Mortality among twins after age 6: fetal origins hypothesis versus twin method

Abstract
Objective: To test the validity of the fetal origins hypothesis and the classic twin method. Design: Follow up study of pairs of same sex twins in which both twins survived to age 6. Setting: Denmark. Subjects: 8495 twin individuals born 1870-1900, followed through to 31 December 1991. Main outcome measures: Mortality calculated on a cohort basis. Results: Mortality among twins and the general population was not significantly different except among females aged 60-89, in whom mortality among twins was 1.14 times (SE 0.03) higher than in the general population. Mortality among female dizygotic twins was 1.77 times (0.18) higher than among monozygotic twins at age 30.59. Otherwise, mortality for monozygotic and dizygotic twins did not consistently differ after age 6. Conclusion: According to the fetal origins hypothesis the risk of adult morbidity and mortality is heightened by retardation in intrauterine growth. Twins, and in particular monozygotic twins, experience growth retardation in utero. The findings in the present study suggest that the fetal origins hypothesis is not true for the retardation in intrauterine growth experienced by twins. Furthermore, the data are inconsistent with the underlying assumption of a recent claim that the classic twin method is invalid for studies of adult diseases. The present study is, however, based on the one third of all pairs of twins in which both twins survived to age 6. The possible impact of this selection can be evaluated in future studies of cohorts of younger twins with lower perinatal and infant mortality. Key messages It has been claimed that twin studies of adult diseases are invalid owing to the link between intrauterine development and adult diseases Contrary to the prediction from the fetal origins hypothesis this study found that mortality among twins and in the general population was similar after age 6 Contrary to the underlying assumption of the claim that the twin method is invalid, this study found that mortality in monozygotic and dizygotic twins was similar after age 6 This study suggests that the fetal origins hypothesis is not true for the retardation in intrauterine growth in these twin cohorts and that the hypothesis is no threat to the validity of the twin method