Institute for International Health, 144 Burren Street, Newtown, Sydney, NSW 2042, Australia. E-mail: rhuxley{at}iih.usyd.edu.au
The fetal-origins hypothesis suggests that an adverse early life environment can have a profound and long-lasting impact on an individuals health in later life.1 A central tenet of the hypothesis is a reported inverse association between birthweight, which is often used as a surrogate measure of fetal nutrition, with subsequently raised blood pressure or hypertension.2 This inverse association between birthweight and blood pressure (but less so with hypertension) has been reported widely in the literature and is considered to provide some of the strongest evidence for an association between an adverse early life environment and chronic disease,3 although a recent overview of the evidence casts doubt on whether there is any association at all.4 An additional feature of the fetal-origins hypothesis, which sprang initially from studies which had information on body size in childhood or adult life, suggests that catch-up growth in childhood5 (defined as being above average height or weight or both, combined with a low birthweight), further predisposes to raised blood pressure in later life, as well as with increased rates of insulin resistance and coronary heart disease. However, an increased risk of coronary heart disease and type 2 diabetes has also been reported to be associated with a reduced catch-up growth in childhood.
It is in this context that the study by Zhao and colleagues was conducted.6 In this large population-based study of 13 467 Chinese women, the authors firstly examined the relationship of birthweight with hypertension, which they defined either as confirmed (n = 1433) or possible (n = 940) on the basis of past or current use of antihypertensive medication. Secondly, the authors proceeded to investigate the effects of growth in adolescence and young adulthood in conjunction with birthweight on the risk of developing hypertension in later life. Rather than relying on height and weight measurements to assess adolescent growth, innovatively, the authors used self-reported perceptions of body size relative to their peers. As with some, but not all, previous studies, a dose-response association of birthweight with the prevalence of early-onset hypertension (but not with late-onset hypertension) was reported. Moreover, the risk of developing early-onset hypertension was far higher in those individuals who were both born with a low birthweight (<2500 g) and who exhibited some measure of catch-up growth in adolescence (but not in young adulthood). Findings which would seem to be in general accord with the fetal-origins hypothesis.5
However, the evidence for a dose-response relationship of birthweight with hypertension in this population is at best, limited. Although individuals who were born with a birthweight 2500 g had an increased risk of hypertension, there was only weak evidence for a dose-response trend with birthweight in women with confirmed cases of hypertension (P = 0.16). Even after the inclusion of possible cases of hypertension, the evidence for an inverse trend, although strengthened, remained weak (P = 0.07), which suggests that the increase in prevalence of hypertension was largely confined to those women born weighing <2500 g. In these individuals, the association between low birthweight and increased prevalence of hypertension may have been confounded by genetic factors that are associated with both low birthweight and with raised blood pressure in later life, e.g. maternal hypertension.
Furthermore, only in an analysis of the relationship between birthweight and blood pressure, stratified by age of onset of hypertension, did the relationship with birthweight reach conventional levels of significance, but interestingly, only in those individuals diagnosed with early onset hypertension (2040 years) (P = 0.01). In women who were diagnosed with hypertension between 41 and 70 years (i.e. late-onset hypertension) there was no evidence of an association with birthweight (P = 0.70) (Figure 1). This is at odds with the widely held view of an inverse relationship between birthweight and blood pressure at all ages2 as well as with the suggestion that the strength of the inverse association is amplified with age.5
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From a public health perspective, more relevant findings from the study by Zhao and colleagues are that, regardless of birthweight, being above average weight in adolescence or young adulthood predisposes individuals towards an increased risk of hypertension in later life. Furthermore, the risk of hypertension in this population begins at much lower levels of body mass index compared with Western populations. Although overweight individuals, who are born light, may have the greatest relative risk of hypertension, birthweight, unlike current weight, is not so easily modified. Recent estimates suggest that a 2-kg reduction in body weight could reduce systolic blood pressure by 1%,9 which is equivalent to the expected reduction in blood pressure estimated for a 1-kg increase in birthweight.5 Obesity, a condition normally associated with prosperous developed countries, is becoming endemic in developing nations, including China, due in large part to the adoption of westernized dietary and lifestyle habits. Paralleling these trends is the alarming rise in chronic western disorders including type 2 diabetes, dyslipidaemia and raised blood pressure. Combating these rising trends will require the implementation of simple and effective interventions aimed at preventing and reducing the overall prevalence of overweight and obesity in all individuals, irrespective of their childhood growth. Even modest, but achievable, reductions in weight across the population would have a significant and worthwhile impact on reducing blood pressure and overall incidence of coronary heart disease.10
Acknowledgments
Gary Whitlock for helpful comments on an earlier draft.
References
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