|Year : 2018 | Volume
| Issue : 2 | Page : 139-144
Vaginal fluid prolactin in cases of suspected premature rupture of fetal membranes
Mahmoud E.A. Donia, Gamal M Hashish
Department of Obstetric and Gynacology, Shebin El-Kom Teaching Hospital, Menoufia, Egypt
|Date of Submission||03-Aug-2017|
|Date of Acceptance||15-Oct-2017|
|Date of Web Publication||17-Aug-2018|
Dr. Mahmoud E.A. Donia
Department of Obstetric and Gynacology, Shebin El-Kom Teaching Hospital, Menoufia, 32511
Source of Support: None, Conflict of Interest: None
Objectives The aim of this study was to evaluate vaginal fluid prolactin (PRL) as a diagnostic tool in cases of suspected premature rupture of fetal membranes and to get a cutoff value of PRL level for the definitive/diagnosis of premature rupture of membranes (PROM).
Backgrounds Preterm PROM refers to a patient who is before 37 weeks’ gestation and has presented with rupture of membranes (ROM) before the onset of labor. Spontaneous PROM is ROM after or with the onset of labor. Prolonged PROM is any ROM that persists for more than 24 h and before the onset of labor.
Patients and methods This case–control study was performed on 150 pregnant women attending casualties and outpatient clinics at Shebin El-Kom Teaching Hospital. The study included three groups: group 1 included 50 women with suspected PROM; group 2 included 50 women with definitive PROM; and group 3 included 50 healthy pregnant women as a control group. All study participants were subjected to full history, examination, ultrasonography, collection of 3 ml of vaginal fluid, and measurement of PRL concentration.
Results There were high statistically significant differences between women of the three groups concerning amniotic fluid index and cervicovaginal PRL concentration (P=0.001). Receiver operating characteristic curve was constructed for vaginal PRL concentration as a predictor of PROM. Vaginal PRL concentration is a good predictor of PROM (P=0.001).
Conclusion Vaginal fluid PRL can be used in suspected cases of ROM; the cutoff value was 4.38 ng/ml and vaginal fluid PRL is a simple, cheap, rapid, and reliable test.
Keywords: fetal membranes, preterm premature rupture of membranes, prolactin, vagina
|How to cite this article:|
Donia ME, Hashish GM. Vaginal fluid prolactin in cases of suspected premature rupture of fetal membranes. Benha Med J 2018;35:139-44
| Introduction|| |
Preterm premature rupture of membranes (PROM) refers to a patient who is before 37 weeks’ gestation and has presented with rupture of membranes (ROM) before the onset of labor. Spontaneous PROM is ROM after or with the onset of labor. Prolonged ROM is any ROM that persists for more than 24 h and before the onset of labor . For over 70 years, there has been controversy among healthcare professionals about the optimal approach to clinical assessment and diagnosis of prematurely ruptured membranes. In most cases, membrane rupture can be confirmed by documenting amniotic fluid leakage from the cervical os with visualization of pooling in the posterior vaginal fornix .
Previable ROM also can lead to potter’s syndrome, which results in pressure deformities of the limbs and face, and pulmonary hypoplasia. The incidence of this syndrome is related to the gestational age at which rupture occurs and to the level of oligohydramnios .
The occurrence of fetal membrane rupture during the canalicular phase of fetal lung development, and subsequent oligohydramnios, carries a specific risk of pulmonary hypoplasia even if a prolonged latency period is achieved. The greatest risk of pulmonary hypoplasia is observed if PROM occurs at less than 20 weeks’ gestation, with a rate of 50% reported among neonates who subsequently delivered at more than 24 weeks’ gestation, although pulmonary hypoplasia may occur with PROM up to 26 weeks’ gestation .
Respiratory distress syndrome due to hyaline membrane disease is the greatest threat to the fetus when PROM occurs before term. Extremely wide variations are evident in the incidence of PROM associated respiratory distress syndrome, which occur in 9–81% of newborn infants and is the cause of 28–70% of neonatal deaths .
The traditional minimally invasive gold standard for diagnosis of PROM relies on clinician’s ability to document three clinical signs on sterile speculum examination: visual pooling of clear fluid in the posterior fornix of the vagina or leakage of the fluid from the cervical os; an alkaline pH of the cervicovaginal discharge, which is typically demonstrated by nitrazine paper; and/or microscopic ferning of the cervicovaginal discharge .
