Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202201828512110 Date of Registration: 24/01/2022
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title School-aged follow-up of the Sanitation, Hygiene, Infant Nutrition Efficacy (SHINE) Cluster Randomised Trial
Official scientific title School-aged follow-up of the Sanitation, Hygiene, Infant Nutrition Efficacy (SHINE) Cluster Randomised Trial
Brief summary describing the background and objectives of the trial Stunting affects 22% (149 million) children under 5 years. Stunting is associated with increased child mortality, long-term cognitive and health deficits, poorer school performance and lower adult earnings. Improved infant and young child feeding (IYCF) targets the most vulnerable window between 6-18 months of age but only increases linear growth modestly (+0.11 HAZ). Water, sanitation and hygiene (WASH) has shown a minimal impact on growth, but may have later impacts on neurodevelopment. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (clinicaltrials.gov NCT01824940) was a 2x2 factorial, cluster-randomized trial in rural Zimbabwe conducted between 2012-2017. Women were enrolled in early pregnancy, with detailed data collection on home, maternal, birth and early-life factors. Clusters were randomised to standard of care, IYCF, WASH or IYCF plus WASH. All available children born during the trial were previously followed up to 18 months of age, with primary outcomes of height-for-age Z-score and haemoglobin. This follow-up study will further evaluate a subgroup of 1300 of these children born into the SHINE trial, who are now aged 7 years. It will measure their growth, physical and cognitive function: Following written informed consent, we will re-enrol 1000 HIV-unexposed children (approximately 250 per arm), and 300 children who were HIV-exposed uninfected (HIV-negative children born to HIV-positive mothers). Outcomes will be measured using the School-aged Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox at a single home visit. Children will then be followed monthly by village health workers to evaluate illness episodes from 8-9 years of age, and undergo an annual assessment using an abbreviated SAHARAN toolbox. At 10-11 years, measurements include child wellbeing, brain MRI imaging, leg pQCT, renal, heart and muscle ultrasound scans and hair, blood and urine samples. A substudy will perform EEG in 150 children.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) SHINE follow up
Disease(s) or condition(s) being studied Nutritional, Metabolic, Endocrine
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Nutrition and Water, Sanitation and Hygiene
Anticipated trial start date 30/03/2021
Actual trial start date
Anticipated date of last follow up 16/07/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 1300
Actual target sample size (number of participants) 1275
Recruitment status Closed to recruitment,follow-up continuing
Publication URL https://wellcomeopenresearch.org/articles/8-306
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group IYCF Daily supplement for ages 6 to18 months 1 year In the IYCF arms, households received a 20 g small-quantity lipid-based nutrient supplement (LNS) to be fed daily to the infant from 6 to 18 months of age, and messages promoting nutrient-dense, diverse infant diets processed to facilitate mastication and swallowing, with frequent responsive feeding during illness. 325
Experimental Group WASH Latrine built and monthly visits enrolment to 18 months age In the WASH arms, builders installed a ventilated improved pit latrine and two handwashing stations; a mat and play space were provided to reduce geophagia and contact with animals; and VHW provided regular deliveries of soap and chlorine solution and messages promoting their use. 325
Control Group Standard of care Monthly mesuring visits 18 months In the SOC arm, VHW promoted early and exclusive breastfeeding, antenatal care including PMTCT and immunizations 325 Uncontrolled
Experimental Group IYCF WASH Latrine built and monthly visits, daily lipid-based supplement from 6 to 18 months. IYCF for 6 to 18 months, WASH from enrolment to 18 months 1 intervention arm had both IYCF (providing both nutrition supplements (6-18 months)) as well as WASH (latrine from enrolment, monthly visits to 18 months). 325
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
- Enrolled in SHINE and had primary outcome measurement at 18 months of age - Mother tested and HIV status known in pregnancy - Written informed consent of parent / guardian - Age 7 years (defined as between 7 years and 7 years + 364 days of age) - Resident in Shurugwi district - <7 years or >8 years of age - Not resident in Shurugwi district Child: 6 Year-12 Year 7 Year(s) 8 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 08/02/2021 Medical Research Council of Zimbabwe
Ethics Committee Address
Street address City Postal code Country
Mazowe Street Harare PO CY573 Zimbabwe
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 04/11/2021 Medical Research Council of Zimbabwe
Ethics Committee Address
Street address City Postal code Country
Mazowe Street Harare PO CY573 Zimbabwe
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 06/04/2021 Medical Research Council of Zimbabwe
Ethics Committee Address
Street address City Postal code Country
Mazowe Street Harare PO CY573 Zimbabwe
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 25/06/2021 Medical Research Council of Zimbabwe
Ethics Committee Address
Street address City Postal code Country
Mazowe Street Harare PO CY573 Zimbabwe
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 17/04/2023 Medical Research Council of Zimbabwe
Ethics Committee Address
Street address City Postal code Country
20 Cambridge Rd Harare H20 Zimbabwe
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Mental processing index MPI from Kaufmann Assessment Battery for Children KABC-2 7 years of age, post-intervention
Secondary Outcome Total of Writing Reading and Arithmetic Test score 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Fine motor from Total time to complete finger tapping task 7 years of age, post-intervention
Secondary Outcome Plus EF executive function score 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Height, weight, head circumference, MUAC 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Kaufmann subtest scores, SAT subtest scores, individual fine motor scores, Plus-EF subtest scores and reaction times 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Bioimpedance-based lean mass index, phase angle 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Sum of skinfold thickness 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Knee- heel length 7 years of age, post-intervention
Secondary Outcome Waist circumference, calf circumference 7year only, 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Subscapular, triceps, suprailiac and calf skinfold thicknesses 7 years, 8-9 years, 10-11 years of age, post-interventions
Secondary Outcome Average grip strength for both hands 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Grip strength in dominant and non-dominant hand 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Broad jump distance 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Shuttle run test level 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Composite outcome of combined standardised scores of grip strength, broad jump and shuttle run test 7 years of age, post-intervention
Secondary Outcome Resting blood pressure and blood pressure 1 minute after exercise 7 years, 10-11 years of age, post-intervention.
