Pregnancy involves dramatic changes to the maternal proteome that are essential for the growth and development of babies. Remarkably, very little is known about the importance of pregnancy zone protein (PZP), a major pregnancy-associated plasma protein that's been shown to stabilise misfolded proteins in vitro (1). A few studies have reported an association between decreased maternal plasma PZP in preeclampsia (PE) (2, 3), but conflicting data has also been reported (4).
We quantified PZP in maternal plasma by ELISA (N=32 normotensive, N=31 PE) at 34 weeks' gestation. PZP was abundant in third trimester (mean 222.6 µg/mL, SD 182.2. µg/mL) but substantially less than reported previously (2, 5). PZP was also significantly lower in women with PE compared to normotensive pregnancy (median 123.1 µg/mL, IQR 50.1–247.5 µg/mL; 252.4 µg/mL, 88.3–405.1 µg/mL, respectively; p=.016; matched by maternal age, gestational age, and BMI). Interestingly, a moderate positive correlation between PZP level and parity was identified in normotensive pregnancy (rs=0.461, p=.009), but not in PE, suggesting that parity is an important consideration.
To address this, and other methodological limitations that potentially confound the association between PZP and PE reported in prior studies, we are currently analysing maternal PZP levels in two large nulliparous pregnancy cohorts, SCOPE and STOP (Table 1). Our preliminary analyses suggest that in the first trimester the odds of a woman having PE increase as PZP concentration increases.
Early identification of PE risk is essential for enhancing outcomes for mother and baby, but this remains a key clinical challenge. Increased protein misfolding has been shown in PE (6, 7, 8, 9), so elevated PZP concentration may indicate an adaptive response to physiological stress. A deeper understanding of PZP actions in pregnancy and the factors influencing its changing abundance across gestation is needed to uncover its potential as a prognostic biomarker.