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ORIGINAL ARTICLE |
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Year : 2016 | Volume
: 3
| Issue : 1 | Page : 11-15 |
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Procalcitonin and endothelin-1 levels in severe preeclamptic and eclamptic patients and effect on fetal outcome
Sultan Bugday1, Yasemin Yildirim2, Ahmet Var3, Asli Goker2, Esra Bahar Gur1, Kemal Kusçu2
1 Department of Obstetrics and Gynecology, Faculty of Medicine, Sifa University, Izmir, Turkey 2 Department of Obstetrics and Gynecology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey 3 Department of Biochemistry, Faculty of Medicine, Celal Bayar University, Manisa, Turkey
Date of Web Publication | 29-Feb-2016 |
Correspondence Address: Dr. Esra Bahar Gur Department of Obstetrics and Gynecology, Sifa University Faculty of Medicine, Bornova, İzmir - 35100 Turkey
Source of Support: None, Conflict of Interest: None | Check |
Objective: To compare serum procalcitonin (PCT) and endothelin-1 (ET-1) levels in pregnant women with pregnancy-related serious hypertensive disorders (severe preeclampsia and eclampsia) with healthy controls. Materials and Methods: Serum PCT and ET-1 levels were analyzed in 27 cases with severe preeclampsia/eclampsia and 22 healthy controls. Umbilical artery Doppler was performed before the onset of labor. Umbilical artery blood pH and Apgar scores were recorded. The relationship between PCT and fetal well-being was evaluated. Results: The level of PCT was significantly higher in the pregnancy-related severe hypertensive disorders (preeclampsia and eclampsia) than the control group. Apgar scores at minute 1 were lower in the eclampsia group compared to preeclampsia and control group; but, Apgar scores for minute 1 were not correlated with PCT levels (r = 0.2, P = 0.4). There was no significant difference in umbilical artery pulsatility index (PI) values between the groups. There was no significant correlation between umbilical artery PI values and PCT (r = 0.17, P = 0.9). Conclusion: The high levels of PCT confirm that an inflammatory process takes place in the etiopathogenesis of severe preeclampsia and PCT may be used as a marker for severe preeclampsia. A negative fetal outcome has not been associated with high levels of PCT. Keywords: Eclampsia, endothelin-1, preeclampsia, procalcitonin
How to cite this article: Bugday S, Yildirim Y, Var A, Goker A, Gur EB, Kusçu K. Procalcitonin and endothelin-1 levels in severe preeclamptic and eclamptic patients and effect on fetal outcome. Sifa Med J 2016;3:11-5 |
How to cite this URL: Bugday S, Yildirim Y, Var A, Goker A, Gur EB, Kusçu K. Procalcitonin and endothelin-1 levels in severe preeclamptic and eclamptic patients and effect on fetal outcome. Sifa Med J [serial online] 2016 [cited 2024 Mar 28];3:11-5. Available from: https://www.imjsu.org/text.asp?2016/3/1/11/177690 |
Introduction | | |
Preeclampsia is generally defined as hypertension and proteinuria that develop during or after the 20 th week of gestation. This disorder, which is specific to human pregnancies, has a prevalence of 3-8% in Western countries, and is a major cause of maternal and fetal morbidity and mortality. [1] The exact underlying mechanism of preeclampsia is unknown; however, various studies support the hypothesis of a genetic and immunologic etiology. [2],[3] The failure to develop an adequate blood supply to the placenta results in placental oxidative stress and the release of syncytiotrophoblast debris and soluble fms-like tyrosine kinase-1 (sFlt-1) into the maternal circulation; these, in turn, trigger an inflammatory response and endothelial dysfunction. [3],[4],[5] Inflammation is believed to be a consequence of preeclampsia, and appears to enhance the pathology. [6] Women with autoimmune diseases or risk factors for chronic inflammation (such as obesity, diabetes mellitus, and chronic hypertension) have a higher likelihood of developing preeclampsia, especially severe preeclampsia. [7],[8],[9]
Endothelin-1 (ET-1) was initially characterized as a potent vasoconstrictor derived from the endothelium. [10] It has been demonstrated that elevated ET-1 production results in hypertension, congestive heart failure, and renal failure. [11],[12] There is also evidence suggesting the involvement of ET-1 as a pathophysiological factor in the development of preeclampsia. However, whether the level of circulating ET-1 correlates with the severity of preeclampsia symptoms is currently a matter of debate. [13],[14]
Procalcitonin (PCT) is a 116-amino acid polypeptide precursor of calcitonin, a calcium regulating hormone. [15] Although the exact biological role of PCT has not been elucidated, it has been suggested that it plays an important role in the pathogenesis of sepsis. PCT is a useful marker for monitoring the treatment of intensive care patients. [16] The limited amount of published data on PCT during pregnancy focuses on the premature rupture of membranes and preterm delivery. According to the available data; the cut-off level of PCT for ruling out infection during the third trimester, at delivery, and in the immediate postpartum period is 0.25 μg/L. [17],[18] There is limited data regarding the relationship between PCT and preeclampsia. To our knowledge, only three studies show an association between PCT and preeclampsia. [19],[20],[21]
The aim of this study was to evaluate changes of serum levels of PCT and ET-1 in pregnant women complicated with severe preeclampsia/eclampsia and their matched controls and relate this results to fetal well-being.