Secondary Outcome Haemoglobin level 7 years of age, post-intervention
Secondary Outcome Acute illnesses in school age health and visits to traditional healer, clinic and hospital 8 to 10 years of age, post-intervention
Secondary Outcome Annual monitoring visits that measure child growth, body composition, handgrip strength, literacy, numeracy and executive function. 8-12 years of age, post-intervention.
Secondary Outcome Child Socioemotional scale 7 - 12 years of age, post-intervention
Primary Outcome Mental processing index MPI from Kaufmann Assessment Battery for Children KABC-2 7 years of age, post-intervention
Secondary Outcome Total of Writing Reading and Arithmetic Test score 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Fine motor from Total time to complete finger tapping task 7 years of age, post-intervention
Secondary Outcome Plus EF executive function score 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Height, weight, head circumference, MUAC 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Kaufmann subtest scores, SAT subtest scores, individual fine motor scores, Plus-EF subtest scores and reaction times 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Bioimpedance-based lean mass index, phase angle 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Sum of skinfold thickness 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Knee- heel length 7 years of age, post-intervention
Secondary Outcome Waist circumference, calf circumference 7year only, 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Subscapular, triceps, suprailiac and calf skinfold thicknesses 7 years, 8-9 years, 10-11 years of age, post-interventions
Secondary Outcome Average grip strength for both hands 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Grip strength in dominant and non-dominant hand 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Broad jump distance 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Shuttle run test level 7 years, 8-9 years, 10-11 years of age, post-intervention
Secondary Outcome Composite outcome of combined standardised scores of grip strength, broad jump and shuttle run test 7 years of age, post-intervention
Secondary Outcome Resting blood pressure and blood pressure 1 minute after exercise 7 years, 10-11 years of age, post-intervention.
Secondary Outcome Haemoglobin level 7 years of age, post-intervention
Secondary Outcome Acute illnesses in school age health and visits to traditional healer, clinic and hospital 8 to 10 years of age, post-intervention
Secondary Outcome Annual monitoring visits that measure child growth, body composition, handgrip strength, literacy, numeracy and executive function. 8-12 years of age, post-intervention.
Secondary Outcome Child Socioemotional scale 7 - 12 years of age, post-intervention
Secondary Outcome Child WHO wellbeing total, Center for Epidemiology Studies Depression in Children CESDC score, SCARED anxiety score, self-efficacy, self-esteem, future orientation, highly sensitive personality, parent-child relationship, social support, bullying, school environment, loneliness, optimism scores 10-11 years of age, post-intervention. The intervention finished at 18 months.
Secondary Outcome Brain MRI measurements- Grey matter volume, white matter volume, regions of interest volume 10-11 years of age, post-intervention.
Secondary Outcome Peripheral quantitative computed tomography -pQCT- bone and muscle indices 10-11 years of age, post-intervention.
Secondary Outcome Ultrasound measurements- heart echo shape and function, bilateral renal size, muscle cross-sectional area and echogenecity 10-11 years of age, post-intervention.
Secondary Outcome Lung function from spirometry- FEV1 (Forced Expiratory Volume in 1 second) and FVC (Forced Vital Capacity), sitting height 10-11 years of age, post-intervention
Secondary Outcome Pulse wave velocity PWV, Augmentation index and central blood pressure 10-11 years of age, post-intervention.
Secondary Outcome Event related potentials ERP - substudy in 150 children 75 HEU 75 HUU 10-11 years of age, post-intervention.
Secondary Outcome Verbal fluency total 10-11 years of age, post-intervention.
Secondary Outcome Jump plate mechanography- Maximum jump power, efficiency of the motion 10-11 years of age, post-intervention
Secondary Outcome Heart rate variability, maximum heart rate, time to recover from maximal exercise 10-11 years of age. Post-intervention
Secondary Outcome Hair cortisol 10-11 years of age, post-intervention.
Secondary Outcome Blood metabolic, inflammatory and micronutrient markers, metabolomics, transcriptomics 10-11 years of age, post-intervention.
Secondary Outcome Urine renal markers and urine metabolomics 10-11 years of age, post-intervention
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Shurugwi District Shurugwi Hub Shurugwi Zimbabwe
FUNDING SOURCES
Name of source Street address City Postal code Country
Wellcome Trust 215 Euston Road London NW1 2BE United Kingdom
National Institutes of Health 10 Center Drive Bethesda 200892 United States of America
Thrasher Research Fund 68 S. Main Street Salt Lake City UT 84101 United States of America
Innovative Methods and Metrics for Agriculture and Nutrition Actions Keppel Street London WC1E 7HT United Kingdom
Medical Research Council UK Polaris House, North Star Avenue, Swindon, Swindon SN2 1FL United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Zvitambo Institute for Maternal and Child Health Research 16 Lauchlan Avenue - Meyrick Park Harare Zimbabwe Non-profit Research Organisation
COLLABORATORS
Name Street address City Postal code Country
Professor Melissa Gladstone Institute of Translational Medicine-Crown Street Liverpool L69 3BX United Kingdom
Professor Jonathan Wells Institute of Child Health-30 Guilford Street London WC1N1EH United Kingdom
Professor Michael Pluess University of Surrey Guildford GU2 7JN United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Andrew Prendergast a.prendergast@qmul.ac.uk +442078822269 Blizard Institute, Queen Mary University of London, 4 Newark Street
City Postal code Country Position/Affiliation
London E12AT United Kingdom Professor of paediatric infection and immunology
Role Name Email Phone Street address
Public Enquiries Virginia Sauramba v.sauramba@zvitambo.com +263242306028 Zvitambo Institute for Maternal and Child Health Research, 16 Lauchlan Avenue, Meyrick Park
City Postal code Country Position/Affiliation
Harare Zimbabwe Research Administration and Compliance Manager
Role Name Email Phone Street address
Scientific Enquiries Lisa Langhaug l.langhaug@zvitambo.com +263242306028 Zvitambo Institute for Maternal and Child Health Research, 16 Lauchlan Avenue, Meyrick Park
City Postal code Country Position/Affiliation
Harare Zimbabwe Associate Director for Research Administration
