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Thanking you
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Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
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On May 11,2011

Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
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Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
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Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
On April 2011

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.

Dr. Anuradha
On Jan 2020

Important Notice

Original article / research
Year : 2023 | Month : January | Volume : 17 | Issue : 1 | Page : QC01 - QC04 Full Version

Detection of Creatinine in Vaginal Secretions of Women with Premature Rupture of Membranes in Third Trimester from Semiurban Population: A Cross-sectional Study

Published: January 1, 2023 | DOI:
Hemant Gopalrao Deshpande, Monalisa Sarkar, Madhukar Jagannath Shinde, Chetan Gulati, Shubham Joon

1. Head, Department of Obstetrics and Gynaecology, Dr DY Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India. 2. Resident, Department of Obstetrics and Gynaecology, Dr DY Patil Medical College, hospital and Research Centre, Pune, Maharashtra, India. 3. Assistant Professor, Department of Obstetrics and Gynaecology, Dr DY Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India. 4. Resident, Department of Obstetrics and Gynaecology, Dr DY Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India. 5. Student, Department of Obstetrics and Gynaecology, Dr DY Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India.

Correspondence Address :
Dr. Chetan Gulati,
Resident, Obstetrics and Gynaecology, Dr DY Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India.


Introduction: Spontaneous rupture of the membranes any time beyond the 28th week of pregnancy but before the onset of labour is called Premature Rupture of Membranes (PROM). There are many techniques for diagnosing PROM that is based on both clinical assessments and biological studies. Each of these procedures has benefits and drawbacks. Since foetal urine is the major source of amniotic fluid, the presence of vagina and a high creatinine level may aid in the diagnosis of PROM.

Aim: To determine the cut-off levels of serum creatinine in predicting the PROM.

Materials and Methods: A cross-sectional study was conducted at Dr. DY Patil Medical College, Hospital and Research Centre in Pune, Maharashtra, India from June 1 2020 to June 5 2021. Two equal groups of 140 each pregnant women with gestational ages ranging from 28-42 weeks were created: one with a history of vaginal leaking (the study group, P), and the other with gestationally matched no leakage (the control group, C). Patient’s details such as age, gestational age, and obstetric history were noted. Each patient was examined and cervicovaginal secretions were collected. A 5 mL of saline was flushed in the posterior fornix of vagina. This fluid with vaginal wash was aspirated and creatinine concentration from vaginal fluid was determined by Jaffee synthetic chemical colorimetric method. The Student’s t-test and the Chi-square test were used to analyse the data.

Results: The study group’s vaginal fluid creatinine level was substantially higher (p-value<0.001). The cut-off value of 0.6 mg/dL had highest sensitivity 96.1% and specificity 100%. The area under the Receiver Operating Characteristics (ROC) curve was 0.917. The Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of serum creatinine at cut-off 0.6 mg/dL was 100% and 96.3% respectively.

Conclusion: Vaginal fluid creatinine is simple and easily available, which makes it acceptable to the candidate for a diagnosis of PROM.


Amniotic membrane, Fetoprotein, Fibronectin, Gonadotropin, Prelabour, Prolactin

Rupture of the amniotic sac before the onset of labour is referred to as PROM. Risk factors include: low socio-economic status, underweight women, preterm labour history, urine infection, vaginal bleeding, cerclage, and amniocentesis (1). It complicates about 8-10% of term pregnancies and approximately 1% of preterm pregnancies (2). Gestational age and co-morbidities determine the course of treatment (3). One of the most frequent side-effects of preterm PROM is early delivery. The length of the latent period, which is the interval between membrane rupture and delivery, is inversely related to the gestational age at which PROM takes place (4). An analysis of a study evaluating patients with preterm PROM between 16 and 26 weeks’ gestation found that 57% of patients delivered within one week, and 22% had a latent period of four weeks (5). For instance, a large study of patients at term found that 95% of patients delivered within roughly one day of PROM (4). PROM is diagnosed by amniotic fluid at posterior fornix with a speculum examination. Nitrazine test observing a basic pH change on indicator paper. A fern test of dried amniotic fluid under the microscope (6). An ultrasound, but rarely done as one cannot differentiate PROM from other causes of oligohydramnios (7). Detection of alpha fetoprotein, insulin growth factor binding protein-1, foetal fibronectin, human chorionic gonadotropin, prolactin, urea, creatinine (8),(9),(10),(11),(12).

