Evaluation of fetal fibronectin rapid bedside test as a predictor of preterm labour: a prospective study

Background: Preterm birth defined as birth before 37 weeks of gestation is a significant public health issue. Identification of patients at risk of preterm labour while ruling out those who are not is a fundamental but challenging goal for clinicians. This study was done to evaluate bed side dipstick test for detecting fetal fibronectin in cervico-vaginal secretions as a predictor of preterm delivery in symptomatic and asymptomatic high risk group.Methods: This was a hospital based prospective, double blinded study. We enrolled 100 pregnant women presenting with or without symptoms of preterm delivery, between 20 and 35 weeks of gestation. A rapid bed side dipstick test was performed to detect FFN in cervico-vaginal secretions of all enrolled women (symptomatic and asymptomatic high risk women) and results were evaluated for prediction of preterm labour. Qualitative data were analyzed by using Chi-square and Fisher’s exact test and quantitative data were analyzed by using unpaired Student’s t test and Mann-Whitney test. P value < 0.05 was considered significant.Results: In symptomatic group sensitivity, specificity, PPV and NPV of FFN test in predicting delivery within 48 hours, 7days 14days and preterm delivery was 100%, 63.2%, 46.2%, 100%; 100%, 72.7%, 65.4%, 100%; 100%, 75%, 69.2%, 100%; 80%, 76%, 76.9%, 79.2% respectively. In asymptomatic high risk group, sensitivity, specificity, PPV and NPV of FFN test in predicting preterm delivery (<37weeks) was 0%, 87.5%, 0%, 77.8%.Conclusions: The high negative predictive value may be of value in avoiding unnecessary interventions with potentially hazardous medications and identifying symptomatic women who are not in true labour and also allaying anxiety of asymptomatic high risk women.

Parto pretérmino: causas y medidas de prevención

Preterm birth is the final common pathway of a series of different physiopathological processes, so it is considered a syndrome. Spontaneous preterm birth represents two thirds of preterm deliveries. Prevention can be primary or secondary, and is basically focused on prediction, which is currently done by risk calculators that combine medical history, cervical length and fetal fibronectin. Vaginal progesterone reduces the rate of spontaneous preterm birth to 35-40%, if used from week 16 through week 34.

El parto pretérmino es la vía final común de una serie de procesos fisiopatológicos diferentes, por lo que constituye un síndrome. El parto pretérmino espontáneo representa las dos terceras partes del parto pretérmino. Su prevención puede ser primaria o secundaria, y se centra básicamente en la predicción, la que actualmente se realiza mediante calculadoras de riesgo que combinan factores de historia clínica, longitud cervical y fibronectina fetal. La progesterona vaginal reduce la tasa de parto pretérmino espontáneo en 35 a 40%, si se administra desde las 16 hasta las 34 semanas.

El parto pretérmino: herramientas predictivas y preventivas en la práctica clinica / Preterm birth: predictive and preventive tools in clinical practice

Despite advances in both neonatal care and our understanding of the pathophysiology of the condition as a whole, preterm birth is a phenomenon that continues to have significant impact globally. It remains the leading cause of perinatal morbidity and mortality worldwide, and the prevalence is increasing. Not only does it carry significant social cost, preterm birth places huge economic burden on the healthcare system. It is increasingly recognised that preterm birth is a multifactorial syndrome, rather than a single condition and we have seen a number of exciting advances in predictive and preventative tools for clinical practice. The ability of quantitative fetal fibronectin to predict spontaneous preterm birth in both high and low risk women has been one of these recent promising developments. Exploration continues into the potential for quantitative fetal fibronectin to be used in synergy with transvaginal ultrasound measurement of cervical length to improve predictive accuracy. Developments focus on enabling clinicians to predict risk at the point of care. Research continues to explore cervical cerclage, progesterone and the Arabin pessary as prophylactic interventions for women at risk of preterm birth, with increasing evidence for their potential role. Latest exploration of reactive management for imminent preterm birth is altering our clinical approach and is likely to improve outcomes. This review article will discuss some of the recent developments we have seen in this exciting area

