Growth, physical, and cognitive function in children who are born HIV-free: School-age follow-up of a cluster-randomised trial in rural Zimbabwe.

BACKGROUND: Globally, over 16 million children were exposed to HIV during pregnancy but remain HIV-free at birth and throughout childhood by 2022. Children born HIV-free (CBHF) have higher morbidity and mortality and poorer neurodevelopment in early life compared to children who are HIV-unexposed (CHU), but long-term outcomes remain uncertain. We characterised school-age growth, cognitive and physical function in CBHF and CHU previously enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. METHODS AND FINDINGS: The SHINE trial enrolled pregnant women between 2012 and 2015 across 2 rural Zimbabwean districts. Co-primary outcomes were height-for-age Z-score and haemoglobin at age 18 months (clinicaltrials.gov NCT01824940). Children were re-enrolled if they were aged 7 years, resident in Shurugwi district, and had known pregnancy HIV-exposure status. From 5,280 pregnant women originally enrolled, 376 CBHF and 2016 CHU reached the trial endpoint at 18 months in Shurugwi; of these, 264 CBHF and 990 CHU were evaluated at age 7 years using the School-Age Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox. Cognitive function was evaluated using the Kaufman Assessment Battery for Children (KABC-II), with additional tools measuring executive function, literacy, numeracy, fine motor skills, and socioemotional function. Physical function was assessed using standing broad jump and handgrip for strength, and the shuttle-run test for cardiovascular fitness. Growth was assessed by anthropometry. Body composition was assessed by bioimpedance analysis and skinfold thicknesses. A caregiver questionnaire measured demographics, socioeconomic status, nurturing, child discipline, food, and water insecurity. We prespecified the primary comparisons and used generalised estimating equations with an exchangeable working correlation structure to account for clustering. Adjusted models used covariates from the trial (study arm, study nurse, exact child age, sex, calendar month measured, and ambient temperature). They also included covariates derived from directed acyclic graphs, with separate models adjusted for contemporary variables (socioeconomic status, household food insecurity, religion, social support, gender norms, caregiver depression, age, caregiver education, adversity score, and number of children's books) and early-life variables (length-for-age-Z-score) at 18 months, birthweight, maternal baseline depression, household diet, maternal schooling and haemoglobin, socioeconomic status, facility birth, and gender norms. We applied a Bonferroni correction for the 27 comparisons (0.05/27) with threshold of p < 0.00185 as significant. We found strong evidence that cognitive function was lower in CBHF compared to CHU across multiple domains. The KABC-II mental processing index was 45.2 (standard deviation (SD) 10.5) in CBHF and 48.3 (11.3) in CHU (mean difference 3.3 points [95% confidence interval (95% CI) 2.0, 4.5]; p < 0.001). The school achievement test score was 39.0 (SD 26.0) in CBHF and 45.7 (27.8) in CHU (mean difference 7.3 points [95% CI 3.6, 10.9]; p < 0.001); differences remained significant in adjusted analyses. Executive function was reduced but not significantly in adjusted analyses. We found no consistent evidence of differences in growth or physical function outcomes. The main limitation of our study was the restriction to one of two previous study districts, with possible survivor and selection bias. CONCLUSIONS: In this study, we found that CBHF had reductions in cognitive function compared to CHU at 7 years of age across multiple domains. Further research is needed to define the biological and psychosocial mechanisms underlying these differences to inform future interventions that help CBHF thrive across the life-course. TRIAL REGISTRATION: ClinicalTrials.gov The SHINE follow-up study was registered with the Pan-African Clinical Trials Registry (PACTR202201828512110). The original SHINE trial was registered at NCT https://clinicaltrials.gov/study/NCT01824940

Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: a cluster-randomised trial.

