Chorioamnionitis and Diagnostic Value of C-reactive Protein, Erythrocyte Sedimentation Rate and White Blood Cell Count in its Diagnosis Among Pregnant Women with Premature Rupture of Membranes
Several laboratory parameters have been used in these studies to diagnose chorioamnionitis leading to controversies to some extent. The aim of this study was to assess the diagnostic value of C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR) and White Blood Cell (WBC) count in chorioamnionitis among pregnant women with Premature Rupture Of Membranes (PROM). In a cross-sectional diagnostic test research, 71 patients presented with PROM before the 37th week of gestation were enrolled. A blood sample was taken from all the patients. Hematologic automatic blood cell counter was used to count the blood cells and their differentiation. ESR and CRP were also measured using the same blood sample at the laboratory. Sensitivity, specificity, correct classification rate and likelihood ratios were calculated. Receiver operating curves were plotted and area under curve was estimated along with its 95% confidence interval. A total of 71 patients were studied. None of the patients had a positive drug history or a history of hypertension before the 20th week of gestation or during her previous pregnancy. Contrary to ESR, WBC count and CRP results didnt provide minimum acceptable diagnostic accuracy measures for diagnosis of chorioamnionitis. The sensitivity and specificity of a positive ESR test at a cutoff value of 52 were 66.7 and 60%, respectively. The area under curve was calculated to be 0.62. The findings of the present study were not supportive of using CRP, WBC as a reliable diagnostic test to identify chorioamnionitis in women with PROM. The results of CRP and WBC were not acceptable but ESR diagnostic value was minimally acceptable.
to cite this article:
Afsaneh Amirabi, Siamak Naji, Zahra Yekta and Yeganeh Sadeghi, 2012. Chorioamnionitis and Diagnostic Value of C-reactive Protein, Erythrocyte Sedimentation Rate and White Blood Cell Count in its Diagnosis Among Pregnant Women with Premature Rupture of Membranes. Pakistan Journal of Biological Sciences, 15: 454-458.
May 31, 2012; Accepted: August 11, 2012;
Published: September 07, 2012
Premature Rupture Of Membranes (PROM) is still a significant problem in obstetrics
and gynecology needing proper management and investigation (Garland
et al., 2002; Wiwanitkit, 2005). Preterm
PROM occurs in three percent of pregnancies and is the main cause of at least
one third of premature births (Rudigoz, 2008).
Up to 50% of the cases of premature rupture of membranes could be attributed
to an infectious cause (Ratanakorn et al., 2005).
Chorioamnionitis can be considered as an unwanted aftermath of PROM and is capable
of causing considerable perinatal morbidity and mortality. It is not much recent
that a strong association between existence of the histopathologic chorioamnionitis
and preterm delivery is reported suggesting that occult antepartum infection
of the genital tract is an important cause of preterm delivery (Guzick
and Winn, 1985). Recent systematic reviews have shown that chorioamnionitis
is a risk factor of cerebral palsy (Wu and Colford Jr.,
2000). Acute chorioamnionitis has also been recognized as a major threat
to both mother and fetus. A major challenge will be to distinguish reliable
diagnostic methods for timely identification and treatment of the problem. Some
studies have addressed this issue. Several laboratory parameters have been used
in these studies to diagnose chorioamnionitis, among which we can mention Erythrocyte
Sedimentation Rate (ESR), CRP and White Blood Cell (WBC) counts (Gojnic
et al., 2005; Van der Ham et al., 2008;
Wiwanitkit, 2005; Woldesenbet et
al., 2008; Yoon et al., 1996). These
tests are of low cost and easily accessible. However, the results of the studies
have been controversial not resulting in a definite conclusion.
The aim of this study was to assess the diagnostic value of CRP, ESR and WBC count in chorioamnionitis among pregnant women with Premature Rupture of Membranes (PROM).
