Placental Alpha Microglobulin-1 Detection in Cervico ... · Placental Alpha Microglobulin-1 Detection in Cervico-vaginal Secretions ... Premature Rupture of Membranes ... preterm

European International Journal of Science and Technology Vol. 4 No. 5 June, 2015

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Placental Alpha Microglobulin-1 Detection in Cervico-vaginal Secretions in

the Diagnosis of Preterm Premature Rupture of The Membranes

Mouhamed Roshdy Mahmoud1, Foad Abd El Kader Abo Hamela

1, Mariem Mahmoud Mouhamed

1

and Medhat Mounir Kamel2*

1 Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt; 2 National

Research Center, Cairo, Egypt

* Corresponding author:

Medhat Mounir Kamel, M.B.B.CH.

Research fellow, National Research Center,

Cairo, Egypt

Email: [email protected]

Abstract

Objective: This study aimed to evaluate the value of detection of placental alpha macroglobulin-1 (PAMG-1)

in cervicovaginal discharge as a diagnostic test for Premature Rupture of Membranes (PROM) compared

with traditional methods.

Methods: A comparative study was conducted on 60 pregnant women 20-37 weeks of gestation in Cairo

University Maternity Hospital, Egypt. PROM was evaluated using U/S, Ferning test, Nitrazine test, pooling,

and PAMG-1 immunoassay. The studied women were divided into two groups based on the presence or

absence of PROM. Confirmed diagnosis of PROM was based an artificial gold standard. Sensitivity,

specificity, positive and negative predictive values and overall accuracy of the diagnostic tests were

calculated.

Results: PAMG-1 was superior to other tests regarding sensitivity (96%), specificity (97.14%), positive

predictive value (96%), negative predictive value (97.14%) and accuracy (96.67%).

Conclusion: PAMG-1 has a higher accuracy than the traditional methods, with high sensitivity and specificity

and is easy to use.

Key words: Placental alpha macroglobulin-1;cervico-vaginal secretions; premature rupture of membranes

European International Journal of Science and Technology ISSN: 2304-9693 www.eijst.org.uk

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1. Introduction

Membrane rupture is one of the most common disorders during pregnancy. It may occur at any time

in the pregnancy. It may happen appropriately with the onset of labor at term, or prematurely, prior to the

onset of labor. When occurring prior to the onset of labor for more than 24 hours at term, it is referred to as

premature rupture of membranes or PROM. Alternatively, it may occur in a preterm gestation, less than 37

weeks and is referred to as preterm premature rupture of membranes or PPROM ( Deering, et al., 2007).

Regardless of when membrane rupture takes place, the method of diagnosis is the same.

PROM occurs in approximately 10% of all pregnancies after 37 weeks gestation and in 2-3.5% of

pregnancies before 37 weeks gestation. PROM constitutes a major etiological factor of prenatal and

postnatal complications. It is a significant cause of premature delivery and other maternal and neonatal

complications (Simhan, et al., 2005).

The management of a patient with PROM and PPROM is expensive and difficult as the clinician

attempts to balance the risk of prolonging pregnancy against the risks of acquiring intrauterine and maternal

infection and the immaturity of lung development. Therefore, correct and timely diagnosis of this disorder is

critical (Hofmeyr, et al., 2014).

Membrane rupture, either PROM or PPROM, can be conducted when the following

symptoms/conditions occur: i) Vaginal secretions increase or become watery, especially in women at the risk

of preterm delivery or after an insult to the abdomen, as a fall, strike or shake of the stomach, leading to

potential rupture of fetal membranes.ii) Visible or unnoticed leakage of amniotic fluid (Caughey, et al.,

2008). .

Evaluation of the patient begins with full history taking, full general and local examination. Then a

sterile speculum examination is done, from which three signs of membrane rupture are sought; pooling,

positive Ferning test,and positive Nitrazine test. Additionally, oligohydramnios (low amnioticfluid level)

may be detected by sonographic examination suggestive of amniotic fluid loss secondary to membrane

rupture but not conclusive (Medina & Hill, 2006).

