Vaginal fluid urea and creatinine for diagnosis of premature rupture of membranes Текст научной статьи по специальности «Клиническая медицина»

UDC: 618.346-007.251:618.15-002-07

MOHAMMED HUSSAIN MOSTAFA

VAGINAL FLUID UREA AND CREATININE FOR DIAGNOSIS OF PREMATURE

RUPTURE OF MEMBRANES

Ain Shams University, Abbasiya - Cairo, Egypt

Department of Obstetrics and Gynecology, Faculty of Medicine, Mohammed H.M. - MD, lecturer of Obstetrics and Gynecology, Email: moh marwa [email protected]

Abstract. Objectives. To detect the accuracy of vaginal fluid urea and creatinine for diagnosis of premature rupture of membranes (PROM). Patients and methods. The current diagnostic accuracy test was conducted at Ain Shams University Maternity Hospital during the period between June 2011 to December 2011. One hundred women (100) were included in this study and studied women were divided into two groups; group I (cases): fifty pregnant women with PROM were included and group II (controls): fifty pregnant women without PROM were included. Women with multiple pregnancies, preterm labour, fetal distress, vaginal bleeding, congenital fetal malformations, and/or serum creatinine level more than 0.9 mg/dl were excluded from this study. All women were subjected to trans-abdominal ultrasound and sterile Cusco speculum examination to diagnose PROM and 5ml of sterile saline solution was injected into the posterior vaginal fornix using a sterile syringe. Three ml of the injected saline was aspirated using the same syringe and sent immediately to the laboratory. Each specimen was centrifuged at 50 revolutions/ second and the supernatant fluid was separated. Measurements of both urea and creatinine were performed by enzymatic urease method and Rate Jaffe method respectively to determine their exact levels.

Results. There was no significant difference between two studied groups regarding; maternal age, parity and gestational age at time of sampling (P>0.05). There was significant difference between two studied groups regarding vaginal fluid urea and creatinine levels (P <0.001) as the mean vaginal fluid urea and creatinine levels was 40.3±9 mg/dl and 1.45±0.26 mg/dl in group II versus 7.8±2.8 mg/dl and 0.42±0.20 mg/dl in group II. In the current study; the sensitivity & the specificity of vaginal fluid urea to diagnose PROM were 99% & 99% respectively, while its positive predictive value (PPV), negative predictive value (NPV) and over all accuracy were 98%, 97% and 96%; respectively, with a cut-off value of 12 mg/dl. While the sensitivity & the specificity of vaginal fluid creatinine to diagnose PROM were 98% & 97%; respectively, while its PPV,NPV and over all accuracy were 96%, 98% and 97%; respectively, with a cut-off value of 1 mg/dl. Conclusion. Detection of vaginal fluid urea and creatinine to diagnose PROM is a simple, reliable and rapid test with high sensitivity, specificity, PPV, NPV and over all accuracy.

Key words: urea, creatinine, premature rupture of membrane.

inter-ventricular hemorrhage, cerebral palsy, and sepsis [3]. A study by Kafali and Oksuzler has shown that either urea or

creatinine determination in vaginal fluid

maturation and functionality throughout

for the diagnosis of PROM is a reliable, simple and rapid test. 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 cutoff value of 12 and 0.6 mg/dl, respectively. Analysis of creatinine and urea in amniotic fluid permits an evaluation of renal

pregnancy [4].The aim of the present work was to detect the accuracy of vaginal fluid urea and creatinine for diagnosis of PROM.

Patients and methods. The current diagnostic accuracy test was conducted at Ain Shams University Maternity Hospital during the period between June 2011 to December 2011. Studied women were divided into two groups; group I I (cases): fifty pregnant women with PROM were included and group II (controls): fifty pregnant women without PROM were included. A written informed consent was obtained from all women after approval of study protocol by ethical and research committee of council of Obstetrics and Gynecology Department, Ain Shams University. Women with multiple pregnancies, preterm labour, fetal distress, vaginal bleeding, congenital fetal malformations, and/or serum creatinine level more than 0.9 mg/dl were excluded from this study. All women were subjected

