Barker Hypothesis

David Barker, of the University of Southampton, England, was among the first to argue that impaired fetal growth is an important contributor to coronary heart disease and its metabolic precursors. In the original formulation of the hypothesis, maternal malnutrition in pregnancy was the underlying determinant of suboptimal birth size, and Barker hypothesized that the effect of prenatal malnutrition was trimesterspecific, producing different later metabolic consequences depending on when in pregnancy nutrition was impaired. Small size at age 1 year was also found to be associated with later coronary heart disease, implying a causal role in heart disease of both infant and fetal malnutrition. Barker and his colleagues made ingenious use of several old databases, most notably the records of birthweights and infant weights collected during the 1920s and 1930s in Hertfordshire by a dedicated nurse, which were then linked to contemporary death records. Critics of the Barker opus have asserted that large losses to follow-up; inadequate attention to socioeconomic, environmental, and genetic confounding; and other methodological problems weaken the evidentiary base of the hypothesis.

The hypothesis has broadened beyond its nutritional origins, but it still focuses principally on the relationship of impaired fetal growth to elevated blood pressure, glucose intolerance, and other contributors to coronary heart disease and stroke. The hypothesis has stimulated a great deal of research, both in the laboratory and in human populations. In animal studies, components of the Barker hypothesis have been confirmed; dietary restrictions in pregnancy producing smaller offspring have been accompanied by elevations in cardiovascular risk factors, although at times these nutritional effects have not been dependent on alterations in birthweight. A relatively common model involves halving caloric intake in pregnant animals. How closely these experimental interventions parallel the common human experience is uncertain. This laboratory work has in turn led to the concept of ‘fetal programming,’ that is, that some of the cardiovascular risk profile may be determined by subtle alterations in nutrition or metabolism occurring at critical periods in development, especially in fetal life. In human studies, the Barker hypothesis has been studied in many different settings across the globe. It has been broadened by several investigators to include other components of early social and environmental disadvantage, producing what has sometimes been termed the life course hypothesis that posits a major role for many kinds of experiences in fetal, infant, and child lifeinshapingriskofadultdisease. Many of these critical experiences are hypothesized to be social and environmental in origin, with biological effects (such as small size) operating as mediators of subsequent cardiovascular risk.

The net contribution of the Barker hypothesis to public health has as yet been modest. Birthweight is notoriously resistant to change in human populations, and the effects of birthweight are modest in determining blood pressure and glucose levels, especially when compared with current weight. But the hypothesis has made many investigators more conscious of the possibility that fetal, infant, and child experiences may have long-lasting consequences for human health.