Studies of twins: can they shed light on the fetal origins of adult disease hypothesis?

There has been much interest in evidence that people with lower birthweight have higher risk of adult cardiovascular disease, but the causal pathways underlying such observations are uncertain. Study of twins offers an opportunity to shed light on these pathways, in three different ways. First, in a twin pregnancy maternal nutritional resources and the "supply line" to the fetuses will be more "stretched". We hypothesise that study of twin pregnancies is a more efficient way to identify modifiable maternal factors that influence later health than studies of singleton pregnancies. Second, twins have lower birthweight than singletons. Comparison of cardiovascular disease risk in twins versus that in singletons will provide insight into whether birthweight per se is in the underlying causal pathway of interest, and whether factors constraining fetal growth of twins (versus singletons) affect later outcome. Third, twin cohorts provide an opportunity to investigate the role of "shared" factors versus factors affecting each individual fetus, by comparing results of within-cohort versus within-pair analyses. Generalisability of findings in twins is debated. We suggest that findings in monochorionic twins (or in the absence of chorionicity data, those from monozygotic twins) need to be interpreted with caution.