It is with interest but not without surprise that we read the case-control study of Tyler et al, which attempted to evaluate the association between antiinflammatory drugs and cerebral palsy in very preterm neonates. Beyond the fact that the authors’ conclusions are not in agreement with the highest level of evidence and do not acknowledge the numerous limitations, they have the potential to mislead both women and health care providers by suggesting that aspirin may cause brain damage, thereby compromising the appropriate use of an inexpensive and widely available treatment that can prevent serious maternal and neonatal morbidities.

Randomized controlled trials and metaanalysis—the highest levels of evidence available—have demonstrated that low-dose aspirin initiated before 16 weeks’ gestation is associated with a significant decrease of preeclampsia and intrauterine growth restriction, and most likely the severe and preterm forms of these diseases. It remains unclear whether low-dose aspirin prevents the placenta-mediated disease or delay its onset by improving impaired placentation. Nevertheless, as observed by Tyler et al and in agreement with current best evidence, aspirin leads to a decrease of early-onset preeclampsia and therefore a decrease in the rate of very preterm births related to preeclampsia. High-risk women who delivered before 28 weeks despite the appropriate use of aspirin were potentially destined to worse perinatal outcomes without the use of aspirin. Moreover, initiation of aspirin in women with preterm labor or premature rupture of membrane could have led to the prolongation of pregnancy and the further growing of intraamniotic infection and inflammation: a major contributor to cerebral palsy. The current study design does not allow for adjustment for such potential selection biases.

Data concerning the dosage and timing of aspirins’ use could have definitively affected the results of the study. Aspirin initiated when deep placentation disorders are irreversible, is not beneficial, and in fact potentially harmful. An increased risk of placenta abruption cannot be excluded when low-dose aspirin is begun after 16 weeks (relative risk, 1.56; 95% confidence interval, 0.96–2.55).

Finally, it is submitted that in accordance with the highest level of evidence, the only conclusions that can validly be derived from the Tyler et al study are as follows: (1) random use of aspirin during pregnancy may be harmful; (2) aspirin should not be used when intraamniotic infection is suspected; and (3) low-dose aspirin should be reserved for accurately identified women at high-risk for placenta mediated complications and initiated in early gestation.