MATERIALS AND METHODS
Study design and participants: In a cross-sectional diagnostic test research, 71 patients presented with PROM before the 37th week of gestation were enrolled. Patients with a history of any known inflammatory disease such as rheumatoid arthritis and lupus, history of hepatic cirrhosis, history of long-term use of immunosuppressive drugs and those suffering from acute febrile disease due to other etiologies at presentation were excluded from the study. Consecutive sampling method was used in this study and all the eligible patients during the year 2009 were studied.
The main studied variables included patient demographics, pregnancy history, the reason for referral and the onset and type of presenting symptoms.
Ethical issues: The study protocol was approved by the committee of ethics in Urmia University of medical sciences. Informed consent was obtained from all the participants of the study. The patients were not charged for the laboratory assessments. The security of the information was guaranteed by the main researcher.
Laboratory measurements: A blood sample was taken from all the patients and was sent to the laboratory as soon as possible. Hematologic automatic blood cell counter was used to count the blood cells and their differentiation. ESR and CRP were also measured using the same blood sample at the laboratory. Quantitative method was used for CRP measurement and its blood level was obtained. After delivery, a macroscopic examination of the placenta was performed and its characteristics were recorded. It was sent intact to the pathology laboratory to be evaluated for chorioamnionitis by a pathologist.
Statistical analysis: SPSS statistical software package was used for statistical data analysis applying independent t-test, chi-square and non-parametric Mann-Whitney U tests as appropriate. Sensitivity, specificity, correct classification rate and likelihood ratios were calculated. Receiver operating curves were plotted and area under curve was estimated along with its 95% confidence interval.
A total of 71 patients were studied. None of the patients had a positive drug
history or a history of hypertension before the 20th week of gestation or during
her previous pregnancy. Only one of the cases had a past medical history of
diabetes with disease duration of 4 years. Heart and lung auscultation was normal
in all patients. Most of the samples included individuals within their first
pregnancy (51.4%), experiencing their first delivery (61.4%), with no history
of abortion (84.3%) and trying vaginal delivery (62.9%). Demographic and obstetric
characteristics of the samples are presented in Table 1. Placental
pathology was normal in 91.5% of the samples and chorioamnionitis was present
Male was the dominant sex (53.1%) among newborns. 27 newborns (33.3%) had some problems at birth. Most of the newborns were in good condition at discharge (86.4%). Among the 11 died neonates, 2 were born during a twin pregnancy and 3 were born during a triplet pregnancy.
The results did not show a significant relationship between chorioamnionitis in the recent pregnancy and history of previous abortion.
The results did not show any significant relationship between chorioamnionitis in the recent pregnancy and type of delivery. Contrary to ESR, WBC count and CRP results didnt provide acceptable diagnostic accuracy measures for diagnosis of chorioamnionitis. The area under curve was 0.42 and 0.46, respectively for CRP and WBC. the area under curve was under 0.5 for both cases and the receiver operating curve was plotted and presented As only for the ESR for which the area under curve was calculated to be above 0.6 (Fig. 1).
|| Demographic and obstetrical characteristics of the study
||The receiver operating curve (ROC) for ESR in diagnosis of
||Sensitivity, specificity, correct classification rates and
likelihood ratios for possible cutoff values of ESR in diagnosing chorioamnionitis
The sensitivity and specificity of a positive ESR test at a cutoff value of 52 were 66.7 and 60%, respectively. Sensitivity, specificity, correct classification rates and likelihood ratios (LR) for other possible cutoff values are given in Table 2. As can be sought in this table the sensitivity and specificity measures may be considered for a tradeoff through cutoff value ranges of 47-52. The highest sensitivity value while keeping specificity above 50% was 66.7% that belonged to the ESR cutoff ≥41. The highest specificity value while keeping sensitivity above 50% was 60% that belonged to the ESR cutoff ≥51.
There was no significant relationship between chorioamnionitis in the recent pregnancy and the mother's vital signs. Mothers vital sign statistics are compared between chorioamnionitis and others in Table 3. As can be found in Table 3, only very tiny differences were observed between the two groups in most cases. For example both systolic and diastolic blood pressures were trivially higher in normal group, but the observed difference was not found to be statistically significant. Although none of the differences between the groups was found to be statistically significant, the lowest probability of rejecting the null hypothesis was 23% belonging to the difference in heart rate.
