Theilen LH, Campbell HD, Mumford SL, et al. - Given a possible role of platelet activation in the pathophysiology of placenta-mediated obstetric complications, as evidenced by the efficacy of aspirin for preventing preeclampsia, researchers sought to ascertain if maternal plasma concentrations of platelet factor 4 are linked with risk of placenta-mediated adverse obstetric outcomes. Further, they examined if these links are affected by low-dose aspirin. In this ancillary study, they included estimate of platelet factor 4 among 1,185 of the 1,228 reproductive-age women recruited in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial with available plasma samples, with relevant outcomes investigated among 584 women with pregnancies lasting at least 20 weeks’ gestation. Plasma samples collected at the prepregnancy study visit (prior to randomization to low-dose aspirin or placebo), 12 weeks of gestation, and 28 weeks of gestation were assessed for measures of platelet factor 4.  During follow-up, the composite adverse obstetric outcome occurred in 95 women, with 57 cases of hypertensive disorders of pregnancy, 35 of small-for-gestational age (SGA), and 6 of placental abruption. Increased risk of placenta-mediated adverse pregnancy outcomes, particularly for hypertensive disorders of pregnancy, was observed in correlation with high concentrations of platelet factor 4 prior to pregnancy. The increased risk of these outcomes may mitigate with providing aspirin to women with higher plasma concentrations of preconception platelet factor 4, but higher doses of aspirin or alternate therapies may be needed in low-dose aspirin non-responders to achieve obstetric risk reduction.