Fetal Fibronectin, Endotoxin, Bacterial Vaginosis and Cervical Length as Predictors of Preterm Birth and Neonatal Morbidity in Twin Pregnancies

Abstract

Objective To evaluate the predictive values of fetal fibronectin, bacterial vaginosis, endotoxin and cervical length for preterm birth (< 35 and < 37 weeks) and neonatal morbidity in twin pregnancies.Participants One-hundred and twenty-one women with twin pregnancies recruited into a prospective longitudinal study at three antenatal clinics in the southwest of Sweden.Methods Cervical or vaginal fluid was sampled and determined for fetal fibronectin (2 0.05 pg/mL was used as cutoff), endotoxin (2 100 pg/mL) and bacterial vaginosis (presence of clue cells) at two week intervals from 24 to 34 weeks of gestation. The cervical length was measured with transvaginal sonography at the same time intervals.Main outcome measures Occurrence of preterm birth (< 35 and < 37 weeks of gestation) and neonatal morbidity. ResultsAll positive fetal fibronectin samples obtained at screening between 24 and 34 weeks predicted birth < 35 weeks (RR 18.0; 95% CI 2-2-145.9). A positive fetal fibronectin at 28 weeks of gestation predicted delivery < 35 weeks (RR 6.3; 95% CI 2.6-15.1) with a sensitivity, specificity, positive and negative predictive value of 50-0, 92.0, 62.5 and 87.3%, respectively. An independent association between fetal fibronectin at 28 weeks and preterm birth (< 35 weeks) was verified with logistic regression (P = 0.03). A positive fetal fibronectin at 28 weeks of gestation predicted neonatal morbidity (RR 5.1; 95% CI 2.4-1 1.0) and a longer period of care at the neonatal intensive care unit. The predictive power of cervical sonography was generally low but cervical length (cutoff 5 33 mm) measured at 28 weeks of gestation was significantly associated with birth < 37 weeks (RR 2.2; 95% CI 1.1-4-2). The presence of endotoxin correlated to bacterial vaginosis, but these tests were not significantly related to preterm birth or neonatal morbidity.Conclusions Fetal fibronectin predicted preterm birth and neonatal morbidity in twin pregnancies. The predictive value of cervical length determinations was low. Endotoxin and bacterial vaginosis had no predictive power for preterm delivery in this study.

Cervicovaginal fetal fibronectin for the prediction of spontaneous preterm birth in multiple pregnancies: a systematic review and meta-analysis

“…Ten studies (67%) were performed in the United States [28, 29, 32, 33, 35–39, 41], and one each in Italy [27], Sweden [30], Brazil [31], United Kingdom [34], and France [40]. The sample size ranged from 29 [28] to 169 [36] in asymptomatic women and from 38 [38] to 87 [41] in symptomatic women.…”

“…The sample size ranged from 29 [28] to 169 [36] in asymptomatic women and from 38 [38] to 87 [41] in symptomatic women. Cervicovaginal fetal fibronectin was measured using enzyme-linked immunoabsorbent assay quantitative method (nine studies [28–30, 33, 35–39]), membrane immunoassay qualitative method (three studies [27, 31, 34]), and rapid TLi system qualitative method (one study [41]). Two studies [32, 40] did not report method for measuring fetal fibronectin.…”

Spontaneous Preterm Birth in Multiples

“…A Swedish study with 121 twin pregnancies reported that all patients with a positive fFN screening result between 24 and 34 weeks had a subsequent preterm birth before 35 weeks' gestation and that the predictive value was higher for fFN than cervical length. 32 One potential explanation for this discordance in results is that a positive FFN may be more predictive of a preterm birth as it is associated with both spontaneous preterm labor as well as PPROM, whereas a shortened cervical length has not been associated with preterm premature rupture of membranes in multifetal gestations. 33 A retrospective cohort study with routine fFN and cervical length screening for all twin gestations showed improved rates of antenatal corticosteroid administration within 7 days of delivery when both screening modalities were used to identify women at risk for preterm delivery.…”

Accuracy of cervico-vaginal fetal fibronectin test in predicting the risk of spontaneous preterm birth—a systematic review

“…Eight studies examined the use of fibronectin as a screening tool in low risk pregnancy and nine as a selective screening tool in high risk pregnancy. Most studies 75 Goldenberg (1996) 75 Goldenberg (1996) 75 Goldenberg (1996) 75 Chang (1997) 25 Nageotte (1994) 66 Oliveira (1998) 67 Morrison (1996) 40 Morrison (1996) 40 Goldenberg (2000) 77 Heath (2000) 45 Tolino (1996) 41 Goldenberg (1997) 76 Wennerholm (1997) 94 Goldenberg (1996) Tolino (1996) 41 Wennerholm (1997) 94 Hux (1995) 78 Overall (95% CI) were carried out during the second trimester or early in the third trimester. Meta-regression analysis showed the accuracy of the test did not depend on the method of testing, how often the test was done, classification of risk, or gestation at testing.…”

“…Metaregression analysis showed that the accuracy of the test did not depend on the method of testing, how often the test was done, or classification of risk. As for asymptomatic women, the accuracy of the in predicting sponGarcia (1999) 71 Greenhagen (1996) 72 Di Stefano (1999) 27 Zamora (2000) 73 Chang (1997) 25 Roubille (1999) 84 Nageotte (1994) 66 Nageotte (1994) 66 Bittar (1996) 23 Bittar (1996) 23 Nageotte (1994) 66 Oliveira (1998) 67 Nageotte (1994) 66 Leeson (1996) 61 Leeson (1996) 61 Krems (1995) 69 Goldenberg (2000) 77 Lockwood (1993) 80 Tolino (1996) 41 Lockwood (1993) 80 Tolino (1996) 41 Goldenberg (1997) 76 Wennerholm (1997) 94 Goldenberg (1996) 75 Hellemans (1995) 43 Crane (1999) 44 Faron (1997) 42 Hux (1995) 78 Inglis (1994) 79 Crane (1999) 44 Vercoustre (1996) Figure 9 shows the summary receiver operating characteristic curve for symptomatic women. Figures 10, 11, and 12 give details of individual results used to create the summary curve.…”