Early Life Exposures And Development Of Non-communicable Diseases In Adolescence: The Drakenstein Child Health Study

Non-communicable diseases are a major cause of ill health and premature death globally, with a particularly large burden in low- and middle-income countries. These include many common diseases, including respiratory disorders such as asthma and chronic obstructive pulmonary disease, heart disease, obesity, diabetes and mental illness. In low- and middle-income countries, these diseases occur at an earlier age and are more severe compared to high-income countries. Studies from high-income countries have shown that the roots of these diseases lie in childhood, and that their development through the life course tracks from early childhood into adolescence and adulthood. The burden and the type of exposures which adversely affect their development, such as pneumonia, tuberculosis, cigarette smoke, biomass exposure, allergens or intense level of stress, are very different in Africa compared to high-income countries. However, despite the high number of affected people and higher severity of non-communicable diseases, as well as many harmful environmental exposures, there are no data on early-life factors associated with their development in Africa.
Adolescence is an important period during which non-communicable diseases emerge and in which behaviours or exposures such as heightened risk-taking (for example smoking) and increased risk of infections (such as TB) may affect disease development. Importantly, adolescence is a period in which we may intervene to improve lifetime health. However, there are very limited studies on non-communicable diseases or early-life determinants in adolescents in low- and middle-income countries, especially in Africa. Identifying these is crucial to develop ways to prevent these diseases and reduce their burden.

Building on a unique South African birth cohort, the Drakenstein Child Health study, we wish to establish a resource for detailed study of non-communicable diseases in African adolescents and help researchers around the world to access many valuable datasets. To achieve this, in our study of 1000 mother-child pairs, we collected detailed measures of infectious diseases and non-infectious exposures through pregnancy and childhood, stored their biological samples, and completed repeated measurements of health from birth to age 8 years. We now propose to follow participants through the critical period of adolescence from 9 to 15 years of age, to measure heath status across broad domains (respiratory, heart disease, obesity, diabetes, mental health), and assess ongoing exposures. We will collect biological samples through this time, adding to the existing repository to enable many future studies to address mechanisms of how these diseases develop. We will consolidate and verify different data sets, so that they can be easily accessed and reused, thereby enhancing their global value. This will create a unique resource unparalleled anywhere in low- and middle-income countries, for study of non-communicable diseases.

We will bring together leading UK, South African and Australian experts, building African research capacity through collaborations and training. Our overall vision is to inform the development of intervention strategies to reduce the risk of non-communicable diseases and improve health during the key period of adolescence and into adulthood. This will be very important for the development of new strategies reduce disease burden, prevent ill health and premature death, an area of critical need.

Non-communicable diseases (NCDs) are increasing globally, with a disproportionate burden in low- and middle-income countries (LMICs), where more than three quarters of global NCD deaths occur. Further, in LMICs, NCDs occur at an earlier age and with greater severity than in high-income countries. Adolescence is a key developmental period during which NCD phenotypes emerge, and specific behaviours or exposures may promote or prevent disease development. However, despite the high prevalence and severity of NCDs and many harmful environmental exposures, there are very limited data on NCD phenotypes or determinants in adolescents in LMICs.

This proposal builds on our work in the Drakenstein Child Health Study (DCHS), a birth cohort of 1000 exceptionally well phenotyped South African children who have been followed from antenatal period through age 8 years, including longitudinal assessment of symptoms, growth, adiposity, lung function, neurocognitive development and mental health measures, linked with a comprehensive collection of early life exposures, and very high retention (90%). We will extend the follow-up in DCHS through the critical period into adolescence (age 15years) with detailed phenotyping, measurements of relevant exposures and collection of biological material for research. We will apply FAIR (Findability, Accessibility, Interoperability, Reusability) guiding principles for data management and stewardship to enable efficient and error-free data analysis and increase reusability. Phenotypic data and linked samples in a biorepository will form an invaluable resource for research globally on adolescent NCDs (respiratory, cardio-vascular, mental health). FAIRified data assets will ensure wide global use and optimise potential impact. The overall vision is to identify modifiable risk factors and inform development of intervention strategies to reduce the risk of NCDs and prevent morbidity and premature death in African populations, an area of critical need.