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ORIGINAL ARTICLE
Year : 2018  |  Volume : 31  |  Issue : 1  |  Page : 52-56

Urea and creatinine in diagnosis of premature rupture of membrane


1 Department of Obstetrics and Gynecology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Obstetrics and Gynecology, QuesnaCentralHospital, Menoufia, Egypt

Date of Submission22-Jan-2017
Date of Acceptance11-Mar-2017
Date of Web Publication14-Jun-2018

Correspondence Address:
Amany M Galal Khalaf
Shibin El Kom, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_74_17

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  Abstract 


Objective
The aim of this article was to evaluate the reliability of vaginal fluid urea and creatinine levels for diagnosis of premature rupture of membranes(PROMs) and its relation to gestational age.
Background
PROMs occurs in 8–10% of all pregnant women at term. The risk of maternal and fetal infection increases as the time between the rupture of membrane and the onset of labor increases. It is therefore important to achieve accurate diagnosis by identifying the presence of specific amniotic fluid markers in vaginal environment. Vaginal fluid urea and creatinine levels may be helpful in the diagnosis of PROM because fetal urine is the most important source of amniotic fluid in the second half of pregnancy.
Patients and methods
A prospective case–control study was conducted. The study was performed on pregnant women in the third trimester between 28 and 42weeks of gestation with a history of possible leakage of amniotic fluid, attending Menoufia University Hospitals and Quesina General Hospital during the period from January 2013 to December 2015. Atotal of 90cases were subdivided into three groups: groupI(30cases)–confirmed PROM, groupII(30cases)–suspected PROM, and groupIII(30cases)–control group. All patients underwent speculum examination, nitrazine paper test, and ultrasonography.
Results
The creatinine levels were 0.64±0.018, 0.28±0.013, and 0.14±0.006mg/dl in confirmed cases, suspected cases, and controls, respectively. The urea levels were 29.67±3.75, 5.51±0.87, and 1.63±0.50mg/dl in confirmed cases, suspected cases, and controls, respectively. There was a highly significant difference regarding creatinine level and urea level between the studied groups(P<0.001). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for creatinine level as a screening test for PROM were 98, 45, 40, 100, and 60%, respectively. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for urea level as a screening test for PROM were 100, 100, 55, 100, and 70, respectively, with a cut-off value of 0.52mg/dl for creatinine level and 11.8mg/dl for urea level.
Conclusion
Urea and creatinine level assays are reliable methods and have a higher sensitivity and specificity to establish accurate diagnosis.

Keywords: pregnant women, premature rupture of membrane, urea and creatinine


How to cite this article:
Gada MS, Abdel Gaied AM, ElKhouly NI, Galal Khalaf AM. Urea and creatinine in diagnosis of premature rupture of membrane. Menoufia Med J 2018;31:52-6

How to cite this URL:
Gada MS, Abdel Gaied AM, ElKhouly NI, Galal Khalaf AM. Urea and creatinine in diagnosis of premature rupture of membrane. Menoufia Med J [serial online] 2018 [cited 2018 Aug 17];31:52-6. Available from: http://www.mmj.eg.net/text.asp?2018/31/1/52/234256




  Introduction Top


Premature rupture of the membranes(PROMs) constitutes one of the most important dilemmas in current obstetric practice; it could be defined as the rupture of the fetal membranes before the onset of labor irrespective of gestational age(GA) [1].

PROMs occur in 8–10% of all pregnant women at term. Aprolonged interval from rupture of membranes to delivery is associated with an increase in the incidence of chorioamnionitis and neonatal sepsis [2].

The risk of maternal and fetal infection increases as the time between the rupture of membranes and the onset of labor increases. Maternal infection is termed chorioamnionitis, whose incidence varies from 3 to 15% of cases of PROM, whereas fetal infection may occur as septicemia, pneumonia, skin infection, urinary tract infection, or local infections such as, omphalitis(infection of the umbilical cord) or conjunctivitis. Fetal infection occurs in 5% of all cases of PROM and in 15–20% of those with chorioamnionitis [3].

It is therefore important to achieve accurate diagnosis by identifying the presence of specific amniotic fluid markers in vaginal environment. These tests include measurement of vaginal pH, prolactin, α fetoprotein, diamine oxidase, insulin-like growth factor binding protein-1, human chorionic gonadotropin, and fetal fibronectin. All these tests have their advantages and drawbacks [4],[5].