In diagnosing PROM, the history and physical examination alone often are inadequate to confirm the

status of the membranes. Fluid may not be present in the vagina for evaluation; the fluid may be

contaminated with urine, cervical mucus, vaginal discharge, blood, or meconium. Because of these

difficulties, multiple cytological, biochemical, colorimetric and sonographic methods have been developed

for detection of ruptured membranes. Despite significant advances in technology, no one test has been

found to be completely accurate, and the diagnosis still requires an integration of historic factors, physical

examination, and laboratory testing (Caughey, et al., 2008).

Noting that pooling strongly supports the diagnosis of Rupture of Membranes (ROM)(Alexander, et

al., 2000).However, this finding is not always present in a patient with ROM(Wiberg-Itzel, et al., 2005).

Amniotic fluid produces a delicate ferning pattern, in contrast to the thick and wide arborization pattern of

dried cervical mucus. However, the method of “Ferning” has been associated with false positive results

described secondary to contamination with fingerprints on a slide or contamination with semen and cervical

mucus. False negatives may be caused by inadequate amniotic fluid on swabs or contamination with

blood(Mercer & Lewis, 1997). The strength of the fern test to differentiate between amniotic and non-

amniotic fluid in vaginal discharge was investigated in the laboring and non-laboring patient with noted

differences in sensitivity and specificity. Sensitivity and specificity in the laboring group were 98.0% and

88.0%. In the non-laboring group, sensitivity and specificity were only 51.4% and 70.8%, respectively(De

Haan, et al., 1994).

The Nitrazine test is designed only to confirm an alkaline pH in the cervico-vaginal secretion, the pH

of the vaginal secretions is generally 4.5-6.0 whereas amniotic fluid usually has a pH of 7.1-7.3. Yet it is the


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most common test used to diagnose PROM, it is associated with false-positive results ranging from 1% to

17% that can result from alkaline urine, blood, semen, vaginal discharge in cases of bacterial vaginosis, or

Trichomonas infection. Sensitivity and specificity have been reported at 90.7% and 77.2% respectively

(Cousins, et al., 2005; ACOG, 2007).

Membrane rupture is suspected to have occurred if any of the above three findings are present and

diagnosis is confirmed when all three findings are noted. However, all three findings are not mandatory for

the diagnosis of membrane rupture. When two of three are present, clinical correlation is exercised.

Frequently, equivocal results are obtained when diagnostic criteria are not met and result in false positive

and false negative diagnosis of ruptured membranes (Medina & Hill, 2006).

There are many biochemical tests, which have been studied for the diagnosis of ROM.A good test

must be reliable, simple and rapid(Esim, et al., 2002).These biochemical markers include prolactin (Shahin

& Raslan, 2007; Kariman, et al., 2012), alpha-feto-protein (AFP)(Shahin & Raslan, 2007),fetal fibronectin

(Lockwood, et al., 1991), diamine-oxidase, insulin-like growth factor binding protein-1 (IGFBP-

1)(Lockwood, et al., 1994; Gaucherand, et al., 1997),beta-subunit of human gonadotropin (B-HCG) (Esim,

et al., 2003; Shahin & Raslan, 2007)and urea-creatinine(Osman & Elghazaly, 2014).However, prolactin

and AFP were not useful markers for PROM because of the overlap in concentrations between pregnant

women with and without ruptured membranes(Phocas, et al.,1989).Moreover, chorionic release of fetal

fibronectin preceding delivery in patients with intact membranes may also lead to false-positive results.

IGFBP-1 is a major protein of amniotic fluid, which can be detected by a dipstick method in 5 minutes

(Erdemoglu & Mongan, 2004).

When the diagnosis remains unclear, an invasive method may be applied where amniocentesis is

done and a dye (Evans Blue or Fluorescein) is injected and leakage from the cervix is visualized. This

method is highly invasive and has many complications and can itself induce a PROM and miscarriage.

Therefore, a rapid, accurate, inexpensive, and noninvasive test for the diagnosis of PROM is urgently needed

(Caughey, et al., 2008).

The use of PAMG-1 detection in cervico-vaginal discharge as a simple, easy, rapid and minimally

invasive diagnostic test for PROM is getting popularity nowadays. It has high concentration in the amniotic

fluid, low level in blood and extremely low background level in cervico-vaginal secretions with intact fetal

membranes (Cousins, et al., 2005).

