Identifying biomarkers of neurodevelopmental and mental health outcomes in a prospective longitudinal cohort of South African children: design and feasibility of the Safe Passage BONO study

BACKGROUND: Early adversities before and after birth can impact children's cognitive and socioemotional development by altering critical brain maturational and functional processes. Some of these processes may be linked to later neurodevelopmental and/or mental health conditions. While most research is conducted in high-income countries, the majority of children live in low- and middle-income countries (LMICs) where they are more frequently exposed to poverty-related adversities. To address this gap, well-characterised longitudinal pregnancy cohorts in LMICs are needed to track trajectories of neurodevelopmental and mental health conditions in children exposed to cumulative environmental adversities. The Safe Passage Study (SPS) originally enrolled 7060 pregnant women from socioeconomically disadvantaged peri-urban communities in Cape Town, South Africa, to investigate the association between prenatal alcohol, multiple environmental risk factors and pregnancy outcome. The Safe Passage-Biomarkers of Neurodevelopmental Outcomes (BONO) study aims to follow up 2000 SPS children, aged 4-16 years, to assess the role of pre- and postnatal environmental factors in cognitive, neurodevelopmental and mental health outcomes. This report outlines the design and results of a feasibility study with 100 children, primarily aimed to confirm recruitment, assess participant retention, select measures and establish criteria for a deep-phenotyping visit. METHODS: Between March and October 2019, 100 SPS children were screened during a "broad-phenotyping visit" for adverse childhood experiences and protective factors, autistic traits and socioemotional and behavioural symptoms, and they completed cognitive tests and eye-tracking and electroencephalography assessments to measure brain function. Criteria for a second "deep-phenotyping" visit were established based on autistic traits, internalising/externalising scores and/or cognitive difficulties, to assess children and their mothers in terms of clinical and neurocognitive profile. RESULTS: Recruitment was adequate with a 96% retention rate for the deep-phenotyping visit. Feasibility study participants resembled the larger SPS cohort in most demographic and prenatal factors, except for higher prenatal depression and overcrowding indices. Most clinical and experimental measures were deemed suitable with minor modifications, and acquisition rates were high. The nature and length of visits were acceptable to families and testers. Threshold scores were adjusted to include 30% of participants for deep phenotyping. CONCLUSIONS: The feasibility study fulfilled progression criteria for the planned multimodal study.