BACKGROUND: Child stunting reduces survival and impairs neurodevelopment. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF) on stunting and anaemia in in Zimbabwe. METHODS: We did a cluster-randomised, community-based, 2 × 2 factorial trial in two rural districts in Zimbabwe. Clusters were defined as the catchment area of between one and four village health workers employed by the Zimbabwe Ministry of Health and Child Care. Women were eligible for inclusion if they permanently lived in clusters and were confirmed pregnant. Clusters were randomly assigned (1:1:1:1) to standard of care (52 clusters), IYCF (20 g of a small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counselling; 53 clusters), WASH (construction of a ventilated improved pit latrine, provision of two handwashing stations, liquid soap, chlorine, and play space plus hygiene counselling; 53 clusters), or IYCF plus WASH (53 clusters). A constrained randomisation technique was used to achieve balance across the groups for 14 variables related to geography, demography, water access, and community-level sanitation coverage. Masking of participants and fieldworkers was not possible. The primary outcomes were infant length-for-age Z score and haemoglobin concentrations at 18 months of age among children born to mothers who were HIV negative during pregnancy. These outcomes were analysed in the intention-to-treat population. We estimated the effects of the interventions by comparing the two IYCF groups with the two non-IYCF groups and the two WASH groups with the two non-WASH groups, except for outcomes that had an important statistical interaction between the interventions. This trial is registered with ClinicalTrials.gov, number NCT01824940. FINDINGS: Between Nov 22, 2012, and March 27, 2015, 5280 pregnant women were enrolled from 211 clusters. 3686 children born to HIV-negative mothers were assessed at age 18 months (884 in the standard of care group from 52 clusters, 893 in the IYCF group from 53 clusters, 918 in the WASH group from 53 clusters, and 991 in the IYCF plus WASH group from 51 clusters). In the IYCF intervention groups, the mean length-for-age Z score was 0·16 (95% CI 0·08-0·23) higher and the mean haemoglobin concentration was 2·03 g/L (1·28-2·79) higher than those in the non-IYCF intervention groups. The IYCF intervention reduced the number of stunted children from 620 (35%) of 1792 to 514 (27%) of 1879, and the number of children with anaemia from 245 (13·9%) of 1759 to 193 (10·5%) of 1845. The WASH intervention had no effect on either primary outcome. Neither intervention reduced the prevalence of diarrhoea at 12 or 18 months. No trial-related serious adverse events, and only three trial-related adverse events, were reported. INTERPRETATION: Household-level elementary WASH interventions implemented in rural areas in low-income countries are unlikely to reduce stunting or anaemia and might not reduce diarrhoea. Implementation of these WASH interventions in combination with IYCF interventions is unlikely to reduce stunting or anaemia more than implementation of IYCF alone. FUNDING: Bill & Melinda Gates Foundation, UK Department for International Development, Wellcome Trust, Swiss Development Cooperation, UNICEF, and US National Institutes of Health.The SHINE trial is funded by the Bill & Melinda Gates Foundation (OPP1021542 and OPP113707); UK Department for International Development; Wellcome Trust, UK (093768/Z/10/Z, 108065/Z/15/Z and 203905/Z/16/Z); Swiss Agency for Development and Cooperation; US National Institutes of Health (2R01HD060338-06); and UNICEF (PCA-2017-0002)

Adaptation of the Kaufman Assessment Battery for Children—2nd edition (KABC-II) to assess school-age neurodevelopment in rural Zimbabwe

There remains an urgent need for neurodevelopment assessment tools that can be applied in low-resource settings, where over 250 million children remain at risk of poor cognitive development. This project describes the adaptation of two subtests (pattern reasoning and story completion) within the Kaufman Assessment Battery for Children--2nd edition (KABC-II) for use in rural Zimbabwean children aged 7 years, both within the planning domain

Adaptation of the Kaufman Assessment Battery for Children—2nd edition (KABC-II) to assess school-age neurodevelopment in rural Zimbabwe

There remains an urgent need for neurodevelopment assessment tools that can be applied in low-resource settings, where over 250 million children remain at risk of poor cognitive development. This project describes the adaptation of two subtests (pattern reasoning and story completion) within the Kaufman Assessment Battery for Children--2nd edition (KABC-II) for use in rural Zimbabwean children aged 7 years, both within the planning domain

Adaptation of the Kaufman Assessment Battery for Children—2nd edition (KABC-II) to assess school-age neurodevelopment in rural Zimbabwe

There remains an urgent need for neurodevelopment assessment tools that can be applied in low-resource settings, where over 250 million children remain at risk of poor cognitive development. This project describes the adaptation of two subtests (pattern reasoning and story completion) within the Kaufman Assessment Battery for Children--2nd edition (KABC-II) for use in rural Zimbabwean children aged 7 years, both within the planning domain