The aim of this study was to evaluate vaginal fluid prolactin (PRL) as a diagnostic tool in cases of suspected premature rupture of fetal membranes and to get a cutoff value of PRL level for the definitive/diagnosis of PROM.
| Patients and methods|| |
The present study was a prospective case–control study; it was conducted at Shebin El-Kom Teaching Hospital during the period from August 2015 to October 2016.
Group l consisted of 50 cases of pregnant women with suspected PROM based on history of watery vaginal discharge but normal amniotic fluid index (AFI) by ultrasound, suspicious speculum examination, or leakage of fluid from vagina.
Group 2 consisted of 50 pregnant women with definitive PROM based on history of watery vaginal discharge plus decreased AFI, plus positive speculum examination, and pooling of amniotic fluid from vagina.
Group 3 consisted of 50 healthy pregnant women as a control group, with no previous complaints or complications.
Inclusion criteria were single viable pregnancy between 28 and 42 weeks, and agreement to participate in the study (consent).
Exclusion criteria were multiple pregnancies, presence of fetal anomalies, intrauterine fetal death, visible blood in vaginal secretions, use of vaginal medications, sexual intercourse in the previous night, meconium in the amniotic fluid, any medical history or drugs related to maternal PRL level, regular uterine contractions, and refusal to participate in the study.
After a verbal consent, all study participants were subjected to the following: informed consent, and full history taking, including age, parity, last menstrual period, and history of vaginal fluid leakage. The study was approved by ethical committee of Menoufia Faculty of Medicine.
General and abdominal examinations were done, including vital signs to exclude chorioamnionitis.
Patients lay in lithotomy position in good illumination, and sterile speculum examination was done to assess leakage of fluid from vagina. Ultrasonography was done to assess AFI and exclude multiple pregnancies and fetal anomalies. Gestational age was determined based on the first day of last menstruation period in reliable cases, or one ultrasound in less than 14 weeks or two ultrasound documents between 14 and 24 weeks of pregnancy. Sterile speculum examination was done in which 5 ml of sterile saline was washed into the posterior fornix by means of a sterile syringe. Results were registered as positive, negative, or suspicious.
A volume of 3 ml of the fluid was collected by means of a syringe and sent to the laboratory. Vaginal washing fluid PRL sampling was performed. The study participants were followed up until delivery.
As regards assessment of neonatal well-being, APGAR score was used at 1 and 5 min after delivery. At 1 min, scores greater than 6 indicate normal newborn and scores less than 6 indicate fetal distress (asphyxia), which needs resuscitation. Distressed newborn score of 0–3 indicates severe asphyxia and a score of 4–6 indicates mild asphyxia.
The score is determined again at 5 min after delivery.
A low score after 5 min indicates increased risk of infant mortality and morbidity.
The Apgar score entails five parameters − appearance, pulse, grimace, activity, and respiration, where every parameter takes a score of 0, 1, and 2 according to pediatrician assessment .
Vaginal fluid prolactin measurement
Three milliliters of sterile normal saline was washed into the posterior fornix of the vagina while the patient is in lithotomy position and then it was aspirated with the same syringe and sent to the laboratory. Samples were spun, separated, and frozen at −20°C until batch analysis was performed. PRL concentration was measured by ELISA kit (DI source, Louvain-la-Neuve, Belgium) according to the manufacturer’s instructions.
| Results|| |
The study included three groups: group 1 (n=50) included women with suspected PROM (as diagnosed by visible pooling of liquor in the posterior fornix on Cusco speculum examination); group 2 (n=50) included women with definitive PROM; and group 3 (n=50) included healthy pregnant women as a control group ([Table 1]).
There was no statistically significant difference between women of the three groups concerning demographic data (P=0.44, 0.58), except for gestational age at recruitment, which exhibited a highly significant difference (P=0.001) ([Table 1]).
