Head size at birth and long-term mortality from coronary heart disease.

BACKGROUND Many studies have shown that low birthweight is associated with increased risk of heart disease in adulthood. It is controversial whether this association is caused by genetic or non-genetic factors, and whether life course exposures, such as adult overweight, could modify the association. We have studied the association of head circumference at birth with later deaths from coronary heart disease (CHD), and assessed whether maternal height and adult body mass could modify the association. METHODS Population-based cohort study of 35,846 men and women born between 1920 and 1959 with mortality follow-up from 1961 to 2005. RESULTS During follow-up, 630 people died from CHD and there was an inverse association of head circumference with deaths from CHD (Ptrend = 0.010). The association was modified by maternal height (Pinteraction = 0.01) and by adult body mass (Pinteraction = 0.05). People in the lowest third of head circumference, who had a tall mother or a high body mass index in adulthood, were at the highest risk of death from CHD. CONCLUSIONS Head circumference at birth was inversely associated with deaths from CHD, and the combination of small head and tall mother, or small head and high adult body mass, was associated with the highest risk. These findings suggest that combined effects of genetic factors (growth potential and intrauterine growth) and non-genetic factors acting throughout the life course (intrauterine growth restriction and later weight gain) could mediate the effects of birth size on adult heart disease.