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual patient data included in the primary analysis will be made available as de-identified data together with a data dictionary. Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol 6 months after publication of the primary analysis Researchers should provide a methodologically sound plan to access data for the aims outlined in the plan. Proposals should be directed to Virginia Sauramba at v.sauramba@zvitambo.com.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://osf.io/w93hy/ No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 14/01/2022 Clarification added that the follow-up study of the SHINE trial is for 1300 children born to the 6250 mothers previously randomised to SHINE interventions. Stunting affects 22% (149 million) children under 5 years. Stunting is associated with increased child mortality, long-term cognitive and health deficits, poorer school performance and lower adult earnings. Improved infant and young child feeding (IYCF) targets the most vulnerable window between 6-18 months of age but only increases linear growth modestly (+0.11 HAZ). Water, sanitation and hygiene (WASH) has shown a minimal impact on growth, but may have later impacts on neurodevelopment. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (clinicaltrials.gov NCT01824940) was a 2x2 factorial, cluster-randomized trial in rural Zimbabwe conducted between 2012-2017. Women were enrolled in early pregnancy, with detailed data collection on home, maternal, birth and early-life factors. Clusters were randomised to standard of care, IYCF, WASH or IYCF plus WASH, and children were followed to 18 months of age with primary outcomes of height-for-age Z-score and haemoglobin. This follow-up study will evaluate growth, physical and cognitive function among SHINE children who are now aged 7 years. Following written informed consent, we will re-enrol 1000 HIV-unexposed children (approximately 250 per arm), and 300 children who were HIV-exposed uninfected (HIV-negative children born to HIV-positive mothers). Outcomes will be measured using the School-aged Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox at a single home visit. Children will then be followed monthly by village health workers to evaluate illness episodes from 7-12 years of age, and undergo an annual assessment using an abbreviated version of the SAHARAN toolbox. Stunting affects 22% (149 million) children under 5 years. Stunting is associated with increased child mortality, long-term cognitive and health deficits, poorer school performance and lower adult earnings. Improved infant and young child feeding (IYCF) targets the most vulnerable window between 6-18 months of age but only increases linear growth modestly (+0.11 HAZ). Water, sanitation and hygiene (WASH) has shown a minimal impact on growth, but may have later impacts on neurodevelopment. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (clinicaltrials.gov NCT01824940) was a 2x2 factorial, cluster-randomized trial in rural Zimbabwe conducted between 2012-2017. Women were enrolled in early pregnancy, with detailed data collection on home, maternal, birth and early-life factors. Clusters were randomised to standard of care, IYCF, WASH or IYCF plus WASH, and children were followed to 18 months of age with primary outcomes of height-for-age Z-score and haemoglobin. This follow-up study will evaluate a subgroup of 1300 children born to the 6250 mothers originally randomised to the SHINE interventions. It will measure the growth, physical and cognitive function among 1300 SHINE children who are now aged 7 years: Following written informed consent, we will re-enrol 1000 HIV-unexposed children (approximately 250 per arm), and 300 children who were HIV-exposed uninfected (HIV-negative children born to HIV-positive mothers). Outcomes will be measured using the School-aged Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox at a single home visit. Children will then be followed monthly by village health workers to evaluate illness episodes from 7-12 years of age, and undergo an annual assessment using an abbreviated version of the SAHARAN toolbox.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 14/01/2022 Clarification added that the follow-up study of the SHINE trial is for 1300 children born to the 6250 mothers previously randomised to SHINE interventions. Stunting affects 22% (149 million) children under 5 years. Stunting is associated with increased child mortality, long-term cognitive and health deficits, poorer school performance and lower adult earnings. Improved infant and young child feeding (IYCF) targets the most vulnerable window between 6-18 months of age but only increases linear growth modestly (+0.11 HAZ). Water, sanitation and hygiene (WASH) has shown a minimal impact on growth, but may have later impacts on neurodevelopment. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (clinicaltrials.gov NCT01824940) was a 2x2 factorial, cluster-randomized trial in rural Zimbabwe conducted between 2012-2017. Women were enrolled in early pregnancy, with detailed data collection on home, maternal, birth and early-life factors. Clusters were randomised to standard of care, IYCF, WASH or IYCF plus WASH, and children were followed to 18 months of age with primary outcomes of height-for-age Z-score and haemoglobin. This follow-up study will evaluate a subgroup of 1300 children born to the 6250 mothers originally randomised to the SHINE interventions. It will measure the growth, physical and cognitive function among 1300 SHINE children who are now aged 7 years: Following written informed consent, we will re-enrol 1000 HIV-unexposed children (approximately 250 per arm), and 300 children who were HIV-exposed uninfected (HIV-negative children born to HIV-positive mothers). Outcomes will be measured using the School-aged Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox at a single home visit. Children will then be followed monthly by village health workers to evaluate illness episodes from 7-12 years of age, and undergo an annual assessment using an abbreviated version of the SAHARAN toolbox. Stunting affects 22% (149 million) children under 5 years. Stunting is associated with increased child mortality, long-term cognitive and health deficits, poorer school performance and lower adult earnings. Improved infant and young child feeding (IYCF) targets the most vulnerable window between 6-18 months of age but only increases linear growth modestly (+0.11 HAZ). Water, sanitation and hygiene (WASH) has shown a minimal impact on growth, but may have later impacts on neurodevelopment. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (clinicaltrials.gov NCT01824940) was a 2x2 factorial, cluster-randomized trial in rural Zimbabwe conducted between 2012-2017. Women were enrolled in early pregnancy, with detailed data collection on home, maternal, birth and early-life factors. Clusters were randomised to standard of care, IYCF, WASH or IYCF plus WASH, and children were followed to 18 months of age with primary outcomes of height-for-age Z-score and haemoglobin. This follow-up study will evaluate a subgroup of 1300 children born to the mothers originally randomised to the SHINE interventions. It will measure the growth, physical and cognitive function among 1300 SHINE children who are now aged 7 years: Following written informed consent, we will re-enrol 1000 HIV-unexposed children (approximately 250 per arm), and 300 children who were HIV-exposed uninfected (HIV-negative children born to HIV-positive mothers). Outcomes will be measured using the School-aged Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox at a single home visit. Children will then be followed monthly by village health workers to evaluate illness episodes from 7-12 years of age, and undergo an annual assessment using an abbreviated version of the SAHARAN toolbox.