Introduction. Spontaneous rupture The membrane rupture itself should be to trans-abdomina| u|trasound and steri|e

of membranes (ROM) represents one of characterized as preterm or term [2]. The Cusco speculum examinati°n to diagn°se

components of labor and delivery, While, fetal membranes serve as a barrier to PROM|. PROM was diagnosed based on

premature rupture of membranes (PROM) ascending infection. Once the membranes sudden gush of watery vaginal fliiid, passing

refers to rupture of the fetal membranes rupture, both the mother and fetus are at of watery fluid from external cervical os

to the onset of labor whatever the risk of infection and of other complications during sterile Cusco speculum examinati°n,

gestational age [1]. The term "pre-labor" [1]. The major cause of perinatal morbidity an alkaline pH of the cervicovaginal

should be used rather than "premature" and mortality associated with preterm discharge, which change yellow nitrazine

"preterm" because the latter two PROM is prematurity. Morbidities related paper to blue (nitrazine test); and/or

relate neither to gestational age nor to prematurity include respiratory distress ferning of the cervicovaginal discharge

to the weight of the fetus or neonate. syndrome, necrotizing enterocolitis, on drying using microscopy (ferning test)

prior

or

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[1,5]. 5 ml of sterile saline solution was injected into the posterior vaginal fornix using a sterile syringe. 3 ml of the injected saline was aspirated using the same syringe and sent immediately to the laboratory. Each specimen was centrifuged at 50 revolutions/ second and the supernatant fluid was separated. Measurements of both urea and creatinine were performed by enzymatic urease method and Rate Jaffe method (Roche Integra 700 ®, Roche Diagnostics, Germany) respectively to determine their exact levels.

Statistical analysis. Data were analyzed using SPSS® for Windows®, version 18.0 (SPSS, Inc, USA). Description of quantitative (numerical) variables was performed in the form of mean, standard deviation (SD) and range. Description of qualitative (categorical) data was performed in the form of number of cases and percent. Analysis of numerical variables was performed by using independent student's t-test. Analysis of categorical data was performed by using Chi-square test. Diagnostic accuracy was assessed using the following terms: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy. ROC (receiver operator characteristic) curve was used to find out the best cut off value of certain variable). Sensitivity: ability of the test to detect positive cases and calculated as true positive cases/true positive cases + false negative cases. Specificity: ability of the test to exclude negative cases and calculated as true negative cases/true negative cases + false positive cases.

PPV is the percentage of true positive cases to all positive (proportion of all individuals with positive tests, who have the disease). NPV is the percentage of true negative cases to all negative (the proportion of all individuals with negative tests, who are non-diseased. While over all Accuracy means true negative +true positive / all cases.

A difference with P value <0.05 was considered statistically significant.

Results. A total of 100 pregnant women were included in the study. The studied women were divided into 2 groups according to presence or absence of PROM Group I I (cases): fifty pregnant women with PROM were included. Group II (controls): fifty pregnant women

S

Table (1): Comparison between both groups regarding maternal age, parity and gestational age at time of sampling*.

Group I Group II P **

Age(years) 26.2+2 26.2+4 >0.05 (NS)

Parity 2±1 1±0.6 >0.05 (NS)

Gestational age (weeks) 32.4±2.9 31.4±3.1 >0.05 (NS)

** Analysis using Independent Student's t-Test NS: non-significant

Table (2): Comparison between both studied groups as regard vaginal urea and creatinine levels*

Group I Group II P **

Urea(mg/dl) 40.3±9 7.8±2.8 <0.001(S)

Creatinine(mg/dl) 1.45±0.26 0.42±0.20 <0.001(S)

** Analysis using Independent Student's t-Test S: significant

ROC Curve

vaginal fluid urea and creatinine levels (P

Source of the Curve n Reference Line CR

_n UREA

.25 .50 .75 1X10

1 - Specificity

Figure (1) shows the Receiver operator characteristic (ROC) curve for vaginal fluid urea and creatinine as predictors of premature rupture of membranes.

without PROM were included. There was its PPV, NPV and over all accuracy were

no significant difference between both 96%,98% and 97%; respectively, with a

groups regarding maternal age, parity cut-off value of 1 mg/dl. Figure (1) shows

and gestational age at time of sampling the Receiver operator characteristic (ROC)

(P>0.05) table1. There was significant curve for vaginal fluid urea and creatinine

difference between the 2 groups regarding as predictors of PROM.

