Abstract
This study aims to investigate the risk factors and the joint biochemical indicators predictive value for preeclampsia. Related factors and biochemical indicators were investigated in 558 patients with preeclampsia and 435 normal pregnant women. Multiplicity analysis was performed by logistic regression. The predictive value of the biochemical index and joint biochemical indicators for predicting the incidence of pregnant women preeclampsia were analyzed by ROC curve. A progestation BMI of >24 kg/m2 (OR = 5.412, 95% CI: 1.169–9.447), hypertension history (OR = 7.487, 95% CI: 2.541–11.247) and advanced age (>35 years old, OR = 6.321, 95% CI: 3.142–20.342) are risk factors for preeclampsia. Tumor necrosis factor‐α and plasma protein‐A are valuable for preeclampsia prediction. The predictive success of preeclampsia could be improved by clinical risk factors associated with biochemical indicators detection.
Keywords: Preeclampsia, Risk factors, Biochemical indexes, Prediction analysis
Introduction
Preeclampsia is a vasospasm, the leading cause of death in pregnant women, and the most common cause of premature labor due to iatrogenic treatment. Acompany with the mortality of pregnant women with preeclampsia increasing, the fetal mortality and disability rates rise [[1], [2], [3]]. At present, epidemiologic study have raised more aware of the risk factors for preeclampsia [[4], [5], [6], [7], [8]]. It has been found that early intervention in pregnant women with high risk factors for preeclampsia play an obvious significance in clinical value. However, due to changes in people's lifestyle and the existence of regional and racial differences, there are significant differences in high risk factors and low risk factors for preeclampsia. Studies on most biochemical markers in late pregnancy did not reveal any predictive value for preeclampsia. Few studies have investigated the predictive value of biochemical markers in the peripheral blood of pregnant women in early pregnancy, and there is also no study on the predictive value of the combination of clinical factors and laboratory markers for preeclampsia. Therefore, in the present study, the predictive value of the combination of clinical high risk factors and biochemical markers for preeclampsia in pregnant women was investigated.
Methods
General information
A total of 558 pregnant women with preeclampsia who received medical service and delivered in the Obstetric Department of our hospital between June 2015 and June 2016 were enrolled into this study. These patients had a gestational age of within 22–40 weeks, with a mean gestational age of 37.01 ± 3.26 weeks. All patients met the diagnostic criteria for preeclampsia. At the same time, 435 pregnant women who underwent antenatal care during the same time period and were found to have no obstetric complications were enrolled as the control group. All patients provided a signed informed consent before the investigation.
Methods and basic information
The basic data of these pregnant women including age, gender, height, body weight, history of hypertension, hyperlipidemia, diabetes, family history of eclampsia, marital status, smoking history, drinking history, education level, other systemic organ diseases, gravidity, complications, organ function, body temperature, heart rate, respiratory rate, arterial systolic blood pressure, arterial diastolic blood pressure and blood index data, were recorded. Biochemical index detection: Two ml of peripheral blood was withdrawn from each patient at the gestational age of within 10–14 weeks. In the present study, enzyme‐linked immunosorbent assay (ELISA) was used to detect the levels of pregnancy‐associated plasma protein‐A, fetal hemoglobin, placental growth factor, D‐dimer, C‐reactive protein (CRP), interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α).
Statistical analysis
Data were statistically analyzed using statistical software SPSS 15.0. Measurement data were expressed as mean ± standard deviation ( ± SD), and t‐test was used to evaluate the characteristics in the clinical data of pregnant women. Furthermore, the risk factors for preeclampsia were analyzed using univariate logistic regression analysis, and the independent risk factors for preeclampsia were analyzed using multivariate logistic regression analysis. The best combination of clinical factors and biochemical indexes were explored using the receiver operating characteristic (ROC) curve, in order to improve the predictive value and optimize the prediction system. P < 0.05 was considered statistically significant.
Results
Analysis of clinical risk factors for preeclampsia
These risk factors were analyzed using univariate analysis, and 13 variables were analyzed using multivariate logistic regression analysis. Hence, five high‐risk factors related to preeclampsia were revealed, which are listed in the following order according to the odds ratio (OR) values: history of hypertension, advanced age, high blood lipids, body mass index (BMI), and history of diabetes mellitus (Table 1).
