IJE Advance Access originally published online on July 26, 2006
International Journal of Epidemiology 2006 35(4):877-879; doi:10.1093/ije/dyl150
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Commentary |
Commentary: Early life determinants of blood pressure in childhood—where do we go from here?
Division of Community Health Sciences, St George's, University of London, Cranmer Terrace, London. SW17 0RE, UK.
E-mail: pwhincup{at}sgul.ac.uk
An important component of the evidence suggesting that cardiovascular disease has its origins in early life, possibly influenced by poor fetal nutrition, is provided by the studies (now more than a hundred in all) that have reported on the relationship between size at birth and subsequent blood pressure. Most of these studies have suggested that small size at birth, particularly lower levels of birth weight, is related to a higher blood pressure in later life, particularly systolic blood pressure.1,2 Despite the large number of studies supporting the existence of this association, much remains uncertain. The strength of the association and its public health importance has been disputed.1 Moreover, the underlying basis of the association remains unknown. It has been suggested that birth weight (a crude measure of fetal nutrition3) is not itself the relevant exposure; other, possibly more specific markers of poor fetal nutrition, particularly thinness at birth, could be more relevant.3 Placental weight, or the ratio of placental weight to birth weight, is another potential marker of poor fetal nutrition, which has been related to raised blood pressure.4 The potential importance of placental size has been demonstrated in rat models, in which dietary restriction in early pregnancy, around the time of conception, appears particularly to influence placentation so that the offspring has a relatively high placental: body weight ratio at term.5
New insights into the relations between early life exposures and blood pressure are therefore needed; studies of these associations in childhood could be particularly helpful in defining the contemporary relevance of the fetal origins hypothesis.6 The new report by Hemachandra et al.7 in the current issue of the journal is, therefore, of potential interest. The study is based on the Collaborative Perinatal Project, in which 58 960 expectant mothers in the US were enrolled between 1959 and 1965. The present analyses are based on 29 973 live offspring of mothers of clearly defined major ethnic groups, who remained in the study long enough for their offspring to be followed to 7 years of age. Results are based on comparisons of the birth characteristics of subjects with and without high blood pressure (defined as the top 10% of the study blood pressure distributions standardized by gender and race) and corresponding odds ratios. The results show a positive association between placental ratio (placental weight: birth weight) and systolic blood pressure, which remained statistically significant after adjustment for gender, education, and race. The strength of the association is modest—every 3% increase in placental ratio increases the risk of raised systolic pressure by 1%, which suggests a limited public health as well as individual impact. Although results are presented entirely without any adjustment for current body size, the authors report that the addition of body mass index at 7 years did not affect the direction of this association. Neither birth weight, nor ponderal index at birth, was consistently related to risk of high blood pressure. Placental ratio was positively associated with risk of high blood pressure within each third of the birth weight distribution. The highest risk of raised systolic blood pressure was observed in subjects with the highest placental ratio and the lowest birth weight, though no strong evidence of interaction between placental ratio and birth weight was presented. Being black was strongly related to risk of high blood pressure in this population. The authors conclude that the placental ratio is a useful marker of intrauterine growth retardation for study of the developmental origins of adult cardiovascular disease.
Do these findings help to advance our understanding of the developmental origins of high blood pressure? It would be useful to have clear evidence of the role of placental weight (and not just the placental ratio) in the association with blood pressure. Moreover, it is difficult to compare the findings of this study with earlier studies, particularly those in children, for two reasons. First, earlier studies have generally presented the relations of size at birth to blood pressure as continuous linear regressions. Second, the present study estimates were presented without adjustment for current body size, unlike those of earlier studies. The absence of an appreciable inverse association between birth weight and blood pressure is not surprising, since adjustment for current body size has been essential in most studies in childhood if the inverse association between birth weight and blood pressure is to be observed.6 This situation appears to contrast with that in adults, where the presence of an inverse association between birth weight and blood pressure has not been so dependent on adjustment.4,8 The validity of adjustment for current body size has been disputed. It is likely that adjustment for body mass index represents overadjustment, and may well exaggerate the strength of the relation between birth weight and blood pressure. However, in studies in children, it may well be appropriate to adjust for height, which in childhood is strongly associated positively with both birth weight and blood pressure and may be a temporary confounder of the birth weight–blood pressure association.9 With increasing age, the association of birth weight to height becomes increasingly attenuated and the relation between height and blood pressure disappears or reverses.
On the basis of the present, very large, study it is possible that placental weight, or the placental ratio, has a specific association with later blood pressure. This could reflect placental growth in early pregnancy or intrauterine growth retardation in the later stages of pregnancy (which tends to be associated with diminished birth weight without marked effects on placental size). However, although some earlier epidemiological studies have found positive associations between placental size, placental ratio, and blood pressure,4,10 this observation has not been consistently reported.8 A more formal examination of the results of the large number of studies with different measures of size at birth, exploring the apparent heterogeneity of findings between studies, could help to resolve the issue. More individual studies examining the relations of size at birth (including placental size) to blood pressure in populations in which maternal undernutrition is prevalent could also be helpful. However, although research on birth size measures is important, reports from the Dutch famine studies (and animal studies) have suggested that early life exposures, particularly maternal undernutrition, may influence chronic disease risk markers without affecting size at birth.11 This should serve as a stimulus to move beyond size at birth to attempt to identify exposures (nutritional or otherwise), which are related to chronic disease risk markers in later life and may be amenable to preventive measures. Finally, the results of the present study also draw attention to the striking influence of ethnicity on blood pressure even at this early age; this may provide clues to key early life determinants of chronic disease risks, which should not be neglected.
Conflict of Interest: None.
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References |
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11 Ravelli AC, van der Meulen JH, Michels RP et al. Glucose tolerance in adults after prenatal exposure to famine. Lancet 1998;351:173–77.[CrossRef][ISI][Medline]
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