Overview of On-going Research

To fulfill its mandate, DPHRU applies a life-course epidemiological approach to study and understand how biological and environmental exposures, particularly in early life (foetal, infancy and childhood), subvert physiological and other developmental systems resulting in latent vulnerabilities. These vulnerabilities, together with adversities and adjustments occurring during other critical developmental periods (childhood and adolescence) lead to long-term risk of poor adult health, and even extend across generations. Consequently, the research activities of DPHRU cover various developmental stages of the life-course: from pregnancy to ageing adults.

Longitudinal Studies

Birth to Twenty Plus Cohort (Bt20+)

One of DPHRU’s flagship projects is the Bt20+ cohort (3273 mothers and their newborns) that was established in 1990 in Soweto-Johannesburg and continues to be followed. Currently, the cohort participants are 25 years of age and nearly 70% are still in contact with the study. The latest wave of data collection has recently been completed and focused on transitions to adulthood (education; livelihoods; final adult height; metabolic disease risk). One of the key hypotheses tested was whether participants who experience both early life-growth failure and later-childhood obesity have increased cardiometabolic risk (blood pressure, glucose metabolism, adiposity) as young adults.

Adolescence and the pubertal growth spurt is critical in the attainment of final adult bone mass, and therefore, if bone accretion can be optimized during this period, then peak bone mass will be higher and fracture risk in later life lower. DPHRU took the opportunity afforded by the Bt20+ cohort, to specifically study a sub-cohort and investigate the factors influencing bone mass during adolescence in an urban South African environment. Approximately 475 black and white children from the Bt20+ cohort were enrolled into the Bone Health Cohort at the age of 9 years and have been studied annually since then. We completed the last data collection wave (young adulthood) of this longitudinal study in 2012 and data analyses are underway.

From the Bt20+ cohort, a sample of over 1000 urban Black women (mothers/caregivers), were enrolled into a longitudinal study investigating the cardiometabolic risk, and hormonal and body composition profile of these women across the menopausal transition. This is the longest running study of women’s ageing and health in South Africa.

Bt20+ is at a stage where it is possible to examine the impact of personal, social and family history on child, adolescent and adult health and wellbeing across generations. We have information on four generations. We have limited information about Generation zero (0G) the grandparents of the Bt20 cohort through health histories obtained from the Generation 1 (1G) women who gave birth to the Generation 2 (2G) cohort in 1990. Information on 1G women and their 2G offspring has been obtained prospectively on 22 repeated occasions. The 2G cohort have begun to have their own children (Generation 3; 3G). We have been enrolling the 3G cohort into a study investigating the effect of exposures over two generations on infant biological outcomes assessed in the third generation.

Consortium of Health Orientated Research in Transitioning Societies (COHORTS)

The COHORTS collaboration of 5 birth cohorts (Brazil, India, Guatemala, Philippines and South Africa), of which Bt20+ is one, was formed to conduct pooled analyses on maternal and child health and nutrition. A major focus of COHORTS has been the development of an approach to data analysis that takes into account: (i) the heterogeneity of methods and timing of data collection; and (ii) the correlation over time of measures of growth obtained from a panel of individuals representing the various cohorts. Currently we are focusing on how early life nutrition and socioeconomic conditions impact on later adult health (cardiometabolic risk) and human capital (education) outcomes.

Women’s Bone Study (WBS): An investigation into changes in bone mineral density and vitamin D status in urban, South African HIV positive women and HIV negative controls

HIV and osteoporosis are global public health concerns, and over the last decade there has been an appreciation that HIV infection, and use of antiretroviral medication (ART) to treat HIV, are associated with low vitamin D concentrations and bone mineral density (BMD). To date there have been only a few longitudinal studies in the field of HIV-ART-VitaminD-Bone interactions in Sub Saharan Africa where the burden of HIV is the greatest. WBS is investigating the effect of HIV and ART on vitamin D status and BMD, as well as cardiometabolic risk, in urban South African women. It is also assessing the role of diet, physical activity, socio-economic status and sunlight exposure on these parameters. Over 245 women from Soweto, Johannesburg has been followed up longitudinally. These women are both HIV-positive and negative; the HIV positive group are further divided into those requiring initiation of ART and those not yet eligible for ART (as per South African Department of Health national guidelines). Participants have completed their 0, 6, 12 and 24 month data collection visits. At each visit women underwent blood and urine testing, anthropometry, DXA and pQCT scanning and a variety of socio-demographic, physical activity and dietary intake questionnaires. Baseline laboratory analysis and imaging has taken place prior to initiation of ART so that changes can be monitored over time. WBS is a collaborative study between DPHRU and the MRC Human Nutrition Research Unit in Cambridge, UK.