A pesar de los avances en la atención prenatal y en la comprensión de la fisiopatología del cuadro como un todo, el parto pretérmino es un fenómeno que continúa provocando un impacto significativo global. Continúa como la causa principal de morbilidad y mortalidad perinatal en todo el mundo y su prevalencia está en aumento. No solamente conlleva un costo social significativo, sino que el parto pretérmino produce una carga económica importante para el sistema de salud. Cada vez más, hay datos que indican que el parto pretérmino es un síndrome multifactorial, más que un cuadro único y nosotros documentamos un gran número de avances en las herramientas predictivas y preventivas en la práctica clínica. Uno de estos avances más recientes es la capacidad de la fibronectina fetal cuantitativa para predecir un parto pretérmino espontáneo, tanto en mujeres de alto riesgo como de bajo riesgo. La investigación continúa hacia el uso potencial de la fibronectina fetal cuantitativa en sinergia con la medición de la longitud cervical por ecografía transvaginal para mejorar la precisión predictiva. Los avances están dirigidos a que los clínicos puedan predecir el riesgo en el lugar de atención. Las investigaciones continúan con la evaluación del cerclaje cervical, la progesterona y el pesario de Arabin como intervenciones profilácticas para las mujeres en riesgo de parto pretérmino, con pruebas crecientes para su papel potencial. Las exploraciones ulteriores con terapia reactiva para el parto pretérmino inminente alteran nuestro enfoque clínico y probablemente mejoren los desenlaces clínicos. Esta revisión analizará algunos de los avances recientes observados en esta área apasionante

Clinical Value of Combination Detection of Inhibin A, Progesterone and Fetal Fibronectin in Predicting the Outcome of Threatened Abortion / 医学研究杂志

Objective To study the clinical value of combination dection of inhibin A,progesterone and fetal fibronectin in predicting the outcome of threatened abortion.Methods One hundred and seventy patient with symptoms of threatened abortion were selected as the object of this study.After miscarriage treatment,75 patients continued the pregnancy as the threatened abortion group and 45 patients miscarriage after miscarriage treatment as the abortion group,another 50 normal pregnant women at same period in our hospital were as the control group.Inhibin A,progesterone and fetal fibronectin were detected and compared between the three groups.Results The inhibin A and progesterone levels increased in turn from abortion group,threatened abortion group to normal pregnancy group.fFN positive rates were lower in turn.The difference were statistically significant (P ＜ 0.05).The area under the ROC curve (AUC) of inhibin A,and progesterone levels fFN positive rate for prediction of threatened abortion were 0.899,0.866,0.785,while the AUC of the combine that three index was 0.944.The sensitivity of the combined detection was 92.04％,the specificity was 89.17％,accuracy was 87.95％,positive predictive value was 98.45％,negative predictive value was 89.38％,and Youden index was 0.812.Conclusion Combined detection of inhibin A,progesterone and fetal fibronectin in predicting the outcomes of threatened abortion of pregnant women have a better predictive value than single index,it can enhance the accuracy,specificity and accuracy of forecasts.

Clinical Value of Combination Detection of Inhibin A, Progesterone and Fetal Fibronectin in Predicting the Outcome of Threatened Abortion / 医学研究杂志

Objective To study the clinical value of combination dection of inhibin A,progesterone and fetal fibronectin in predicting the outcome of threatened abortion.Methods One hundred and seventy patient with symptoms of threatened abortion were selected as the object of this study.After miscarriage treatment,75 patients continued the pregnancy as the threatened abortion group and 45 patients miscarriage after miscarriage treatment as the abortion group,another 50 normal pregnant women at same period in our hospital were as the control group.Inhibin A,progesterone and fetal fibronectin were detected and compared between the three groups.Results The inhibin A and progesterone levels increased in turn from abortion group,threatened abortion group to normal pregnancy group.fFN positive rates were lower in turn.The difference were statistically significant (P ＜ 0.05).The area under the ROC curve (AUC) of inhibin A,and progesterone levels fFN positive rate for prediction of threatened abortion were 0.899,0.866,0.785,while the AUC of the combine that three index was 0.944.The sensitivity of the combined detection was 92.04％,the specificity was 89.17％,accuracy was 87.95％,positive predictive value was 98.45％,negative predictive value was 89.38％,and Youden index was 0.812.Conclusion Combined detection of inhibin A,progesterone and fetal fibronectin in predicting the outcomes of threatened abortion of pregnant women have a better predictive value than single index,it can enhance the accuracy,specificity and accuracy of forecasts.