For gestational age-specific obstetric measures to improve perinatal outcome and reduce significant consequences, like cord prolapse and infectious morbidity, a primary and accurate diagnosis of preterm PROM would be necessary (chorioamnionitis, neonatal sepsis). On the other hand, a false-positive preterm PROM diagnosis may result in needless obstetric treatments, such as hospitalisation, the administration of antibiotics and corticosteroids, or even labour induction. Therefore, an early and precise PROM diagnosis is essential for maximising pregnancy outcomes; in fact, it is so important that an amnio-dye test (also known as a tampon test) may be advised if other tests for preterm PROM are inconclusive and if the pregnancy is far from the term. Amniocentesis is used during this test, and the amniotic cavity is injected with dye (13).

The PROM diagnosis is challenging and unreliable with conventional techniques. This study sought to establish the cut-off value and assess the validity of vaginal washing fluid creatinine for PROM diagnosis.

Material and Methods

A cross-sectional study was conducted at Dr DY Patil Medical College, Hospital and Research Centre in Pune, Maharashtra, India, from June 1 2020 to June 5 2021. Institutional Ethics Committee (IEC) approval was obtained (IESC/PGS/2019/137). Prior to the study, the patients provided written informed consent.

Inclusion criteria:

• Age group >18 years
• Confirmed PROM cases by positive nitrazine test and positive fern test
• Gestational age 24 to 36 weeks
• Cervical dilatation < 3 cm
• High-risk pregnancies include those in which the mother experienced preterm PROM during a previous pregnancy, preterm labour in the past, direct abdominal trauma, polyhydramnios, or numerous pregnancies.

Exclusion criteria:

• Active vaginal bleeding
• Preeclampsia
• Liver or kidney disease
• Vaginal bleeding or vaginal infection
• Foetal congenital anomalies or intrauterine foetal death
• Any circumstances that might affect the creatinine amounts in vaginal fluid.

Sample size calculation: The sample size included 280 women who complained of PROM, fitting the inclusion criteria. The prevalence of PROM was reported to be 10% (2), precision was set at 5% =0.05, Z value at 95% confidence= 1.96. Therefore, a total of 140 patients with confirmed PROM and 140 patients without PROM were enrolled in the study.

Patient’s details such as age, gestational age, obstetric history were noted. General and systemic examination was performed. Each patient was examined and cervicovaginal secretions were collected. These secretions were subject to:

• Fern test: A small drop of sample was spread evenly on a glass slide and air dried. It was observed under the light microscope (10x magnification) for an arborisation pattern. A single observer performed the test in all patients.
• Nitrazine test: In the deep vagina, a cotton tip applicator was used to deposit the substance onto nitrazine paper. Change in colour is suggested if pH <6.5 and test is considered positive (14).
• Measurement of creatinine levels: The posterior fornix of the vagina was flushed with 5 mL of saline. The same syringe was used to aspirate both fluids, which were then submitted right away to the central laboratory for creatinine measurement. Creatinine concentration from vaginal fluid was determined by Jaffee synthetic chemical colorimetric method (15).

Statistical Analysis

Mean and Standard Deviation (SD) were used to present quantitative data. According to the findings of the normalcy test, a comparison between the research groups was carried out using an unpaired t-test. The Fisher test, Student’s t-test, and Chi-square test were used to see whether there was any association between the research groups. A p-value <0.05 was considered significant. Analysis of Variance (ANOVA) test was used to find whether there was a significant association between serum creatinine levels with the gestational age of patients. For statistical analysis, appropriate statistical software was utilised, such as MS Excel and Statistical Package for the Social Sciences (SPSS) version 20.0.