I

Discussion. The results of this

<0.001) table 2. In the current study; the study showed that both vaginal fluid

sensitivity & the specificity of vaginal fluid creatinine and urea concentrations are

urea to diagnose PROM were 99% & 99%; good predictors of PROM. The best

respectively, while its PPV, NPV and over cutoff point for vaginal fluid creatinine

vaginal fluid creatinine to diagnose PROM concentration as diagnostic of PROM was were 98% & 97%; respectively, while 23 mg/dl (sensitivity 99%-specificity 99%).

all accuracy were 98%, 97% and 96%; concentration as diagnostic of PROM was respectively, with a cut-off value of 12 mg/ 1 mg/dl (sensitivity 98% specificity 97%). dl. While the sensitivity & the specificity of The best cutoff point for vaginal fluid urea

Li and colleagues, found creatinine less expensive and easier to measure than human chorionic gonadotropin (hCG) and alpha feto protein (AFP) and appears to be more accurate than hCG [6]. Also, Gurbuz et al, concluded that vaginal fluid creatinine is an extremely useful marker in doubtful cases of PROM. In these cases, new methods such as AFP, Beta-hCG and fetal fibronectin were investigated. However, they have low specificity owing to overlap between the values of AFP, hCG, and fibronectin in patients with and without intact membranes , while, creatinine assay is cheaper and faster than other methods and has higher sensitivity and specificity to establish accurate diagnosis. It is a possible candidate to become a gold standard test for PROM [7].

Gurbuz et al. , reported that the sensitivity, specificity, positive predictivity, and negative predictivity were all 100% in detecting PROM by evaluation of vaginal fluid creatinine concentration [8].

It also agrees with the study conducted by Kafali et al, who were the first who conducted study using urea to diagnose PROM. In this study a total of 139 pregnant women were recruited. Group I consisted of 47 patients with diagnosis of PROM confirmed by amniotic fluid pooling and nitrazine paper test. Group II consisted of 36 patients in whom diagnosis of PROM was suspected but unconfirmed by amniotic fluid pooling and / or nitrazine paper test. Group III consisted of 56 pregnant women without any complaint or complication. The results were evaluated with a significance level of P<0.01 the sensitivity, specificity, positive predictivity, and negative predictivity were all 100% in detecting PROM by evaluation of vaginal fluid urea and creatinine with

a cut-off value of 12 and 0.6 mg/dl, respectively [4].

Creatinine values in the amniotic fluid that best represent fetal maturity are 1.5-2.0 mg/dl [4]. A creatinine concentration of 1.75 mg/dl or more correlates significant with a gestational age of 37 weeks or more. Which confirmed

renal maturation, the increasing growth profile of creatinine and urea throughout

normal pregnancy is due to glomerular filtrations and maturation of tubular function [9]. So it can be concluded that

vaginal and creatinine determination can be used not only in the diagnosis of PROM but also used as fetal maturation test in

case of preterm labour [4].

The strengths of the current study included the use of more than one criterion to diagnose PROM including symptoms , signs and investigations, Most of study results similar to those reported in other studies which makes our results are robust. Our study is limited by lack of comparison between vaginal fluid urea and creatinine and the diagnostic test ^

that is available and widely used in Europe and has also been approved by the Food and Drug Administration (FDA) which is AmniSure® test due to lack of financial resources as the study was funded by

authors only.

Conclusion. Detection of vagina l fluid

« -----------------i

urea and creatinine to diagnose PROM is a

sample, reliable and rapid test with high sensitivity, specificity, PPV, NPV and over all accuracy.

Declaration of interest. The author

reported no conflict of interest and the study was funded by author himself.

Reference list:

Diagnosis and Management of Preterm Premature Rupture of Membranes. Rev Obstet Gynecol;1(1):11-22

2. Budisan C and Ilie C (2010): Infections associated with Pregnancy and Childbirth. Fiziologia; 66: 11-14

3. El-Messidi A and Cameron A (2010): Diagnosis of Premature Rupture of Membranes: Inspiration From the Past and Insights for the Future. J Obstet Gynaecol Can;32(6):561-569

4. Kafali H and Oksuzler C (2007): Vaginal fluid urea and creatinine in diagnosis of premature rupture of membranes. Arch Gynecol Obstet. 275 (3): 157-160.

