Association Between Birth Weight and Blood Pressure Is Robust, Amplifies With Age, and May Be Underestimated Anna A. Davies, George Davey Smith, Margaret T. May, Yoav Ben-Shlomo Abstract—Data on the early life origins of adult hypertension have been widely reported: however, recent research shows that the strength of association between small size at birth and higher blood pressure weakens as study size increases. In this article, we retest the association between birth weight and systolic blood pressure in a large cohort, examine whether age interacts with birth weight to predict blood pressure, and explore reasons why birth weight– blood pressure associations tend to weaken with increasing study size. Measurements from 25 874 employees of a large United Kingdom company (mean [SD] age: 38.0 [7.9] years), undertaking voluntary occupational health screening, were available. Using linear regression analysis, we observed that systolic blood pressure changed -0.8 (95% CI: -1.1 to -0.5) mm Hg per 1-kg increase in birth weight (P0.001) adjusted for age and sex and -1.1 (95% CI: -1.3 to -0.8) mm Hg/kg (P0.001) after further adjustment for body size. This inverse association amplified with age (age/birth weight interaction term P0.001). In participants reporting birth weight from hospital records (n=744), systolic blood pressure changed -1.4 (95% CI: -3.1 to 0.2) mm Hg/kg compared with -0.8 (95% CI: -1.0 to -0.5) mm Hg/kg in all of the other participants. Finally, the data show evidence of “fixed-category blood pressure allocation,” where participants are allocated certain blood pressure values, such as 120/80 mm Hg, independent of actual blood pressure. Although the association between birth weight and systolic blood pressure was weaker than observed in smaller studies, recalled birth weight and fixed blood pressure measurement error may generate a trend toward weaker associations in larger studies. (Hypertension. 2006;48:431-436.) Key Words: blood pressure  epidemiology  infant nutrition  blood pressure determination T he “fetal origins” hypothesis suggests that “insults” at critical periods during fetal development can lead to permanent metabolic and structural changes in the fetus increasing the risk of many diseases in adulthood. 1 One key finding in support of this hypothesis is the observation, now replicated in many populations, that lower birth weight is associated with higher adult systolic blood pressure (SBP) 1,2 : an association observed independently of socioeconomic position. 3 Surprisingly, despite the wealth of literature in this field, the precise nature of the association between birth weight and blood pressure remains contentious. One important area of recent debate has focused on the strength of association between birth weight and blood pres- sure. In the most recent systematic review, Huxley et al 4 concluded that birth weight had little relevance in determin- ing blood pressure levels in later life. This finding was at odds with previous systematic reviews, which have suggested that SBP decreases by between 2 and 4 mm Hg for each 1-kg increase in birth weight. 5,6 Central to the argument put forward by Huxley et al 4 was that after ordering studies by statistical size (derived from the inverse of the variance of the regression coefficient), a clear trend (P0.0001) was ob- served toward weaker associations between birth weight and blood pressure in the larger studies. In small studies (typically with 1000 participants), a 1-kg increase in birth weight was associated with a 1.9 mm Hg decrease in SBP, whereas in large studies (typically with 3000 participants), SBP was reduced by only 0.6 mm Hg/kg. Huxley et al 4 suggested that this was evidence of publication bias, with smaller studies being more likely to be published if they found strong inverse birth weight– blood pressure associations. 7 The authors ar- gued that because larger studies are known to be less prone to publication bias, a decrease of 0.6 mm Hg/kg was nearer to the true association. An additional contentious area in the literature has been the actual nature of the association be- tween birth weight and blood pressure. Even within the large studies reviewed by Huxley et al, 4 the association was inconsistent, with some large studies reporting a perfectly linear association across the birth weight continuum 8 and others reporting a reverse J-shape pattern, whereby those individuals with the highest birth weight also tended toward slightly raised SBP. 9 Finally, the hypothesis advanced 10 years ago, that the association between low birth weight and higher SBP strengthens with age, 10 is still debated, with, most recently, Huxley et al 4 arguing that studies provided little evidence of any amplification with age effect. Received November 15, 2005; first decision January 1, 2006; revision accepted April 20, 2006. From the Department of Social Medicine, University of Bristol, Bristol, United Kingdom. Correspondence to Yoav Ben-Shlomo, Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Rd, Bristol, BS8 2PR, United Kingdom. E-mail Y.Ben-Shlomo@bristol.ac.uk © 2006 American Heart Association, Inc. Hypertension is available at http://www.hypertensionaha.org DOI: 10.1161/01.HYP.0000236551.00191.61 431 Birth Weight and Blood Pressure by guest on May 16, 2016 http://hyper.ahajournals.org/ Downloaded from