Invited commentary: disaggregating preterm birth to determine etiology.

Identifying the causes of preterm birth has been problematic, in part because of heterogeneous pathways leading to the same event, early delivery. If a risk factor affects only a subset of cases, then studies that address the aggregate outcome will generate diluted measures of association. McElrath et al. (Am J Epidemiol. 2008;168(9):980-989) examined an array of potential influences on very early preterm birth (<28 weeks' gestation) and divided cases on the basis of proximal causes. Through factor analysis, they found empirical support for dividing preterm cases into 2 groups: intrauterine inflammation (preterm labor, preterm membrane rupture, placental abruption, and cervical insufficiency) and abnormal placentation (preeclampsia and intrauterine growth restriction). Replication of this classification in less extreme preterm births is needed, requiring large numbers of preterm births that have been characterized in detail. Nonetheless, this division is worthy of study by using previously collected data to determine whether, in fact, stronger associations are found for these subsets than for preterm birth in the aggregate. Ultimately, the test of the approach is in improving our understanding of etiology, ideally generating stronger, more consistent associations with preterm birth subsets than have been found for preterm birth in the aggregate.