Maternal anti-protein Z antibodies in pregnancies complicated by pre-eclampsia, SGA and fetal death

Abstract

Objective. Low maternal plasma protein Z (PZ) concentrations were reported in patients with pre-eclampsia (PE), a small for gestational age (SGA) neonate, and a fetal demise (FD). Anti-protein Z antibodies (APZ-AB) have been proposed as a possible underlying mechanism leading to low plasma PZ concentrations. The objective of this study was to determine the maternal plasma concentration of APZ-AB in women with a normal pregnancy, and patients with PE, an SGA neonate or a FD.Study design. A cross-sectional study included women in the following groups: (1) non-pregnant women (n = 45); and pregnant women with: (2) normal pregnancies (n = 70); (3) PE (n = 123); (4) SGA neonates (n = 51); and (5) a FD (n = 51). Plasma concentrations of anti-protein Z IgM and IgG antibodies were measured by ELISA. Elevated APZ-AB was defined as >75th, 90th and 95th percentile of the normal pregnancy group. Non-parametric statistics were used for analyses.Results. (1) Patients with an SGA neonate had a higher median maternal plasma IgG APZ-AB concentration than women with normal pregnancies (p < 0.001), and patients with PE (p < 0.001) or with a FD (p = 0.001). (2) The proportion of patients with a maternal plasma IgM APZ-AB concentration >90th percentile was higher in the SGA group than in the PE group (p = 0.01). (3) Patients with PE maternal plasma IgM APZ-AB concentration >90th percentile had a higher rate of villous thrombosis (p = 0.03) and persistent muscularisation of basal plate arteries (p = 0.01) than those with IgM APZ-AB concentration <90th percentile; and (5) Patients with FD and maternal plasma IgM APZ-AB concentration >90th percentile had a higher rate of umbilical phlebitis and arteritis than those with IgM APZ-AB concentration <90th percentile (p = 0.003).Conclusions. (1) Patients with SGA neonates have a higher median plasma concentration of IgG APZ-AB than normal pregnant women, or patients with PE or FD; and (2) maternal plasma IgM APZ-AB concentration >90th percentile was associated with vascular placental lesions in patients with PE, but not in those with an SGA neonate, suggesting that in a subset of patients, these antibodies can be associated with abnormal placentation and pregnancy complications.