The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods

Kerina Duri, Felicity Z Gumbo, Privilege T Munjoma, Precious Chandiwana, Kudakwashe Mhandire, Asaph Ziruma, Andrew Macpherson, Simbarashe Rusakaniko, Exnevia Gomo, Benjamin Misselwitz, Lovemore Ronald Mazengera, UZ-CHS Birth Cohort Team, M Altfeld, M Bunders, S Rowland Jones, C Dandara, V Mleya, J Mutambara, G Kandawasvika, P Kuona, S Chimhuya, R Nyamakura, S Mtapuri-Zinyowera, S P Chandiwana, C Marashiki, H Mataramvura, E Mazengera, N Taremeredzwa, Kerina Duri, Felicity Z Gumbo, Privilege T Munjoma, Precious Chandiwana, Kudakwashe Mhandire, Asaph Ziruma, Andrew Macpherson, Simbarashe Rusakaniko, Exnevia Gomo, Benjamin Misselwitz, Lovemore Ronald Mazengera, UZ-CHS Birth Cohort Team, M Altfeld, M Bunders, S Rowland Jones, C Dandara, V Mleya, J Mutambara, G Kandawasvika, P Kuona, S Chimhuya, R Nyamakura, S Mtapuri-Zinyowera, S P Chandiwana, C Marashiki, H 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.

Keywords: Adverse birth outcomes; Breastfeeding; Immune-metabolic dysfunction; Maternal comorbidities; Microbiota dysbiosis; Neonatal/infant/childhood adverse outcomes; Perinatal HIV/ART exposures; Resource limited setting.

Conflict of interest statement

Authors have no competing interests.

Figures

Fig. 1
Fig. 1
Main Study and sub-studies Flow Diagram. ART: Antiretroviral therapy, BM: Breast milk, Co-infections include hepatitis B virus, hepatitis C virus, CMV:cytomegalovirus, and intestinal parasites. HEI: HIV exposed and infected, HEU: HIV exposed but uninfected HIV: Human immunodeficiency virus, HUU: HIV unexposed and uninfected, MIPs: Mother -infant pairs, NCD: Non-communicable diseases and these include hypertensive disorders, malnutrition and diabetes, STIs: Sexually transmitted infections

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