There were high statistically significant differences between women of the three groups concerning AFI and cervicovaginal PRL concentration (P=0.001) ([Table 2]).
|Table 2 Amniotic fluid index and cervicovaginal prolactin concentration in the three studied groups (n=50)|
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There were high statistically significant differences between women of the three groups concerning gestational age at delivery and fetal weight (P=0.001), significant differences concerning interval between presentation and delivery and APGAR score at 1 and 5 min, and a nonsignificant difference concerning the mode of delivery (P=0.022, 0.013, and 0.003) ([Table 3]).
|Table 3 Gestational age at delivery, mode of delivery, and neonatal outcomes in the three studied groups (n=50)|
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Receiver operating characteristic curve was constructed for vaginal PRL concentration as a predictor of PROM. Vaginal PRL concentration is a good predictor of PROM (P=0.001) ([Table 4]).
|Table 4 Receiver operating characteristic curve analysis for differentiation between confirmed premature rupture of membrane and suspected or no premature rupture of membrane using cervicovaginal prolactin concentration|
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There were nonsignificant correlations between cervicovaginal PRL concentration and the AFI in the three studied groups (P=0.53, 0.114, 0.104), but there was a high statistically significant correlation in all patients (n=150) (P=0.0001) ([Table 5]).
|Table 5 Correlation between cervicovaginal prolactin concentration and the amniotic fluid index|
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| Discussion|| |
In ∼8% of women with pregnancy at term, the fetal membrane rupture before labor begins, with same morbidity and mortality in developing and developed countries .
As the time between the ROM and the onset of labor (interval period) increases, so may the risk of maternal and fetal infection. Maternal infection occurs in about 3–15% of all cases of PROM and in 15–20% of these with chorioamnionitis .
Other complications that may be associated with PROM include umbilical cord prolapse, placental abruption, fetal distress, postpartum hemorrhage, and postpartum infection. For these reasons, many physicians recommend that labor be induced if the pregnancy is at term and labor does not begin spontaneously shortly after the membrane rupture .
The study was conducted to assess the reliability of the vaginal washing fluid PRL level assay for the diagnosis of PROM and to determine a diagnostic cutoff value.
The absence of a noninvasive, gold-standard test for the diagnosis of PROM has led to the search for alternative diagnostic methods.
In this context, studies related to the detection of biochemical markers in vaginal fluids that have high amniotic fluid concentration but low vaginal fluid concentration − for example fetal fibronectin, α-fetoprotein, PRL, β-human chorionic gonadotropin (β-hCG), and creatinine − have accelerated in recent years.
This study shows that group 3 (control group) and group 1 (suspected group) have more average liquor in comparison with group 2 (confirmed group), in which more than 82% are below average, with a high statistically significant difference in between where AFI in the three groups are 10, 5, and 10 in the suspected group of PROM, confirmed group, and control group, respectively.
The current study shows that group 2 (confirmed group of PROM) had higher levels of vaginal washing fluid PRL hormone compared with group 1 (suspected group), with a high statistically significant difference in between as regards values, which were 1.83±0.81, 21.19±4.22, and 0.50±0.17 for the suspected group of PROM, confirmed group, and control group, respectively.
In addition, this current study shows that the confirmed group of PROM had a higher level of vaginal washing fluid PRL level compared with the control group, with a statistically significant difference in between.
Also, this study shows that the suspected group of ROM had a higher level of vaginal washing fluid PRL level as compared with control, with a statistical difference in between them.
The results of this current study showed that validity of using vaginal washing PRL level for diagnosis of ROM by detecting cutoff value was 4.38 ng/ml.
As regards sensitivity, specificity, positive predictive value, and negative predictive value, they were in the same order (100, 100, 100, 100%) as regards diagnosis of PROM.
The present data suggest that maternal and fetal PRL levels do not differ significantly in normal and abnormal pregnancies. The decidua is the principal source of amniotic fluid PRL: the significantly lower levels of PRL in amniotic fluid of pregnancies complicated by hypertension or polyhydramnios are probably due to adverse effects of these conditions on the synthesis and release of PRL by deciduas .
A rapid rise in amniotic fluid PRL to reach a peak at 19 weeks (median level: 99–850 mU/l) was found. The pattern of increase of PRL in amniotic fluid is similar to, but occurs 2 weeks later than, that for insulin-like growth factor-binding protein-1, another major decidual product .
As the PRL concentration in amniotic fluid is always higher than in maternal serum, the vaginal washing fluid PRL test can be used even in the presence of vaginal bleeding .
These results are in keeping with results obtained from Buyukbayrak et al. .
Cutoff value of PRL in vaginal washing fluid for the diagnosis of ROM was found to be l.41 ng/ml by the receiver operating characteristic curve analysis, with 95% sensitivity, 78% specificity, 84% positive predictive value, 93% negative predictive value, and 87% accuracy.
Our study agrees with study conducted by Shahin and Rslan , who found that vaginal fluid concentrations of the three markers were significantly higher in women with ruptured membranes than women with intact membranes.