This study aimed to evaluate the detection of PAMG-1 in cervico-vaginal discharges as a diagnostic test for

ROM in comparison with traditional tests.

2. Methodology

This comparative study was carried out in Cairo University Maternity Hospital, Cairo, Egypt from

October 2009 to March 2010. The study included 60 pregnant women between 20-37 weeks of gestations

who were divided into two groups based on the presence or absence of PROM. The study excluded pregnant

women who had active vaginal bleeding or infection, placenta previa, complicated pregnancy, fetal distress

or known fetal anomalies.

A written informed consent (in Arabic language) was obtained from all participants. It included all

details about the purpose of the study and the method of sample collection.

Full history taking, physical examination, sterile speculum examination and transabdominal

ultrasound examination were performed. All participants were assessed using Amniotic Fluid Index (AFI),

pooling test, Nitrazine test, Ferning test and PAMG-1 rapid immunoassay test (AmniSure).

AFI was calculated by 4 quadrants method during the ultrasound examination. This consists of the

sum of the vertical diameters of the largest pockets seen in each of the four quadrants of the uterus. The AFI


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is considered normal between 8.1 and 18 cm, low between 5.1 and 8.0 cm, very low <5 cm, and high >18

cm. for optimum accuracy, the mean of three AFI measurements was calculated, when the AFI is <10

cm(Nabhan & Abdelmoula, 2008).

The Nitrazine test was carried out by swapping the posterior vaginal fornix with a Litmus paper. A

positive result was interpreted as a change of the Litmus paper colour into dark blue indicating alkaline pH

of the amniotic fluid.

For doing the Ferning test, a drop of vaginal secretion from the posterior fornix was collected by a

sterile syringe and put on a dry clean glass slide. Then waiting for 3 minutes to dry and microscopic

examination was done. A positive fern test is defined as visualization of arborization(the tree like pattern) is

observed(ACOG, 2007).

Detection the presence of PAMG-1 in cervicovaginal discharge was carried out using the Amnisure

kits(Lee, et al., 2007). Rapid immunoassay of PAMG-1 was performed by placing a sterile swab at the

posterior vaginal fornix for about one minute. It was then rinsed into a vial containing solvent for another 1

minute and then disposed. The test strip was inserted in the solvent, and the result would be available in 5

minutes. The test was considered negative If only a control line is visible. While if both control and test

lineswere visible, the test result was positive. If no lines were visible, the test result was invalid(Joong&

Errol, 2005).

Blood samples were collected from participants to do CBC for TLC, ESR and CRP.

2.1. Statistical analysis

For the diagnosis of ROM, an artificial gold standard was used. This included the sum of the results of

Nitrazine, Ferning, and pooling tests. If two or more out of three were positive, the patient was considered to

have a confirmed ROM. If less than two were positive in spite of the positive history of gush of fluid

vaginally, this patient was considered not to have ROM; if less than two were positive and the patient had

no history of leakage this patient was included in the control group (Cousins, et al., 2005).

The collected data were described in terms of mean ±Standard Deviation (± SD), range, frequencies

and percentages as appropriate. Comparisons between the study groups were carried out using the

independent Student t-test for quantitative data when normally distributed. The test of proportion (Z-test)

was used to compare the proportions of women who had trauma or coitus before the onset of vaginal leak

and those who did not. The Chi square (χ2) test and Fisher’s Exact Test (FET) were used to compare more

than two proportions as appropriate. Accuracy was represented using the terms sensitivity, specificity,

positive predictive value, negative predictive value and overall accuracy. A probability value (p-value) less

than 0.05 was considered statistically significant. All statistical calculations were done using computer

programs Microsoft Excel 2003 (Microsoft Corporation, NY, USA) and SPSS (Statistical Package for the

Social Science; SPSS Inc., Chicago, IL, USA) version 15 for Microsoft Windows.

3. Results

A total of 60 pregnant women were evaluated for PROM according to the artificial golden role

discussed before. Of these, 25 (41.7%) were positive for PROM and 35 (58.3%) were negative for PROM.

