Quantitative fetal fibronectin to predict preterm birth in asymptomatic women at high risk.

OBJECTIVE: To evaluate the diagnostic accuracy of cervicovaginal fluid quantitative fetal fibronectin, measured by a bedside analyzer, to predict spontaneous preterm birth before 34 weeks of gestation. METHODS: We conducted a prospective masked observational cohort study of cervicovaginal fluid quantitative fetal fibronectin concentration in asymptomatic women at high risk of spontaneous preterm birth (n=1,448; 22-27 6/7 weeks of gestation) measured using a rapid bedside analyzer. The routine qualitative result (positive-negative) was made available to clinicians at the time of testing, but the quantitative result remained blinded until after delivery. RESULTS: Spontaneous preterm birth (less than 34 weeks of gestation) increased from 2.7%, 11.0%, 14.9%, 33.9%, and 47.6% with increasing concentration of fetal fibronectin (less than 10, 10-49, 50-199, 200-499, and 500 ng/mL or greater, respectively). A threshold of 200 ng/mL had a positive predictive value of 37.7 (95% confidence interval [CI] 26.9-49.4) with specificity 96% (95% CI 95.3-97.3). Women with a fetal fibronectin concentration of less than 10 ng/mL had a very low risk of spontaneous preterm birth at less than 34 weeks of gestation (2.7%), no higher than the background spontaneous preterm birth rate of the general hospital population (3.3%). The quantitative fetal fibronectin test predicted birth at less than 34 weeks of gestation with an area under the curve (AUC) of 0.78 (95% CI 0.73-0.84) compared with the qualitative test AUC 0.68 (95% CI 0.63-0.73). Quantitative fetal fibronectin discriminated risk of spontaneous preterm birth at less than 34 weeks of gestation among women with a short cervix (less than 25 mm); 9.5% delivered prematurely less than 10 ng/mL compared with 55.1% greater than 200 ng/mL (P<.001). DISCUSSION: Alternative risk thresholds (less than 10 ng/mL and greater than 200 ng/mL) improve accuracy when using quantitative fetal fibronectin measurements to define risk of spontaneous preterm birth. This is particularly relevant for asymptomatic women with a short cervix. LEVEL OF EVIDENCE: II.

Loss of progesterone receptor-mediated actions induce preterm cellular and structural remodeling of the cervix and premature birth.

A decline in serum progesterone or antagonism of progesterone receptor function results in preterm labor and birth. Whether characteristics of premature remodeling of the cervix after antiprogestins or ovariectomy are similar to that at term was the focus of the present study. Groups of pregnant rats were treated with vehicle, a progesterone receptor antagonist (onapristone or mifepristone), or ovariectomized on day 17 postbreeding. As expected, controls given vehicle delivered at term while rats delivered preterm after progesterone receptor antagonist treatment or ovariectomy. Similar to the cervix before term, the preterm cervix of progesterone receptor antagonist-treated rats was characterized by reduced cell nuclei density, decreased collagen content and structure, as well as a greater presence of macrophages per unit area. Thus, loss of nuclear progesterone receptor-mediated actions promoted structural remodeling of the cervix, increased census of resident macrophages, and preterm birth much like that found in the cervix at term. In contrast to the progesterone receptor antagonist-induced advance in characteristics associated with remodeling, ovariectomy-induced loss of systemic progesterone did not affect hypertrophy, extracellular collagen, or macrophage numbers in the cervix. Thus, the structure and macrophage census in the cervix appear sufficient for premature ripening and birth to occur well before term. With progesterone receptors predominantly localized on cells other than macrophages, the findings suggest that interactions between cells may facilitate the loss of progesterone receptor-mediated actions as part of a final common mechanism that remodels the cervix in certain etiologies of preterm and with parturition at term.

The value of combined cervical length measurement and fetal fibronectin testing to predict spontaneous preterm birth in asymptomatic high-risk women.

OBJECTIVES: To determine the value of the combined use of fetal fibronectin (fFN) testing and transvaginal ultrasound measurement of cervical length (CL) for prediction of preterm birth (PTB) in asymptomatic high-risk women. METHODS: One hundred and forty-seven asymptomatic women at high-risk of PTB were referred to specialist antenatal clinics and underwent CL and fFN testing over a 12-month period. Women had both tests undertaken between 22(+0) and 30(+0) weeks' gestation, on one or more occasions. RESULTS: In those who labored spontaneously (n = 132), positive fFN and CL ≤ 25 mm was associated with a 53% risk of PTB at  < 37(+0) weeks' gestation, compared to a 10% risk in those with a negative fFN and CL  >  25 mm. With a known CL, the addition of positive fFN yielded significant hazard ratios regardless of CL (CL  >  25 mm-HR 2.78, CL  ≤ 25 mm-HR 3.14, p < 0.05). The hazard ratios were insignificant when CL results were added to a known fFN. CONCLUSIONS: In high-risk asymptomatic women, fFN may be used as a primary screening tool with CL measurement being reserved for those with a positive fFN result. Further prospective studies are needed to confirm our findings.

Is dynamic cervical shortening during symptomatic contractions predictive of preterm delivery in patients with a normal baseline cervical length?

