Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915-29BMJ 1998; 317 doi: https://doi.org/10.1136/bmj.317.7153.241 (Published 25 July 1998) Cite this as: BMJ 1998;317:241
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Re: Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915-29
David Leon and colleagues 1add to the body of observational evidence 2 3that fetal nutritional experience in itself may be an important determinant of adult coronary heart disease (CHD) risk, rather than simply being an indicator for later-life environmental and behavioural coronary risk factors. The authors speculate as to how much the variation in growth rate within their relatively well nourished population is likely to be dependent on maternal nutritional status. As they state, it is impossible to retrospectively determine this within their population, however systematic review of trials of maternal nutritional supplementation has concluded that supplementation is associated with similar small but significant increases in birth weight in both undernourished and adequately nourished populations 4.
The overall short- and long-term influence of maternal nutritional supplementation is not well characterised. With the exception of the recent large MRC trial in the Gambia 5, which showed a reduction in perinatal mortality in the offspring of the supplemented mothers, supplementation has not been associated with significant health gain. If maternal nutritional supplementation were shown to lead to significant improvement in cardiovascular disease risk and risk factor profiles among the offspring, without any evidence of potentially detrimental effects on markers of risk of other diseases (such as cancer), then this approach to improving population health is of potentially great public health significance.
While confounding is an unlikely reason for the association between birthweight and CHD risk, it is still not clear whether this association is potentially modifiable, i.e. if increasing birthweight will lead to improved CHD risk profiles among offspring. It could equally be the case that common unmodifiable factors, such as particular gene polymorphisms, influence both birthweight and later CHD risk. If this is the case then altering birthweight through improved maternal nutrition (whether during pregnancy or during the early life of future mothers) will not alter CHD risk among the offspring.
The conventional approach to the general epidemiological problems of both confounding and modifiability of risk is to incorporate random allocation of study subjects to exposure category into an experimental study design. In the context of the fetal origins hypothesis this could be achieved either through the setting up de novo of trials, involving the experimental manipulation of maternal nutritional status, or through the long-term follow-up of study subjects from completed supplementation trials. The - now extensive - body of observational evidence on possible fetal origins of adult disease encourages the detailed experimental examination of this important idea. Without such studies it will remain unclear as to whether we are missing an opportunity to significantly improve population health.
Clinical Research Fellow
Department of General Practice, University of Birmingham, Birmingham B15 2TT.
George Davey Smith
Professor of Clinical Epidemiology
Department of Social Medicine, University of Bristol, Bristol BS8 2PR.
1 Leon DA, Lithell HO, Vagero D, Koupilova I, Mohsen R, Berglund I et al. Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915-29. BMJ 1998;317:241-45.
2 Frankel S, Elwood P, Sweetnam P, Yarnell J, Davey Smith G. Birth weight, body mass index in middle age, and incident coronary heart disease. Lancet 1996;348:1478-80.
3 Rich-Edwards JW, Stampfer MJ, Manson JE, Rosner B, Hankinson SE, Colditz GA et al. Birth weight and risk of cardiovascular disease in a cohort of women followed up since 1976. BMJ 1997;315:396-400.
4 Kramer MS. Balanced protein/energy supplementation in pregnancy (Cochrane Review). In: The Cochrane Library, Issue 3, 1998. Oxford: Update Software.
5 Ceesay SM, Prentice AM, Cole TJ, Foord F, Poskitt EME, Weaver LT, Whitehead RG. Effects on birth weight and perinatal mortality of maternal dietary supplements in rural Gambia: 5 year randomised controlled trial. BMJ 1997;315:786-790.
Competing interests: No competing interests