Stress biomarkers and child development in young children in Bangladesh.

BACKGROUND: Hundreds of millions of children in low- and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh. METHODS: We assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables. RESULTS: We analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We detected a significant relationship between HPA axis activity and child development, where increased HPA axis activity was associated with poor development outcomes. Specifically, we found that cortisol reactivity (coefficient -0.15, 95% CI (-0.29, -0.01)) and post-stressor levels (coefficient -0.12, 95% CI (-0.24, -0.01)) were associated with CDI comprehension score, post-stressor cortisol was associated with combined EASQ score (coefficient -0.22, 95% CI (-0.41, -0.04), and overall glucocorticoid receptor methylation was associated with CDI expression score (coefficient -0.09, 95% CI (-0.17, -0.01)). We did not detect a significant relationship between SAM activity or oxidative status and child development. CONCLUSIONS: Our observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress.

Stress Biomarkers and Child Development in Young Children in Bangladesh.

Background: Hundreds of millions of children in low- and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh. Methods: We assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders (hereafter referred to as contrasts) using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables. Results: We analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We observed 135 primary contrasts of the differences in child development outcomes at the 75th and 25th percentiles of stress biomarkers, where we detected significant relationships in 5 out of 30 contrasts (17%) of HPA axis activity, 1 out of 30 contrasts (3%) of SAM activity, and 3 out of 75 contrasts (4%) of oxidative status. These findings revealed that measures of HPA axis activity were associated with poor development outcomes. We did not find consistent evidence that markers of SAM system activity or oxidative status were associated with developmental status. Conclusions: Our observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress.

Pilot of a Low-Cost Elementary School Handwashing Intervention in Bangladesh: Acceptability, Feasibility, and Potential for Sustainability.

Schoolchildren frequently transmit respiratory and gastrointestinal infections because of dense person-to-person contact in schools. We piloted a low-cost handwashing intervention among elementary schoolchildren in Bangladesh. We trained teachers to lead behavior change communication sessions using flipcharts to encourage students' handwashing before eating, after defecating, and after cleaning school toilets; provided handwashing stations (reservoirs with taps and stool + basin + soapy water solution [mix of 30 gm detergent with 1.5 L water] + pump top bottle with steel holder); and formed hygiene committees for maintenance and covering the recurrent cost of detergent. We evaluated intervention acceptability, feasibility, and potential for sustainability at 1 and 14 months after the intervention. At baseline, of 300 before eating events, no one washed hands with soap, and 99.7% (299) did not wash hands at all as soap was unavailable. Out of 269 after toileting events, 0.7% (2) washed hands with soap, and 88% (237) did not wash hands. After 4 weeks of the intervention, 45% (87/195 before eating events), 83% (155/186 after toileting events), and 100% (15/15 after cleaning toilet events) washed both hands with soapy water as children found it accessible, low cost, and child friendly. After 14 months, 9.4% (55/586 before eating events) and 37% (172/465 after toileting events) washed both hands with soapy water for health benefits. The intervention was acceptable and feasible; it overcame limited access to soap and water and was affordable as schools covered the recurrent costs of detergent. Further research should explore long-term habit adoption and impact on health and attendance.

Complementary feeding practices among rural Bangladeshi mothers: Results from WASH Benefits study.

Inappropriate complementary feeding contributes to linear growth faltering in early childhood. Behaviour change interventions have been effective at improving practice, but few studies have investigated the effects of multicomponent integrated interventions. We conducted a cluster-randomized controlled trial in rural Bangladesh in which geographic clusters were randomized into seven arms: water treatment (W), sanitation (S), handwashing (H), water, sanitation, and handwashing (WSH), improved nutrition with infant and young child feeding messages and lipid-based nutrient supplementation for 6- to 24-month olds (N), N+WSH, and control. The objective of this paper was to examine the independent and combined effects of interventions on indicators of complementary feeding. Approximately 1 and 2 years after initiation of the intervention, research assistants surveyed mothers about infant feeding practices. Complementary feeding was examined using the World Health Organization indicators of infant and young child feeding practices. We used Poisson regression models to estimate prevalence ratios and linear regression models for prevalence differences with clustered sandwich estimators to adjust for clustering. A total of 4,718 households from 720 clusters were surveyed at year 1 and 4,667 at year 2. The children in the nutrition arms had a higher prevalence of meeting the minimum dietary diversity score compared with controls (year 1: N: 66.4%; N+WSH: 65.0% vs. C:32.4%; year 2: N: 91.5%; N+WSH: 91.6% vs. C:77.7%). Children in the nutrition arms received diverse food earlier than the children in control arm. In addition, the average consumption of lipid-based nutrient supplementation was >90% in each follow-up. Nutrition-specific interventions could be integrated with nutrition-sensitive interventions such as WSH without compromising the uptake of the nutrition intervention.

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 diarrhoea and child growth in rural Bangladesh: a cluster randomised controlled trial.