Materials and Methods | | |
This prospective case-control study was carried out between May 2009 and Jun 2010 at Celal Bayar University Hospital, Department of Obstetrics and Gynecology, Manisa, Turkey. The study was approved by the local ethics committee at the Celal Bayar University and informed consent was obtained from all participants. During the study period, there were 768 vaginal and 804 cesarean section deliveries in our hospital. Pregnant women with hypertension who applied to the obstetrics clinic were evaluated according to their eligibility for the study.
Preeclampsia was defined as gestational hypertension with proteinuria, specifically, blood pressure of 140 mmHg systolic or higher or 90 mmHg diastolic or higher; and 24-hour urinary protein greater than or equal to 300 mg or proteinuria greater than or equal to 1+ by dipstick testing, after the 20 th week of pregnancy in a previously normotensive and nonproteinuric woman. Pregnant women meeting the following criteria were diagnosed as severe preeclamptic and constituted the preeclampsia group (SPE):
- Blood pressure of 160 mmHg systolic, or 110 mmHg diastolic, or higher on two occasions at least 6 hours apart while the patient is in bed rest;
- Proteinuria or 5 g, or higher protein in a 24-hour urine specimen, or 3 + or greater on two random urine samples collected at least 4 hours apart;
- Oliguria of less than 500 ml in 24 hours;
- Cerebral or visual disturbances;
- Pulmonary edema or cyanosis;
- Epigastric or right upper-quadrant pain;
- Impaired liver function;
- Thrombocytopenia, and
- Fetal growth restriction.
Women without a history of convulsion and/or neurologic deficit, who were diagnosed as eclamptic constituted the eclampsia group (E). Normotensive, healthy third trimester women were chosen as the controls (C).
Exclusion criteria were chronic renal disease; chronic hypertension; diabetes mellitus; gestational diabetes; cardiovascular disease; premature rupture of membranes; urinary tract infection; autoimmune disease; malignancy; and aspirin, heparin, or tobacco use.
Venous blood was obtained before any intervention. Plasma ET-1 levels were measured by enzyme-linked immunosorbent assay (ELISA) method (Phoenix Pharmaceuticals, USA, Kat. No: EK-023-01). Analytic sensitivity was 0.13 ng/ml and range was 0-25 ng/ml. PCT levels were measured by enzyme-linked fluorescent assay (ELFA) method using mini VIDAS analyzer (Bio Merieux, Fransa, ref: 30450). Levels below 0.05 ng/ml were considered as normal.
Fetal umbilical artery Doppler sonography was done before the onset of labor. Doppler velocimetry measurements were done using Voluson 730 Expert sonography. The pulsatility index (PI) values were used for evaluation.
Cord blood was obtained after clamping and was analyzed for umbilical artery pH by cobas b 121 (Roche Diagnostics, Switzerland). A value less than 7.20 was interpreted as acidosis. Apgar scores were recorded at minutes 1 and 5 postpartum and a value less than 7 was considered as abnormal.
Statistical analysis was performed by Statistical Package for Social Sciences (SPSS) version 16.0. Mann-Whitney test, Fisher's exact test, chi-square test, and Pearson correlation test were used and a P-value less than 0.05 was considered statistically significant.
Results | | |
There was a total of 22 women in SPE, five women in E, and 22 women in C groups. Clinical data of the study and control groups are shown in [Table 1]. There were no significant differences between the groups with respect to maternal age.
Because of the very low number of pregnant women in eclampsia group, eclamptic and preeclamptic pregnancies were evaluated as pregnancy-related severe hypertensive disorders group. PCT levels were significantly higher in the pregnancy related severe hypertensive disorders group than in the control group (P < 0.05); but interestingly, PCT values were lower in E group than SPE group. ET-1 levels were not different between groups [Table 2] and [Figure 1]. | Figure 1: PCT and ET-1 levels in preeclampsia, eclampsia, and control groups. PCT = Procalcitonin, ET-1 = endothelin-1
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| Table 2: PCT and ET-1 levels in pre-eclampsia/ eclampsia and control groups
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Fetal well-being was evaluated according to Apgar scores at minute 1 and 5, umbilical artery pH, and umbilical artery Doppler ultrasound PI values. There was no significant difference between pregnancy-related severe hypertensive disorders group than the control group in these parameters. Only 1-minute Apgar score in the eclampsia group was significantly lower. These are shown in [Table 3]. There was no significant correlation between umbilical artery PI values and PCT levels (r = 0.17, P = 0.9) and there was no significant correlation between Apgar scores for minute 1 and PCT levels (r = 0.2, P = 0.4). | Table 3: Umbilical artery PI, umbilical artery pH, APGAR 1 and 5 values
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Discussion | | |
Enhanced maternal inflammatory response and endothelial cell activation are believed to play a key role in preeclampsia. The relationship between the levels of commonly used inflammatory mediators such as C-reactive protein (CRP) or high sensitive CRP and preeclampsia has already been studied. [21],[22],[23] However, these markers are influenced by factors such as age, ethnicity, smoking, labor, and body mass index (BMI). [24] Consequently, the use of these markers in the prediction and follow-up of preeclampsia is still controversial.