Characterising school-age health and function in rural Zimbabwe using the SAHARAN toolbox

AbstractIntroductionSchool-age health, growth and development are poorly characterised in low- and middle-income countries. We developed the School-Age Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox to measure growth, cognitive and physical function in rural Zimbabwe.MethodsThe SAHARAN toolbox was developed using a stepwise approach, with tool selection based on COSMIN principles. Growth was measured with anthropometry, skinfold thicknesses and bioimpedance analysis to obtain lean mass index (LMI) and phase angle. Cognition was assessed using a fine motor finger tapping task, school achievement test (SAT), and the Kaufmann Assessment Battery for Children (KABC-2) to determine the mental processing index (MPI). Physical function combined grip strength, broad jump and the 20m shuttle run test to produce a total physical score (TPS). A detailed caregiver questionnaire was performed in parallel.Results80 Zimbabwean children with mean (SD) age 7.6 (0.2) years had mean height-for-age (HAZ) and weight-for-age Z-scores (WAZ) of −0.63 (0.81) and −0.55 (0.85), respectively. For growth measures, LMI and total skinfold thicknesses were highly related to both WAZ and BMI Z-score, but not to HAZ. For physical function, TPS was associated with unit rises in HAZ (1.29, 95%CI 0.75,1.82, p&lt;0.001), and LMI (0.50, 95%CI 0.16,0.83, p=0.004), but not skinfold thicknesses. For cognition, the SAT was highly associated with unit increases in the MPI (0.9 marks, 95%CI 0.4,1.3, p&lt;0.001) and a child socioemotional questionnaire (8.2 marks, 95%CI 2.9,13.5, p=0.003). Phase angle was associated with 3.5 seconds quicker time to complete the finger tapping task (95%CI 0.6,6.4, p=0.02). No child outcomes were associated with socioeconomic status, nurturing, discipline, food and water insecurity, or household adversity.ConclusionsWe found clear associations between growth, height-adjusted lean mass and physical function, but not cognitive function, in a cohort of Zimbabwean children. The SAHARAN toolbox could be deployed to characterise school-age growth, development and function in sub-Saharan Africa.What is already known?There are a lack of available tools to measure school-age health, growth, physical function and cognitive function together, particularly in low-resource settings.Early-life quality of growth is associated with future chronic disease risk.What are the new findings?School-age markers of growth and lean mass (but not fat mass) were strongly associated with physical function.Cognitive function was related to schooling and to the child’s perceived socioemotional score.What do the new findings imply?The SAHARAN toolbox enables an integrated assessment of school-age health, growth, physical and cognitive function.The quality of early-life growth and relative lean mass is important at school-age, since it is associated with better physical function and reduced chronic disease risk.</jats:sec

Characterising school-age health and function in rural Zimbabwe using the SAHARAN toolbox

IntroductionWe developed the School-Age Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox to address the shortage of school-age assessment tools that combine growth, physical and cognitive function. Here we present i) development, acceptability and feasibility of the SAHARAN toolbox; ii) characteristics of a pilot cohort; and iii) associations between the domains measured in the cohort.MethodsGrowth was measured with anthropometry, knee-heel length and skinfold thicknesses. Bioimpedance analysis measured lean mass index and phase angle. Cognition was assessed using the mental processing index, derived from the Kaufman Assessment Battery for Children version 2, a fine motor finger-tapping task, and School Achievement Test (SAT). Physical function combined grip strength, broad jump and the 20m shuttle-run test to produce a total physical score. A caregiver questionnaire was performed in parallel.ResultsThe SAHARAN toolbox was feasible to implement in rural Zimbabwe, and highly acceptable to children and caregivers following some minor modifications. Eighty children with mean (SD) age 7.6 (0.2) years had mean height-for-age (HAZ) and weight-for-age Z-scores (WAZ) of -0.63 (0.81) and -0.55 (0.85), respectively. Lean mass index and total skinfold thicknesses were related to WAZ and BMI Z-score, but not to HAZ. Total physical score was associated with unit rises in HAZ (1.29, 95% CI 0.75, 1.82, pConclusionsThe SAHARAN toolbox provided a feasible and acceptable holistic assessment of child growth and function in mid-childhood. We found clear associations between growth, height-adjusted lean mass and physical function, but not cognitive function. The SAHARAN toolbox could be deployed to characterise school-age growth, development and function elsewhere in sub-Saharan Africa

