Perinatal risk factors for ischemic heart disease: disentangling the roles of birth weight and preterm birth.

BACKGROUND Several studies have reported an association between low birth weight and ischemic heart disease, but it remains unclear whether the association is mediated through poor fetal growth or short gestational duration. METHODS AND RESULTS In a cohort study, we have identified all subjects born preterm or with a low birth weight at 4 major delivery units in Sweden from 1925 through 1949. For comparison, an equal number of subjects with none of these criteria were identified within the same source population. The study population consists of 6425 subjects, of whom 2931 were born before 37 weeks of gestation and 2176 had a birth weight < 2500 g. Fetal growth was estimated through birth weight for gestational age. The cohort was followed up for occurrence of ischemic heart disease through the nationwide Hospital Discharge and Cause of Death Registries during the period of 1987 through 2002. In the cohort, 617 cases of ischemic heart disease occurred. Compared with subjects with a normal fetal growth, those born small for gestational age (birth weight < or = -2 SD below the mean) were at increased risk of ischemic heart disease (adjusted hazard ratio, 1.64; 95% confidence interval, 1.23 to 2.18). The negative association between fetal growth and risk of ischemic heart disease was independent of gestational duration. CONCLUSIONS The association between low birth weight and adult risk of ischemic heart disease appears to be mediated entirely by poor fetal growth.