trial designed to evaluate the impact of a childcare centre-based integrated nutritional and agricultural intervention on the diets, nutrition and development of young children in Malawi. The intervention includes activities to improve nutritious food production and training/behaviour-change communication to improve food intake, care and hygiene practices. This paper presents the rationale and study design for this randomised control trial. METHODS: Sixty community-based childcare centres (CBCCs) in rural communities around Zomba district, Malawi, were randomised to either (1) a control group where children were attending CBCCs supported by Save the Children's Early Childhood Health and Development (ECD) programme, or (2) an intervention group where nutritional and agricultural support activities were provided alongside the routine provision of the Save the Children's ECD programme. Primary outcomes at child level include dietary intake (measured through 24-h recall), whilst secondary outcomes include child development (Malawi Development Assessment Tool (MDAT)) and nutritional status (anthropometric measurements). At household level, primary outcomes include smallholder farmer production output and crop-mix (recall of last production season). Intermediate outcomes along theorised agricultural and nutritional pathways were measured. During this trial, we will follow a mixed-methods approach and undertake child-, household-, CBCC- and market-level surveys and assessments as well as in-depth interviews and focus group discussions with project stakeholders. DISCUSSION: Assessing the simultaneous impact of preschool meals on diets, nutrition, child development and agriculture is a complex undertaking. This study is the first to explicitly examine, from a food systems perspective, the impact of a preschool meals programme on dietary choices, alongside outcomes in the nutritional, child development and agricultural domains. The findings of this evaluation will provide evidence to support policymakers in the scale-up of national programmes. TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN96497560 . Registered on 21 September 2016.

Cluster-randomised controlled trials of individual and combined water, sanitation, hygiene and nutritional interventions in rural Bangladesh and Kenya: the WASH Benefits study design and rationale.

INTRODUCTION: Enteric infections are common during the first years of life in low-income countries and contribute to growth faltering with long-term impairment of health and development. Water quality, sanitation, handwashing and nutritional interventions can independently reduce enteric infections and growth faltering. There is little evidence that directly compares the effects of these individual and combined interventions on diarrhoea and growth when delivered to infants and young children. The objective of the WASH Benefits study is to help fill this knowledge gap. METHODS AND ANALYSIS: WASH Benefits includes two cluster-randomised trials to assess improvements in water quality, sanitation, handwashing and child nutrition-alone and in combination-to rural households with pregnant women in Kenya and Bangladesh. Geographically matched clusters (groups of household compounds in Bangladesh and villages in Kenya) will be randomised to one of six intervention arms or control. Intervention arms include water quality, sanitation, handwashing, nutrition, combined water+sanitation+handwashing (WSH) and WSH+nutrition. The studies will enrol newborn children (N=5760 in Bangladesh and N=8000 in Kenya) and measure outcomes at 12 and 24 months after intervention delivery. Primary outcomes include child length-for-age Z-scores and caregiver-reported diarrhoea. Secondary outcomes include stunting prevalence, markers of environmental enteropathy and child development scores (verbal, motor and personal/social). We will estimate unadjusted and adjusted intention-to-treat effects using semiparametric estimators and permutation tests. ETHICS AND DISSEMINATION: Study protocols have been reviewed and approved by human subjects review boards at the University of California, Berkeley, Stanford University, the International Centre for Diarrheal Disease Research, Bangladesh, the Kenya Medical Research Institute, and Innovations for Poverty Action. Independent data safety monitoring boards in each country oversee the trials. This study is funded by a grant from the Bill & Melinda Gates Foundation to the University of California, Berkeley. REGISTRATION: Trial registration identifiers (http://www.clinicaltrials.gov): NCT01590095 (Bangladesh), NCT01704105 (Kenya).

Developmental effects of micronutrient supplementation and malaria in Zanzibari children.

BACKGROUND: Children's development is affected by the interplay of internal and external factors and changes in one factor can precipitate changes in multiple developmental domains. AIMS: The aim of this study was to test a theoretical model of children's development using structural equation modeling. STUDY DESIGN: This was designed as a substudy of a randomized, placebo-controlled, 2 × 2 factorial trial of the effects of daily supplementation with iron (12.5 mg) + folic acid (50 µg) (FeFA) with or without zinc (10 mg) (Zn) on child mortality. SUBJECTS: Zanzibari children aged 5-9 mo (n = 106) and 10-14 mo (n = 141) at baseline were included in this sub study. OUTCOME MEASURES: Longitudinal data on children's hemoglobin, growth, malaria infection, motor development, motor activity, and language development and caregiver behavior were used to test the fit of the theoretical model for two age groups and to examine the direct and indirect relationships among the variables in the model. RESULTS: The theoretical models were a good fit to the data for both age groups and revealed that FeFA with or without Zn had positive effects on motor development. FeFA alone had negative effects on language development in both age groups and Zn alone had negative effects on language development in children aged 10-14 mo. The incidence of malaria had negative effects on the majority of health and development outcomes in children aged 5-9 mo, and on motor development and hemoglobin in children aged 10-14 mo. CONCLUSIONS: These findings illustrate how nutrition and health factors can affect different domains of development and how these changes can precipitate changes in other domains. More work is needed to better understand the multiple impacts of internal and external factors on children's development and how changes in developmental domains interact with each other over time to determine children's overall developmental trajectory. The randomized, placebo-controlled study was registered as an International Standard Randomized Controlled Trial, number ISRCTN59549825.

Socioeconomic gradients in child development in very young children: evidence from India, Indonesia, Peru, and Senegal.