The majority of the patients in group P were in the age range of 21 to 30. The average age for group P was 26.49 ±5.03 years. Most of the patients in group C were between the ages of 21 and 30. In group C, the average age was 27.11± 4.80 years (Table/Fig 1).

It was observed that 48.6% and 51.4% patients in group P were primigravida and multigravida respectively while 42.1% and 57.9% patients in group C were primigravida and multigravida respectively (Table/Fig 2).

The mean gestational age of patients in group P and group C was 31.09±3.35 weeks and 31.53±3.37 weeks respectively (Table/Fig 3).

In group P, the cervix was 1 cm dilated in 47.9% patients while it was 2 cms and 3 cms dilated in 30% and 22.1% patients respectively. In group C, the cervix was 1 cm dilated in 49.3% patients while it was 2 cms and 3 cms dilated in 31.4% and 19.3% patients respectively (Table/Fig 4).

The mean vaginal fluid creatinine was considerably higher in group P than group C (Table/Fig 5).

There was no significant association of serum creatinine levels with gestational age of patients as per ANOVA test (p>0.05) in both the groups (Table/Fig 6). A cut-off value of 0.6 mg/dL for serum creatinine had the best sensitivity (96.1%) and specificity (100%). Serum creatinine’s positive and negative predictive values are 100% and 96.3%, respectively. The ROC curve’s area under it was 0.917 (Table/Fig 7),(Table/Fig 8).


There is no non invasive method that can be used as the gold standard. Other non invasive diagnostic methods, which include pooling assessment, microscopic fern test, and pH examination of cervicovaginal discharge (nitrazine test) are not cost-effective, and diagnostic accuracy is not high if time has passed since membranes ruptured. The gold standard test currently used for diagnosis of PROM, the amnio-dye test, is invasive and there are risks of infection, abruption, and abortion (16). Recently, the focus of studies has been to detect various biochemical markers in cervicovaginal discharge when ROM occurs. These markers include alpha fetoprotein, foetal fibronectin, nsulin growth factor binding protein-1, prolactin, beta human chorionic gonadotropin, urea, lactate, placental alpha-microglobulin-1 and 2, and creatinine. Authors have speculated that analysis of vaginal creatinine and urea can be used as a foetal maturation test, in cases of preterm labour, as the creatinine level depends on gestational age (17),(18),(19). In the present study, the majority of the patients (63.6%) in group P were in the age group of 21-30 years. The mean age in group P was 26.49±5.03 years. The mean age in group C was 27.11±4.80 years. There was no significant difference between the groups as per Student’s t-test (p-value >0.05). In a study by Sharma A et al., mean ages were similar in all three groups (23.44, 23.40, and 23.30 in Group 1 (Confirmed PROM), group 2 (Unconfirmed PROM), and control group respectively) (18).

In the present study, 68 (48.6%) and 72 (51.4%) patients in Group P were primigravida and multigravida respectively while 59 (42.1%) and 81 (57.9%) patients in group C were primigravida and multigravida respectively. Sharma A et al., study, showed most of the patients were primiparous and were well matched in all the three groups (18). The mean gestational age of patients in group P and group C was 31.09±3.35 weeks and 31.53±3.37 weeks respectively. There was no significant difference between the groups. This was similar to the studies of Sharma A et al., and Begum J et al., (18),(19). Sharma A et al., found mean gestational age in weeks were 34.86, 34.98, 35.11 in group 1, group 2 and control group respectively (18). Begum J et al., study, evaluating cervicovaginal fluid for urea and creatinine for diagnosis of PROM had no particular difference between both groups with respect to maternal age, obstetric score and gestational age of the participants (19). A creatinine concentration of 1.75 mg/dL or more correlated significantly with a gestational age of 37 weeks or more (3). It was observed in present study that the mean vaginal fluid creatinine was strikingly higher in group P than in group C. The mean vaginal fluid creatinine in groups I, II, and III were 1.74±0.8 mg/dL, 0.45±0.2 mg/dL and 0.25±0.1 mg/dL, respectively. The creatinine level was significantly higher in the confirmed group (group I) than in the other two groups (p-value<0.0010) as reported in Zanjani MS and Haghighi L study (20). The mean urea levels were 26.35 mg/dL in the study group 1 and 3.12 mg/dL in the control group in Sharma A et al., study (18).

