Developmental+Origins+of+Health+and+Disease+(DOHaD)

toc = Developmental Origins of Health and Disease (DOHaD) =

Definition
The developmental origins of health and disease paradigm (DOHaD) is a multi-disciplinary field that examines how “environmental factors acting during the phase of developmental plasticity interact with genotypic variation to change the capacity of the organism to cope with is environment in later life.” The main focus of DOHaD has been on nutritional insults (e.g. low caloric intake or nutritional deficiency) linked with the manifestation of chronic disease in adult life (i.e. metabolic syndrome, type 2 diabetes, etc.). The link between environmental perturbations and other disease risk (i.e. schizophrenia, osteoporosis, etc.) has also been explored. DOHaD research is done in multiple disciplines, including evolutionary medicine, anthropology, public health and clinical practice.

History
The developmental origins of health and disease paradigm developed over the last twenty-five years reflects ideas that have been debated since the field of genetics gained widespread acceptance. James Neel (1962) was a geneticist who came up with the //thrifty genotype hypothesis// as a response to the high rates of diabetes experienced by certain groups of people. He asserts that genes are responsible for this phenomenon. . As a rebuke to this idea, Hales and Barker proposed the //thrifty phenotype hypothesis//, emphasizing the importance of developmental plasticity in phenotypic variability. This ultimately led to the recognition that the environment interacts with genes in a way that has implications for not only adult health, but also for public health strategies, evolutionary theory, life history theory and evolutionary developmental biology.

In the 1980’s, David Barker identified a link between low birthweight (LBW) and ischemic heart disease in adult life. The link between LBW and adult disease risk was later called the Barker Hypothesis. Barker asserted that LBW and disproportionate head size was an indication of poor nutrition or inadequate oxygen during various stages of gestation. The Barker Hypothesis was an important development in the DOHaD field. The research completed by Barker and colleagues in the 1980's and 90's demonstrated the association between the prenatal environment and disease risk in adult life. Unfortunately, this work also promoted LBW as an indication of pathology that could be used a marker for predisposition to adult disease. Using birthweight (BW) as a causal marker of pathology has been debated due to other existing factors that can influence BW (e.g. maternal constraint) and the strong role the postnatal environment also plays in development.

Further development in the field extended this idea into what became known as fetal origins of adult disease (FOAD). FOAD contends that environmental influences during fetal life can influence adult health through various mechanisms, including developmental plasticity, fetal programming and epigenetics. This idea was further extended to the developmental origins of health and disease paradigm. The shift in name emphasizes the role of both the pre- and postnatal environment in shaping developmental trajectories that influence health throughout the lifecourse. This idea is rooted in life history theory, which posits that an organism must make certain developmental trade-offs in order to survive under suboptimal conditions. These trade-offs may be immediately adaptive, in allowing the short-term survival and reproduction of the organism, at a cost to long-term health. This includes increased risk for chronic diseases (i.e. metabolic syndrome, type 2 diabetes, hypertension, cardiovascular disease, etc.), schizophrenia, osteoporosis, overweight/obesity, and asthma later in life. Today, many DOHaD researchers believe that this paradigm should be used in public health policy and clinical practice aimed at improving maternal and family health.

Medical anthropologists have been part of the establishment of the DOHaD paradigm and continue to make important contributions to the field. Anthropologists such as Jared Diamond have continued to critique the Neel's Thrifty Genotype Hypothesis and offer alternative explanations into the 21st century. Currently, work by Daniel Benyshek and Christopher Kuzawa have contributed to our understanding of the DOHaD paradigm and how it intersects with anthropology. Benyshek has contributed to our knowledge about the intergenerational effects of the developmental origins of disease through animal models and currently advocates for the use of prevention/intervention strategies among Native Americans based on his findings. Benyshek is currently involved with a diabetes prevention program in Las Vegas, Nevada aimed to help Native Americans. He has also published on the developmental origins of obesity. Chris Kuzawa has published on the link between epigenetics and race, DOHaD within an evolutionary framework, and is currently a collaborator with the Cebu Longitudinal Health and Nutrition Survey, a longitudinal study that aims to explore many of the principles and associations related to the developmental origins of health and disease. .

Background
The Cebu longitudinal health and nutrition survey is an ongoing cohort study in Cebu, Philippines that began with a cohort of Filipino women who gave birth between May 1, 1983-April 30, 1984. Researchers from the United States and the Philippines have collaborated to make this study possible. Collaborators include researchers at the Population Center at the University of South Caroline, researchers at the Office of Population Studies Foundation, University of San Carlos, Cebu, Philippines and others at Northwestern University and Johns Hopkins University. Notably, two anthropologists from Northwestern University, Chris Kuzawa and Thomas McDade, are active collaborators and have published extensively on the study.

Goals
Originally aimed at looking at infant feeding patterns in a natural setting, the project has expanded to include many other features described within the developmental origins framework, such as growth and development patterns, and chronic disease risk. Researchers involved in this study are going to use this opportunity to look at intergenerational effects of specific variables as well, contributing immensely to the literature on links between maternal and child health. This study provides a unique opportunity to study the effects of fetal programming in a natural setting.

Findings
The Cebu longitudinal health and nutrition survey has already produced strong evidence in support of the fetal and developmental origins of health and disease. Major findings include: a relationship between maternal diet and subcutaneous fat and adolescent blood pressure was identified, a relationship between prenatal undernutrition and thymic function (related to immune function), and a positive association between breastfeeding and psychosocial development in childhood.

//**The Dutch Hunger Winter**//
The Dutch Hunger Winter is another example of how the DOHaD paradigm is useful and can be applied. In the winter of 1944-45, the German occupation of the Netherlands resulted in blockade that cut off food from entering into the country. The entire population was under severe caloric restriction (less than 1000 calories a day) during this time. Records kept by the Dutch allowed researchers to examine patterns between famine, gestation and birth outcomes. Researchers have shown a link between gestational age at the time of famine and later disease risk for cardiovascular disease and high body mass index. This situation reflects how political-economic stressors can impact health and nutrition. These effects may not manifest directly, but can be seen throughout the lifecourse and potentially across generations.

Related Terms
Diabetes Mellitus, Schizophrenia

Online Resources
The Cebu longitudinal health and nutrition survey http://www.cpc.unc.edu/projects/cebu

International Society for the Developmental Origins of Health and Disease http://www.mrc.soton.ac.uk/dohad/