Gradients across socio-economic position exist for many measures of children's health and development in higher-income countries. These associations may not be consistent, however, among the millions of children living in lower- and middle-income countries. Our objective was to examine child development and growth in young children across socio-economic position in four developing countries. We used cross-sectional surveys, child development assessments, measures of length (LAZ), and home stimulation (Family Care Index) of children in India, Indonesia, Peru, and Senegal. The Extended Ages and Stages Questionnaire (EASQ) was administered to parents of all children ages 3-23 mo in the household (n =8,727), and length measurements were taken for all children 0-23 mo (n = 11,102). Household wealth and maternal education contributed significantly and independently to the variance in EASQ and LAZ scores in all countries, while controlling for child's age and sex, mother's age and marital status, and household size. Being in the fifth wealth quintile in comparison with the first quintile was associated with significantly higher EASQ scores (0.27 to 0.48 of a standardized score) and higher LAZ scores (0.37 to 0.65 of a standardized score) in each country, while controlling for maternal education and covariates. Wealth and education gradients increased over the first two years in most countries for both EASQ and LAZ scores, with larger gradients seen in 16-23-mo-olds than in 0-7 mo-olds. Mediation analyses revealed that parental home stimulation activities and LAZ were significant mediating variables and explained up to 50% of the wealth effects on the EASQ.

Indicators of family care for development for use in multicountry surveys.

Indicators of family care for development are essential for ascertaining whether families are providing their children with an environment that leads to positive developmental outcomes. This project aimed to develop indicators from a set of items, measuring family care practices and resources important for caregiving, for use in epidemiologic surveys in developing countries. A mixed method (quantitative and qualitative) design was used for item selection and evaluation. Qualitative and quantitative analyses were conducted to examine the validity of candidate items in several country samples. Qualitative methods included the use of global expert panels to identify and evaluate the performance of each candidate item as well as in-country focus groups to test the content validity of the items. The quantitative methods included analyses of item-response distributions, using bivariate techniques. The selected items measured two family care practices (support for learning/stimulating environment and limit-setting techniques) and caregiving resources (adequacy of the alternate caregiver when the mother worked). Six play-activity items, indicative of support for learning/stimulating environment, were included in the core module of UNICEF's Multiple Cluster Indictor Survey 3. The other items were included in optional modules. This project provided, for the first time, a globally-relevant set of items for assessing family care practices and resources in epidemiological surveys. These items have multiple uses, including national monitoring and cross-country comparisons of the status of family care for development used globally. The obtained information will reinforce attention to efforts to improve the support for development of children.

A multi-micronutrient beverage enhances the vitamin A and zinc status of Nigerian primary schoolchildren.

Schoolchildren in Nigeria are rarely targeted by micronutrient interventions. We completed a 6-mo, double-blind, placebo-controlled trial to determine the effects of a multi-micronutrient beverage on biochemical and anthropometric indicators of nutritional status among schoolchildren participating in a pilot school feeding program in Nasarawa State, Nigeria. Children received 1 of 2 interventions 5 d/wk during school hours: 1) 250 mL/d of a multi-micronutrient beverage that included vitamin A, iron, and zinc (micronutrient); or 2) an isoenergetic control beverage (control). At baseline, 566 children 5-13 y old were randomized to groups (micronutrient: n = 288; control: n = 278). Height, weight, hemoglobin, and serum concentrations of C-reactive protein, ferritin, retinol, and zinc were measured at baseline and at the end of the study. A total of 270 children in the micronutrient group and 264 children in the control group completed the study. Self-reports of vomiting increased in both groups at 6 mo; however, the prevalence tended to be greater in the micronutrient group (21%) compared to the control group (14%) (P = 0.06). Biochemical changes were greater in the micronutrient group compared to control for serum retinol (0.10 ± 0.02 µmol/L vs. 0.02 ± 0.02 µmol/L; P = 0.016) and zinc (1.0 ± 0.2 µmol/L vs. 0.6 ± 0.2 µmol/L; P = 0.031). The intervention did not significantly affect hemoglobin or serum ferritin concentrations. The cost effectiveness of the intervention needs to be further evaluated, as does the efficacy of the beverage on anemia and indicators of iron status.

The effects of iron and/or zinc supplementation on maternal reports of sleep in infants from Nepal and Zanzibar.

BACKGROUND: There is some evidence that sleep patterns may be affected by iron deficiency anemia but the role of iron in sleep has not been tested in a randomized iron supplementation trial. OBJECTIVE: We investigated the effect of iron supplementation on maternal reports of sleep in infants in 2 randomized, placebo-controlled trials from Pemba Island, Zanzibar, and Nepal. DESIGN: In both studies, which had parallel designs and were carried out in years 2002 to 2003, infants received iron-folic acid with or without zinc daily for 12 months, and assessments of development were made every 3 months for the duration of the study. Eight hundred seventy-seven Pemban (12.5 +/- 4.0 months old) and 567 Nepali (10.8 +/- 4.0 months) infants participated. Maternal reports of sleep patterns (napping frequency and duration, nighttime sleep duration, frequency of night waking) were collected. RESULTS: Mean Hb concentration was 9.2 +/- 1.1 for Pemban and 10.1 +/- 1.2 g/dL for Nepali infants. Approximately, one-third of the children were stunted. Supplemental iron was consistently associated with longer night and total sleep duration. The effects of zinc supplementation also included longer sleep duration. CONCLUSIONS: Micronutrient supplementation in infants at high risk for iron deficiency and iron deficiency anemia was related to increased night sleep duration and less night waking.