Table 1 shows differences between the positive and negative groups for PROM regarding some clinical

characteristics. Parity was higher among women who were positive for PROM than those who were negative

(P=0.02). There were no significant differences as regard age, duration of marriage, gestational age,

gravidity, abortion and history of ROM in previous pregnancies.

There were no significant differences between patient with positive PROM and those with negative

PROM as regard to markers of infection (Table 2).

European International Journal of Scien

There were no significant differ

leaking (n=30) and had history of trauma

positive for PROM (n=25) and those wh

Figure 1 Comparison between the st

within 48 hrs. and trauma before leak

The number of patients who

examination and oligohydraminos on U

compared to those who were negativ

significant at P<0.001.Similarly, PAMG

(P<0.001). AFI was higher among co

difference in between (7±3.14 vs. 13.6±4

Table 4 shows that PAMG-1 was

positive and negative predictive value a

and specificity (97.14%) compared t

sensitivity(88%). While AFI detection b

PAMG-1 in cervicovaginal discharge w

value, negative predictive value and ac

had less negative predictive value (92%

96.67%respectively).

0

5

10

15

20

25

30

35

40

45

Trauma before leaking

20

0

%

Positive PRO

ence and Technology Vol. 4 No. 5

ferences in the proportions of pregnant women

ma before leaking or coitus within 48 hours betwe

ho were negative (n=5)(Figure 1).

studied women with leaking (n=30) as regar

king by the diagnosis of PROM

o had positive Nitrazine test, Ferning test, po

U/S examination was higher among women w

tive PROM (Table 3). These differences were

G-1 was more likely detected among PROM p

control group compared to PROM group wit

±4.17; P<0.001).

as superior to other diagnostic tests as regard to se

e and accuracy collectively.PAMG-1 had both hi

to other tests. Pooling had specificity of 1

n by U/S had specificity of 91.3% but low sensi

was superior to other diagnostic tests as regard t

accuracy. Although pooling had positive predicti

2%)and less accuracy (95%) than PAMG-1 det

ing Coitus within 48 hrs

44

20

PROM Negative PROM

June, 2015

n who presented with

weenwomen who were

ard history of coitus

pooling on speculum

with positive PROM

re statistically highly

patients than controls

ith highly significant

sensitivity, specificity,

high sensitivity (96%)

100% but had low

nsitivity (64%). Again,

to positive predictive

ctive value of 100% it

detection (97.14% and

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Table 1 Clinical characteristics of the studied groups

Characteristics

Positive PROM group

(n = 25)

Negative PROM group

(n = 35) Test

statistics P

Mean±SD Range Mean±SD Range

Maternal age

(years) 29.44±6.28 19-41

30.80

±7.26 18-44 t= 0.75 0.45

Duration of marriage

(years)

6.52

±4.75 1-19

7.23

±5.28 1-20 t=0.53 0.59

Calculated gestational age

(weeks)

32.80

±2.33 29-36

33.71

±2.55 31-36 t=1.41 0.16

Gravidity 2.88

±1.86 1-5

3.09

±1.77 2-5 t=0.44 0.66

Parity 1.80

±1.08 0-4

1.11

±1.13 0-4 t=2.37 0.02

Abortion 0.80

±1.80 0-3

0.97

±1.20 1-2 t=0.44 0.66

History of ROM in previous

pregnancy (n=39)

No (%)

Yes (%)

12 (70.59)

5 (29.41)

14 (63.64)

8 (36.36)

χ2 = 0.209

0.65

Table 2 Results of CBC, ESR and CRP In the studied groups

*Obtained using the Fisher’s Exact Test

Variable

Positive PROM group

(n = 25)

Negative PROM group

(n = 35) P*

No. % No. %

CBC (leukocytosis) Yes

No

3

22

12.00

88.00

3

32

8.57

91.43 0.69

ESR Yes

No

4

21

16.00

84.00

2

33

5.71

94.29 0.22

CRP Yes

No

5

20

20

80

3

32

8.57

91.43 0.26


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Table 3 Results of Nitrazine test, Fernning test, pooling test, PAMG-1 immunoassay, oligohydraminos

and AFI by the diagnosis of PROM in the studied groups

Test

Positive PROM

group

(n = 25)

