Abstract
ObjectThis study aimed to investigate the diagnostic value of placenta-derived macrophage-stimulating protein α-chain (MSP-α) before the 20th week of gestation for the early diagnosis of preeclampsia (PE).Methods and MaterialsTwo parts of this nested case-control study were simultaneously executed, and 1500 pregnant women were recruited. A total of 124 pregnant women were included in the plasma analysis part of this study. The MSP-α plasma level was measured before the 20th week of gestation, and the participants were followed until delivery. A case group of 62 women with PE and a control group of 62 women matched by gestational age, maternal age, and pre-pregnancy BMI (with normotensive pregnancies) were evaluated. In the placenta analysis part of this nested case-control study, the placentas of 34 pregnant women were randomly obtained. The placental levels of MSP were measured in 17 individuals with PE (case group) and in 17 women with a normotensive pregnancy matched by gestational age and maternal age (control group).ResultsThe plasma level of MSP-α was higher in the PE group than in the control group before the 20th week of gestation (p < 0.001). In addition, compared to the women with severe features in the PE group, those without severe features had a significantly higher plasma MSP-α level before the 20th week of gestation (p < 0.001). The area under the receiver operating characteristic curve (AUC) of MSP-α before the 20th week of gestation was 0.905 (95% CI, 0.811–0.962) for the women with early-onset PE without severe features. With regard to the placenta, the PE group (accumulated optical density, IOD [SUM] = 8862.37 ± 2064.42) exhibited increased MSP staining (more intense MSP staining or more extensive staining) compared with the control group (normal pregnancies (IOD [SUM] = 447.92 ± 114.72, P < 0.001). Furthermore, increased MSP staining was detected among the women without severe features compared with those with severe features in the PE group (IOD [SUM]: 12192.65 ± 5325.56 vs. 4104.83 ± 2383.06, P = 0.021).ConclusionAccording to the findings of this study, the plasma level of MSP-α may be associated with PE, and MSP-α may be considered a candidate protein for further analysis in studies of PE. Multicenter studies with larger sample sizes must be performed in the future to obtain accurate results regarding the predictive value of MSP-α in combination with other protein factors for the early diagnosis of PE.
Highlights
According to the ACOG criteria (2013), preeclampsia (PE) is defined by a systolic blood pressure 140 mmHg or a diastolic blood pressure 90 mmHg on two occasions measured at least 4 hours apart, with a proteinuria level 300 mg/d or with severe features (1) in the absence of proteinuria after the 20th week of gestation in women with previously normal blood pressure [1]
The plasma level of macrophage-stimulating protein α-chain (MSP-α) was higher in the PE group than in the control group before the 20th week of gestation (p < 0.001)
The area under the receiver operating characteristic curve (AUC) of Macrophage-stimulating protein (MSP)-α before the 20th week of gestation was 0.905 for the women with early-onset PE without severe features
Summary
According to the ACOG criteria (2013), preeclampsia (PE) is defined by a systolic blood pressure 140 mmHg or a diastolic blood pressure 90 mmHg on two occasions measured at least 4 hours apart, with a proteinuria level 300 mg/d (or a minimum protein/creatinine ratio of 0.3 mg/dL or a proteinuria level 1+) or with severe features (1) in the absence of proteinuria after the 20th week of gestation in women with previously normal blood pressure [1]. It may be useful to identify additional plasma proteins that can be used as predictive biomarkers of PE in a future prediction model study. Another marker of interest is receptor tyrosine kinase Ron (RON), which regulates cell growth, differentiation, and morphology [5]. Surrounding the implanting embryo during pregnancy, and it assumes a paracrine role in trophoblasts, which express its ligand, MSP [6]. It has been demonstrated that activation of RON by HGFL/MSP may assist in implantation, thereby improving trophoblast function and viability [6]. The presence of an abnormal plasma level of MSP-α has not been found to be useful for the early diagnosis of PE before clinical symptoms arise. We analyzed the diagnostic efficacy of this marker in PE with severe features, PE without severe features, early-onset PE and late-onset PE
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