Piloting the adaptation of the Kaufman Assessment Battery for Children—2nd edition (KABC-II) to assess school-age neurodevelopment in rural Zimbabwe

Background: Neurodevelopment assessment tools for low-resource settings are urgently needed. However, most available tools were developed in high-income settings and may lack cross-cultural validity. Methods: We piloted and adapted two subtests (pattern reasoning and story completion) within the Kaufman Assessment Battery for Children-2nd edition (KABC-II) for use in rural Zimbabwean children aged 7 years old, both within the planning domain. After initial assessments of face validity, we substituted and added items in the test battery through a co-design process with fieldworkers and child development experts. To assess how successful the changes were, T-tests adjusting for unequal variances were used to compare scores between the original and adapted versions of the same subtest. ANOVA and pairwise analysis was performed to compare the performance of KABC-II subtests across domains. Intraclass correlation coefficient was calculated to explore the variability between domains. Results: Initial test scores on the planning domain were significantly lower than the other three domains of learning, sequential memory and simultaneous reasoning (P&lt;0.001) in 50 children. Modified subtests were administered to another 20 children, who showed story completion scores that were 0.7 marks higher (95% CI 0.0, 1.4; P=0.05) and pattern reasoning scores 1.8 marks higher (95% CI 0.5, 3.2; P=0.01). Overall, the planning domain mean score increased from 8.1 (SD 2.9) to 10.6 (SD 3.4). The intra class correlation coefficient between all four KABC-II domains was initially 0.43 (95% CI 0.13, 0.64) and after modification was 0.69 (95% CI 0.37, 0.87), suggesting an increase in the construct validity. Conclusions: The KABC-II planning domain was successfully adapted to improve cross-cultural validity. Construct validity was enhanced, based on increased inter-correlations among scales. This pilot has since been applied to the SHINE follow-up study. The process of co-design to modify tests for new settings may be beneficial for other commonly used neurodevelopmental tools.</ns3:p

Piloting the adaptation of the Kaufman Assessment Battery for Children—2nd edition (KABC-II) to assess school-age neurodevelopment in rural Zimbabwe [version 2; peer review: 2 approved]

Background Neurodevelopment assessment tools for low-resource settings are urgently needed. However, most available tools were developed in high-income settings and may lack cross-cultural validity. Methods We piloted and adapted two subtests within the planning domain of the Kaufman Assessment Battery for Children-2nd edition (KABC-II) for use in rural Zimbabwean children aged 7years. After initial assessments of face validity, we created 4 substitutions for the story completion subtest and 7 additions for the pattern reasoning subtest through a co-design process with fieldworkers and child development experts. To assess how successful the changes were, T-tests adjusting for unequal variances were used to compare scores between the original and adapted versions of the same subtest. ANOVA and pairwise analysis was performed to compare the performance of KABC-II subtests across domains. Intraclass correlation coefficient was calculated to explore the variability between domains. Results Initial test scores on the planning domain were significantly lower than the other three domains of learning, sequential memory and simultaneous reasoning (P<0.001) in 50 children (mean age 7.6(SD 0.2) years). Modified subtests were administered to another 20 children (mean age 7.6(SD 0.2) years), who showed story completion scores that were 0.7 marks higher (95% CI 0.0, 1.4; P=0.05) and pattern reasoning scores 1.8 marks higher (95% CI 0.5, 3.2; P=0.01). Overall, the planning domain mean score increased from 8.1 (SD 2.9) to 10.6 (SD 3.4). The intra class correlation coefficient between all four KABC-II domains was initially 0.43 (95% CI 0.13, 0.64) and after modification was 0.69 (95% CI 0.37, 0.87), suggesting an increase in the construct validity. Conclusions The KABC-II planning domain was successfully adapted to improve cross-cultural validity. Construct validity was enhanced, based on increased inter-correlations among scales. The process of co-design to modify tests for new settings may be beneficial for other commonly used neurodevelopmental tools

Baseline characteristics of participants, household and selected adversity factors in the sample.

Baseline characteristics of participants, household and selected adversity factors in the sample.</p