Negative PROM

group

(n = 35)

Test

statistic P

No. % No. %

Nitrazine test Positive

Negative

23

2

92.00

8.00

5

30

14.29

85.71 χ

2=35.39 <0.001

Ferning test Positive

Negative

23

2

92.00

8.00

5

30

14.29

85.71 χ

2=35.39 <0.001

Pooling test Positive

Negative

22

3

88.00

12.00

0

35

0.00

100.00 χ

2=48.63 <0.001

PAMG-1 Positive

Negative

24

1

96.00

4.00

1

34

2.86

97.14 χ

2=52.05 <0.001

Oligohydraminos Yes

No

16

9

64.00

36.00

3

32

8.57

91.43 χ

2=20.70 <0.001

AFI (cm) Mean± SD;

(range) 7±3.14; (3-15) 13.6±4.17; (6-25) t=6.67 <0.001

Table 4 Comparison between the studied groups as regard the results of PAMG-1, Nitrazine test,

Ferning test, pooling test and AFI.

Test Sensitivity

(%)

Specificity

(%)

Positive

predictive

value (%)

Negative

predictive

value (%)

Accuracy

(%)

PAMG-1 96.00 97.14 96.00 97.14 96.67

Nitrazine test 92.00 85.71 82.14 93.75 88.33

Ferning test 92.00 85.71 82.14 93.75 88.33

Pooling test 88.00 100.00 100.00 92.11 95.00

AFI (cm) 64.00 91.30 84.21 78.04 80.00

4. Discussion

PROM is a condition, which occurs in pregnancy when the amniotic sac ruptures before the onset of

labor. PPROM is a condition where the amniotic sac leaks fluid before 37 weeks of gestation(Deering et al.,

2007).Correct diagnosis of PROM has great importance because failure of diagnosis can lead to unwanted

obstetric complications like chorioamnionitis. On the other hand over diagnosis can lead to unnecessary

interventions like hospitalization and preterm birth (Kim, et al., 2005).

Diagnosis of PROM is easy when the rupture is obvious but difficult and indeed impossible when the

leaking is minimal. Therefore, there is a growing need to discover a reliable, simple and rapid biochemical test

for the diagnosis of ROM (Esim et al., 2002).A number of biochemical markers for the diagnosis of ROM have

been studied. However, none of them was proved to be a gold standard marker for routine diagnosis, so it


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was necessary to discover a new marker for the diagnosis of PROM.

PAMG-1protein was isolated from amniotic fluid in 1975. It can be measured in amniotic fluid using

immunochemical methods.PAMG-1 was selected as a marker of fetal membrane rupture due to its

unique characteristics; high concentration in the amniotic fluid, low level in blood, and extremely low

background level in cervicovaginal secretions with intact fetal membranes(Cousins, et al., 2005).

Furthermore, small quantities of amniotic fluid in vaginal secretions could be detected by the use of a

combination of monoclonal antibodies. By setting its sensitivity threshold at 5 ng/ml, detection of PAMG-1

minimizes the probability of false-positive and false-negative results. In addition, the increased levels of

PAMG-1 in the vaginal secretions is highly predictive of ROM (Mulhair, et al., 2009).

In this study,PAMG-1 detection in cervicovaginal discharge by AmniSure was compared to an artificial

gold standard for diagnosis of ROM. The latter included the sum of results of Nitrazine, Ferning, and

Pooling tests.

The results of this study revealed that the sensitivity, specificity, positive predictive value, negative

predictive value and accuracy of Nitrazine test were 92%, 85.71%, 82.14%, 93.75%, and 88.33% respectively.

These results are in line with those mentioned in the study by Gaucherand, et al. (1997) who reported a

sensitivity and specificity of 90.7%and 77.2%respectively. They stated that Nitrazine evaluation was

associated with false-positive results up to 17.4% secondary to cervicitis, vaginitis (bacterial vaginosis or

trichomonas), alkaline urine, blood, semen, and antiseptics. A significant false negative rate (12.9%) for

Nitrazine test was observed.