Table 1.
Analysis of clinical risk factors for preeclampsia.
| B | S E | Wald | OR | P | 94% CI | |
|---|---|---|---|---|---|---|
| Advanced age | 3.541 | 0.485 | 7.146 | 6.321 | 0.01 | 3.142–20.342 |
| History of hypertension | 2.432 | 0.574 | 14.257 | 7.487 | 0.004 | 2.541–11.247 |
| High blood lipids | 3.845 | 0.624 | 11.264 | 5.578 | 0.033 | 3.145–26.642 |
| History of diabetes mellitus | 1.234 | 0.454 | 17.218 | 4.568 | 0.039 | 2.451–15.264 |
| BMI | 0.157 | 0.062 | 6.414 | 5.412 | 0.026 | 1.169–9.447 |
Analysis of biochemical indexes using the ROC curves
The predictive value of the plasma levels of pregnancy‐related plasma protein‐A, growth factor, D‐dimer, CRP, IL‐6 and TNF‐α in pregnant women for preeclampsia were analyzed. These results suggest that TNF‐α and plasma protein‐A have predictive values for preeclampsia (Table 2).
Table 2.
Analysis of biochemical indexes using the ROC curves.
| Sensitivity (%) | Specificity (%) | AUC value (95% CI) | |
|---|---|---|---|
| TNF‐α | 85.4 | 68.5 | 0.854 (0.773–0.935) |
| Plasma protein‐A | 83.6 | 65.5 | 0.836 (0.747–0.925) |
| Fetal hemoglobin | 63.7 | 58.6 | 0.637 (0.523–0.751) |
Analysis of the clinical risk factors for preeclampsia and prediction based on the combination of risk factors and biochemical indexes
The analysis results are shown in Table 3.
Table 3.
Analysis of the clinical risk factors for preeclampsia and prediction based on the combination of risk factors and biochemical indexes.
| Combination | Sensitivity (%) | Specificity (%) |
|---|---|---|
| BMI + TNF‐α | 89.25 | 74.74 |
| BMI + plasma protein‐A | 85.32 | 70.23 |
| History of hypertension + plasma protein‐A | 84.25 | 68.95 |
| History of hypertension + TNF‐α | 85.52 | 70.52 |
| BMI + history of hypertension + TNF‐α + plasma protein‐A | 90.70 | 78.54 |
Combination BMI + history of hypertension + TNF‐α + plasma protein‐A can improve the predictive value of pre eclampsia.
Discussion
Preeclampsia is a vasospasm. The incidence of this disease in primipara is approximately 3–8%. In some certain populations, the incidence can be triple increased. The fundamental pathophysiological changes involve systemic arteriolar spasm, loss of function of endothelial cells, and systemic target organ damage as well as different clinical signs due to blood flow decreased [[9], [10], [11]]. Although the etiology and pathogenesis are unclear yet, it is generally deemed that as an idiopathic systemic disease in duration of pregnancy, although Preeclampsia has been generally believed that multiple factors are jointly involved in its pathogenesis.
Analysis of clinical risk factors for preeclampsia
Epidemiological studies have increased the people's understanding of the risk factors for preeclampsia. Maternal medical diseases such as chronic hypertension, diabetes mellitus, kidney disease and autoimmune diseases have been considered to be high risk factors for preeclampsia. Catov et al. [12] revealed that in 2117 pregnant women, the relative risk (RR) of preeclampsia was 3.4 (95% CI: 2.8–4.1) for patients with chronic hypertension and 2.1 (95% CI: 1.4–3.0) for diabetic patients. In this study, the OR value was 7.487 (95% CI: 2.541–11.247) for patients with a history of hypertension, and 4.568 (95% CI: 2.451–15.264) for patients with a history of diabetes. Leung et al. [13] revealed that in 29,303 women in China, the incidence of preeclampsia in severely obese people increased by 3.97 times, the incidence of preeclampsia in obese people with a BMI of 27.5–30.0 kg/m2 increased by 3.25 times, and the incidence of preeclampsia in people with a BMI of 25.0–27.5 kg/m2 increased by 1.60 times. In this study, the OR value of BMI was 5.412 (95% CI: 1.169–9.447). This suggests that obesity is a high‐risk factor for preeclampsia. In this study, after these risk factors were analyzed by univariate analysis, multivariate logistic regression analysis was conducted and revealed that history of hypertension, advanced age, high blood lipids, increase in gestational body weight and history of diabetes were high risk factors for preeclampsia.