Soweto First 1000 Days Cohort (S1000)

S1000 is a prospective pregnancy cohort in Soweto, which aims to enrol over 5000 women recruited 14 weeks pregnant with frequent follow up (14x in total) during pregnancy (5x), at delivery, and during the first two years of infancy (8x). S1000 aims to address the independent and interactive effects of multiple maternal morbidities and factors (obesity, gestational hypertension, gestational diabetes, anaemia, depression, and HIV) on foetal growth (ultrasound (4D) scanning), pregnancy outcomes, and infant growth, body composition and development. S1000 is contributing data to a consortium of 7 country sites (University of Oxford is the co-ordinating centre; Gates Foundation funded) to study foetal growth during pregnancy and delivery outcomes to better understand the causes of intrauterine growth restriction, small for gestational age and preterm birth syndromes.

Prevalence of Gestational Diabetes and the Study of Growth and Body Composition of Infants Born to Gestational Diabetic Mothers

3000 pregnant Soweto women will be screened for gestational diabetes (GDM) by an oral glucose tolerance test to estimate the prevalence of GDM in Soweto. Those women that are diagnosed with GDM will be surveyed post-partum around health service access and treatment, and a group of mothers and infants will be followed every 4 weeks for 6 months to examine infant growth and body composition and compared to a control group of non-GDM exposed infants.

Cross-Sectional Studies

H3Africa Collaborative Centre research study: genomic and environmental risk factors for cardiometabolic disease in Africans

The Sydney Brenner Institute for Molecular Bioscience at Wits was awarded one of nine worldwide prestigious Human Heredity and Health in Africa (H3Africa) research grants by the two funding organisations, the U.S. National Institutes of Health (NIH) and the Wellcome Trust. Our research grant is funded by the NIH and is for an H3Africa Collaborative Centre. The long-term vision of the Collaborative Centre is to build capacity in Africa for research that leads to an understanding of and response to the interplay between genetic, epigenetic and environmental risk factors for obesity and associated cardiometabolic disease in sub-Saharan Africa. Soweto is 1 of 6 collaborating sites across Africa. Each site will collect phenotypic data and DNA on 1000 women and 1000 men age 40-60 years to understand the genomic architecture of sub-Saharan African populations and its impact on disease susceptibility; and to identify genetic, genomic and environmental risk factors for obesity by leveraging on existing longitudinal cohorts and adding a genomic dimension to the research.

Intervention Studies

Project Ntshembo (Hope): Improving the Health and Nutrition of Adolescents and Their Infants to Reduce the Intergenerational Risk of Metabolic Disease

Adolescents have previously been considered a low risk group for poor health, and thus receive few healthcare resources and attention. However, adolescent girls in sub-Saharan Africa are now recognised to be at particularly high risk for several negative health outcomes, including anaemia, unplanned pregnancy, HIV, burgeoning obesity risk, poor access to health care, and delivery complications. While these risks impact the health and quality of life of the women themselves, they also affect their offspring, setting up transgenerational cycles of risk, such as mother-to-child transmission of HIV, poor infant development, and increased risk of non-communicable disease in later life among their infants. Persisting low birth weight and stunting among infants in sub-Saharan Africa, coupled with emerging female adolescent obesity in some settings, establishes another cycle that can result in increased risk for gestational diabetes, and obstructive labour complications. Given that healthy mothers raise healthier children through better nutrition and education, interventions that target young women can lead to improved health, and stronger families and communities. All the formative work, intervention development, and piloting are complete and a phase III cluster RCT in the Agincourt Demographic Surveillance Site is ready to begin.