PCT is a new inflammatory marker whose circulating level in mothers delivering at term is similar to the levels observed in the healthy population. Furthermore, it has been determined that PCT is not affected by pregnancy-related disorders, the mode of delivery, the type of anesthesia administered, the duration of active labor, and stressful labor. [25] Maternal plasma PCT concentration was used in pregnancies complicated by premature rupture of membranes and preterm delivery in obstetrics. [17],[18] Nevertheless, there is limited data regarding the relationship between PCT and preeclampsia. The study presented here shows significantly higher levels of PCT in severe preeclamptic patients than in control women. However, we did not observe a significant difference between preeclamptic and eclamptic patients. Although eclampsia is a clinically more severe disease than preeclampsia, the phenomenon of more severe inflammation in eclampsia still remains unknown. Our findings, that demonstrate lower PCT levels in eclamptic patients than preeclamptic patients, support this theory. Montagnana et al., reported that PCT values in preeclamptic woman were related to severity of the disease. They postulated that PCT may be an additional diagnostic marker for investigating women with suspected severe preeclampsia, in which its clinical usefulness might even be superior to that of high sensitive CRP. [19] In addition, Can et al., reported similar findings for PCT in severe preeclampsia. [20] In Gulec et al.,'s study, it was found that PCT was significantly higher in preeclamptic patients, and there was a significant correlation between both PCT and CRP and D-Dimer as well as PCT and mean arterial pressure. [21] Sapmaz et al., found that PCT was significantly higher in eclamptic patients compared to preeclamptic patients. Based on this data, the investigators claimed that PCT levels correlated with severity of disease. [26] However, none of the studies mentioned above addressed the relationship between PCT level and the fetal well-being. In our study, we investigated the correlation between PCT levels and umbilical artery Doppler PI in the fetal period, umbilical cord pH in labor, and 1- and 5- minute Apgar scores in the postnatal period. We did not find a significant relationship between PCT and fetal outcome.
In many studies, higher levels of ET-1 have been observed in pregnant women with preeclampsia. [15],[27] The mechanism(s) for the increase in ET-1 levels during preeclampsia remains unknown, yet several hypotheses have been proposed to explain this phenomenon. The first of these hypotheses is that ET-1 might be a local factor acting at the junction between the endothelium and the vascular smooth muscle layer. Hence, the disruption and destruction of these anatomical boundaries can lead to an ET-1 leakage from its local environment to the bloodstream, consequently resulting in higher ET-1 levels in the peripheral blood. The second hypothesis is that abnormal ET-1 production by an affected endothelium might be the primary mechanism for the increase in ET-1, both locally and in the bloodstream. The third hypothesis is that increased ET-1 production by placental or fetal tissue, or the increased diffusion of ET-1 into the maternal circulation, might account for the elevated levels observed during preeclampsia. [28] However, in some studies including our study, a significant relationship between ET-1 and preeclampsia or eclampsia was not observed. [29] Evaluation of the ET-1 levels in our study before clinical progression may have led to similar results. In some studies that measured ET-1 levels in series, it was found that ET-1 increased following the progression of clinical preeclampsia. [15] Based on this data, it is postulated that the increase in the level of ET-1 in preeclampsia occurs secondary.
During preeclampsia, incomplete trophoblastic invasion leads to a highly resistant vascular system. As a result, both the uterine and umbilical artery blood flow patterns are altered such that higher systolic/diastolic (S/D), PI, and resistance index (RI) values are observed. [30] These parameters are normally used to evaluate fetal well-being during the third trimester of pregnancy. We observed that only the Apgar scores at minute 1 were lower in the eclampsia group compared to preeclampsia and the control group. But there was no significant correlation between the Apgar scores for minute 1 and PCT levels.
This study had several limitations. One of the limitations was that it was performed on a sample consisting of a small number of women; especially the number of eclamptic pregnant women was very low. For this reason, it is necessary to conduct studies with larger samples and broader participation. Second, we did not investigate the relationship between PCT or ET-1 levels and the clinical parameters such as the mean arterial pressure or proteinuria levels. Third, investigating these markers in early stage of pregnancy may contribute to the prediction of preeclampsia. Thus, serial measurements of these markers are advisable in future studies.
Conclusion | | |
The study results indicated the occurrence of exaggerated inflammation during severe preeclampsia. High PCT levels were associated with preeclampsia, but did not affect fetal well-being. Our study findings suggested that ET-1 levels, which are an indication of endothelial cell dysfunction, are not altered in patients with severe preeclampsia or eclampsia. However, further longitudinal studies are necessary in order to determine the role of these markers in the etiopathogenesis of preeclampsia, and for effectively predicting preeclampsia severity.
Acknowledgment | | |
All authors have contributed significantly, and that all authors are in agreement with the content of the manuscript. In this study, authors gave informed consent and patient anonymity is preserved.
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[Figure 1]
[Table 1], [Table 2], [Table 3]
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