Vaginal fluid urea and creatinine levels may be helpful in the diagnosis of PROM, because fetal urine is the most important source of amniotic fluid in the second half of pregnancy [5].

Accordingly, in the near future, a vaginal dipstick may be designed to diagnose PROM in a reliable, simple, accurate, and rapid way. Consequently, the simplicity of this test may make it attractive in our clinical practice.

The aim of the study was to evaluate the reliability of vaginal fluid urea and creatinine levels for the diagnosis of PROM and its relation to GA.


  Patients and Methods Top


The study was a prospective case–control study performed on pregnant women in the third trimester between 28 and 42weeks of gestation with history of possible leakage of amniotic fluid attending Menoufia University Hospitals and Quesina General Hospital during the period from January 2013 to December 2015.

After approval of the local Institutional Ethical Committee of Menoufia University Hospitals, informed consent was taken from patients after explaining about the aim of this study and procedure.

Inclusion criteria

A total of 90 singleton pregnant women with GA 28–42weeks were included in this study.

Exclusion criteria

Any amount of vaginal bleedingeitherspontaneous or traumatic present on speculum examination, prenatal complications(e.g.,liver diseases diagnosed by liver function tests and liver enzymes, kidney diseases diagnosed by kidney function tests, hypertension, diabetes mellitus diagnosed by measuring fasting random blood sugar and glucose tolerance test, Rh sensitized, women with serum creatinine level≥0.9mg/dl, chorioamnionitis, and dysmorphic features suggestive of chromosomal abnormalities and evaluated through genetic study), and multiple pregnancies were the reasons for exclusion.

Sample size was based on prior review of literature [6].

Creatinine level in PROM group was 1. 45±0.26mg/dl and in control group was 0.42±0.20mg/dl. The sample size had been calculated at 95% confidence interval, power 80%, and α error at 0.5. Atotal of 90cases were included in the study. The sample was distributed into 30cases controls, 30cases confirmed PROM, and 30 suspected PROM.

The cases were then divided according to amniotic fluid, nitrazine paper result, and amniotic fluid index(AFI) by ultrasonography into the following:

  • GroupI(30cases): confirmed PROM cases by amniotic fluid pooling and positive nitrazine paper test result and AFI by ultrasonography
  • GroupII(30cases): suspected PROM and need confirmation by any of the above three tests
  • GroupIII(30cases)(control group): patients without any complaint or complication with negative amniotic fluid pooling and negative nitrazine paper test result, and normal AFI by ultrasonography.


After explaining about the aim ofthisstudy and procedure to the patients and obtaining informed consent, the patients were included. Athorough history was taken, and physical examination was done. All patients underwent a sterile speculum examination and amniotic fluid pooling with or without Valsalva maneuver. Nitrazine paper test was done for all cases as a screening test for amniotic fluid leak and an abdominal ultrasonography for GA, AFI, fetal viability, placental site, and congenital anomalies.

Vaginal fluid washing was done through flushing of 3ml saline in the posterior vaginal fornix, and then all the fluid was aspirated from posterior fornix for detection of urea and creatinine levels.

Each specimen was centrifuged at 5000rpm, and the supernatant fluid was separated. Measurements of both urea and creatinine levels were performed by enzymatic urease method and rateGaffemethod, respectively, to determine their exact level [7].

Statistical analysis

Data were collected, tabulated, and statistically analyzed by computer using SPSS(SPSS Inc., Chicago, Illinois, USA). Two types of statistics were done.

Descriptive statistics

Quantitative data are expressed to measure the central tendency of data and diversion around the mean, mean, and SD.

Qualitative data were expressed in number and percentage.

Analytic statistics

χ Test was used to compare between categorical variables.

  • Analysis of variance test was used to compare between more than two groups of quantitative data normally distributed
  • Pearson correlation(r) was used to detect association between quantitative variables.



  Results Top


There was a nonsignificant difference regarding age(years) and GA(weeks) at sampling between the studied groups(P=0.060 and 0.259, respectively) [Table1].
Table 1: Demographic data of cases

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There was a nonsignificant difference regarding gravidity between the studied groups(P=0.430)[Table1].

