The Healthy Life Trajectories Initiative (HeLTI) program
Drs Stephen Matthews and Stephen Lye of the Departments of Obstetrics and Gynaecology, Physiology and Medicine, UofT and the Alliance for Human Development at LTRI have recently been funded through The Healthy Life Trajectories Initiative (HeLTI) program.
The HeLTI program was developed by the Canadian Institutes of Health Research (CIHR), Institute of Human Development, Child and Youth Health led by Dr Shoo Lee. The program represents a partnership between CIHR, the South African MRC, the Department of Biotechnology, India, the National Natural Science Foundation of China and the World Health Organization. HeLTI was developed to address the increasing burden of non-communicable diseases (i.e. obesity, diabetes, cardiovascular disease and poor mental health) around the world. There are four separate but harmonized projects that are commencing in Soweto (South Africa), Mysore (India), Shanghai (China), and across Canada. All projects are focused towards developing evidence-based interventions that span from pre-conception across pregnancy and into the postnatal period with a goal improving maternal, infant and child health.
Dr Matthews is the Canadian lead on the HeLTI-India Project with Dr Kalyanaraman Kumaran (Holdsworth Memorial Hospital, Mysore) and Dr Lye is Canadian lead on the HeLTI-South Africa Project with Dr Shane Norris (Wits University, Johannesburg). Both projects are initially funded for 5-years and have each received $5M. Several investigators from Toronto and across Canada are involved in the projects.
Healthy Life Trajectories Initiative: India-Canada
Early Interventions to Support Trajectories for Healthy Life in India (EINSTEIN)
Dr Matthews is the Canadian lead on the HeLTI-India Project
The health and economic burden of non-communicable diseases (NCDs) is increasing rapidly globally and falls disproportionally on low- and middle-income countries (LMICs). In India, an estimated 65 million people have diabetes and a further 77 million are pre-diabetic. Unchecked, the population with diabetes is expected to reach 109 million by 2035. The rising burden of cardiometabolic disease is accompanied by a growing burden of mental health disorders; 13% of young people aged 1-16 years in India experience mental health disorders. Undernutrition remains a significant problem in India. In children under 5, the prevalence of stunting is ~48%; wasting ~20%; underweight ~43%, and anaemia ~69%. In women aged 15-49 years, 33% are underweight while ~55% are anaemic. These factors are reflected in a high prevalence of low birth weight (<2500g) in ~25% of babies born in India each year. Low birth weight (LBW), poor infant nutrition, and rapid childhood weight gain and obesity are well-established risk factors for poor health trajectories and development of NCDs in later life. Rates of obesity in children and adults are also increasing in India; 19% of children and adolescents and 15% of women of reproductive age are overweight or obese.
The ‘developmental origins of health and disease’ (DOHaD) hypothesis proposes that adverse conditions during critical periods of early development permanently ‘programme’ the body’s metabolic tissues and systems , leading to increased susceptibility to disease in later life. The DOHaD concept may be particularly applicable to the Indian situation. Optimising early growth and development may help to control and prevent the rising burden of non-communicable disease and break the cycle of intergenerational transmission of susceptibility.
The interdisciplinary team for the EINSTEIN Project brings together researchers from 11 Indian and 7 Canadian institutions with complementary skills, further developing a national resource in DOHaD research, intervention cohorts, longitudinal studies, data management and knowledge translation/policy development. The overarching hypothesis is that integrated interventions administered pre-conceptionally and at appropriate points across the life-course (pregnancy, infancy and childhood) will reduce childhood adiposity, improve cardiovascular and metabolic health, and improve child development outcomes. The study is a community-based, cluster randomized trial with three arms (pre-conception, pregnancy and control) set in rural Mysore, South India, with individual villages forming the basis for the cluster. Women of reproductive age will receive a longitudinal multi-faceted intervention delivered by community health workers comprising: a) multiple micronutrients; b) a group parenting program to address maternal depression and improve child development; c) hygiene and infection prevention measures; d) the reduction of environmental pollution exposure; and e) underpinned by a lifestyle behavior change intervention.
The primary outcome at age 5 years in the children across all HeLTI cohorts is adiposity. Other key outcomes at 5 years include; overweight and obesity, glucose metabolism, blood pressure, and infant/child development. In addition, the project will report on a host of intermediate and process outcomes, including the efficacy and acceptability of the intervention package, compared with standard care. The project will also assess the relative costs and benefits of starting the intervention in early pregnancy compared with pre-pregnancy.
HeLTI South Africa – BUKHALI Project
Dr Lye is Canadian lead on the HeLTI-South Africa Project
The health, societal and economic burden of non-communicable diseases (N&Ds) is significant, increasing, and propagated by early life environments (undernutrition/stress) and later life adiposity, decreasing physical activity, increasing sedentary behaviour, poor dietary diversity, and intergenerational factors. The N&D burden falls heavily on low- and middle-income countries and this pattern is predicted to intensify dramatically in the near future. South Africa’s (SA) devolving burden of disease is complex due to: (i) persisting malnutrition (infant stunting of 20%); (ii) the highest prevalence of overweight and obesity (OWO) in Sub-Saharan Africa, particularly among women; and (iii) rising rates of non-communicable diseases such as of type 2 diabetes (T2D). Global initiatives to mitigate adversity during the first 2000 days have resulted in significant improvements in maternal and child survival. However, the longer-term impact of interventions delivered preconception/prenatally/early childhood on child growth and social/cognitive development has been less clear. Therefore, there is a need to begin laying the foundation for healthy trajectories by optimizing women’s health prior to and during pregnancy and reinforcing optimal health in the infant to offset obesity and cardiometabolic risk and improve cognitive development.
To address this need, the BUKHALI project has assembled a multidisciplinary team of experts from 7 Institutions across South Africa (SA) and 6 institutions across Canada who will focus on a longitudinal analysis of how early-life exposures in the preconception period and during pregnancy, infancy and childhood impact life-long trajectories of health and development of children in South Africa. The study population will be drawn from Soweto, SA, a historically disadvantaged urban area of the city of Johannesburg, where the SA team members have significant existing research infrastructure and demonstrated experience in recruitment for pregnancy and child cohort studies. The project team hypothesizes that an integrated intervention starting pre-conceptionally in women and at appropriate points across the lifecourse (pregnancy, infancy and childhood) will improve cardiovascular and metabolic health, reduce childhood adiposity and improve child development outcomes. Ultimately this will reduce the risk of NCDs.
Using a cluster, randomized design the team will test the efficacy of interventions that address behavior change to improve diet and physical activity preconception, health during pregnancy, reduce perinatal depression, increase exclusive breastfeeding and improve parental nurturing care.
Primary outcome at age 5-6 years in the children is Adiposity. Other key outcomes at 5-6 years in the children include overweight and obesity and other indicators of body composition and distribution; Glucose metabolism; blood pressure; and neurodevelopment. The project also includes a comprehensive series of measures to track maternal and child growth and development as well as the collection of biospecimens that will support studies into the science of the developmental origins of health and disease.