BACKGROUND: Diarrhoea and growth faltering in early childhood are associated with subsequent adverse outcomes. We aimed to assess whether water quality, sanitation, and handwashing interventions alone or combined with nutrition interventions reduced diarrhoea or growth faltering. METHODS: The WASH Benefits Bangladesh cluster-randomised trial enrolled pregnant women from villages in rural Bangladesh and evaluated outcomes at 1-year and 2-years' follow-up. Pregnant women in geographically adjacent clusters were block-randomised to one of seven clusters: chlorinated drinking water (water); upgraded sanitation (sanitation); promotion of handwashing with soap (handwashing); combined water, sanitation, and handwashing; counselling on appropriate child nutrition plus lipid-based nutrient supplements (nutrition); combined water, sanitation, handwashing, and nutrition; and control (data collection only). Primary outcomes were caregiver-reported diarrhoea in the past 7 days among children who were in utero or younger than 3 years at enrolment and length-for-age Z score among children born to enrolled pregnant women. Masking was not possible for data collection, but analyses were masked. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCC01590095. FINDINGS: Between May 31, 2012, and July 7, 2013, 5551 pregnant women in 720 clusters were randomly allocated to one of seven groups. 1382 women were assigned to the control group; 698 to water; 696 to sanitation; 688 to handwashing; 702 to water, sanitation, and handwashing; 699 to nutrition; and 686 to water, sanitation, handwashing, and nutrition. 331 (6%) women were lost to follow-up. Data on diarrhoea at year 1 or year 2 (combined) were available for 14 425 children (7331 in year 1, 7094 in year 2) and data on length-for-age Z score in year 2 were available for 4584 children (92% of living children were measured at year 2). All interventions had high adherence. Compared with a prevalence of 5·7% (200 of 3517 child weeks) in the control group, 7-day diarrhoea prevalence was lower among index children and children under 3 years at enrolment who received sanitation (61 [3·5%] of 1760; prevalence ratio 0·61, 95% CI 0·46-0·81), handwashing (62 [3·5%] of 1795; 0·60, 0·45-0·80), combined water, sanitation, and handwashing (74 [3·9%] of 1902; 0·69, 0·53-0·90), nutrition (62 [3·5%] of 1766; 0·64, 0·49-0·85), and combined water, sanitation, handwashing, and nutrition (66 [3·5%] of 1861; 0·62, 0·47-0·81); diarrhoea prevalence was not significantly lower in children receiving water treatment (90 [4·9%] of 1824; 0·89, 0·70-1·13). Compared with control (mean length-for-age Z score -1·79), children were taller by year 2 in the nutrition group (mean difference 0·25 [95% CI 0·15-0·36]) and in the combined water, sanitation, handwashing, and nutrition group (0·13 [0·02-0·24]). The individual water, sanitation, and handwashing groups, and combined water, sanitation, and handwashing group had no effect on linear growth. INTERPRETATION: Nutrient supplementation and counselling modestly improved linear growth, but there was no benefit to the integration of water, sanitation, and handwashing with nutrition. Adherence was high in all groups and diarrhoea prevalence was reduced in all intervention groups except water treatment. Combined water, sanitation, and handwashing interventions provided no additive benefit over single interventions. FUNDING: Bill & Melinda Gates Foundation.

Effect of Groundwater Iron on Residual Chlorine in Water Treated with Sodium Dichloroisocyanurate Tablets in Rural Bangladesh.

We assessed the ability of sodium dichloroisocyanurate (NaDCC) to provide adequate chlorine residual when used to treat groundwater with variable iron concentration. We randomly selected 654 tube wells from nine subdistricts in central Bangladesh to measure groundwater iron concentration and corresponding residual-free chlorine after treating 10 L of groundwater with a 33-mg-NaDCC tablet. We assessed geographical variations of iron concentration using the Kruskal-Wallis test and examined the relationships between the iron concentrations and chlorine residual by quantile regression. We also assessed whether user-reported iron taste in water and staining of storage vessels can capture the presence of iron greater than 3 mg/L (the World Health Organization threshold). The median iron concentration among measured wells was 0.91 (interquartile range [IQR]: 0.36-2.01) mg/L and free residual chlorine was 1.3 (IQR: 0.6-1.7) mg/L. The groundwater iron content varied even within small geographical regions. The median free residual chlorine decreased by 0.29 mg/L (95% confidence interval: 0.27, 0.33, P < 0.001) for every 1 mg/L increase in iron concentration. Owner-reported iron staining of the storage vessel had a sensitivity of 92%, specificity of 75%, positive predictive value of 41%, and negative predictive value of 98% for detecting > 3 mg/L iron in water. Similar findings were observed for user-reported iron taste in water. Our findings reconfirm that chlorination of groundwater that contains iron may result in low-level or no residual. User reports of no iron taste or no staining of storage containers can be used to identify low-iron tube wells suitable for chlorination. Furthermore, research is needed to develop a color-graded visual scale for iron staining that corresponds to different iron concentrations in water.