As regards Ferning, the results of the present study detected that the sensitivity, specificity, positive

predictive value, negative predictive value and accuracy were 92%, 85.71%, 82.14%, 93.75%, and 88.33%

respectively. These corresponds to Rosemond, et al. (1990) who mentioned that Ferning has been associated

with false-positive results in 5 to 30% of patients; the result was described secondary to contamination with

fingerprints on the slide or contamination with semen and cervical mucus. False-negative results (5 to

12.9%) might be caused by dry swabs, contamination with blood and heavy discharge. In the non-laboring

group, sensitivity and specificity were 51.4% and 70.8%, respectively (De Haan, et al., 1994).

As for pooling, the results of the present study detected that the sensitivity, specificity, positive predictive

value, negative predictive value and accuracy were 88%, 100%, 100%, 92.11 and 95% respectively.

Indeed Lee et al. (2007) stated that the traditional diagnostic methods using nitrazine/pH, assessment

of pooling, and microscopic ferning testing lack reliability and become progressively less accurate with

passage of time since membrane rupture. Thus in cases of prolonged PROM, these tests provide no better

diagnostic information than that obtained by simple clinical examination.

In this study, AFI was proved to be significantly lower in the group positive for ROM. These findings

confirm the results of the study done by Frigo et al. (1998) who suggested that U/S examination was an

important tool for the diagnosis of PROM. On the other hand, Kafali and Oksuzler (2007) concluded that there

was no significant statistical difference between women with confirmed diagnosis of PROM, as indicated by

positive Nitrazine and pooling tests, those with suspected PROM and controls regarding AFI. However, amongst

the studied tests, AFI showed the least sensitivity (64%), positive predictive value (84%), negative predictive

value (78%) and accuracy (80%). These results are in contrast with those reported by Erdemoglu and Munganl

(2004) who found that the sensitivity, and accuracy of AFI were 94%, and 92% respectively.

The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of detection of

PAMG-1 in cervicovaginal discharge in detecting ROM were 96%, 97.14%, 96%, 97.14%, and 96.67%

respectively. These results are consistent with those reported by Cousins et al. (2005) who stated that the

AmniSure diagnostic test demonstrated a sensitivity of 98.9%, specificity of 100%, positive predictive value

of 100%, and a negative predictive value of 99.1%.


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Lee et al. (2007) performed a prospective observational study in consecutive patients with signs or

symptoms of rupture membranes. Of a total 183 patients, 157 (87%) had rupture of membranes at their initial

presentations using the same gold standard employed in the present study.PAMG-1 immunoassay was proved to

have a sensitivity of 98.7%, specificity of 87.5%, positive predictive value of 98.1%, and negative predictive

value of 91.3%. A false-positive test (defined as a positive placental immunoassay in women who were

subsequently determined not to have ROM) was documented in three cases.

Chen and Dudenhausen (2008) compared two rapid strip tests for the detection of amniotic fluid,

based on the detection of insulin-like growth factor-binding protein-1 (IGFBP-1) and of PAMG-1. Samples

of amniotic fluid were taken from 20 pregnant women between 31 and 41 gestational weeks at elective

Cesarean section before delivery of the newborn. These samples were diluted with 0.9 % saline solution in a

dilution series down to the concentrations of 1:320. Comparison between the two tests was carried out to

evaluate their ability to detect different concentrations of amniotic fluid. The test based on PAMG-1 proved

to be superior in 15 cases by detecting amniotic fluid at least at one descending concentration below the test

based on IGFBP-1. Thus, it was concluded that the rapid strip test based on PAMG-1 is a more sensitive

bedside test compared with the test based on IGFBP-1 for the detection of amniotic fluid. Furthermore,

PAMG-1 immunoassay was recommended as a promising and noninvasive test for the diagnosis of

ROM(Caughey, et al., (2008);Duff, (2009)).

Lee et al. (2009) concluded that a positive Amnisure test is present in about one-third nulliparous women at

term presenting in labor with intact membranes; and patients with a positive Amnisure test had a shorter

admission-to-delivery interval than those with a negative test. This may imply restriction of the use of the

test in preterm patients. In fact, this is the group of patients expected to really benefit from such testing

where the decision making regarding active intervention may really make a difference.