Malchi F et al., reported, the overall mean of creatinine in the case group was significantly higher than the control. It was noted that the sensitivity and specificity of creatinine was higher than urea in the diagnosis of PROM (21). Sharma A et al., cross-sectional study assessing creatinine levels in vaginal fluid as a marker of PROM found cervicovaginal fluid creatinine levels were more marked in women with confirmed leaking than the women in the control group (18). The findings of these studies were in agreement with the findings of the index study. Zanjani MS and Haghighi L study evaluating the reliability of vaginal fluid creatinine for the diagnosis of PROM showed mean vaginal fluid creatinine in groups I, II, and III were 1.74±0.8, 0.45±0.2 and 0.25±0.1 mg/dL, respectively. The creatinine level was significantly higher in the confirmed group (group I) than in the other two groups (p<0.0010) (20). In the present study, for serum creatinine a cut-off 0.6 mg/dL had highest sensitivity 96.1% and specificity of 96.3%. The area under the ROC curve was 0.917. Similar observations were noted in other studies (17),(18),(19),(22),(23),(24). The sensitivity, specificity, positive predictivity, and negative predictivity were all 100% in detecting PROM by evaluation of vaginal fluid urea and creatinine concentration with a cut-off value of 12 and 0.6 mg/dL, respectively (17).


Contamination of sample by blood, urine, or meconium. The estimation of vaginal fluid creatinine level is effective for patients not in labour and it is not accurate for patients with congenital foetal malformations.


Correct and prompt diagnosis of the condition is crucial to achieving the best pregnancy result. A proper diagnosis should serve as the foundation for management. This test is appealing in clinical practice due to its accessibility and simplicity. Vaginal fluid creatinine is therefore a potential contender to be accepted as a test for PROM diagnosis.


