Could signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 be a therapeutic target in the pathogenesis of preeclampsia?

OBJECTIVE: Determination of biomolecules that play a role in the etiopathogenesis of preeclampsia and their application as therapeutic targets may increase surveillance in this patient group. The aim of this study was to investigate the relationship between signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1, a marker of endothelial dysfunction and platelet activation, and the development of preeclampsia. METHODS: In this observational cross-sectional study conducted between April 2021 and December 2022, 73 consecutive pregnant women with preeclampsia and 73 healthy pregnant women were included. Blood samples were taken from all patients with preeclampsia to measure signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 levels at the time of hospitalization. Excluded from the study were pregnant women with certain medical conditions or treatments, and the signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 levels of the groups were compared according to the development of preeclampsia. RESULTS: Signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 levels were significantly higher in the preeclampsia group than in the controls (p<0.001). In multivariate analysis, signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 was determined as an independent predictor for preeclampsia (OR: 1.678, 95%CI 1.424-1.979, p<0.001). Receiver operating characteristic curve analysis showed that the best cutoff value of signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 at 3.25 ng/mL predicted the development of preeclampsia with 71% sensitivity and 68% specificity (area under the curve, 0.739; 95% confidence interval (95%CI), 0.681-0.798, p<0.001). CONCLUSION: Signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 is significantly elevated in pregnant women with preeclampsia compared with healthy controls.

Low pregnancy-specific beta-1-glycoprotein is associated with nondipper hypertension and increased risk of preeclampsia in pregnant women with newly diagnosed chronic hypertension.

Chronic hypertension is one of the major risk factors for preeclampsia. Pregnancy-specific beta-1-glycoprotein (PSG-1) is a protein that plays a critical role in fetomaternal immune modulation and has been shown to be closely associated with pregnancy adverse events such as preeclampsia. It is also known that PSG-1 and its source placenta are associated with many molecular pathways associated with blood pressure regulation. In addition, the nondipping pattern (NDP) of chronic hypertension has been shown to be an independent risk factor for preeclampsia. Dipper individuals experience a notable nighttime drop in blood pressure, typically around 10% or more compared to daytime levels, while nondipper individuals show a smaller nighttime blood pressure decrease, indicating potential circadian blood pressure regulation disruption. In this context, we aimed to reveal the relationship between PSG-1, NDP and preeclampsia in this study. A total of 304 pregnant women who were newly diagnosed in the first trimester and started on antihypertensive medication were included in this study. All subjects performed 24-h ambulatory blood pressure monitoring twice throughout pregnancy, the first in the 1. trimester to confirm the diagnosis of hypertension and the second between 20+0 and 21+1 gestational weeks to determine the dipper-nondipper status of hypertension. Subjects were grouped as dipper and nondipper according to blood pressure, and groups were compared in terms of PSG-1 levels. In this study, low PSG-1 levels and NDP were independently associated with preeclampsia. Findings from this study suggest that PSG-1 may play an important role in the causal relationship between NDP and preeclampsia.

Cervical phosphorylated insulin-like growth factor binding protein-1 for the prediction of preterm delivery in symptomatic cases with intact membranes.

AIM: This prospective, observational study was an attempt to evaluate whether a positive cervical phosphorylated insulin-like growth factor binding protein-1 admission test in women with signs and symptoms of preterm labor (PTL) may be useful in the prediction of women who will deliver prematurely. METHODS: Pregnant women with confirmed gestational age between 24 and 37 weeks' gestation with <3 cm cervical dilatation and intact membranes were included in the study. Prior to digital examination, a sterile speculum examination was performed using a dacron swab rotated in the external cervical os for 15 s. The test was based on immunochromatographic qualitative analysis of cervical phosphorylated insulin-like growth factor binding protein-1. Test (+) and (-) cases were evaluated in terms of maternal demographic characteristics and neonatal outcomes. RESULTS: A total of 68 cases were enrolled in the study. There were no statistically significant differences between test (+) and (-) groups, in terms of maternal characteristics or adverse neonatal outcomes. However, cases with + test had high Bishop scores on admission (P = 0.01) and gestational age at delivery (P = 0.003). For deliveries within 7 days of admission, the strongest predictors were test positivity (RR:24,%95CI:2.8-204, P < 0.0001) and Bishop score (RR:1.3, %95CI: 1.0-1.6, P = 0.03). For deliveries <34 weeks' gestation, the test had a sensitivity, specificity, positive predictive values, negative predictive values, +likelihood ratios and -likelihood ratios of 70%, 74%, 48%, 88, 2.8 and 0.39, respectively. CONCLUSION: Among women with signs and symptoms of PTL, the high negative predictive value of this test to predict the PTL <34 weeks' gestation as well as within 7 days of delivery may be of value in the reassurance of patients, avoiding unnecessary medical interventions.