Analysis of the predictive value of the biochemical index for preeclampsia in pregnant women
At present, the biochemical indexes closely related to the onset of preeclampsia include the following: pregnancy‐related plasma protein‐A, fetal hemoglobin, alpha 1‐microglobulin, placental growth factor, soluble Eng, placental protein‐13, activin A, inhibin A and peptide [[6], [7], [8], [9], [10]]. Merely a small part of studies have used the prospective observation method to reveal the predictive value of the biochemical indexes of peripheral blood from pregnant women in early pregnancy (at approximately 12 weeks of pregnancy) for preeclampsia [[14], [15], [16], [17], [18]]. In this study, the predicting biochemical indexes for preeclampsia were correlated to the occurrence of preeclampsia. Furthermore, 2 ml of peripheral blood were collected from each patient in 10–14 weeks gestation period. Then, plasma concentrations of pregnancy‐related plasma protein‐A, fetal hemoglobin, placental growth factor, D‐dimer, CRP, IL‐6 and TNF‐α were detected by ELISA. With preeclampsia as the research target, the ROC curve revealed that the area under the curve (AUC) value of TNF‐α was 0.854 (0.773–0.935), the AUC value of plasma protein‐A was 0.836 (0.747–0.925), and the AUC value of fetal hemoglobin was 0.637 (0.523–0.751). Among these, it could be observed that TNF‐α and plasma protein‐A have a certain accuracy. Hence, these have high predictive values for preeclampsia.
Analysis of the predictive value of the combination of clinical risk factors and biochemical indexes for preeclampsia
At present, there are a number of laboratory indexes related to the occurrence and development of preeclampsia. However, few prospective studies have revealed the predictive value of biochemical markers in early pregnancy for preeclampsia, and there are no systematic studies on the combination of clinical factors and laboratory indexes for the prediction of preeclampsia. In this study, two risk factors for preeclampsia, BMI and history of hypertension, were selected and combined with TNF‐α and plasma protein‐A to form different sets; and the predictive values of these sets for preeclampsia were analyzed and compared. The ROC analysis was conducted to reveal the best combination of clinical factors and biochemical indexes. Results revealed that the sensitivities of BMI + TNF‐α, BMI + plasma protein‐A, history of hypertension + plasma protein‐A, history of hypertension + TNF‐α, BMI + history of hypertension + TNF‐α, and BMI + history of hypertension + TNF‐α + plasma protein‐A for the preeclampsia prediction were 89.25%, 85.32%, 84.25%, 85.52% and 90.70%, respectively. When these biochemical indexes and clinical risk factors were jointly used, the sensitivity and specificity were both improved. Among these, the predictive value of BMI + history of hypertension + TNF‐α + plasma protein‐A was the highest; and its sensitivity and specificity was 90.70% and 78.54%, respectively.
In conclusion, multivariate analysis results in this study revealed that the following elements are high risk factors for preeclampsia: hypertension history, advanced age, high blood lipids, high BMI and pregnant women with diabetes history. In the biochemical indicators, TNF‐α and plasma protein‐A show certain accuracy in predicting preeclampsia. The examination of clinical risk factors combined with biochemical indexes can improve the predictive success of preeclampsia, and has important clinical value in improving the prognosis of pregnant women and fetuses.
Acknowledgements
We are particularly grateful to all the people who have given us help on our article.
This project is funded: Analysis of the risk factors of preeclampsia and prediction based on combined biochemical indexes; Scientific and technological projects in Jinhua city: 2015‐3‐037.
Conflicts of interest: All authors declare no conflicts of interest.
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