The concept that adult disease may be determined by pre-natal factors has led to the development of a number of animal models to analyse the pathophysiological effects of the fetal environment. The focus of these studies has, however, been on the importance of maternal nutrition on the development of systemic hypertension. Recently, however, there have been some studies examining the role of the fetal environment on specific vascular beds. Ozaki et al8
have demonstrated that in rats, global undernutrition during gestation causes enhanced thromboxane induced contraction in the femoral arteries of the male offspring. Koukkou et al9
have also reported that mothers fed a high fat diet produce offspring whose femoral arteries show reduced endothelium dependent vasodilatation. In addition, further work by the same group has demonstrated that the aortas of these offspring have an altered fatty acid content.10
Using a sheep model, Nishina et al11
have shown that protein and global nutrient restriction in early gestation produce offspring with impaired endothelium dependent and independent femoral artery dilation, and that this dysfunction is most pronounced in the protein restricted group. Although these animal models provide indirect evidence that maternal nutrition may contribute to the development of lower limb vascular dysfunction in humans, it is important to inject a degree of caution in reviewing these data. After all, the relative calibre of the femoral artery in humans is far larger than that of rats and sheep, and it is questionable whether data from a quadruped species has relevance to a bipedal human.
So what evidence, if any, is there from human studies on the effects of uterine environment on peripheral vascular function? Unfortunately, to date no group has performed detailed examination of the pathopharmacological properties of femoral arteries in the context of birth weight. There have, however, been several studies examining the in vivo function of other arteries. Martin et al12
have shown that low birth weight neonates show impaired endothelial function in skin arterioles. Additional studies have demonstrated that low birth weight is associated with reduced flow mediated dilatation of the brachial artery and that this dysfunction persists into adult life.13,14
In addition to demonstrating the role of the fetal environment in affecting peripheral vascular tone, Napoli et al15
have shown that maternal hypercholesterolaemia can cause an increase in the number of fatty streaks in fetal aortas. Furthermore, children of hypercholesterolaemic mothers appear to show faster progression of atherosclerosis, and this finding cannot be explained by conventional postnatal risk factors for atherosclerosis or genetic factors. Interestingly these studies appear to correlate with the findings of the animal studies in emphasising the importance of both maternal dietary imbalance and global undernutrition in influencing vascular dysfunction.
Although these studies add strong circumstantial evidence to the hypothesis that impaired fetal growth causes an increased susceptibility to PVD, several provisos must be made. Firstly, there is a lack of consistency in these findings, with several groups failing to find an association between birth weight and vascular dysfunction16
or accelerated atherosclerosis.17
Moreover, the differing geometries and haemodynamics of the femoral and brachial arteries raise questions about the validity of extrapolating data from different vascular beds. Finally, it should be noted that although endothelial dysfunction has been shown to be a reliable marker of atherogenesis,16
the presence of atherosclerosis is not necessarily an indicator of symptomatic disease. Indeed the progression of atherosclerotic plaques into clinically significant lesions is a highly complex process and as yet there are virtually no data on exactly how the fetal environment might influence this progression.