Curative effect between ritodrine hydrochloride and magnesium sulfate treated with threatened premature labor and its effect to fetal fibronectin / 中国基层医药

Objective To discuss curative effect between ritodrine hydrochloride and magnesium sulfate treated with threatened premature labor and its effect to fetal fibronectin .Methods 368 cases threatened premature labor puerperants were selected and randomly divided into the ritodrine hydrochloride treatment group ( short for obser-vation group) and magnesium sulfate treatment group (short for control group),The two group puerperants′curative effect,changes of fetal fibronectin positive rate and safety evaluation were observed .Results Compared with the con-trol group,the observation group′s medicine effect time ,treatment failure proportion obviously decreased;prolongation pregnancy days,treatment success proportion obviously increased ,the differences all had statistical significances (t=103.4,9.6,χ2 =12.0,all P0.05);after the treatment,the observation group′s fFN positive rates was 28.26%,wich of the control group was 42.39%,compared the two groups′fFN positive rates,the observa-tion group obviously decreased ,the differences had statistical significances (χ2 =8.0,P <0.05).The observation group′s untoward effect rate was 1 9 .5 7%, which was lower than that of the control group (χ2 =4 .8 , P<0 .0 5 ) .Conclusion Ritodrine hydrochloride treated with threatened premature labor not only can get good treatment effect , shorten medicine effect time ,prolong pregnancy days;but also can obviously decrease fetal fibronectin positive rate , which has good safety ,and is suitable for clinical application .

The value of corticotropin-releasing hormone and fetal fibronectin in predicting premature delivery / 中国综合临床

ObjectiveTo study the value of plasma corticotropin-releasing hormone (CRH) and the fetal fibronectin (fFN) in vaginal secretions and cervical length in predicting preterm labor.MethodsThe plasma CRH levels and fFN levels in vaginal secretions from 24 -37 weeks pregnant woman checked up in our hospital from Dec.2009 to Dec.2010 were detected by ELLISA method.The changes of these three indexes were observed with the pregnant time and were analyzed according to different pregnancy outcomes.Results Among the 112 cases of pregnant women,premature delivery in 54 cases,full-term birth 58 cases.At the 24 week of pregnancy,there were significant difference on the cervical length( [2.8 ±0.4]cm vs [3.3 ±0.5]cm,t =3.254,P =0.021 ) between premature delivery group and full-term birth group.At the 28 - 30 week,31 -32 week,33 - 34 week,35 - 36 week,the CRH were ( 162.33 ± 16.49 ) ng/L,(60.01:±: 14.56) ng/L;(352.12 ±61.01 )ng/L,( 118.04 ±53.74)ng/L; (364.55 ±56.71 )ng/L,( 122.95 ±71.41 )ng/L; (372.78 ±149.89)ng/L,(124.00 ± 19.05 )ng/L respectively in premature delivery group and full-term birth group,and there were significant differences on CRH at the four different pregnant time(t =3.687,6.875,8.652,8.524,respectively,P ＜ 0.05 ).It shows better sensitivity ( 97.92％ ),specificity ( 90.00％ ),positive predictive value(95.92％ ) and negative predictive value(94.73％ ) in predicting premature delivery by detection of CRH,fFN combined with cervical length.ConclusionDetection of plasma CRH,fFN combined with cervix length measurement can improve the predictability of premature and provide a good,reliable clinical basis for the early diagnosis and treatment for preterm premature.

