Zambia Infant Cohort Study - Brains Optimized for Surviving and Thriving (ZICS-BOOST)

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).

Study Overview

• Status: Completed
• Conditions: Child Development
• Intervention / Treatment: Other: ECD intervention for CHEUs; Other: Usual care for CHEUs

• Study Type: Interventional
• Enrollment (Actual): 469
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University School of Public Health
• Zambia
  • Longacres
    • Lusaka, Longacres, Zambia
      • Right to Care Zambia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 9 months (Child)
• Accepts Healthy Volunteers: No

Description

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 26 weeks gestation by ultrasound

Exclusion Criteria:

• Mother-infant dyads not enrolled in ZICS
• Mother-infant dyads where mother is <18 years of age

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1- CHEU + ECD intervention; Participants randomized to this arm will receive a bi-weekly community health worker-delivered ECD intervention for CHEUs	Other: ECD intervention for CHEUs; 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
Active Comparator: Arm 2- CHEU without ECD intervention; 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; 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.
Active Comparator: Arm 3- HIV Unexposed (HUU) without ECD intervention; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurodevelopment at 18 months post enrollment	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.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurodevelopment at 6 months post enrollment	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.	6 months
Language development at 6, 12, and 18 months post enrollment	Children's language development will be assessed at 12 and 24 months using an adapted MacArthur-Bates Communicative Development Inventories (CDI) tool.	6 months. 12 months, 18 months
Child's age-specific tasks at 6, 12, and 18 months post enrollment	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.	6 months, 12 months, 18 months
Caregiver mental health and wellbeing at 6, 12 and 18months post enrollment	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.	6 months, 12 months, 18 months

Collaborators and Investigators

• Sponsor: Boston University
• Collaborators: Thrasher Research Fund
• Investigators: Principal Investigator: Julie M Herlihy, MD MPH, BU School of Public Health; Principal Investigator: Ethan Zulu, MBChB MSc, Right to Care - Zambia

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2022
• Primary Completion (Actual): October 31, 2024
• Study Completion (Actual): October 31, 2024

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: November 3, 2021
• First Posted (Actual): November 15, 2021

Study Record Updates

• Last Update Posted (Estimated): November 1, 2024
• Last Update Submitted That Met QC Criteria: October 31, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Home visits; Community health workers; Zambia; Children exposed to HIV in-utero but uninfected (CHEUs); Early childhood developmental (ECD) interventions
• Other Study ID Numbers: H-42282

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No