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)

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

Growth indices, anemia, and diet independently predict motor milestone acquisition of infants in South Central Nepal

The acquisition of bipedal locomotion is an important aspect of gross motor development that ultimately affects the cognition of young children. Evidence for associations between nutrition-related variables and walking acquisition exist; however, questions remain about the importance of weight-for-length and dietary factors and the independent contribution of anemia and growth to walking. We examined the effect of nutritional factors on the acquisition of walking in a cross-sectional cohort of 4- to 17-mo old Nepali children (n = 485) adjusting for age, sex, caste, and socioeconomic status (SES). Participants were identified from census data collected in 1 village development committee in Sarlahi District and enrolled in a cross-sectional, community-based study between January and March 2002. Hemoglobin and erythrocyte protoporphyrin (EP) were measured at baseline using a heel-prick technique. The mean hemoglobin concentration was 101 ± 12.5 g/L; 58% were anemic (hemoglobin \u3c 105 g/L), 2.1% were severely anemic (hemoglobin \u3c 70 g/L), and 43% of the children had iron-deficiency anemia (hemoglobin \u3c 105 g/L; EP ≥ 90 μmol/mol heme). Growth was delayed, i.e., 33.7% were stunted and 20.6% were wasted. Multivariate logistic models that controlled for age, sex, caste, and SES revealed that children with higher length-for-age and weight-for-length Z-scores, no anemia, and meat consumption walked at an earlier age than children with lower scores, anemia, and no meat consumption. We conclude that growth, anemia, and diet are independently associated with delays in the onset of bipedal locomotion among young Nepali children. © 2005 American Society for Nutrition

Combined iron and folic acid supplementation with or without zinc reduces time to walking unassisted among Zanzibari infants 5- to 11-mo old

Iron and zinc deficiencies have been associated with delayed motor development in nutritionally at-risk children, albeit inconsistently. In this community-based, randomized double-blind trial, iron+folic acid (FeFA) (12.5 mg Fe + 50 μg folic acid), zinc (Zn) (10 mg), and iron+folic acid+zinc (FeFA+Zn) supplements or a placebo were given daily for 1 y to nutritionally at-risk children in Pemba, Zanzibar. The effects of these treatments on attaining unassisted walking were evaluated using survival analysis for 354 children aged 5-11 mo at the start of supplementation. Treatment effects on changes in hemoglobin (Hb) and zinc protoporphyrin (ZPP) and height-for-age (HAZ) and weight-for-age (WAZ) Z scores were evaluated using linear regression. Attained motor milestone was recorded every 2 wk for 1 y. Hb, ZPP, HAZ, and WAZ were measured at baseline and after 6 mo of treatment. FeFA with or without Zn reduced the time it took for children to walk assisted. Children who received any iron walked unassisted sooner than those who received no iron [median difference ∼15 d, P = 0.035, risk ratio (RR) = 1.28, 95% CI = 1.02, 1.61] and this effect was stronger in those who had iron deficiency anemia (IDA) at baseline (median difference was ∼30 d; P = 0.002; RR = 1.68; 95% CI = 1.21, 2.32). FeFA alone and Zn alone improved Hb and ZPP compared with placebo. There were no significant treatment effects on changes in HAZ or WAZ. The effects of treatment on time to walking may have been mediated by improvements in iron status or hemoglobin, but were not mediated through improvements in growth. © 2006 American Society for Nutrition

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. © 2009 Lippincott Williams & Wilkins, Inc

Iron deficiency and physical growth predict attainment of walking but not crawling in poorly nourished Zanzibari infants

Locomotion allows infants to explore their environment, promoting development in other domains. Motor progression involves biological systems and experiential factors. Nutritional deficiencies could interfere with systems involved in locomotion. This study examined the associations between height-for-age (HAZ), weight-for-height (WHZ) Z-scores and anemia-iron status on locomotion in 646 Zanzibari infants. Motor milestones were assessed by trained observers using a 14-item scale. Two mutually exclusive samples were created. The crawling sample (n = 167, 6-18 mo old) included infants that crawled only or did not crawl; the walking sample (n = 479, 9-18 mo old) included children that walked alone or did not walk alone. Of the crawling and walking samples, 82.6 and 83.9% respectively, were iron deficient and/or anemic (hemoglobin \u3c 100 g/L; zinc protoporphyrin ≥ 90 μmol/mol heme). Stunting (HAZ less than -2) occurred in 30.5% of the crawling sample and 38.4% of the walking sample. Logistic regression models estimated the influence of factors on crawling vs. not crawling or walking vs. not walking. Two models were tested: 1) included sex, age, SES, HAZ and WHZ; 2) added anemia-iron status category to Model 1. HAZ improved the odds of crawling by 30%, but was not significant in either model. Model 2 fit the walking sample data best (P \u3c 0.0001); an increase in HAZ doubled the odds of walking and nonanemic, noniron deficient children were 66% more likely to walk than those with anemia and/or iron deficiency. In this sample of poorly nourished infants, growth and anemia-iron status are significant predictors of walking, but not crawling. © 2005 American Society for Nutritional Sciences