Prediction of Preterm Birth by Using Qualitative Fetal Fibronectin Test Combined with C-reactive Protein / 대한산부인과학회잡지

OBJECTIVE: The qualitative test of fibronectin of the cervices and vaginae as well as the C-reactive protein test of pregnant mothers with symptoms of preterm labor were performed in an attempt to examine clinical validity of these factors as predictable elements of preterm delivery. METHODS: This prospective study was conducted on ninety (90) single pregnancies of gestational age from 24 weeks and 1 day to 34 weeks and 6 days admitted to the hospital with symptoms of preterm labor, which occurred in the period from October 1, 1999 through March 31, 2001. Among these pregnant women, those with a uterine contraction rate of 4 per hour or greater and uterine dilatation of less than 3 cm without PROM were used as the subjects. The qualitative test of fetal fibronectin (ROM check, Adeza Biochemical, USA) of the cervices and vaginae as well as the C-reactive protein test by means of latex agglutination method using maternal blood were performed on these subjects. Of the 90 mothers that participated in this study, 15 dropped out and 75 underwent the qualitative test of fetal fibronectin and C-reactive protein test. The results of each test and the combined tests of both at preterm delivery (1) within 1 week, (2) prior to 34 weeks and (3) prior to 37 weeks were compared and analyzed. RESULTS: 1. 22.4% (15/67) resulted in preterm delivery prior to 34 weeks while 48.0% (36/75) ended up with preterm delivery prior to 37 weeks. 2. In predicting preterm delivery within 7 days and prior to 37 weeks after the test, the fetal fibronectin and C-reactive protein qualitative test were statistically insignificant. The combined tests of both fetal fibronectin and C-reactive protein were statistically insignificant in predicting preterm delivery within 7 days (Odds ratio of 4.2; 95% CI 0.7-23.3 p=0.199) and prior to 37 weeks (Odds ratio of 5.3; 95% CI 0.6-48.3 p=0.116). 3. In predicting preterm delivery prior to 34 weeks, fetal fibronectin and C-reactive protein qualitative test were insignificant statistically. Nevertheless, these two tests in combination showed a statistical significance for preterm delivery prior to 34 weeks: It showed a sensitivity of 26.7% (4/15), a specificity of 95.6% (43/45), a positive predictability of 66.7% (4/6), and negative predictability of 79.6% (43/53) [Odds ratio of 7.8; 95% CI 1.3-48.3, p=0.03]. CONCLUSION: Specificity and positive predictive value improved when the combined fetal fibronectin and C-reactive protein tests in pregnancies with symptoms of preterm labor were performed for preterm delivery before 34 weeks. Consequently, this is a clinically valid predictor of preterm delivery before the 34th week.

Clinical Efficacy of Cervicovaginal Fetal Fibronectin in Induction of Labor / 대한산부인과학회잡지