To summarize, PAMG-1 detection in cervicovaginal discharges by the use of Amnisure test is a useful

method for the diagnosis of PROM as it was more accurate than the traditionally available tests, with high

sensitivity and specificity, and easy to use as mentioned previously .

References

1. Alexander, J. M., Mercer, B. M., Miodovnik, M., Thumau, G. R., Goldenberg, R. L., Das, A. F., et al.

(2000). The impact of digital cervical examination on expectantly managed preterm rupture of

membranes. Am J Obstet Gynecol., 183, 1003-1007.

2. American College of Obstetrician and Gynecologists (ACOG) Committee on Practice Bulletins–

Obstetrics, Authors. (2007). ACOG Practice Bulletin No. 80: premature rupture of membranes.

Clinical management guidelines for obstetrician-gynecologists. Obstet Gynecol., 109, 1007:1019.

3. Caughey, A. B., Robinson, J. N. and Norwitz, E. R. (2008). Contemporary diagnosis and

management of preterm premature rupture of membranes. Rev Obstet Gynecol., 1, 11-22.

4. Chen, F. C. and Dudenhausen, J. W. (2008). Comparison of two rapid strip tests based on IGFBP-1

and PAMG-1 for the detection of amniotic fluid. Am J Perinatol., 25, 243:246.

5. Cousins, L. M., Smok, D. P., Lovett, S. M. and Poeltler, D. M. (2005). AmniSure placental alpha

macroglobulin-1 rapid immunoassay versus standard diagnostic methods for detection of rupture of

membranes. Am J Perinatol., 22, 317-320.

6. De Haan, H. H., Offermans, P. M., Smits, F., Schouten, H. J. and Peeters, L. L. (1994). Value of the

fern test to confirm or reject the diagnosis of ruptured membranes is modest in nonlaboring women

presenting with nonspecific vaginal fluid loss. Am J Perinatol.,11, 46-50.


30

7. Deering, S. H., Patel, N., Spong, C. Y., Pezzullo, J. C. and Ghidini, A. (2007). Fetal growth after

preterm premature rupture of membranes: is it related to amniotic fluid Volume. J Matern Fetal

Neonatal Med., 20, 397-400.

8. Duff, P. (2009). Preterm premature rupture of membranes. UpToDate [online serial]. Waltham, MA:

UpToDate.

9. Erdemoglu, E. and Mungan, T. (2004). Significance of detecting insulin – like growth factor binding

protein-1 in cervicovaginal secretions: comparison with nitrazine test and amniotic fluid volume

assessment. Acta Obstet Gynecol Scand., 83, 622-626.

10. Esim, E., Turan, C., Unal, O., Dansuk, R. and Cengizlu, B. (2003). Diagnosis of premature rupture of

membranes by identification of beta-HCG in veginal washing fluid. Eur J Obstet Gynecol Reprod

Biol., 107, 37:40.

11. Frigo, P., Lang, C., Sator, M., et al. (1998). Membranes thickness and PROM- high frequency

ultrasound measurements. Prenatal Diagn., 18, 333-337.

12. Gaucherand, P., Salle, B., Sergeant, P., Guibaud, S., Brun, J., Bizollon, C. A., Rudigoz, R. C. (1997).

Comparative study of three vaginal markers of the premature rupture of membranes. Insulin like

growth factor binding protein 1, diamine-oxidase and pH. Acta Obstet Gynecol Scand., 76, 536-540.

13. Hofmeyr, G. J., Eke, A. C. and Lawrie, T. A. (2014). Amnioinfusion for third trimester preterm

premature rupture of membranes. Cochrane Database Syst Rev. Doi:

10.1002/14651858.CD000942.pub3.

14. Joong, S. and Errol, R. (2005). Technical innovations in clinical obstetrics., Contemporary OB/GYN

Special Technology Issue3, Vol. 50 ;203:214.

15. Kafali, H. and Oksuzler, C. (2007). Vaginal fluid urea and creatinine in diagnosis of premature

rupture of membranes. Arch. Gynecol. Obstet., 160, 157:205.