Project IINDIAGO: Integrated Intervention for Diabetes Risk After Gestational Diabetes

This is a RCT in Cape Town and Soweto to test an integrated health system intervention aimed at reducing type 2 diabetes risk in disadvantaged women after gestational diabetes. This trial is in collaboration with the University of Cape Town.

Mobile Phone Text-Messaging to Support Treatment for People with Type-2 Diabetes in Sub-Saharan Africa: A Pragmatic Individually Randomised Trial

The Global Alliance for Chronic Disease in partnership with the UK Medical Research Council recently awarded a collaborative grant across three sites (Soweto, Cape Town and Malawi). Following an initial intervention development phase to better understand the context in which care for people with diabetes is delivered and how best to tailor SMS texts to inform participants about the benefits of their diabetes treatment and provide reminders and encouragement to take it regularly, this intervention will be evaluated through a RCT. Patients will be sent either informative messages or non-health related SMS text-messages and will be followed up for twelve months to investigate if the intervention leads to improved glucose control.

Other Studies

Bone Health Cohort

Adolescence and the pubertal growth spurt are considered to be important in the attainment of final adult bone mass, and therefore, if bone accretion can be optimized during this period, then peak bone mass will be optimized and fracture risk in later life will be reduced. Because of the importance of adolescence for bone health, the Unit took the opportunity afforded by the Bt20 cohort, to specifically study a sub-cohort and investigate the factors influencing bone mass during adolescence in an urban South African environment. Approximately 475 black and white children from the Bt20 cohort were enrolled into the Bone Health study at the age of 9 years and have been studied annually since then. We completed the last data collection wave (young adulthood) of this longitudinal study in 2012 and longitudinal data analyses are underway.

Study of Women Entering and in Endocrine Transition (SWEET Study)

Drawing upon a sample of over 1000 urban Black women (sample of mothers/caregivers of the Bt20 cohort), we are investigating in detail the cardiometabolic, hormonal and body composition profile of these women, and examining if the menopausal transition is associated with changes in these parameters. This study will draw upon the 20 years of historical data on these women as part of Bt20, but will also to continue to collect extensive longitudinal data on ageing and health as these women get older.

Biorepository and Genetic Association Studies

In collaboration with the Sydney Brenner Institute for Molecular Bioscience at Wits, a DNA biorepository (approx 4000 samples; 2000 mother-child pairs) from the Birth to Twenty cohort participants has been established. Two research projects aimed exploring genetic associations with obesity and bone mass outcomes, and one genome wide sequencing study have recently been completed. The first has been published, the second is in press and the third will soon be submitted for publication. It is planned that additional DNA samples will be collected as part of current and future projects so as to expand the biorepository with DNA samples that have well characterized phenotypic data.

METABO

The primary aim of the study is to identify factors that predict risk for future type 2 diabetes (T2D) in urban black South African (SA) women. Specifically, we hypothesize that lifestyle factors (diet, physical activity and socioeconomic status) may alter an individual’s metabolic profile and increase their risk for insulin resistance (IR), impaired glucose tolerance (IGT) and T2D

This study will investigate the following 3 specific objectives:

1. Identify metabolites and/or metabolic pathways that predict progression to IGT and T2D in black SA women.
2. Identify metabolites and/or metabolic pathways that associate with insulin sensitivity and secretion in black SA women
3. Determine whether lifestyle factors, including diet, physical activity and socioeconomic status, modify these metabolites/metabolic pathways.

Infant Feeding in the Context of HIV: Soweto

Through a mixed methods study, we aim to explore the infant feeding practices and determinants of mothers with infants below age six months who are attending five public clinics in Soweto. This study is set in the context of high HIV prevalence and changing infant feeding guidelines, which currently promote exclusive breastfeeding for six months. A cross-sectional questionnaire will explore the infant feeding practices of an anticipated 300 mothers, segmented by HIV status, predominant infant feeding practice and the age of her infant. A subset of this group will also be invited to participate in in-depth interviews to explore their experiences, decision-making processes and influences. In addition, healthcare workers at the five clinics, family members of the women, and community organisation representatives who work with infant nutrition will be interviewed to gain insight into norms around infant feeding. Finally, the researchers will interview policy makers and infant feeding experts in South Africa to provide a broader context for the recent guideline changes.