5. ACOG Practice Bulletin. Premature rupture of membranes. Clinical management guidelines for obstetrician-gynecologists. American College of Obstetricians and Gynecologists. Int J Gynecol Obstet 1998; 63 (1): 75-84.

6. Li HY and Chang TS (2000): Vaginal fluid creatinine human chorionic gonadotropin and alpha-fetoprotein levels for detecting premature rupture of membranes. Zhonghua Yi Xue ZaZhi (Taipei); 63: 686-690

7. Gurbuz A, Karateke A, Kabaca C (2003): Vaginal fluid creatinine in premature rupture of membranes. Int J Gynaecol. Obste; 84 -270-271.

8. Gurbuz A, Karateke A, Kabaca C (2004): Vaginal fluid creatinine in premature rupture of membranes. Int J Gynaecol. Obste; 85 270-271.

9. Oliveira FR, Barros EG, Magalhaes JA (2002): Biochemical profile of amniotic fluid for the assessment of fetal and renal development

10. BrazJ. Med Biol Res 35: 215-222.

1. Caughey AB, Robinson JN, Norwitz ER (2008): Contemporary

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MOHAMMED HUSSAIN MOSTAFA

ДИАГНОСТИЧЕСКАЯ ЗНАЧИМОСТЬ ОПРЕДЕЛЕНИЯ МОЧЕВИНЫ И КРЕАТИНИНА В ВАГИНАЛЬНОЙ СЛИЗИ В ДИАГНОСТИКЕ ПРЕЖДЕВРЕМЕННОГО РАЗРЫВА ПЛОДНЫХ ОБОЛОЧЕК

Айн Шамс университету Аббасия-Каир, Египет

Мацсаты. ¥рыц цабыцшаларынын уацытынан бурын ажырауын (¥К,УБА) диагностикалауда цынап шырышындаFы несепнэр мен креатининнщ диагностикалыц дэлдiгiн аныцтау. Емделушмлер мен эдiстер: Берiлген диагностикалыц нацты тест Айн Шамс университетiнiн перзентханасында 2011 жылдын маусым айынан желтоцсан айына дейiнгi аралыцта eткiзiлген болатын. Зерттеуге екi топца бeлiнген 100 эйел: I топца ¥КУБА бар 50 ЖYKтi эйел жэне II топца (бацылау) ¥КУБА жоц 50 ЖYKтi эйел цосылды. Эйелдердщ кеп урыцтыц ЖYKтiлiгi, уацытынан бурын босануы, урыц патологиясы, жатырдан цан кетуЬ урыц дамуынын туа бiткен ацауы мен/немесе цан сарысуында креатинин денгейшщ 0,9 мг / дл асуы 0Fан жатпайды. Барлыц эйелдерге ¥КУБА аныцтау Yшiн трансабдоминалды УДЗ жэне Куско бойынша залалсыздандырылFан айналармен тексеру ЖYргiзiлдi, заласыздандырылFан шприцтiн кeмегiмен цынаптын артцы дeнесiне 5 мл заласыздандырылFан физиологиялыц ерiтiндi енгiзiлдi. 3 мл себтген физиологиялыц ерiтiндiнi сол шприцтщ кeмегiмен сорып тастап, шуFыл TYPде зертханаFа жеткiздi. Эрбiр Yлгi секундына 50 айналымда центрифугалады жэне o^^îy^ шырыш бeлiнiп алынды. Несепнэрдi eлшегендей, креатинин де ферментативтi уреазды эдк жолымен жэне сэйкесiнше, Яффе эдiсiмен eлшендi.