Maternal reports of sleep in 6-18 month-old infants from Nepal and Zanzibar: Association with iron deficiency anemia and stunting

Background: Infants with iron deficiency anemia (IDA) and stunting explore and interact less with their environment. They may also be fatigued more often, suggesting their sleep may be affected. It is unclear whether fatigue in these infants is due to poor nighttime sleep or if it is compensated for with frequent naps or longer sleep. Aims: In 2 studies from Pemba Island, Zanzibar and 1 from Nepal we investigated the relationship between IDA, stunting, and maternal reports of sleep in 6-18 mo old infants. Methods: Parents reported on the number and duration of naps, hours of nighttime sleep, and frequency of night waking. Anemia was defined as Hb \u3c 10 g/dL, iron deficiency as zinc protoporphyrin (ZPP ≥ 90 μmol/mol heme), stunting as HAZ \u3c - 2 SD, and IDA as Hb \u3c 10 g/dL and ZPP ≥ 90 μmol/mol heme. Results: The prevalence of IDA and stunting was 34-84% and 22-37%, respectively. Most infants napped during the day and took approximately 1.5 naps (mean nap duration 1.4-1.7 h). Mean nighttime sleep duration was 8.3-9.7 h and infants awoke 2.1-2.5 times per night. Both IDA and stunting were associated with differences in reported sleep characterized by shorter night sleep duration and higher frequency of night waking; stunting was also related to shorter nap duration. Conclusions: We found reduced sleep duration and increased night waking among infants with IDA and stunting. Because sleep plays an essential role in infant development, our findings indicate a clear need for further research into these relationships. © 2007 Elsevier Ireland Ltd. All rights reserved

Developmental effects of micronutrient supplementation and malaria in Zanzibari children

Background: Children\u27s 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\u27s 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\u27s 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\u27s development and how changes in developmental domains interact with each other over time to determine children\u27s overall developmental trajectory. The randomized, placebo-controlled study was registered as an International Standard Randomized Controlled Trial, number ISRCTN59549825. © 2013 Elsevier Ireland Ltd

Young Zanzibari children with iron deficiency, iron deficiency anemia, stunting, or malaria have lower motor activity scores and spend less time in locomotion

Motor activity improves cognitive and social-emotional development through a child\u27s exploration of his or her physical and social environment. This study assessed anemia, iron deficiency, hemoglobin (Hb), length-for-age Z-score (LAZ), and malaria infection as predictors of motor activity in 771 children aged 5-19 mo. Trained observers conducted 2- to 4-h observations of children\u27s motor activity in and around their homes. Binary logistic regression assessed the predictors of any locomotion. Children who did not locomote during the observation (nonmovers) were excluded from further analyses. Linear regression evaluated the predictors of total motor activity (TMA) and time spent in locomotion for all children who locomoted during the observation combined (movers) and then separately for crawlers and walkers. Iron deficiency (77.0%), anemia (58.9%), malaria infection (33.9%), and stunting (34.6%) were prevalent. Iron deficiency with and without anemia, Hb, LAZ, and malaria infection significantly predicted TMA and locomotion in all movers. Malaria infection significantly predicted less TMA and locomotion in crawlers. In walkers, iron deficiency anemia predicted less activity and locomotion, whereas higher Hb and LAZ significantly predicted more activity and locomotion, even after controlling for attained milestone. Improvements in iron status and growth and prevention or effective treatment of malaria may improve children\u27s motor, cognitive, and social-emotional development either directly or through improvements in motor activity. However, the relative importance of these factors is dependent on motor development, with malaria being important for the younger, less developmentally advanced children and Hb and LAZ becoming important as children begin to attain walking skills. © 2007 American Society for Nutrition

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