Summary. Objective: We posit that low levels of protein S (PS) and protein Z (PZ) contribute to adverse pregnancy outcome (APO). Patients: We evaluated 103 women with subsequent normal pregnancy outcome (NPO), 106 women with APO, and 20 women with thrombophilia (TP). Methods: We compared first trimester (1st TRI) PZ levels in 103 women with NPO, 106 women with APO, and in 20 women with TP. We compared plasma levels of PZ and free PS antigen during the second (2nd TRI) and third trimesters (3rd TRI) of pregnancy in 51 women with APO and 51 matched women with NPO. Results: The mean 1st TRI PZ level was significantly lower among patients with APO, compared to pregnant controls (1.81 ± 0.7 vs. 2.21 ± 0.8 lg mL )1 , respectively, P < 0.001). Of patients with known TP, those with APO had a tendency for lower mean PZ levels compared to those TP women with NPO (1.5 ± 0.6 vs. 2.3 ± 0.9 lg mL )1 , respectively, P < 0.0631). There was a significant decrease in the PZ levels in patients with APO compared to NPO (2nd TRI 1.5 ± 0.4 vs. 2.0 ± 0.5 lg mL )1 , P < 0.0001; and 3rd TRI 1.6 ± 0.5 vs. 1.9 ± 0.5 lg mL )1 , P < 0.0002). Protein S levels were significantly lower in the 2nd and 3rd TRIs among patients with APO compared to patients with NPO (2nd TRI 34.4 ± 11.8% vs. 38.9 ± 10.3%, P < 0.05, respectively; and 3rd TRI 27.5 ± 8.4 vs. 31.2 ± 7.4, P < 0.025, respectively). Conclusions: We posit that decreased PZ and PS levels are additional risk factors for APO.

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