Корытындысы. Сынамаларды сурыптау (Р> 0,05) кезiнде зерттелген екi топ арасында ана жасына, жаFдайы мен гестациялыц жасына сэйкес, ешцандай айтарлыцтай айырмашылыц болFан жоц. Зерттелген ек топ арасында цынап шырышындаFы (р <0,001) несепнэр мен креатинин денгейлерше сэйкес бiрцатар айырмашылыцтар кeрсетiлдi, осылайша I топтын цынап шырышындаFы несепнэр мен креатининнщ орташа денгейi 40,3 ± 9 мг / дл жэне 1,45 ± 0,26 мг / дл, керiсiнше, II топта 7,8 ± 2,8 мг / дл жэне 0,42 ± 0,20 мг / дл сэйкес болды. Осы зерттеуде ¥КУБА диагностикасында цынап шырышындаFы несепнэрдiн сезiмталдыFы мен ерекшелт 99% жэне 99% болды, сэйкесшше, сол кезде он жэне терк болжау цундылыFы мен толыц дэлдт 98%, 97% жэне 96% болды; сэйкесшше, 12 мг / дл алып-цосцан белпамен. Алайда ¥КУБА диагностикасында цынап шырышындаFы креатининнiн сезiмталдыFы секiлдi ерекшелiгi де 98% жэне 97% болды; сэйкесшше сол кезде ОБК (он болжау цундыль^ы) сияцты ТБК (терiс болжау цундылыFы) жэне толыц дэлдт 96%, 98% жэне 97% болды; сэйкесшше 1 мг / дл айырмашылыц белпамен. ¥ЙFaрым: ¥КУБА диагностикасында цынап шырышындаFы несепнэр мен креaтининдi аныцтау жоFaры сезiмтaлдыFы, он жэне терк болжамдыц цундылыFы, толыц дэлдт бар царапайым, сенiмдi жэне жылдам тест болып табылады.

Негiзгi свздер: несепнэр, креатинин, урыц цабыцшаларынын, уацытынан бурын ажырауы.

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Университет Айн Шамс, Аббасия-Каир, Египет

Цель. Определить диагностическую точность мочевины и креатинина в вагинальной слизи в диагностике преждевременного разрыва плодных оболочек (ПРПО). Пациенты и методы: Данный диагностически достоверный тест был проведен в родильном доме университета Айн Шамс в период с июня 2011 года по декабрь 2011 года. В исследование было включено 100 женщин, которые были разделены на две группы; В I группу было включено пятьдесят беременных женщин с ПРПО и во II группу (контрольная) пятьдесят беременных женщин без ПРПО. Критерием исключения явились женщины: с многоплодной беременностью, с преждевременными родами, с патологией плода, с маточным кровотечением, с врожденными пороками развития плода и / или с уровнем креатинина в сыворотке крови более 0,9 мг / дл. Всем женщинам проведено трансабдоминальное УЗИ и осмотр стерильными зеркалами по Куско, для диагностики ПРПО, 5 мл стерильного физиологического раствора вводили в задний свод влагалища с помощью стерильного шприца. 3 мл впрыскиваемого физиологического раствора отсасывали с помощью того же шприца и немедленно доставляли в лабораторию. Каждый образец центрифугировали при 50 оборотов в секунду и надосадочная слизь была отделена. Измерения как мочевины, так и креатинина проводили путем ферментативного уреазного метода и методом Яффе соответственно.

Результаты. Не было никакого существенного различия между двумя исследуемыми группами согласно возрасту матери, состоянию и гестационному возрасту на момент отбора проб (Р> 0,05). Отмечена значительная разница между двумя исследуемыми группами соответственно уровням мочевины и креатинина в вагинальной слизи (р <0,001), так средний уровень мочевины и креатинина в вагинальной слизи I группы соответствовал: 40,3 ± 9 мг / дл и 1,45 ± 0,26 мг / дл в противоположность II группе 7,8 ± 2,8 мг / дл и 0,42 ± 0,20 мг / дл . В настоящем исследовании чувствительность и специфичность мочевины в вагинальной слизи в диагностике ПРПО были 99% и 99% соответственно, в то время как положительная и отрицательная прогностическая ценность и полная точность были 98%, 97% и 96%; соответственно, со значением отсечки 12 мг / дл. Однако, как чувствительность, так и специфичность креатинина в вагинальной слизи в диагностике ПРПО были 98% и 97%; соответственно, в то время как ППЦ, ОПЦ и полная точность были 96%, 98% и 97%; соответственно, со значением отсечки 1 мг / дл. Вывод: Определение мочевины и креатинина в вагинальной слизи в диагностике ПРПО является простым, надежным и быстрым тестом с высокой чувствительностью, специфичностью, с положительной и отрицательной прогностической ценностью, полной точностью.

Ключевые слова: мочевина, креатинин, преждевременный разрыв плодных оболочек.