OBJECTIVE: The purpose of this study was to determine whether dynamic cervical change in symptomatic patients with a normal baseline cervical length (CL; >or=30 mm) is predictive of preterm delivery (PTD). METHODS: A prospective observational study was performed in 120 symptomatic patients between 23 and 34 weeks' gestation. Patients underwent standardized CL sonography with contraction monitoring, and CL measurements were recorded each minute for approximately 10 minutes. Initial and minimum CLs as well as the presence of dynamic change were assessed for prediction of PTD. RESULTS: Forty-seven patients (39.2%) had dynamic cervical change and delivered at a mean gestational age +/- SD of 37.1 +/- 2.7 weeks compared to 38.7 +/- 1.5 weeks for those without dynamic change (P < .01). A larger proportion of those with dynamic change delivered before 37 weeks (43% versus 15%; P < .01) and before 35 weeks (19% versus 0%; P < .01). Multivariable logistic regression analysis showed that dynamic cervical change was predictive of PTD, but not independently of the minimum CL. Statistical analyses were completed using the Student t test, chi(2) test, Fisher exact test, Wilcoxon rank sum test. and logistic regression as appropriate. CONCLUSIONS: Although symptomatic patients with a normal baseline CL who have dynamic shortening generally deliver at term, they appear to be at increased risk of PTD.

Impact of a 'rescue course' of antenatal corticosteroids: a multicenter randomized placebo-controlled trial.

OBJECTIVE: Previous studies using repetitive courses of antenatal corticosteroids (ACS) have demonstrated marginal or no benefit and concern over potential risk. No prior prospective or randomized studies have evaluated the option of a single rescue course of ACS on neonatal outcome. STUDY DESIGN: A multicenter randomized double-blind placebo-controlled trial was performed from May 2003 through February 2008 in 18 private (15) and university (3) medical centers. Patients with singletons or twins < 33 weeks who had completed a single course of ACS before 30 weeks and at least 14 days before inclusion, and were judged to have a recurring threat of preterm delivery in the coming week, were included. Patients were randomized to receive a single rescue course of betamethasone, 2 12-mg doses 24 hours apart, or placebo. Exclusion criteria included: premature rupture of membranes, advanced dilation (> 5 cm), chorioamnionitis, and other steroid use. RESULTS: In all, 437 patients were randomized (223 rescue steroid group and 214 placebo group). A total of 55% of patients in each group delivered at < 34 weeks. There was a significant reduction in the primary outcome of composite neonatal morbidity < 34 weeks in the rescue steroid group vs placebo (43.9% vs 63.6%; odds ratio, 0.45; 95% confidence interval, 0.27-0.75; P = .002) and significantly decreased respiratory distress syndrome, ventilator support, and surfactant use. Perinatal mortality and other morbidities were similar in each group. Including all neonates in the analysis (regardless of gestational age at delivery) still demonstrated a significant reduction in composite morbidity in the rescue course group (32.1% vs 42.6%, odds ratio, 0.65; 95% confidence interval, 0.44-0.97; P = .0034) and improvement in respiratory morbidities. CONCLUSION: Administration of a single rescue course of ACS before 33 weeks improves neonatal outcome without apparent increased short-term risk.

Quantitative fetal fibronectin screening in asymptomatic high-risk patients and the spectrum of risk for recurrent preterm delivery.

OBJECTIVE: We sought to determine whether a single quantitative vaginal fetal fibronectin (fFN) test at 24 weeks' gestational age (GA) can delineate the spectrum of risk of spontaneous preterm delivery (sPTD) in an asymptomatic high-risk population comprised of patients with a prior preterm birth. STUDY DESIGN: We performed a secondary analysis of a prospectively collected dataset in asymptomatic patients at high risk with singleton gestations who underwent quantitative fFN screening at 24 weeks. Data from 563 women with a history of preterm delivery (PTD) were available. The association between quantitative fFN concentrations collected at 24 weeks and subsequent GA at delivery was analyzed. RESULTS: The overall PTD rate < 34 weeks and < 37 weeks was 6.7% and 19.7%, respectively. In all, 497 of 563 patients (88%) at 24 weeks had an fFN level of 0 ng/mL. As the fFN concentrations increased, sPTD rates progressively increased. Compared with the fFN 0 ng/mL group, the relative risk for sPTD < 34 weeks was sequentially increased in each group, respectively: 2.42 (fFN 1-49 ng/mL; 95% confidence interval [CI], 0.76-5.66), 4.68 (fFN 50-199 ng/mL; 95% CI, 1.28-10.95), and 9.94 (fFN > 200 ng/mL; 95% CI, 2.90-19.67). Similar trends were seen between groups at different GAs from 32-37 weeks. CONCLUSION: In asymptomatic women with a prior PTD, quantitative fFN assessment at 24 weeks effectively delineates the risk of recurrent sPTD. Quantification of fFN may provide additional information regarding the spectrum of risk of subsequent sPTD than would be derived from the standard qualitative screen currently used.

Is transabdominal sonography of the cervix after voiding a reliable method of cervical length assessment?

OBJECTIVE: The purpose of this study was to assess the correlation and agreement between transvagi-nal and transabdominal cervical length measurement after bladder emptying as well as the feasibility of transabdominal sonography in cervical length screening. METHODS: This was a prospective cohort study involving 287 participants (14-34 weeks' gestation) from January to December 2003. After voiding, transabdominal and transvaginal cervical length measurements were obtained. The optimal trans-abdominal technique was established during an unblinded series of transabdominal and transvaginal cervical length measurements (n = 96). The same measurements were obtained in 191 participants under a blinded 2-sonographer protocol. The transabdominal cervical length cutoff to ensure 100% sensitivity in detecting a short cervix (