Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2005; all rights reserved. Advance Access publication 3 March 2005
International Journal of Epidemiology 2005;34:385–386 doi:10.1093/ije/dyi033
Commentary: Maternal diet during pregnancy and blood pressure in the offspring Tessa Roseboom
Academic Medical Centre, Department of Clinical Epidemiology and Biostatistics, PO Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail:
[email protected]
restriction with a balanced reduction of all macro-nutrients.6 Moreover, the effects seem to depend not only on the composition of the diet with respect to macro-nutrients in general, but also with respect to the source of macro-nutrients in the diet. Giving low protein diets to pregnant rats raises blood pressure in the offspring if the diets contain fats rich in linoleic acid,6 whereas no effects on blood pressure are found in similar experiments using a diet containing fats rich in linolenic acid.7 Furthermore, the blood pressure raising effect of protein restriction can be prevented by supplementing the maternal diet with glycine.8 Most studies relating maternal diet to offspring’s blood pressure show that blood pressure of the offspring may be programmed through the maternal diet without affecting the size of the baby at birth.4,5 Evidence from animal studies leads to similar conclusions: the programming of adult physiology can occur as a result of maternal factors that either do not alter fetal growth or result in alterations in organ growth and body composition but have little or no effect on size at birth. Both the maternal diet during pregnancy and fetal growth seem to program offspring’s blood pressure, but through different mechanisms. There is evidence suggesting that maternal glucocorticoids play an important role in the nutritional programming of blood pressure.9 Protein restriction during gestation down regulates the expression of placental 11-hydroxysteroid dehydrogenase, which protects the fetus from exposure to glucocorticoids from the maternal circulation. The ensuing overexposure of the fetus to glucocorticoids permanently increases the number of glucocorticoid receptors in vascular tissue and the brain and raises blood pressure in later life. Recently, the first direct evidence in humans was published suggesting that the blood pressure raising effect of a high protein low carbohydrate diet is mediated through hypercortisolaemia.10 In humans, small babies have reduced nephron numbers at birth. The reduced number of nephrons of people who had low birth weight may be one of the mechanisms underlying the link between reduced fetal growth and raised blood pressure in later life.11 Our understanding of the processes involved in the fetal programming of blood pressure may help in identifying those individuals who will benefit most from public health interventions aimed at improving the health of future generations. Because glycine supplementation reverses the blood pressure raising effect of low protein diets,8 and children whose mothers received calcium supplementation during pregnancy have reduced blood pressures,12 it seems that the
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Like other living creatures, human beings are plastic during development, they are able to adapt to the environment. There is now considerable evidence that coronary heart disease originates in developmental plasticity. Almost 100 studies assessing the link between birth weight and blood pressure have been performed worldwide. Two meta analyses have shown that low birth weight is consistently linked with an increased blood pressure in later life,1 and that this association is similar for men and women.2 Birth weight has been a central feature of epidemiological studies because it is a measurement that is readily available and has been recorded for many years. However, there is now evidence that fetal programming may occur in the absence of changes in fetal size. Recent research therefore has sought to identify the nature of the adverse maternal influences that raise blood pressure and alter levels of cardiovascular risk factors in the offspring. In this issue of the International Journal of Epidemiology, Huh et al. describe their study in which they assessed the direct impact of maternal diet during pregnancy on offspring’s blood pressure.3 They studied the link between maternal protein intake in the first and second trimester and blood pressure of the offspring at the age of 6 months. Although they did confirm the well-described association between low birth weight and raised blood pressure, they could not detect an association between protein intake in the maternal diet during pregnancy and offspring’s blood pressure. The third trimester is thought to be a critical window for programming blood pressure. It is therefore a serious drawback of Huh’s study that the maternal diet was only studied in the first and second, but not third, trimester. Our study of men and women born around the time of the Dutch famine, for instance, has shown that blood pressure was linked to the balance between protein and carbohydrate intake in the maternal diet during the third, but not first and second trimester.4 Similarly, a study in Aberdeen found that the blood pressures of men and women were related to the balance of carbohydrate and protein in their mother’s diet during late pregnancy.5 At either extreme of this balance, their blood pressures were raised, even if their growth in utero was not affected. The influence of the maternal diet on offspring’s blood pressure is complex. Animal studies show that the effects of protein restriction in the diet of pregnant rats on the blood pressure of their offspring are stronger than the effects of caloric
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identification of micro-nutrients that may be added to the diet of pregnant women is a highly attractive avenue to explore.
independently of maternal blood pressure changes. Clin Nutr 1994;13:319–24. 7 Lucas A, Baker BA, Desai M, Hales CN. Nutrition in pregnant or
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