Shahin and Raslan  showed that vaginal fluid concentrations of three markers were significantly higher in the PROM group than in the control group. A cutoff value of 20.2 μIU/ml was proposed for PRL, and its sensitivity, specificity, positive predictive value, negative predictive value, and efficacy of PRL were 70, 76, 71.7, 74.5, and 73%, respectively.
Also, a study carried out by Kariman et al.  was in good agreement with our study; the purpose of this study was to determine the power of crevicovaginal fluid PRL in diagnosis of PROM.They stated that the cutoff value was 9.50 lU/ml for PRL. It was found that the diagnostic power including sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of vaginal fluid PRL were 87.30, 75.0, 75.80, 86.53, and 83.33%, respectively.
This study demonstrated that the measurement of vaginal fluid PRL is a reliable method for diagnosis of PROM.
In addition, Taheripanah et al.  diagnosed PROM in suspected patients by measurement of PRL and β-hCG) levels in vaginal washing in order to reduce perinatal mortality and morbidity. They concluded that the measurement of PRL and β-hCG levels in patients with suspected PROM can help in decision-making and treatment.
However, in contrast to our study, Huber and Bischof  assayed the amount of PRL, α-feto protein, and human placental lactogen in vaginal washing fluid in 19 women with intact membranes and 33 women who had ruptured membranes, and despite the higher concentration levels of the three markers in PROM group they concluded that measurement of these proteins in vaginal fluid could not be a suitable clinical test for diagnosis of PROM. The reason was the presence of considerable overlap between groups and a high rate of false positives.
| Conclusion|| |
Vaginal fluid PRL can be used in suspected cases of ROM to discriminate normal from abnormal; the cutoff value was 4.38 ng/ml and vaginal fluid PRL is a simple, cheap, rapid, and reliable test.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
El Khwad M, Stetzer B, Moore RM, Kumar D, Mercer B, Arikat S. Term human fetal membranes have a weak zone overlying the lower uterine pole and cervix before onset of labor. Biol Reprod 2005; 72:720–726.
Mercer BM. Preterm rupture of the membranes: diagnosis and management. Clin Perinatol 2004; 31:765–782.
Medina TM, Hill DA. Preterm premature rupture of membranes: diagnosis and management. Am Fam Physician 2006; 73:659–664.
McParland PC, Taylor DJ. Preterm prelabour rupture of the membranes. In: Booner J, Dinlop W, editors. Recent advances in obstetrics and gynaecology. London: Royal Society of Medicine Press Ltd; 2005. pp. 27–38.
Alexander JM, Cox SM. Clinical course of premature rupture of the membranes. Semin Perinatol 2006; 20:369–374.
Caughey AB, Robinsons JN, Norwitz ER. Contemporary diagnosis and management of preterm premature rupture of membranes. Rev Obstet Gynecol 2008; 1:11–22.
Huber JF, Bischof P. Are vaginal fluid concentrations of prolactin, alpha-fetoprotein and human placental Lactogen useful for diagnosing ruptured membranes? Br J Obetet Gynaecol 1983; 90:1183–1185.
Hanke K, Hart Z, Manz M, Bendiks M, Heitmann F, Orlikowsky T et al.
Pretem prelabour rupture of membranes and outcome of very low birth weight infants in the German Neonatal Network. PLoS One 2015; 10:e0122564.
Ibishi VA, IsJanovska RD. Prelabour rupture of membranes: mode of delivery and outcome. Open Access Mecedonium J Med Sci 2015; 3:237–240.
Kariman N, Hedayati M, Aval M. The role of vaginal fluid prolactin in diagnosis of premature rupture of membranes. Iran Red Crescent Med J 2012; 14:352–357.
Shahin M, Raslan H. Comparative study of three amniotic markers in premature rupture of membrane: prolactin, β-HCG. AFP Gynecol Obstet 2007; 63:195–199.
Taheripanah R, Zohreh D, Abas E. Diagnostic value of prolactin and B-HCG levels of vaginal fluid in diagnosis of premature rupture of membranes. J Shahid Sadoughi Univ Med Sci Health Serv 2009; 17:24–241.
Buyukbayrak EE, Turan C, Unal O. Diagnostic power of the vaginal washing-fluid prolactin assay as an alternative method for the diagnosis of premature rupture of membranes. J Maten Fetal Neonatal Med 2004; 15:120–125.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]