Fetal origins of adult disease: the Barker hypothesis revisited???2004

Purpose of review The Barker hypothesis implicates the fetal in-utero environment as a significant determinant of risk for major chronic diseases, such as cardiovascular disease, stroke, hypertension, type 2 diabetes, and obesity later in life. Although the Barker hypothesis has gained increasing recognition since it was first introduced 20 years ago, it is still being met with skepticism because of the largely observational and cross-sectional nature of the studies on which it is primarily based. The purpose of this review is to re-examine the Barker hypothesis in the context of new information with a focus on prospective studies in humans and experimental observations made in laboratory animal models. Recent findings The debate on the Barker hypothesis continues, in part fueled by conflicting findings from different studies. While one study from the U.S. found no significant correlation between birth weights and blood pressure at ages 11 to 14 years, another large study of Filipino children found that the highest levels of blood pressure were present among those who were relatively thin at birth but who were later relatively heavy as adolescents. Two relatively recent review papers on the relationship between birth weights and blood pressure levels later in life also drew opposite conclusions. Even animal studies are not free of controversy. A study linking maternal malnutrition during the pre-implantation period of rat development to abnormalities in blastocyst formation was openly faulted for methodologic flaws in its statistical analysis. There is increasing evidence that birth weight per se cannot be viewed as a major culprit for this increased risk. Although the study of Filipino adolescents had methodologic weaknesses readily acknowledged by the authors, their findings still suggests that the postnatal condition of heavier body habitus during adolescence also played a significant role in blood pressure levels as well as smaller birth weights. A study of birth weight and later risk for type 2 diabetes found a higher prevalence of lower birth weight among those with type 2 diabetes, but in the same study, they found that the prevalence of diabetes was also higher among those with larger birth weight and high BMI in childhood. A recent review of the literature found no strong evidence to link birth weight to blood lipid levels later in life. Summary At present, the Barker hypothesis is in need of further scientific insight and stronger supporting evidence. The most recent publications on this subject are review papers and a book rather than original research that presents novel findings. Thus far, there is no information that provides any mechanistic insight into the relationship between the intra uterine milieu and adverse post-natal consequences. There are no unifying theories which link low birth weights to a variety of different outcomes later in life. Hence, there are regrettably more questions remaining than there are answers regarding the Barker hypothesis. It is timely to perhaps, apply some of the generally accepted principles for assessing causality to the available information on the fetal origins hypothesis. The next step might be to conduct studies that test this notion as an a priori hypothesis rather than as post hoc examination of cross-sectional data. The time has also come to further refine the hypothesis to encompass more than mere correlation between birth weight and risk for chronic disease later in life. Surely, life-long exposures to environmental factors such as dietary patterns, physical activity, and stress levels have to play either independent or effect modifying roles in the causal web of chronic disease. It is, therefore, timely to further refine the Barker hypothesis to a testable proposition, Barker Hypothesis-Version 2004.