There was a highly significant difference regarding creatinine level and urea level between the studied groups(P<0.001). The creatinine levels were 0.64±0.018, 0.28±0.013, and 0.14±0.006mg/dl in confirmed cases, suspected cases, and controls, respectively[Table2].
Table 2: Comparison of vaginal fluid creatinine level between the studied groups

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The urea levels were 29.67±3.75, 5.51±0.87, and 1.63±0.50mg/dl in confirmed cases, suspected cases, and controls, respectively[Table2].

There was a highly significant difference regarding AFI between the studied groups[Table3].
Table 3: Comparison of amniotic fluid index between the studied groups

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There was a significant positive correlation between creatinine and urea levels on one side and GA on the other side(P<0.001). There was a nonsignificant correlation between creatinine and urea levels in one side and age on the other side(P=0.098 and 0.851, respectively)[Table4].
Table 4: Correlation between vaginal creatinine and urea versus gestational age and age in control group

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The validity of creatinine level, urea level, and AFI as a screening test for PROM was done as shown in [Table5].
Table 5: Accuracy of vaginal fluid creatinine level, urea level, and amniotic fluid index in differentiating cases and controls

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Sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV), and accuracy for creatinine level as a screening test for PROM were 98, 45, 40, 100, and 60%, respectively.

Sensitivity, specificity, PPV, NPV, and accuracy for urea level as a screening test for PROM were 100, 100, 55, 100, and 70%, respectively.

Sensitivity, specificity, PPV, NPV, and accuracy for AFI as a screening test for PROM were 44, 100, 100, 55, and 67%, respectively.

The area under thecurvewas 93 and 97 for creatinine and urea levels, respectively[Figure1], [Figure2], [Figure3].
Figure 1: Accuracy of vaginal fluid creatinine and urea levels in differentiating cases and controls.

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Figure 2: Correlation between vaginal creatinine level and gestational age.

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Figure 3: Correlation between urea level and gestational age.

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  Discussion Top


This study was designed to evaluate the reliability of vaginal fluid urea and creatinine levels for the diagnosis of PROMs. This study showed that there was a highly significant difference of creatinine level and urea level in the studied groups. The creatinine level was 0.64±0.018, 0.28±0.013, and 0.14±0.006mg/dl, in confirmed cases, suspected cases, and controls, respectively. The urea levels were 29.67±3.75, 5.51±0.87, and 1.63±0.50mg/dl in confirmed cases, suspected cases, and controls, respectively.

This was in agreement with Hussein etal. [6] who found a statistically significant difference between groupI(confirmed PROM) and groupII(control) regarding vaginal fluid urea and creatinine levels, as the mean vaginal fluid urea and creatinine levels were 40.3±9 and 1.45±0.26mg/dl, respectively, in groupI versus 7.8±2.8 and 0.42±0.20mg/dl, respectively, in groupII.

According to Effat etal. [8], there was a highly significant statistical difference among confirmed, suspected, and control groups regarding creatinine level in vaginal fluid.

This study showed that there was highly significant difference regarding AFI between the studied groups.

AFI less than or equal to 5 was present in 100% of confirmed cases, 80% of suspected cases, and 40% of controls.

This was in agreement with Reham etal. [9] who found that there was significant statistical difference between confirmed, suspected, and control groups regarding AFI. The number of patients with AFI less than or equal to 9cm was 32patients in the confirmed group, 17patients in the suspected group, and four patients in the control group. On the contrary, 18patients in confirmed group had AFI greater than 9cm.

Our results are supported by the results obtained by Shetty etal. [10], which stated that PROM is more marked in multigravida.

This study showed the validity of creatinine level, urea level, and AFI as screening tests for PROMs. For creatinine level, the cut-off value was 0.22, and the sensitivity, specificity, PPV, NPV, and accuracy were 100, 45, 40, 100, and 60%, respectively.

For urea, the cut-off value was 7.50, and the sensitivity, specificity, PPV, NPV, and accuracy were 100, 53, 55, 100, and 70%, respectively.

The cut-off value for AFI was 5, and the sensitivity, specificity, PPV, NPV, and accuracy were 44, 100, 100, 55, and 67%, respectively.

