The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods
Kerina Duri, Felicity Zvanyadza Gumbo, Privilege Tendai Munjoma, Precious Chandiwana, Kudakwashe Mhandire, Asaph Ziruma, Andrew J. Macpherson, Simbarashe Rusakaniko, Exnevia Gomo, Benjamin Misselwitz, Lovemore Ronald Mazengera, the UZ-CHS Birth Cohort Team, Marcus Altfeld, Madeleine J. Bunders, Stephanie Jones, Collet Dandara, V. Mleya, Julia Mutambara, Gwendoline Kandawasvika, Patience Kuona, Simbarashe Chimhuya, Rudo Nyamakura, Sekesai Mtapuri‐Zinyowera, S. P. Chandiwana, C. Marashiki, Hope Mataramvura, E. Mazengera, N. Taremeredzwa
Abstract
BACKGROUND: Commencing lifelong antiretroviral therapy (ART) immediately following HIV diagnosis (Option B+), has greatly improved maternal-infant health. Thus, large and increasing numbers of HIV-infected women are on ART during pregnancy, a situation concurrently increasing numbers of HIV-exposed-uninfected (HEU) infants. Compared to their HIV-unexposed-uninfected (HUU) counterparts, HEU infants show higher rates of adverse birth outcomes, mortality, infectious/non-communicable diseases including impaired growth and neurocognitive development. There is an urgent need to understand the impact of HIV and early life ART exposures, immune-metabolic dysregulation, comorbidities and environmental confounders on adverse paediatric outcomes. METHODS: Six hundred (600) HIV-infected and 600 HIV-uninfected pregnant women ≥20 weeks of gestation will be enrolled from four primary health centres in high density residential areas of Harare. Participants will be followed up as mother-infant-pairs at delivery, week(s) 1, 6, 10, 14, 24, 36, 48, 72 and 96 after birth. Clinical, socio-economic, nutritional and environmental data will be assessed for adverse birth outcomes, impaired growth, immune/neurodevelopment, vertical transmission of HIV, hepatitis-B/C viruses, cytomegalovirus and syphilis. Maternal urine, stool, plasma, cord blood, amniotic fluid, placenta and milk including infant plasma, dried blood spot and stool will be collected at enrolment and follow-up visits. The composite primary endpoint is stillbirth and infant mortality within the first two years of life in HEU versus HUU infants. Maternal mortality in HIV-infected versus -uninfected women is another primary outcome. Secondary endpoints include a range of maternal and infant outcomes. Sub-studies will address maternal stress and malnutrition, maternal-infant latent tuberculosis, Helicobacter pylori infections, immune-metabolomic dysregulation including gut, breast milk and amniotic fluid dysbiosis. DISCUSSION: The University of Zimbabwe-College of Health-Sciences-Birth-Cohort study will provide a comprehensive assessment of risk factors and biomarkers for HEU infants' adverse outcomes. This will ultimately help developing strategies to mitigate effects of maternal HIV, early-life ART exposures and comorbidities on infants' mortality and morbidity. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT04087239 . Registered 12 September 2019.