ABSTRACT
“Barker's hypothesis” emerged almost 25 years ago from epidemiological studies of
birth and death records that revealed a high geographic correlation between rates
of infant mortality and certain classes of later adult deaths as well as an association
between birthweight and rates of adult death from ischemic heart disease. These observations
led to a theory that undernutrition during gestation was an important early origin
of adult cardiac and metabolic disorders due to fetal programming that permanently
shaped the body's structure, function, and metabolism and contributed to adult disease.
This theory stimulated interest in the fetal origins of adult disorders, which expanded
and coalesced ~5 years ago with the formation of an international society for developmental
origins of health and disease (DOHaD). Here we review a few examples of the many emergent
themes of the DOHaD approach, including theoretical advances related to predictive
adaptive responses of the fetus to a broad range of environmental cues, empirical
observations of effects of overnutrition and stress during pregnancy on outcomes in
childhood and adulthood, and potential epigenetic mechanisms that may underlie these
observations and theory. Next, we discuss the relevance of the DOHaD approach to reproductive
medicine. Finally, we consider the next steps that might be taken to apply, evaluate,
and extend the DOHaD approach.
KEYWORDS
Barker's hypothesis - DOHaD - predictive adaptive response - IUGR - premature birth
- obesity - stress - epigenetics
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Pathik D WadhwaM.D. Ph.D.
Associate Professor of Psychiatry & Human Behavior, Obstetrics & Gynecology, Pediatrics,
and Epidemiology
University of California, Irvine, School of Medicine, 3117 Gillespie Neuroscience
Research Facility, Irvine, CA 92697-4260
eMail: pwadhwa@uci.edu