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 14/01/2022 Clarification added that all children were previously followed to 18 months. By contrast, the follow-up study of the SHINE trial is for a subgroup of 1300 children only. These children are now aged 7 years. Stunting affects 22% (149 million) children under 5 years. Stunting is associated with increased child mortality, long-term cognitive and health deficits, poorer school performance and lower adult earnings. Improved infant and young child feeding (IYCF) targets the most vulnerable window between 6-18 months of age but only increases linear growth modestly (+0.11 HAZ). Water, sanitation and hygiene (WASH) has shown a minimal impact on growth, but may have later impacts on neurodevelopment. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (clinicaltrials.gov NCT01824940) was a 2x2 factorial, cluster-randomized trial in rural Zimbabwe conducted between 2012-2017. Women were enrolled in early pregnancy, with detailed data collection on home, maternal, birth and early-life factors. Clusters were randomised to standard of care, IYCF, WASH or IYCF plus WASH, and children were followed to 18 months of age with primary outcomes of height-for-age Z-score and haemoglobin. This follow-up study will evaluate a subgroup of 1300 children born to the mothers originally randomised to the SHINE interventions. It will measure the growth, physical and cognitive function among 1300 SHINE children who are now aged 7 years: Following written informed consent, we will re-enrol 1000 HIV-unexposed children (approximately 250 per arm), and 300 children who were HIV-exposed uninfected (HIV-negative children born to HIV-positive mothers). Outcomes will be measured using the School-aged Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox at a single home visit. Children will then be followed monthly by village health workers to evaluate illness episodes from 7-12 years of age, and undergo an annual assessment using an abbreviated version of the SAHARAN toolbox. Stunting affects 22% (149 million) children under 5 years. Stunting is associated with increased child mortality, long-term cognitive and health deficits, poorer school performance and lower adult earnings. Improved infant and young child feeding (IYCF) targets the most vulnerable window between 6-18 months of age but only increases linear growth modestly (+0.11 HAZ). Water, sanitation and hygiene (WASH) has shown a minimal impact on growth, but may have later impacts on neurodevelopment. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (clinicaltrials.gov NCT01824940) was a 2x2 factorial, cluster-randomized trial in rural Zimbabwe conducted between 2012-2017. Women were enrolled in early pregnancy, with detailed data collection on home, maternal, birth and early-life factors. Clusters were randomised to standard of care, IYCF, WASH or IYCF plus WASH. All available children born during the trial were previously followed up to 18 months of age, with primary outcomes of height-for-age Z-score and haemoglobin. This follow-up study will further evaluate a subgroup of 1300 of these children born into the SHINE trial, who are now aged 7 years. It will measure their growth, physical and cognitive function: Following written informed consent, we will re-enrol 1000 HIV-unexposed children (approximately 250 per arm), and 300 children who were HIV-exposed uninfected (HIV-negative children born to HIV-positive mothers). Outcomes will be measured using the School-aged Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox at a single home visit. Children will then be followed monthly by village health workers to evaluate illness episodes from 7-12 years of age, and undergo an annual assessment using an abbreviated version of the SAHARAN toolbox.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 08/10/2025 Monthly illness episodes were measured from 8-9 years of age. Further details of the measurements at 10-11 years were added. Stunting affects 22% (149 million) children under 5 years. Stunting is associated with increased child mortality, long-term cognitive and health deficits, poorer school performance and lower adult earnings. Improved infant and young child feeding (IYCF) targets the most vulnerable window between 6-18 months of age but only increases linear growth modestly (+0.11 HAZ). Water, sanitation and hygiene (WASH) has shown a minimal impact on growth, but may have later impacts on neurodevelopment. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (clinicaltrials.gov NCT01824940) was a 2x2 factorial, cluster-randomized trial in rural Zimbabwe conducted between 2012-2017. Women were enrolled in early pregnancy, with detailed data collection on home, maternal, birth and early-life factors. Clusters were randomised to standard of care, IYCF, WASH or IYCF plus WASH. All available children born during the trial were previously followed up to 18 months of age, with primary outcomes of height-for-age Z-score and haemoglobin. This follow-up study will further evaluate a subgroup of 1300 of these children born into the SHINE trial, who are now aged 7 years. It will measure their growth, physical and cognitive function: Following written informed consent, we will re-enrol 1000 HIV-unexposed children (approximately 250 per arm), and 300 children who were HIV-exposed uninfected (HIV-negative children born to HIV-positive mothers). Outcomes will be measured using the School-aged Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox at a single home visit. Children will then be followed monthly by village health workers to evaluate illness episodes from 7-12 years of age, and undergo an annual assessment using an abbreviated version of the SAHARAN toolbox. Stunting affects 22% (149 million) children under 5 years. Stunting is associated with increased child mortality, long-term cognitive and health deficits, poorer school performance and lower adult earnings. Improved infant and young child feeding (IYCF) targets the most vulnerable window between 6-18 months of age but only increases linear growth modestly (+0.11 HAZ). Water, sanitation and hygiene (WASH) has shown a minimal impact on growth, but may have later impacts on neurodevelopment. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (clinicaltrials.gov NCT01824940) was a 2x2 factorial, cluster-randomized trial in rural Zimbabwe conducted between 2012-2017. Women were enrolled in early pregnancy, with detailed data collection on home, maternal, birth and early-life factors. Clusters were randomised to standard of care, IYCF, WASH or IYCF plus WASH. All available children born during the trial were previously followed up to 18 months of age, with primary outcomes of height-for-age Z-score and haemoglobin. This follow-up study will further evaluate a subgroup of 1300 of these children born into the SHINE trial, who are now aged 7 years. It will measure their growth, physical and cognitive function: Following written informed consent, we will re-enrol 1000 HIV-unexposed children (approximately 250 per arm), and 300 children who were HIV-exposed uninfected (HIV-negative children born to HIV-positive mothers). Outcomes will be measured using the School-aged Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox at a single home visit. Children will then be followed monthly by village health workers to evaluate illness episodes from 8-9 years of age, and undergo an annual assessment using an abbreviated SAHARAN toolbox. At 10-11 years, measurements include child wellbeing, brain MRI imaging, leg pQCT, renal, heart and muscle ultrasound scans and hair, blood and urine samples. A substudy will perform EEG in 150 children.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Final no of participants 11/05/2023 We have recruited 1275 participants (1000 HIV negative, 7 HIV positive, 268 HIV exposed uninfected). This is the total number of HIV exposed uninfected that were able to be located in the time window. 1275
