ArticlesUnravelling the fetal origins hypothesis: is there really an inverse association between birthweight and subsequent blood pressure?
Introduction
One of the original stimuli for the “fetal origins” hypothesis of adult disease was the observation that areas of Britain with the highest rates of neonatal mortality (and, by inference, of impaired fetal growth) early in the 20th century tended to have the highest rates of coronary heart disease later in the century.1 Subsequently, many retrospective studies have investigated associations of birthweight and of various other birth-related measures (such as placental to birthweight ratio, ponderal index, abdominal and head circumference) with vascular disease risk factors and disease in later life. Birthweight has been the most widely studied measure in such retrospective studies (chiefly due to its availability from existing records or personal recall), and the evidence for an association of adverse outcomes with lower birthweight is considered to be strongest for blood pressure.2, 3
Based on review of multivariate regression coefficients from 28 studies reported by March 1996, involving a total of 15 000 people, it was previously estimated that a 1 kg higher birthweight is typically associated with a 2–4 mm Hg lower systolic blood pressure.4 A recent update of that review,5 which included regression coefficients from an additional 27 studies, involving over 367 000 people, continued to suggest an inverse association of −2 mm Hg/kg (as did another recent review of the same studies6). But studies that had not reported the regression coefficient for this association did not contribute to those quantitative estimates, and no allowance was made for the size of the contributing studies. Moreover, whereas almost all of the available regression coefficients had been adjusted for measures of current weight when blood pressure was assessed, few involved adjustment for other potential confounding factors. The purpose of the present paper is to explore the possible impact of these issues, and so determine the likely relevance of birthweight to subsequent blood pressure.
Section snippets
Methods
Studies reporting by March 2000 on the association between birthweight and subsequent blood pressure had been identified previously for two systematic reviews of the available literature.4, 5 Details of the search strategies for such studies, and the inclusion and exclusion criteria, are provided in those reviews. There were 55 eligible studies (ie, individual cohorts, or subsets analysed separately) that had reported regression coefficients of systolic blood pressure on birthweight (web
Impact of publication bias on the apparent association
All but three of the 55 regression coefficients included in the previous reviews4, 5 reported an inverse association between birthweight and later blood pressure (table 1). But ordering the studies according to their statistical size (see Methods) yields a clear trend towards weaker associations in the larger studies (figure 1). For studies with statistical size less than 2 (typically involving fewer than 1000 participants) the inverse-variance-weighted estimate is 1·9 mm Hg lower systolic
Discussion
The present analyses indicate that bias in the reporting of results from studies of the association between birthweight and subsequent blood pressure may have led to substantial over-estimation of the strength of this apparent association. The larger studies are less likely to be prone to such bias, and consideration of the results from those that reported regression coefficients yields a weighted estimate of 0·6 mm Hg lower systolic blood pressure per 1 kg higher birthweight (compared with
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