Birthweight, early environment, and genetics: a study of twins discordant for acute myocardial infarction

Background Epidemiological studies that used birthweight as a crude marker of fetal growth have suggested that low birthweight is associated with increased risk of coronary heart disease. Through investigation of this association within same-sexed twin pairs, confounding by genetic and early environmental factors can be greatly decreased. We undertook a case-control study in twins discordant for acute myocardial infarction (AMI). Methods The case-control study was nested within the population-based Swedish Twin Registry and linked with the national cause-of-death and hospital-discharge registries. We manually retrieved birth records containing information on birth and maternal characteristics for 132 same-sexed twin pairs discordant for AMI and 118 individually matched control twin pairs. Findings In comparisons between AMI cases and external matched control twins, cases had significantly lower birthweight (mean 2556 [SD 500] vs 2699 [530] g, p=0·04), birth length (47·1 [2·8] vs 47·9 [2·7] cm, p=0·04), and head circumference (33·0 [1·8] vs 33·5 [2·0] cm, p=0·03) than controls. In within-pair comparisons between AMI cases and healthy co-twins, no significant differences in birth measurements were found (birthweight 2458 [510] vs 2534 [530] g, p=0·73; birth length 47·1 [2-8] vs 47·2 [2·8] cm, p=0·91; head circumference 33·0 [1·7] vs 33·0 [1·8] cm, p=0·92). Interpretation The lack of an association between birth characteristics and AMI within twin pairs suggests that previously reported associations may be influenced by genetic and early environmental factors, or possibly, by unmeasured maternal factors that operate independently of birthweight.