Schaaf and colleagues have confirmed an increased risk of preterm birth in singleton pregnancies among women with a history of preterm birth in a twin pregnancy. Their comprehensive evaluation of a large dataset should settle the uncertainty that has attended previous smaller studies. The risk is real, so now the question is, Why? Why do women who deliver twins preterm more often deliver a subsequent preterm singleton? The point of this editorial is not to suggest an answer, but rather to add this question to the list of important but unexplained clinical observations that should drive basic research in preterm parturition. Here is the list:

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  Why do African American women have a 2-fold increased risk of preterm birth even when other risk factors are taken into account?

  
  
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  Why is preterm birth recurrent in some women? How do they differ from women with an isolated preterm birth?

  
  
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  Why does progestin supplementation reduce the risk of preterm parturition in some but not all women who seemingly share the same risk factors, eg, prior spontaneous preterm birth and/or short cervix?

  
  
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  Why is the risk of preterm birth increased in some women who conceive a singleton gestation after fertility care, or who have a history of ≥2 first-trimester pregnancy terminations?

  
  
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  Why is the risk of singleton preterm birth increased for some women with a history of preterm, especially early preterm, birth of twins?

These questions are important not only because the answers affect a substantial number of women, but also because they challenge traditional paradigms about prematurity. That the questions are raised at all challenges the usual answers to questions on the list, eg, that African American women have increased rates of preterm birth because of limited access to prenatal care, that preterm birth risk is increased after pregnancy terminations only when performed in the second trimester with procedures that damage the cervix, and increased after fertility care only in multifetal pregnancies. These observations raise questions that should inform basic research as well as clinical care. Schaaf and colleagues have made a signal contribution to the list.