Zambia Infant Cohort Study - Brains Optimized for Surviving and Thriving

Study Overview
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Brief Summary
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Children exposed to HIV in-utero but uninfected (CHEUs) number 14.8 million globally. In Zambia, an estimated 56,000 CHEUs are born annually, a staggering fraction of the national birth cohort. Multiple studies establish that CHEUs are more neurodevelopmentally vulnerable than HIV-unexposed peers. In Zambia, there are existing effective early childhood developmental (ECD) interventions that target other vulnerable populations, but never trialed specifically for CHEUs. Scaling up ECD is now a priority of Zambia's national strategy, but CHEUs are not currently targeted. There is a need to better understand the scope and mechanism of CHEU-related neurodevelopmental differences and what interventions are most effective. This randomized clinical trial (RCT) is a true effectiveness trial as the intervention will deploy a home-based adaptation of the same curriculum that is currently used elsewhere in the country, named Scaling Up Early Childhood Development In Zambia (SUPERCDZ). The effectiveness of a scalable early childhood development (ECD) intervention for CHEUs will be evaluated using normalized Z-scores of neurodevelopmental testing at age 24 months. In this RCT the investigators will test the following hypotheses: Hypothesis 1: An ECD intervention delivered by community health workers via bi-weekly home visits will improve neurodevelopmental outcomes in CHEUs. Hypothesis 2: CHEUs have significantly worse neurodevelopmental outcomes than unexposed peers at 24 months, mediated by preterm birth, disease stage or antiretroviral (ARV) exposure. This RCT will build on an existent, actively recruiting cohort of 1500 pregnant women-infant dyads in a peri-urban hospital in Zambia, the Zambian Infant Cohort Study (ZICS), by extending the follow-up of a subsample of infants from 6 months to 2 years amongst the last 525 children enrolled (ZICS-BOOST- Brains Optimized to Survive and Thrive). The study will have three arms: Arm 1) CHEU + ECD intervention (n=175); Arm 2) CHEU without ECD intervention (n=175); Arm 3) HUU without intervention (n=175).

Official Title
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Zambia Infant Cohort Study - Brains Optimized for Surviving and Thriving

Conditions
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Child Development

Intervention / Treatment
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* Other: ECD intervention for CHEUs
* Other: Usual care for CHEUs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Zambia Infant Cohort Study (ZICS) cohort participants who are >18 years old AND are still pregnant OR whose infants are less than 9 months of age by February 2022. ZICS inclusion criteria were pregnant women (1:1, HIV+:HIV-) presenting for antenatal care at Chawama First Level Hospital and intending to deliver at Chawama First Level Hospital and less than 24 weeks gestation by ultrasound Exclusion Criteria: Mother-infant dyads not enrolled in ZICS or ZICS infants who are older than 9 months of age by February 1, 2022. Mother-infant dyads where mother is < 18 years of age