OBJECTIVE: To determine whether the presence of fetal fibronectin in the cervicovaginal secretion could be used as a clinical marker to predict the outcome of labor induction. METHODS: The study group comprised 58 term pregnant women with intact amnionic membranes, 44 without labor and 14 with irregular labor. All patients had been admitted for induction of labor during Sept. 1, 1999 to Dec. 31, 1999 at the Department of Obstetrics and Gynecology of Yeungnam University Hospital. Fetal fibronectin was assayed with the cervicovaginal secretion. We analyzed the variables of labor outcome by the presence (positove) or absence (negative) of fetal fibronectin and the modified Bishop score. RESULTS: Cervicovaginal fetal fibronectin was detected in 75.0% (33/44) of the women without labor and 85.7% (12/14) with irregular labor, and 76.3% (29/38) with Bishop score 4 or less and 80.0% (16/20) with score 5 or above. There was no statistical differences in the positive rate of fetal fibronectin between the women without labor and those with irregular labor, and the women with Bishop score 4 or less and those with Bishop score 5 or above, respectively. The mean oral PGE2 tablets used for cervical ripening, the mean time interval from the beginning of labor induction to delivery, and the mean cesarean delivery rate were 1.97+/-2.56 tabs and 3.12+/-2.42, 10.12+/- 6.56 hours and 13.88+/-6.14, and 20.0% and 38.4%, in the women with positive fetal fibronectin and those with negative respectively, and 1.83+/-2.50 and 2.42+/-2.60, 10.11+/-7.17 hours and 11.28+/-6.26 hours, and 10.0% and 31.6% in the women with Bishop score 5 or above and those with Bishop score 4 or less, respectively. There were no statistical differences in the mean values between the women with positive and negative fetal fibronectin, and between Bishop score 5 or above and Bishop score 4 or less, respectively. There were no statistical differences in the mean oral PGE2 tablets used for cervical ripening (2.00+/- 2.65 vs. 4.40+/-1.82) and the mean time interval from the beginning of labor induction to delivery (10.11+/- 7.53 vs. 16.17+/-5.38), between the women with positive fetal fibronectin and Bishop score 5 or above and those with negative fetal fibronectin and Bishop score 4 or less, respectively. However, the cesarean delivery rate was significantly lower in the women with positive fetal fibronectin and Bishop score 5 or above than those with negative fetal fibronectin and Bishop score 4 or less (6.3% vs 44.4%, p=0.040). CONCLUSION: The assesment of cervicovaginal fetal fibronectin and Bishop score could be useful in predicting the success or failure of labor induction. But it was not helpful to predict the easiness of labor induction by the presence or absence of fetal fibronectin in the cervicovaginal secretion and/or modified Bishop score.

Prediction of Labor in Term Pregnancy Ising Fetal Fibronectin and Transvaginal Ultrasonography / 대한주산의학회잡지

OBJECTIVE: We performed the transvaginal ultrasonographic evaluation of uterine cervix and fetal fibronectin in cervicovaginal secretions in women after 37 complete weeks of gestation to predict the onset of labor. METHODS: Total 80 primiparous or multiparous women were divided into two groups on the duration between evaluation and onset of labor. The biometric analysis of uterine cervix(cervical index, endocervical length, funneling, funnel length and width) was done by transvaginal ultrasonography. The cervicovaginal fetal fibronectin was measured by fetal fibronectin immunoassay (ELISA kit, Adeza Biochemical, USA). The efficacy of these method was analyzed with Pearson chi-square test, receiver-operator characteristic curves, and multiple logistic regression test. RESULTS: 1) There were no significant differences in clinical characteristics between two groups. 2) Group 1(onset of labor within 7 days after evaluation) showed significantly shorter endocervical length(Group 1: 2.33+/-0.75cm,Group 2: 2.93+/- 0.42cm, p=0.013), higher value of cervical index(Group 1: 1.27+/-0.67, Group 2: 0.62+/-0.34, p=0.008) and higher level of fetal fibronectin(Group 1: 98.65+/-11.34ng/ml, Group 2: 13.37+/- 2.7ng/ml, p=0.004). 3) The ROC curve analysis showed that a level of endocervical length 0.7, fetal fibronectin> 60ng/ml had the diagnostic performance in predicting group 1. Fetal fibronectin level in cervicovaginal secretion> 60ng/ml showed the highest diagnostic index in predicting the onset of labor within 7 days(p<0,001, odds ratio=21.3). CONCLUSION: Cervicovaginal fetal fibronectin predicts delivery within 7 days more accurately than cervical index, endocervical length. Combine use of these tests improve the diagnostic efficiency and allowed prediction of onset of labor, identifying a subgroup of patients who may require aggressive treatment.

The Clinical Usefulness of Cervicovaginal Fetal Fibronectin as a Prediction of the Time of Induction / 대한산부인과학회잡지

OBJECTIVES: Fibronectin is a high-molecular-weight glycoprotein found in the plasma and extracellular matrix. The presence of fetal fibronectin in cervicovaginal secretion of pregnant women during the second and the third trimester has been suggested as a means of identifying women in preterm labor who be delivered prematurely. Therefore, our purpose was to determine the clinical efficacy of the presence of fetal fibronectin in cervicovaginal secretion of patient in full term as biochemical predictor of Time of Induction. METHODS: Fetal fibronectin was obtained at external os and posterior vaginal fornix in 30 women in full term who had no uterine contraction with intact membrane. The cervix was assessed by digital vaginal examination and scored with a modified Bishop score. RESULTS: There was a good correlation in delivery time after induction between the fetal fibronectin and the modified Bishop score (r=0.695,P<0.005) CONCLUSION: The presence of fetal fibronectin is better than Bishop score that is dependent on clinical experience as biochemical predictor of Time of Induction.