Mercer B, Milluzzi C, Collin M. Periviable birth at 20 to 26 weeks of gestation: Proximate causes, previous obstetric history and recurrence risk. Am J Obstet Gynecol. 2005;193(3 Pt 2):1175-80. [crossref] [PubMed]
Reddy R, Kher A. Outcome of neonates born to mothers with premature rupture of membranes. Sri Lanka Journal of Child Health. 2020;49(3):256-62. DOI: [crossref]
Norwitz ER, Arulkumaran S, Symonds I. Oxford American Handbook of Obstetrics and Gynecology. Oxford University Press USA. 2007
Hannah ME, Ohlsson A, Farine D, Hewson SA, Hodnett ED, Myhr TL, et al. Induction of labor compared with expectant management for prelabor rupture of the membranes at term. N Engl J Med. 1996;334:1005-10. [crossref] [PubMed]
Schucker JL, Mercer BM. Midtrimester premature rupture of the membranes. Semin Perinatol. 1996;20:389-400. [crossref] [PubMed]
ACOG committee on practice bulletins.clinical management guidelines for obstetrician-gynecologists.Obstet Gynecol. 2007;109(4):1007-19.
Park J, Lee Si, Norwitz ER. Non-invasive Testing for rupture of the fetal membranes. Fetal and Maternal Healthcare. US Obstetric and Gynecology. 2007:13-16.
Caughey AB, Robinson JN, Norwitz ER. Contemporary diagnosis and management of preterm premature rupture of membranes. Rev Obstet Gynecol. 2008;1:11-22.
Abdelazim IA, Abu-Faza M. Fetal. Fibronectin (Quick Check fFn Test) versus insulin-like growth factor binding protein-1 (Actim PROM Test) for detection of premature rupture of fetal membranes. J Gynecol Obstet Med. 2014;1:1-12. [crossref]
Ruanphoo P, Phupong V. Evaluation of the performance of the insulin-like growth factor-binding protein-1/alpha-fetoprotein test in diagnosing ruptured fetal membranes in pregnant women. J Perinatol. 2015;35:558-60. [crossref] [PubMed]
Tigga MP, Malik S. Comparative analysis of four biomarkers in diagnosing premature rupture of membranes and their correlation with onset of labour. Int J Reprod Contracept Obstet Gynecol. 2015;4:1070-75. [crossref]
Ghasemi M, Jaami R, Alleyassin A, Ansarimoghaddam A. The value of urea, creatinine, prolactin, and beta sub-unit of human chorionic gonadotropin of vaginal fluid in the diagnosis of premature preterm rupture of membranes in pregnancy. Turk J Obstet Gynecol. 2016;13:62-66. [crossref] [PubMed]
Park JS, Yoon BH, Romero R, Moon JB , Oh SY, Kim JC , et al. The relationship between oligohydramnios and the onset of preterm labor in preterm premature rupture of membranes. Am J Obstet Gynecol. 2001;184:459-62. [crossref] [PubMed]
Bennett SL , Cullen JB, Sherer DM , Woods Jr JR. The ferning and nitrazine tests of amniotic fluid between 12 and 41 weeks gestation. Am J Perinatol 1993;10(2):101-04. doi: 10.1055/s-2007-994637. [crossref] [PubMed]
Heinz W. Neue Deutsche Biographie (NDB) Band 10, Berlin, Germany: Duncker &Humblot. 1974,;291.
Li HY, Chang TS. Vaginal fluid creatinine, human chorionic gonadotropin and alpha-fetoprotein levels for detecting premature rupture of membranes. Zhonghua Yi Xue Za Zhi. 2000;63:686-90.
Kafali H, Oksuzler C. Vaginal fluid urea and creatinine in diagnosis of premature rupture of membranes. Arch Gynecol Obstet. 2007;275:157-60. [crossref] [PubMed]
Sharma A, Sharma R, Agarwal T. Evaluation of urea and creatinine levels in vaginal wash fluid for the diagnosis of premature rupture of membranes. Int J Reprod Contracept Obstet Gynecol. 2020;9:3449-57. [crossref]
Begum J, Samal SK, Ghose S, Niranjan G. Vaginal fluid urea and creatinine in the diagnosis of premature rupture of membranes in resource limited community settings. J Fam Reprod Health. 2017;11:43-49.
Zanjani MS, Haghighi L. Vaginal fluid creatinine for the detection of premature rupture of membranes. J Obstet Gynaecol Res. 2012;38(3):505-08. [crossref] [PubMed]
Malchi F, Abedi P, Jahanfar S, Talebi F, Faal S, Zahedian M, et al. Vaginal fluid urea and creatinine as indicators of premature rupture of membranes: A systematic review. Reprod Sci. 2021;28(1):1-11. [crossref] [PubMed]
Gurbuz A, Karateke A, Kabaca C. Vaginal fluid creatinine in premature rupture of membranes. Int J Gynaecol Obstet. 2004;85:270-71. [crossref] [PubMed]
El-Sayed ML, Mahdy ER, El-BakryLashin M, Eman Mohamed El-Tayeb. Diagnosis of premature rupture of membranes by assessment of urea and creatinine in vaginal washing fluid. Zagazig University Medical Journal. 2021;27(4):617-23.
Gezer C, Ekin A, Golbasi C, Kocahakimoglu C, Bozkurt U, Dogan A, et al. Use of urea and creatinine levels in vaginal fluid for the diagnosis of preterm premature rupture of membranes and delivery interval after membrane rupture. J Matern Fetal Neonatal Med. 2017;30;772-78. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2023/56744.17346

Date of Submission: Mar 30, 2022
Date of Peer Review: Apr 27, 2022
Date of Acceptance: Aug 19, 2022
Date of Publishing: Jan 01, 2023

• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

• Plagiarism X-checker: Apr 11, 2022
• Manual Googling: Aug 04, 2022
• iThenticate Software: Aug 18, 2022 (16%)

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