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 9 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1- CHEU + ECD intervention<br>Participants randomized to this arm will receive a bi-weekly community health worker-delivered ECD intervention for CHEUs | Other: ECD intervention for CHEUs<br>* The bi-weekly community health worker-delivered ECD 1 hour intervention using the modules from the SUPERCDZ curriculum which is a Zambian adaptation of UNICEF's Nurturing Care Framework<br>|
| Active Comparator: Arm 2- CHEU without ECD intervention<br>Participants randomized to this arm will receive the current Ministry of Health (MoH) standard of care with no formalized routine assessment of neurodevelopment. | Other: Usual care for CHEUs<br>* No ECD interventions will be provided by community health workers. Children will be followed at clinics for growth and monitoring, vaccinations on a MoH approved schedule.<br>|
| Active Comparator: Arm 3- HIV Unexposed (HUU) without ECD intervention<br>Participants randomized to this arm will receive the current Ministry of Health (MoH) standard of care with no formalized routine assessment of neurodevelopment. | Other: Usual care for CHEUs<br>* No ECD interventions will be provided by community health workers. Children will be followed at clinics for growth and monitoring, vaccinations on a MoH approved schedule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurodevelopment at 24 months | The Malawi Developmental Assessment Tool (MDAT) will be used to assess neurodevelopment. MDAT provides an independent evaluation of development in the domains of gross motor, fine motor, language and social skills. The MDAT can be administered in any environment as it requires minimal equipment and is more culturally relevant to our context. The scores from the MDAT are relatable and comparable to those obtained from the Bayley Scales of Infant and Toddler Development 3rd Edition (BSID-III). Primary outcomes will be z-scores from four neurodevelopmental domain measurements-gross motor, fine motor, language, and social. | 24months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurodevelopment at 12 months | The Malawi Developmental Assessment Tool (MDAT) will be used to assess neurodevelopment. MDAT provides an independent evaluation of development in the domains of gross motor, fine motor, language and social skills. The MDAT can be administered in any environment as it requires minimal equipment and is more culturally relevant to our context. The scores from the MDAT are relatable and comparable to those obtained from the BSID-III. Primary outcomes will be z-scores from four neurodevelopmental domain measurements-gross motor, fine motor, language, and social. | 12 months | 
| Language development at 12 months | Children's language development will be assessed at 12 and 24 months using an adapted MacArthur-Bates Communicative Development Inventories (CDI) tool. | 12 months | 
| Language development at 24 months | Children's language development will be assessed at 12 and 24 months using an adapted MacArthur-Bates Communicative Development Inventories (CDI) tool. | 24 months | 
| Quality of child's environment at 12 months | The Home Observation Measurement of the Environment-Short Form (HOME-SF) will be used to asses the quality of the child's environment. HOME for children 0-3 is designed to observe parental responsivity, acceptance of the child, organization of the environment, learning materials, parental involvement, and variety within the home environment through 45 items. | 12 months | 
| Quality of child's environment at 24 months | The Home Observation Measurement of the Environment-Short Form (HOME-SF) will be used to asses the quality of the child's environment. HOME for children 0-3 is designed to observe parental responsivity, acceptance of the child, organization of the environment, learning materials, parental involvement, and variety within the home environment through 45 items. | 24 months | 
| Child's age-specific tasks at 24 weeks | The Caregiver Reported Early Development Instrument (CREDI) will be used to assess age-specific tasks for early childhood 0-36 months. It is intended to be used at a population level to detect developmental delay, not as an individual diagnostic tool. This open-source, psychometrically sound tool has been tested in over 15 low-and-middle-income countries and is culturally and linguistically neutral. When deployed in its long form it can be analyzed by specific developmental domains including (motor, language and cognitive, socio-emotional). CREDI scores per arm will be described in z-scores from four neurodevelopmental domain measurements. | 24 weeks | 
| Child's age-specific tasks at 12 months | The Caregiver Reported Early Development Instrument (CREDI) will be used to assess age-specific tasks for early childhood 0-36 months. It is intended to be used at a population level to detect developmental delay, not as an individual diagnostic tool. This open-source, psychometrically sound tool has been tested in over 15 low-and-middle-income countries and is culturally and linguistically neutral. When deployed in its long form it can be analyzed by specific developmental domains including (motor, language and cognitive, socio-emotional). CREDI scores per arm will be described in z-scores from four neurodevelopmental domain measurements. | 12 months | 
| Child's age-specific tasks at 18 months | The Caregiver Reported Early Development Instrument (CREDI) will be used to assess age-specific tasks for early childhood 0-36 months. It is intended to be used at a population level to detect developmental delay, not as an individual diagnostic tool. This open-source, psychometrically sound tool has been tested in over 15 low-and-middle-income countries and is culturally and linguistically neutral. When deployed in its long form it can be analyzed by specific developmental domains including (motor, language and cognitive, socio-emotional). CREDI scores per arm will be described in z-scores from four neurodevelopmental domain measurements. | 18 months | 
| Child's age-specific tasks at 24 months | The Caregiver Reported Early Development Instrument (CREDI) will be used to assess age-specific tasks for early childhood 0-36 months. It is intended to be used at a population level to detect developmental delay, not as an individual diagnostic tool. This open-source, psychometrically sound tool has been tested in over 15 low-and-middle-income countries and is culturally and linguistically neutral. When deployed in its long form it can be analyzed by specific developmental domains including (motor, language and cognitive, socio-emotional). CREDI scores per arm will be described in z-scores from four neurodevelopmental domain measurements. | 24 months | 
| Caregiver mental health and wellbeing at 24 weeks | The Self-Reporting Questionnaire 20 (SQR-20) will be used to assess Caregiver mental health and wellbeing. The SQR-20 has 20 questions that assess for common mental health conditions and common physical manifestations of depression or anxiety (e.g., poor appetite, poor sleep, anhedonia). There are 20 questions and more yes answers correlate with higher risk for mental health concerns. | 24 weeks | 
| Caregiver mental health and wellbeing at 12 months | The Self-Reporting Questionnaire 20 (SQR-20) will be used to assess Caregiver mental health and wellbeing. The SQR-20 has 20 questions that assess for common mental health conditions and common physical manifestations of depression or anxiety (e.g., poor appetite, poor sleep, anhedonia). There are 20 questions and more yes answers correlate with higher risk for mental health concerns. | 12 months | 
| Caregiver mental health and wellbeing at 18 months | The Self-Reporting Questionnaire 20 (SQR-20) will be used to assess Caregiver mental health and wellbeing. The SQR-20 has 20 questions that assess for common mental health conditions and common physical manifestations of depression or anxiety (e.g., poor appetite, poor sleep, anhedonia). There are 20 questions and more yes answers correlate with higher risk for mental health concerns. | 18 months | 
| Caregiver mental health and wellbeing at 24 months | The Self-Reporting Questionnaire 20 (SQR-20) will be used to assess Caregiver mental health and wellbeing. The SQR-20 has 20 questions that assess for common mental health conditions and common physical manifestations of depression or anxiety (e.g., poor appetite, poor sleep, anhedonia). There are 20 questions and more yes answers correlate with higher risk for mental health concerns. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Children exposed to HIV in-utero but uninfected (CHEUs), Early childhood developmental (ECD) interventions, Community health workers, Home visits, Zambia