The Clinical Effcacy of C-reactive pretein and Fetal Fibfonectin in patients with Preterm Labor and Intact Membranes / 대한주산의학회잡지

OBJECTIVE: To evaluate the role of C-reactive protein and fetal fibronectin for patients with preterm labor and intact mxmbranes. STUDY DESIGN: The study group was comprised of sixty patients who presented to the Taegu Fatima Hospital between 24-36 gestational weeks who had a diagnosis of preterm labor. The study group underwent assay of C-reactive protein in the matemal serum, and fetal fibronectin from the external os and posterior fomix of the vagina by means of polyester fiber swabs. The study group was categorized to four groups according to the results of CRP and fetal fibronectin, that is 28 cases of CRP(-)/fetal fibronectin(-); group I, 12 cases of CRP(+)/fetal fibronectin (-); groupII, 9 cases of CRP(-)/fetal fibronectin(+); groupIII, 11 cases of CRP(+)/fetal fibronectin(+): grouplV, and the controls were 12 women without preterm labor. Outcome measures were occurrence of preterm delivery, the admission-to-delivery interval, matemal age and parity, fetal body weight, 1min/5min Apgar score, perinatal morbidity and mortality etc. Statistical analyses were performed by means of ANOVA test and Dunnett's t-test. RESULTS: The prevalence of study group were group I 46.7%, group II 20%, group III 15% and group IV 18.3%. There were no significant difference of matemal age, parity and gestational weeks at admission between study group and control group, but in all study group the admission to delivery interval was significantly shorter than that of control group. Analysis indicated also no significant difference of maternal hemoglobin between study group and conuol group but white blood cell count of group II and IV were significantly higher than that of control group. In perinatal outcomes, the mean birth weight and 1 minute Apgar score of study group except group I were significantly lower than those of control group but 5minutes Apgar score was lower only in group IV compared with control group. Perinatal morbidity and mortality of study group were higher than those of control group except group I. This study group was designed to compare the diagnostic performance of cervical fibronectin and of the serum CRP levels. The sensitivity and specificity of fetal fibronectin as a test to predict of preterm labor were 80% and 90%, which were slightly higher than those of CRP(70%, 78%). CONCLUSION: Both positive cervicovaginal fetal fibronectin and positive C-reactive protein in women with preterm uterine contraction can help identify the pregnancies at risk and to select proper management protocol.

The Usefulness of Fetal Fibronectin as a Diagnostic Method of Preterm Ruptere of Membrane / 대한주산의학회잡지

OBJECTIVE: The purpose of this study was to evaluate the fetal fibronectin as a diagnostic method of preterm rupture of membanes and its clinical usefulness compared with standard tests. STUDY DESIGN: Seventy-eight women who had recieved antenatal care and complained of fluid leakage prior to 37 weeks were enrolled in this study. Standard tests-vaginal peculum examination, Nitrazine test, transabdominal sonography-were perfomed. Rupture of membranes was diagnosed if any two of the standard tests were positive. Fetal fibronectin in posterior vaginal fornix was determined qualitatively by ROM kit (Adeza Biochemical, Sunnyvale, USA). RESULTS: The sensitivity of fetal fibronectin for prediction of rupture of membranes in the women who complained of fluid leakage was 90.6% and its specificity, positive and negative predictive value were 65.7%, 76.4% and 85.1% respectively. 12 women were not diagnosed as rupture of membrane on standard tests but were positive for fetal fironectin. CONCLUSION: Fetal fibronectin would be a useful diagnotic method for rupture of membranes, especially in the women who complained of fluid leakage but not diagnosed by standard tests.