Background: Although epidemiological studies suggest that people with low birthweight are at higher risk of coronary heart disease and stroke in adult life than those of higher birthweight, the mechanisms underlying this relation are unclear. We investigated whether impaired fetal growth leads to an increased risk of atherosclerosis by assessment of the carotid and lower-limb arteries in a group of people aged around 70 years for whom birthweight data were available.
Methods: 2232 singleton babies were born to married mothers at a maternity hospital in Sheffield, UK, between 1922 and 1926, and had complete birth records. We traced 829 survivors and invited 395 who still lived in Sheffield to take part in this study. 322 agreed; they were interviewed at home and 181 underwent duplex ultrasonographic examination of the extracranial parts of the carotid arteries. Atherosclerosis in the arteries of the lower limb was assessed in 186 people by the ankle-brachial-pressure index (ABPI).
Findings: The prevalence and severity of carotid atherosclerosis was greatest in those with the lowest recorded birthweight. The risk of carotid stenosis was greater for people who had weighed 6.5 lb or less at birth than for those who weighed over 7.5 lb (odds ratio 5.3 [95% CI 2.0-14.0]), after adjustment for cardiovascular risk factors and gestational age at birth. The odds ratio for atherosclerotic disease in the lower limbs (low ABPI) was highest in people with the lowest recorded birthweight, but this relation was not significant (odds ratio 2.3 [1.0-5.6]).
Interpretation: Increased atherogenesis may be one mechanism mediating the observed epidemiological link between impaired fetal growth and cardiovascular disease. Adaptations made by the fetus in response to influences that retard its growth may have long-term consequences for the structure and metabolism of the vascular system.