- Objective: This study was undertaken to determine whether premature labor is associated with changes in the maternal plasma concentration of soluble CD40 ligand (sCD40L), a marker of platelet activation. Methods: A cross-sectional study included patients in the following groups: 1) non-pregnant (n=21); 2) normal pregnancy (n=71); 3) normal pregnancy at term with (n=67) and without labor (n=88); 4) preterm labor (PTL) with intact membranes (n = 136) that was divided into the following sub-groups: 4a) PTL who delivered at term (n=49); 4b) PTL without intra-amniotic infection and/or inflammation (IAI) who delivered preterm (n=54); and 4c) PTL with IAI who delivered preterm (n=33). sCD40L concentrations were measured by ELISA. Results: The median maternal plasma sCD40L concentration was higher in pregnant than non-pregnant women (P = 0.017). Patients with PTL had a higher median maternal plasma sCD40L concentration than women with normal pregnancies, regardless of the presence or absence of IAI and gestational age at delivery (P<0.001 for all comparisons). IAI was not associated with a higher median maternal plasma concentration of sCD40L. Conclusions: Normal pregnancy is a state in which there is a physiologic increase of sCD40L. PTL was associated with an increased median maternal plasma sCD40L concentration that could not be accounted for by IAI. Thus, our findings suggest that platelet activation occurs during an episode of preterm labor.