16. Kariman, N., Hedayati, M. and Majd, S. A. (2012). The Role of Vaginal Prolactin in Diagnosis of

Premature Rupture of Membranes. Iran Red Crescent Med J., 14, 352-357.

17. Kim, Y. H., Park, Y. W., Kwon, H. S. and Kim, B. J. (2005). Vaginal fluid beta-human chorionic

gonadotropin level in the diagnosis of premature rupture of membranes. Acta Obstet Gynecol Scand.,

84, 802-805.

18. Lee, S. E., Park, J. S., Norwitz, E. R., Kim, K. W., Park, H. S. and Jun, J. K. (2007). Measurement of

placental alpha-microglobulin-1 in cervicovaginal discharge to diagnose rupture of membranes. Obstet

Gynecol., 109, 634-640.

19. Lee, S. M., Lee, J., Seong, H. S., Lee, S. E., Park, J. S., Romero, R. and Yoon, B. H. (2009). The

clinical significance of a positive Amnisure test in women with term labor with intact membranes. J

Matern Fetal Neonatal Med., 22, 305-310.

20. Lockwood, C. J., Senyei, A. E., Dische, M. R., Casal, D., Shah, K. D., Thung, S.N., et al. (1991).

Fetal fibronectin in cervical and vaginal secretions defines a patient population at high risk for

preterm delivery. N Engl J Med., 325, 669-74.

21. Lockwood, C. J., Wein, R., Chien, D., Ghidini, A., Alvarez, M., Berkowitz, R. L. (1994). Fetal

membrane rupture is associated with the presence of insulin-like growth factor-binding protein-1 in

vaginal secretions. Am J Obstet Gynecol., 171, 146-150.

22. Medina, T. M. and Hill, D. A. (2006). Preterm premature rupture of membranes: Diagnosis and

management. Am Fam Physician., 73, 659-664.

23. Mercer, B. M. and Lewis, R. (1997). Preterm labor and preterm premature rupture of the membranes.


31

Diagnosis and management. Infect Dis Clin North Am., 11, 177:201.

24. Mulhair, L., Carter, J., Poston, L., Seed, P., Briley, A. (2009). Prospective cohort study investigating

the reliability of the AmnioSense method for detection of spontaneous rupture of membranes.

BJOG., 116, 313-318.

25. Nabhan, A. F. and Abdelmoula, Y. A. (2008). Amniotic fluid index versus single deepest vertical

pocket as a screening test for preventing adverse pregnancy outcome. Cochrane Database Syst Rev.

16(3): CD006593. doi: 10.1002/14651858.CD006593.pub2.

26. Osman, O. and Elghazaly, M. (2014). Can Vaginal Washing Fluid Urea, Creatinine and Qualitative β-

hCG Diagnose Suspected Premature Rupture of Membranes? Open Journal of Obstetrics and

Gynecology, 4, 967-972.

27. Phocas, I., Sarandakou, A., Kontoravdis, A., Chryssicopoulos, A., Zourlas, P. A. (1989). Vaginal fluid

prolactin: a reliable marker for the diagnosis of prematurely ruptured membranes. Comparison with

vaginal fluid alphafetoprotein and placental lactogen. Eur J Obstet Gynecol Reprod Biol., 31, 133-

141.

28. Rosemond, R. L., Lombardi, S. J. and Boehm, F. H. (1990). Ferning of amniotic fluid contaminated

with blood. Obstet Gynecol., 75, 338–340.

29. Shahin, M. and Raslan, H. (2007).Comparative Study of Three Amniotic Fluid Markers in Premature

Rupture of Membranes: Prolactin, Beta Subunit of Human Chorionic Gonadotropin, and Alpha-

Fetoprotein. Gynecol Obstet Invest., 63, 195-199.

30. Simhan, H. N., Caritis, S. N., Krohn, M. A. and Hillier, S. L. (2005). The vaginal inflammatory

milieu and the risk of early premature preterm rupture of membranes. Am J Obstet Gynecol., 192,

213-218.

31. Wiberg-Itzel, E., Cnattinqius, S. and Nordstrom, L. (2005). Lactate determination in vaginal fluids: a

new method in the diagnosis of prelabor rupture of membranes. BJOG., 112, 754-758.

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