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 11/05/2023 We have recruited 1275 participants (1000 HIV negative, 7 HIV positive, 268 HIV exposed uninfected). This is the total number that were able to be located in the time window. Recruiting Closed to recruitment,follow-up continuing
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Publication URL 08/10/2025 Publication URL added for School-age follow-up https://wellcomeopenresearch.org/articles/8-306
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 23/01/2022 Intervention in WASH desribed as monthly visits to snsure clarity that the combined arm had the same interventions combined, as the individual WASH and IYCF arms. Experimental Group, IYCF WASH, Latrine built and monthly visits, daily lipid-based supplement from 6 to 18 months. , IYCF for 6 to 18 months, WASH from enrolment to 18 months, 1 intervention arm had both IYCF (providing both nutrition supplements (6-18 months)) as well as WASH (latrine from enrolment, monthly visits to 18 months). , 325,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 23/01/2022 Size of intervention reduced to match with subgroup of SHINE study that is being followed up at 7 years. Experimental Group, Lipid based nutrient supplement, Daily supplement for ages 6 to18 months, 1 year, In the IYCF arms, households received a 20 g small-quantity lipid-based nutrient supplement (LNS) to be fed daily to the infant from 6 to 18 months of age, and messages promoting nutrient-dense, diverse infant diets processed to facilitate mastication and swallowing, with frequent responsive feeding during illness., 2500, Experimental Group, Lipid based nutrient supplement, Daily supplement for ages 6 to18 months, 1 year, In the IYCF arms, households received a 20 g small-quantity lipid-based nutrient supplement (LNS) to be fed daily to the infant from 6 to 18 months of age, and messages promoting nutrient-dense, diverse infant diets processed to facilitate mastication and swallowing, with frequent responsive feeding during illness., 325,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 23/01/2022 Changed the name of the nutrient-based arm from "lipid based nutrient supplement" to "IYCF" (Infant and Young Child Feeding) for clarity and to match description. Experimental Group, Lipid based nutrient supplement, Daily supplement for ages 6 to18 months, 1 year, In the IYCF arms, households received a 20 g small-quantity lipid-based nutrient supplement (LNS) to be fed daily to the infant from 6 to 18 months of age, and messages promoting nutrient-dense, diverse infant diets processed to facilitate mastication and swallowing, with frequent responsive feeding during illness., 325, Experimental Group, IYCF, Daily supplement for ages 6 to18 months, 1 year, In the IYCF arms, households received a 20 g small-quantity lipid-based nutrient supplement (LNS) to be fed daily to the infant from 6 to 18 months of age, and messages promoting nutrient-dense, diverse infant diets processed to facilitate mastication and swallowing, with frequent responsive feeding during illness., 325,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 23/01/2022 Number within the WASH arm reduced to 325 to match the approximate number of SHINE participants being followed up at 7 years within this arm. Experimental Group, WASH, Latrine built and monthly visits, enrolment to 18 months age, In the WASH arms, builders installed a ventilated improved pit latrine and two handwashing stations; a mat and play space were provided to reduce geophagia and contact with animals; and VHW provided regular deliveries of soap and chlorine solution and messages promoting their use. , 2500, Experimental Group, WASH, Latrine built and monthly visits, enrolment to 18 months age, In the WASH arms, builders installed a ventilated improved pit latrine and two handwashing stations; a mat and play space were provided to reduce geophagia and contact with animals; and VHW provided regular deliveries of soap and chlorine solution and messages promoting their use. , 325,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 23/01/2022 Number within the Control arm reduced to 325 to match the approximate number of SHINE participants being followed up at 7 years within this arm. Control Group, Standard of care, Monthly mesuring visits, 18 months, In the SOC arm, VHW promoted early and exclusive breastfeeding, antenatal care including PMTCT and immunizations, 1250, Uncontrolled Control Group, Standard of care, Monthly mesuring visits, 18 months, In the SOC arm, VHW promoted early and exclusive breastfeeding, antenatal care including PMTCT and immunizations, 325, Uncontrolled
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 23/01/2022 Combined arm total added for clarity to describe how sample size becomes 1300, due to 325 in each of the 4 randomised arms of IYCF, WASH, IYCF & WASH, control. Experimental Group, IYCF WASH, , IYCF for 6 to 18 months, WASH from enrolement to 18 months, 1 intervention arm had both IYCF (providing both nutrition supplements (6-18 months)) as well as WASH (latrine from enrolment, support to 18 months). , 325,
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Updated to include 10-11 years' measurements Secondary Outcome, Peripheral quantitative computed tomography pQCT bone and muscle indices, 10-11 years Secondary Outcome, Peripheral quantitative computed tomography -pQCT- bone and muscle indices, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Clarified that 7 years of age, post-intervention. The intervention finished at 18 months of age. Primary Outcome, Mental processing index MPI from Kaufmann Assessment Battery for Children KABC-2, 7 years Primary Outcome, Mental processing index MPI from Kaufmann Assessment Battery for Children KABC-2, 7 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Time windows of measurement added Secondary Outcome, Total of Writing Reading and Arithmetic Test score, 7 years Secondary Outcome, Total of Writing Reading and Arithmetic Test score, 7 years, 8-9 years, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Time windows of measurement added, Clarified that 7 years of age, post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Total of Writing Reading and Arithmetic Test score, 7 years, 8-9 years, 10-11 years Secondary Outcome, Total of Writing Reading and Arithmetic Test score, 7 years, 8-9 years, 10-11 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Clarified that 7 years of age, post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Fine motor from Total time to complete finger tapping task, 7 years Secondary Outcome, Fine motor from Total time to complete finger tapping task, 7 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Age ranges of repeated measures added Secondary Outcome, Plus EF executive function score, 7 years Secondary Outcome, Plus EF executive function score, 7 years, 8-9 years, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Age ranges of repeated measures added, Clarified that these are years of age, post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Plus EF executive function score, 7 years, 8-9 years, 10-11 years Secondary Outcome, Plus EF executive function score, 7 years, 8-9 years, 10-11 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Age ranges of repeated measures added Secondary Outcome, Height, weight, head circumference, MUAC, 7 years Secondary Outcome, Height, weight, head circumference, MUAC, 7 years, 8-9 years, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Age ranges of repeated measures added, Clarified that these are years of age, post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Height, weight, head circumference, MUAC, 7 years, 8-9 years, 10-11 years Secondary Outcome, Height, weight, head circumference, MUAC, 7 years, 8-9 years, 10-11 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Age ranges of repeated measures added Secondary Outcome, Kaufmann subtest scores, SAT subtest scores, individual fine motor scores, Plus-EF subtest scores and reaction times, 7 years Secondary Outcome, Kaufmann subtest scores, SAT subtest scores, individual fine motor scores, Plus-EF subtest scores and reaction times, 7 years, 8-9 years, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Age ranges of repeated measures added, Clarified that these are years of age, post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Kaufmann subtest scores, SAT subtest scores, individual fine motor scores, Plus-EF subtest scores and reaction times, 7 years, 8-9 years, 10-11 years Secondary Outcome, Kaufmann subtest scores, SAT subtest scores, individual fine motor scores, Plus-EF subtest scores and reaction times, 7 years, 8-9 years, 10-11 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Age ranges of repeated measures added Secondary Outcome, Bioimpedance-based lean mass index, phase angle, 7 years Secondary Outcome, Bioimpedance-based lean mass index, phase angle, 7 years, 8-9 years, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Age ranges of repeated measures added, Clarified that years of age, post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Bioimpedance-based lean mass index, phase angle, 7 years, 8-9 years, 10-11 years Secondary Outcome, Bioimpedance-based lean mass index, phase angle, 7 years, 8-9 years, 10-11 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Age ranges of repeated measures added, and individual skinfold measurements specified Secondary Outcome, Sum of skinfold thickness, 7 years Secondary Outcome, Sum of skinfold thickness and individual skinfold thicknesses, 7 years, 8-9 years, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Age ranges of repeated measures added Secondary Outcome, Sum of skinfold thickness and individual skinfold thicknesses, 7 years, 8-9 years, 10-11 years Secondary Outcome, Sum of skinfold thickness, 7 years, 8-9 years, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Age ranges of repeated measures added. Clarified that years of age, post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Sum of skinfold thickness, 7 years, 8-9 years, 10-11 years Secondary Outcome, Sum of skinfold thickness, 7 years, 8-9 years, 10-11 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Clarified that 7 years of age, post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Knee- heel length, 7 years Secondary Outcome, Knee- heel length, 7 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Age ranges of repeated measures added, calf circumference measured at 7 years only Secondary Outcome, Waist circumference, calf circumference, , 7 years Secondary Outcome, Waist circumference, calf circumference 7year only, , 7 years, 8-9 years, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Age ranges of repeated measures added in years, calf circumference measured at 7 years of age only, Intervention finished at 18 months. Secondary Outcome, Waist circumference, calf circumference 7year only, , 7 years, 8-9 years, 10-11 years Secondary Outcome, Waist circumference, calf circumference 7year only, , 7 years, 8-9 years, 10-11 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Age ranges of repeated measures added note triceps and subscapular only for 8-9 and 10-11 years Secondary Outcome, Subscapular, triceps, suprailiac and calf skinfold thicknesses, 7 years Secondary Outcome, Subscapular, triceps, suprailiac and calf skinfold thicknesses, 7 years, 8-9 years, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Age ranges of repeated measures added note triceps and subscapular only for 8-9 and 10-11 years of age. Intervention finished at 18 months of age Secondary Outcome, Subscapular, triceps, suprailiac and calf skinfold thicknesses, 7 years, 8-9 years, 10-11 years Secondary Outcome, Subscapular, triceps, suprailiac and calf skinfold thicknesses, 7 years, 8-9 years, 10-11 years of age, post-interventions
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Age ranges of repeated measures added Secondary Outcome, Average grip strength for both hands, 7 years Secondary Outcome, Average grip strength for both hands, 7 years, 8-9 years, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Age ranges of repeated measures added. Clarified that years of age, post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Average grip strength for both hands, 7 years, 8-9 years, 10-11 years Secondary Outcome, Average grip strength for both hands, 7 years, 8-9 years, 10-11 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Age ranges of repeated measures added Secondary Outcome, Grip strength in dominant and non-dominant hand, 7 years Secondary Outcome, Grip strength in dominant and non-dominant hand, 7 years, 8-9 years, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Age ranges of repeated measures added. Clarified that years of age, post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Grip strength in dominant and non-dominant hand, 7 years, 8-9 years, 10-11 years Secondary Outcome, Grip strength in dominant and non-dominant hand, 7 years, 8-9 years, 10-11 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Age ranges of repeated measures added Secondary Outcome, Broad jump distance, 7 years Secondary Outcome, Broad jump distance, 7 years, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Age ranges of repeated measures added. Clarified that years of age, post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Broad jump distance, 7 years, 10-11 years Secondary Outcome, Broad jump distance, 7 years, 8-9 years, 10-11 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Age ranges of repeated measures added Secondary Outcome, Shuttle run test level, 7 years Secondary Outcome, Shuttle run test level, 7 years, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Age ranges of repeated measures added. Clarified that years of age, post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Shuttle run test level, 7 years, 10-11 years Secondary Outcome, Shuttle run test level, 7 years, 8-9 years, 10-11 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Clarified that 7 years of age, post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Composite outcome of combined standardised scores of grip strength, broad jump and shuttle run test, 7 years Secondary Outcome, Composite outcome of combined standardised scores of grip strength, broad jump and shuttle run test, 7 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Age ranges of repeated measures added Secondary Outcome, Resting blood pressure and blood pressure 1 minute after exercise, 7 years Secondary Outcome, Resting blood pressure and blood pressure 1 minute after exercise, 7 years, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Age ranges of repeated measures added. Clarified that years of age, post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Resting blood pressure and blood pressure 1 minute after exercise, 7 years, 10-11 years Secondary Outcome, Resting blood pressure and blood pressure 1 minute after exercise, 7 years, 10-11 years of age, post-intervention.