The understanding on chorioamnionitis is controversial as it refers to a heterogeneous
group of risk factors, clinical pathways and presentations. The general and
remarkable ambiguity in the definition and interpretation of the histological
findings of the disease, makes it difficult to understand how to prevent chorioamnionitis
(Van der Ham et al., 2008). It is postulated
that the inflammatory response of the host is the first effective factor that
influences the events leading to preterm labor and PPROM. Inflammation and inflammatory
factors have been a focus of interest in many studies in the region (Asemi
et al., 2011; Sheikhi et al., 2007; Saeedi
et al., 2007; Mostafa-Gharebaghi et al.,
2010). Some studies have established the participatory role of inflammatory
processes as a response to infection (Goldenberg et al.,
2008; Holzman et al., 2007; Hemalatha
et al., 2008).
During the last three decades, CRP has been used by obstetrics and gynecology
specialists in order to identify many inflammatory conditions such as chorioamnionitis
|| Comparison of placental pathology in the examined samples
regarding the mother's vital signs
In this study, CRP proved to have a low diagnostic value in identifying chorioamnionitis.
This is consistent with most of the previous studies (Trochez-Martinez
et al., 2007; Van der Ham et al., 2008;
Wiwanitkit, 2005; Yoon et al.,
1996). This is while very few studies have identified CRP test as a reliable
diagnostic test for chorioamnionitis (Chavarria et al.,
1989; Nowak et al., 1998).
In a systematic review by Van der Ham et al. (2008)
articles that had enrolled 610 pregnant women diagnosed with chorioamnionitis
were considered. In three of these articles it was concluded that CRP can be
useful for the diagnosis of chorioamnionitis while 5 articles did not achieve
this result (Van der Ham et al., 2008). Considering
the controversial findings of the studies, it seems that CRP is not beneficial
in as an indicator of clinical or histological chorioamnionitis. The differences
in clinical definitions, research projects, gestational age at the time of marker
measurement, research methodology and reference values, as well as differences
in the relationship between the clinical, histological and microbiological findings
in study populations must be considered. On the other hand, it is questioned
if histological chorioamnionitis can be considered as a criterion of infection,
because the researchers have identified this kind of chorioamnionitis in 20-30%
of normal deliveries (18, 19). Histological chorioamnionitis was intended in
the present study as well. Some researchers have recommended CRP to be measured
along with other parameters, not as a pathogenomic test, to prove infection,
as it is obvious that CRP is a non-specific acute phase reactant.
In our study WBC was also found to have a low diagnostic value. Although, the area under curve for ESR was found to be acceptable as a fair diagnostic value, the sensitivity and specificity were not large enough for recommending it in diagnosing chorioamnionitis during the PROM.
Through, multivariate analysis, Yoon et al. (1996)
found that amniotic fluid WBC performs better than C-reactive protein and maternal
blood WBC in the diagnosis of positive amniotic fluid culture, histologic and
clinical chorioamnionitis and neonatal morbidity in women with preterm PROM.
A study comparing CRP , WBC and ESR on serial measurements found that the efficacy
of WBC (abnormal tests: > 12500>15000>12500 mm-3 and increasing
in two consecutive days) and ESR (abnormal tests: >60 mm >60 mm h-1
and increasing in two consecutive days) serial evaluations was significantly
lower than CRP and in cases of chorioamnionitis CRP increased above the upper
limit of normal 3 days earlier than WBC or ESR (Nowak et
The findings of the present study were not supportive of using CRP and WBC as a reliable diagnostic test to identify chorioamnionitis in women with PROM. The results of CRP and WBC were not acceptable but ESR diagnostic value was minimally acceptable. Future research is recommended to focus on ESR investigation rather than CRP or WBC.
This study was granted by Research Deputy of Urmia University of Medical Sciences. The authors would like to thank the staff at Obstetrics and Gynecology ward of Kosar University Hospital, Urmia.
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