Li and Chang [11] have found that the median levels of creatinine in vaginal fluid of normal pregnant woman and pregnant woman with confirmed PROM were 0.05 and 0.95mg/dl, respectively. The sensitivity, specificity, PPV, NPV, and accuracy were 90, 100, 100, 90.9, and 95% respectively.

Ahmed etal. [12] stated that the sensitivity, specificity, PPV, NPV, and accuracy were all 100% for vaginal fluid creatinine level and were 100, 83, 100, 100, and 85.6%, respectively, for urea in detecting PROM, with a cut-off value of 0.31mg/dl for creatinine and 13.2mg/dl for urea.

Kariman etal. [13], stated that vaginal fluid concentrations of urea and creatinine were significantly different among the three groups. The sensitivity, specificity, PPV, NPV, and accuracy were all 100% in detecting PROMs by evaluation of vaginal fluid creatinine concentration, with a cut-off value of 0.45mg/dl.


  Conclusion Top


Urea and creatinine assays are reliable methods and have a higher sensitivity and specificity to establish accurate diagnosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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NgwenyaS, LindowS. 24 hour rhythm in the timing of premature labor spontaneous rupture of membranes at term. Eur J Obstet Gvnecol Reprod Biol 2007; 112:151–320.  Back to cited text no. 1
    
2.
ShabanaAA, El kilani O, El kholy NI, TayelSM. Comparison of oral misoprostol and oxytocin for labor induction in prelabor rupture of membranes at term. Menouf Med J 2015; 28:239–244.  Back to cited text no. 2
    
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BenedettoC, TibaldiC, MarozioL, MariniS, MasuelliG, PelissettoS, etal. Cervicovaginal infections during pregnancy: epidemiological and microbiological aspects. JMatern Fetal Neonatal Med 2006; 16:9–12.  Back to cited text no. 3
    
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EsimE, TuranC, UnalO, DansukR, CengijogluB. Diagnosis of premature rupture of membranes by identification of B-HCG in vaginal washing fluid. Eur J Obstet Gynecol Reprod Biol 2003; 101:37–40.  Back to cited text no. 4
    
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KafaliH, OksuzlerC. Vaginal fluid urea and creatinine in diagnosis of premature rupture of membranes. Arch Gynecol Obstet 2007; 275:157–160.  Back to cited text no. 5
    
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HusseinM, KhaledM, GamalA. Vaginal fluid urea and creatinine for diagnosis of premature rupture of membranes. NY Sci J 2014; 7:7–10.  Back to cited text no. 6
    
7.
Wiberg-ItzelE, NordstromL. Lactate determination in vaginal fluid: a new method in the diagnosis of prelabor rupture of membranes. BJOG 2005; 112:754.  Back to cited text no. 7
    
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EffatD, ElkafrawyM, ElbagouryE. The role of vaginal fluid creatinine versus human chorionic gonadotropin in diagnosis of premature rupture of membrane. AAMJ 2012; 10:299–317.  Back to cited text no. 8
    
9.
RehamS, Rashed, RabeeA, HassaneinA, SaharM. Vaginal fluid creatinine versus human chorionic gonadotropin for diagnosis of premature rupture of membranes. JAm Sci 2015; 11:3339.  Back to cited text no. 9
    
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ShettyA, StewartK, StewartG, RiceP, DanielianP, etal. Active management of term prelabour rupture of membranes with oral misoprostol. BJOG 2002; 109:1354–1358.  Back to cited text no. 10
    
11.
LiHY, ChangTS. Vaginal fluid creatinine, human chorionic gonadotropin and alpha-fetoprotein levels for detecting premature rupture of membranes. Zhonghua Yi Xue Za Zhi 2000; 63:686–690.  Back to cited text no. 11
    
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AhmedM, MagedM, WalaaA, IbrahimM. The value of measurement of vaginal fluid urea, creatinine and beta HCG in the diagnosis of premature rupture of membranes. Kasr Al-Aini J 2011; 2:2.  Back to cited text no. 12
    
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Kariman M HedayatiM, AllviSH. The role of vaginal prolactin in diagnosis of premature rupture of membranes. Iran Red Crescent Med J 2012; 14:352–357.  Back to cited text no. 13
    


    Figures

  [Figure1], [Figure2], [Figure3]
 
 
    Tables

  [Table1], [Table2], [Table3], [Table4], [Table5]



 

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