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 05/06/2023 The heart rate data continues to have challenges in storage and matching to the child and visit Secondary Outcome, resting heart rate, maximum heart rate, heart rate variability,, 7 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Clarified that 7 years of age, post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Haemoglobin level, 7 years Secondary Outcome, Haemoglobin level, 7 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Updated for age range measurements were performed Secondary Outcome, Acute illnesses in school age health and visits to traditional healer, clinic and hospital, 7 to 12 years Secondary Outcome, Acute illnesses in school age health and visits to traditional healer, clinic and hospital, 8 to 10 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Updated for age range measurements were performed. Clarified this is age in years, and post-intervention. The intervention finished at 18 months. Secondary Outcome, Acute illnesses in school age health and visits to traditional healer, clinic and hospital, 8 to 10 years Secondary Outcome, Acute illnesses in school age health and visits to traditional healer, clinic and hospital, 8 to 10 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 11/05/2023 Inclusion of annual monitoring visits that measure child growth, body composition, handgrip strength, literacy, numeracy and executive function once funding was confirmed from NIH. Secondary Outcome, Annual monitoring visits that measure child growth, body composition, handgrip strength, literacy, numeracy and executive function. , 8-12 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Inclusion of annual monitoring visits that measure child growth, body composition, handgrip strength, literacy, numeracy and executive function once funding was confirmed from NIH. Clarified this is post-intervention. The intervention finished at 18 months. Secondary Outcome, Annual monitoring visits that measure child growth, body composition, handgrip strength, literacy, numeracy and executive function. , 8-12 years Secondary Outcome, Annual monitoring visits that measure child growth, body composition, handgrip strength, literacy, numeracy and executive function. , 8-12 years of age, post-intervention.
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 01/06/2023 This has been added as a secondary outcome to be consistent with the Statistical Analysis Plan (SAP) previously published. Secondary Outcome, Child Socioemotional scale, 7 year visit
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 01/06/2023 Child socioemotional scale is also asked in annual visit Secondary Outcome, Child Socioemotional scale, 7 year visit Secondary Outcome, Child Socioemotional scale, 7 - 12 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Child socioemotional scale is also asked in annual visit. Clarified this is in years of age. The intervention finished at 18 months Secondary Outcome, Child Socioemotional scale, 7 - 12 years Secondary Outcome, Child Socioemotional scale, 7 - 12 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Additional measurements at age 10-11 years Secondary Outcome, Child WHO wellbeing total, Center for Epidemiology Studies Depression in Children CESDC score, SCARED anxiety score, self-efficacy, self-esteem, future orientation, highly sensitive personality, parent-child relationship, social support, bullying, school environment, loneliness, optimism scores, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Additional measurements at age 10-11 years. Clarified this is years of age and that this is post-intervention. The intervention finished at 18 months. Secondary Outcome, Child WHO wellbeing total, Center for Epidemiology Studies Depression in Children CESDC score, SCARED anxiety score, self-efficacy, self-esteem, future orientation, highly sensitive personality, parent-child relationship, social support, bullying, school environment, loneliness, optimism scores, 10-11 years Secondary Outcome, Child WHO wellbeing total, Center for Epidemiology Studies Depression in Children CESDC score, SCARED anxiety score, self-efficacy, self-esteem, future orientation, highly sensitive personality, parent-child relationship, social support, bullying, school environment, loneliness, optimism scores, 10-11 years of age, post-intervention. The intervention finished at 18 months.
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Updated to include 10-11 years measurements Secondary Outcome, Brain MRI measurements- Grey matter volume, white matter volume, regions of interest volume, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Updated to include 10-11 years measurements. Clarified this is in years of age and this is post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Brain MRI measurements- Grey matter volume, white matter volume, regions of interest volume, 10-11 years Secondary Outcome, Brain MRI measurements- Grey matter volume, white matter volume, regions of interest volume, 10-11 years of age, post-intervention.
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Updated to include measurements that will be performed at 10-11 years Secondary Outcome, Peripheral quantitative computed tomography pQCT bone and muscle indices, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Updated to include measurements that will be performed at 10-11 years of age. Clarified that this is post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Peripheral quantitative computed tomography -pQCT- bone and muscle indices, 10-11 years Secondary Outcome, Peripheral quantitative computed tomography -pQCT- bone and muscle indices, 10-11 years of age, post-intervention.
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Updated to include 10-11 years' measurements Secondary Outcome, Ultrasound measurements- heart echo shape and function, bilateral renal size, muscle cross-sectional area and echogenecity, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Updated to include 10-11 years' of age. Clarified that this is years of age. This is post-intervention. The intervention finished at 18 months of age. Secondary Outcome, Ultrasound measurements- heart echo shape and function, bilateral renal size, muscle cross-sectional area and echogenecity, 10-11 years Secondary Outcome, Ultrasound measurements- heart echo shape and function, bilateral renal size, muscle cross-sectional area and echogenecity, 10-11 years of age, post-intervention.
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Age ranges of repeated measures added, Secondary Outcome, Lung function from spirometry- FEV1 (Forced Expiratory Volume in 1 second) and FVC (Forced Vital Capacity), 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Additional measurements at age 10-11 years Secondary Outcome, Lung function from spirometry- FEV1 (Forced Expiratory Volume in 1 second) and FVC (Forced Vital Capacity), 10-11 years Secondary Outcome, Lung function from spirometry- FEV1 (Forced Expiratory Volume in 1 second) and FVC (Forced Vital Capacity)., 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Additional measurements at age 10-11 years Secondary Outcome, Lung function from spirometry- FEV1 (Forced Expiratory Volume in 1 second) and FVC (Forced Vital Capacity)., 10-11 years Secondary Outcome, Lung function from spirometry- FEV1 (Forced Expiratory Volume in 1 second) and FVC (Forced Vital Capacity), sitting height, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Additional measurements at age 10-11 years. Clarified this is years of age and that this is post-intervention. The intervention finished at 18 months. Secondary Outcome, Lung function from spirometry- FEV1 (Forced Expiratory Volume in 1 second) and FVC (Forced Vital Capacity), sitting height, 10-11 years Secondary Outcome, Lung function from spirometry- FEV1 (Forced Expiratory Volume in 1 second) and FVC (Forced Vital Capacity), sitting height, 10-11 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Additional measurements at age 10-11 years Secondary Outcome, Pulse wave velocity PWV, Augmentation index and central blood pressure, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Additional measurements at age 10-11 years. Clarified this is years of age and that this is post-intervention. The intervention finished at 18 months. Secondary Outcome, Pulse wave velocity PWV, Augmentation index and central blood pressure, 10-11 years Secondary Outcome, Pulse wave velocity PWV, Augmentation index and central blood pressure, 10-11 years of age, post-intervention.
