Association Between Birth Weight and Blood Pressure Is Robust, Amplifies With Age, and May Be Underestimated

Abstract

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. Key Words: blood pressure Ⅲ epidemiology Ⅲ infant nutrition Ⅲ 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 pressure. In the most recent systematic review, Huxley et al 4 concluded that birth weight had little relevance in determining 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 (PϽ0.0001) was observed toward weaker associations between birth weight and blood pressure in the larger studies. In small studies (typically with Ͻ1000 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 Ͼ3000 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 argued 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 between 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...

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“…Although the referenced studies (9,10) only evaluated male offspring and some rodent studies have demonstrated sex differences in programmed hypertension (24,25), a majority of such studies ultimately reveal programmed hypertension in both genders (26 -32). This is consistent with human epidemiologic studies revealing similar relations between birth weight and cardiovascular death or hypertension in men and women (33)(34)(35). Although we are not aware of any fetal programming models that have demonstrated sex-specific programming of coronary physiology, our inability to perform meaningful subgroup analysis within the context of the present study may hamper the generalization of our results to other model systems.…”

Blunted Stress Response in Small for Gestational Age Neonates

“…The median birth weight of the SGA newborns in our study corresponds to the 1.6th percentile defining a relatively homogeneous cohort of growth-restricted neonates. The majority of epidemiologic studies have correlated just LBW with the risk for hypertension (28). One may expect an even more pronounced effect if only infants with proven intrauterine compromise could have been included in these studies.…”

Modifiable Maternal Exposures and Offspring Blood Pressure: A Review of Epidemiological Studies of Maternal Age, Diet, and Smoking

“…Later studies by Barker and colleagues (1), showing that size at birth was related to adult chronic disease, extended this interest to intrauterine programming. Blood pressure (BP) is strongly and directly associated with mortality from cardiovascular disease (7), and the evidence for associations of low birth weight with adverse outcomes in later life is robust for BP (8) [although this has been disputed (9)]. In addition, there are strong cohort effects for secular changes in BP providing evidence for a role of early exposures (10,11).…”