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Additional measurements at age 10-11 years Secondary Outcome, Event related potentials - substudy in 150 children., 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Additional measurements at age 10-11 years Secondary Outcome, Event related potentials - substudy in 150 children., 10-11 years Secondary Outcome, Event related potentials ERP - substudy in 150 children 75 HEU 75 HUU, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Additional measurements at age 10-11 years. Clarified this is years of age and that this is post-intervention. The intervention finished at 18 months. Secondary Outcome, Event related potentials ERP - substudy in 150 children 75 HEU 75 HUU, 10-11 years Secondary Outcome, Event related potentials ERP - substudy in 150 children 75 HEU 75 HUU, 10-11 years of age, post-intervention.
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Additional measurements at age 10-11 years Secondary Outcome, Verbal fluency subtotal, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Additional measurements at age 10-11 years Secondary Outcome, Verbal fluency subtotal, 10-11 years Secondary Outcome, Verbal fluency total, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Additional measurements at age 10-11 years. Clarified this is years of age and that this is post-intervention. The intervention finished at 18 months. Secondary Outcome, Verbal fluency total, 10-11 years Secondary Outcome, Verbal fluency total, 10-11 years of age, post-intervention.
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Additional measurements at age 10-11 years Secondary Outcome, Jump plate mechanography- Maximum jump power, efficiency of the motion, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Additional measurements at age 10-11 years. Clarified this is years of age and that this is post-intervention. The intervention finished at 18 months. Secondary Outcome, Jump plate mechanography- Maximum jump power, efficiency of the motion, 10-11 years Secondary Outcome, Jump plate mechanography- Maximum jump power, efficiency of the motion, 10-11 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Additional measurements at age 10-11 years Secondary Outcome, Heart rate variability, maximum heart rate, time to recover from maximal exercise, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Additional measurements at age 10-11 years. Clarified this is years of age and that this is post-intervention. The intervention finished at 18 months. Secondary Outcome, Heart rate variability, maximum heart rate, time to recover from maximal exercise, 10-11 years Secondary Outcome, Heart rate variability, maximum heart rate, time to recover from maximal exercise, 10-11 years of age. Post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Additional measurements at age 10-11 years Secondary Outcome, Hair cortisol, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Additional measurements at age 10-11 years. Clarified this is years of age and that this is post-intervention. The intervention finished at 18 months. Secondary Outcome, Hair cortisol, 10-11 years Secondary Outcome, Hair cortisol, 10-11 years of age, post-intervention.
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Additional measurements at age 10-11 years Secondary Outcome, Blood metabolic, inflammatory and micronutrient markers, metabolomics, transcriptomics, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Additional measurements at age 10-11 years. Clarified this is years of age and that this is post-intervention. The intervention finished at 18 months. Secondary Outcome, Blood metabolic, inflammatory and micronutrient markers, metabolomics, transcriptomics, 10-11 years Secondary Outcome, Blood metabolic, inflammatory and micronutrient markers, metabolomics, transcriptomics, 10-11 years of age, post-intervention.
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 08/10/2025 Additional measurements at age 10-11 years Secondary Outcome, Urine renal markers and urine metabolomics, 10-11 years
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 30/10/2025 Additional measurements at age 10-11 years. Clarified this is years of age and that this is post-intervention. The intervention finished at 18 months. Secondary Outcome, Urine renal markers and urine metabolomics, 10-11 years Secondary Outcome, Urine renal markers and urine metabolomics, 10-11 years of age, post-intervention
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 11/05/2023 Shortened CRF 96 (caregiver questionnaire) and CRF 97 (child assessment form) to enable annual monitoring visits with reduced reporting burden for the study participant. Updated CRF 98 (community sensitisation form) to describe the shortened annual monitoring visits. Added an updated study participant exit form (CRF 101). TRUE, Medical Research Council of Zimbabwe, 20 Cambridge Rd, Harare, H20, Zimbabwe, , 17 Apr 2023, 00263242791193, mrcz@mrcz.org.zw, 16147_24391_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 08/10/2025 MRCZ Approval for pilot for the measurements at age 10-11 years for school-aged follow-up. TRUE, Medical Research Council of Zimbabwe, 20 Cambridge Rd, Harare, H20, Zimbabwe, , 10 May 2024, 00263242791193, mrcz@mrcz.org.zw, 16147_33246_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 08/10/2025 MRCZ Approval for the measurements at age 10-11 years for school-aged follow-up. TRUE, Medical Research Council of Zimbabwe, 20 Cambridge Rd, Harare, Harare, H20, Zimbabwe, , 16 Sep 2024, 00263242791193, mrcz@mrcz.org.zw, 16147_33247_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 08/10/2025 MRCZ Approval for additional measurements at age 10-11 years for school-aged follow-up. TRUE, Medical Research Council of Zimbabwe, 20 Cambridge Rd, Harare, Harare, H20, Zimbabwe, , 04 Feb 2025, 00263242791193, mrcz@mrcz.org.zw, 16147_33248_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 08/10/2025 MRCZ Approval for additional measurements at age 10-11 years for school-aged follow-up. TRUE, Medical Research Council of Zimbabwe, 20 Cambridge Rd, Harare, Harare, H20, Zimbabwe, , 09 Apr 2025, 00263242791193, mrcz@mrcz.org.zw, 16147_33249_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 08/10/2025 MRCZ Approval for additional measurements at age 10-11 years for school-aged follow-up. TRUE, Medical Research Council of Zimbabwe, 20 Cambridge Rd, Harare, Harare, H20, Zimbabwe, , 31 Jul 2025, 00263242791193, mrcz@mrcz.org.zw, 16147_33250_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Funding Source FundingSources List 08/10/2025 Additional funding for 10-11 years measurement Medical Research Council UK, Polaris House, North Star Avenue, Swindon, , Swindon, SN2 1FL, United Kingdom, Funding Agency,
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 17/10/2025 Addition of measures of child mental health and wellbeing Professor Michael Pluess, University of Surrey, Guildford, GU2 7JN, United Kingdom