Reduction of circulating annexin A5 levels and resistance to annexin A5 anticoagulant activity in women with recurrent spontaneous pregnancy losses.

OBJECTIVE: We investigated whether levels of annexin A5, evidence for resistance to annexin A5 activity, and levels anti-annexin A5 antibodies might be altered in women with a history of recurrent spontaneous pregnancy losses. STUDY DESIGN: These annexin A5 parameters were assayed in 70 nonpregnant women with a history of > or = 3 recurrent spontaneous pregnancy losses (cases) and 50 women without adverse pregnancy history (control subjects). RESULTS: Cases had significantly lower plasma annexin A5 levels than control subjects (median, 4.7 ng/mL [range, 0.3-40.4 ng/mL] vs 6.7 ng/mL [range, 0.7-56.0]; P = .01), significantly reduced anticoagulant ratios (188% [range, 119%-279%] vs 238% [range, 159%-286%]; P < .0001), and reduced binding of annexin A5 to phospholipid (6.3 ng/aliquot phospholipid [range, 1.5-16.4 ng/aliquot phospholipid] vs 9.7 ng/aliquot phospholipid (range, 3.5-17.0 ng/aliquot phospholipid]; P = .0002). There were no significant differences in anti-annexin A5 antibody levels. CONCLUSION: Reduction of annexin A5 and interference with its anticoagulant and binding activities are associated significantly with a history of recurrent spontaneous pregnancy losses. These data support the concept of a significant role for annexin A5 in the maintenance of pregnancy.

The efficacy of sonographically indicated cerclage in multiple gestations.

OBJECTIVE: The purpose of this study was to determine the efficacy of sonographically indicated cerclage in multiple gestations with sonographic evidence of short cervical length (CL). METHODS: Between 1996 and 2002, all multiple gestations undergoing serial CL determinations in the second trimester were identified in 2 separate institutions. Cervical lengths were measured sonographically with transvaginal probes (4-8 MHz). Short CL was defined as a closed CL of 2.5 cm or less. When a short CL was identified before 24 weeks, the study group underwent sonographically indicated cerclage via the modified Shirodkar technique; control patients were placed on bed rest without surgical intervention. The primary outcome was incidence of spontaneous preterm birth before 32 weeks. The groups were compared with the Mann-Whitney U test and the Fisher exact test, with a 2-sided P<.05 used to define statistical significance. Odds ratios were calculated, and 95% confidence intervals were reported. RESULTS: A total of 414 sets of twin gestations and 92 sets of triplet gestations were identified. The median gestational age at delivery for twin gestations was 34.0 weeks for patients who received cervical cerclage and 34.4 weeks for patients with short cervix and no cerclage (P=.77). The median gestational age at delivery for triplet gestations was 34.1 weeks for patients who received cervical cerclage and 33.0 weeks for patients with short cervix and no cerclage (P=.21). There was no difference in the rate of spontaneous preterm delivery at fewer than 28, 30, 32, and 34 weeks or in the rate of preterm premature ruptured membranes. CONCLUSIONS: In our study of multiple gestations with short CL, sonographically indicated cerclage was not associated with a lower incidence of spontaneous preterm delivery compared with conservative management.

"Blind" vaginal fetal fibronectin as a predictor of spontaneous preterm delivery.

OBJECTIVE: To assess the accuracy of vaginal fetal fibronectin sampling without use of a sterile speculum examination as a screening test for predicting spontaneous preterm birth. METHODS: A historical cohort of patients who were followed up with serial fetal fibronectin testing between 1998 and 2001 was identified. All patients were considered to be at high risk for preterm delivery and were screened with fetal fibronectin testing without using a speculum at 2- to 3-week intervals from 22 weeks to 32 weeks of gestation. Charts were reviewed for fetal fibronectin results and pregnancy outcome data. Groups were compared using chi(2) analysis or Fisher exact test with significance defined as P < .05. RESULTS: A total of 1,396 fetal fibronectin tests from 416 pregnancies were performed via the "blind" sampling technique. Overall, 24.9% of pregnancies delivered spontaneously before 37 weeks; 9.1% delivered spontaneously before 34 weeks. For delivery before 34 weeks of gestation, the test had a sensitivity of 44.7%, a specificity of 88.4%, a positive predictive value of 27.9%, and a negative predictive value of 94.1%. For delivery within 14 and 21 days of a single fetal fibronectin assessment, the test had a sensitivity of 52% and 45.5%, a specificity of 94.5% and 94.9%, a positive predictive value of 14.6% and 22.5%, and a negative predictive value of 99.1% and 98.2%, respectively. CONCLUSION: "Blind" vaginal fetal fibronectin sampling has high negative predictive values and specificities in predicting spontaneous preterm birth. LEVEL OF EVIDENCE: II-2.

Vaginal fetal fibronectin as a predictor of spontaneous preterm delivery after multifetal pregnancy reduction.

OBJECTIVE: The study was undertaken to assess the validity of vaginal fetal fibronectin assay as a screening test for spontaneous preterm delivery in asymptomatic patients who have undergone multifetal pregnancy reduction (MFPR). STUDY DESIGN: A historic cohort of 63 patients who underwent MFPR between 10 and 14 weeks of gestation was identified. All patients underwent serial vaginal fetal fibronectin sampling every 2 to 3 weeks from 22 weeks of gestation until delivery or 32 weeks of gestation. The fetal fibronectin concentration was measured by enzyme-linked immunosorbent assay, with 50 ng/mL or greater indicating a positive result. Charts were reviewed for fetal fibronectin results and pregnancy outcome data. Groups were compared by use of Fisher exact test. RESULTS: There were 13 singleton and 50 twin gestations after MFPR. A median of 4 fetal fibronectin assays were performed per patient. A total of 234 fetal fibronectin assays were performed with 222 (94.9%) negative results and 12 (5.1%) positive results. Overall, 41.3% of gestations were delivered spontaneously before 37 weeks; 7.9% were delivered before 34 weeks. The mean interval between tests was 17.8 days (+/-7.2 days). For delivery within 2 and 3 weeks of a single test, fetal fibronectin had a sensitivity of 66.7% and 50%, a specificity of 95.7% and 96.1%, a positive predictive value of 16.7% and 25%, and a negative predictive value of 99.5% and 98.6%, respectively. CONCLUSION: The fetal fibronectin test has similar validity to predict spontaneous preterm delivery in these high-risk pregnancies as in previously published cohorts.

Vaginal fetal fibronectin as a predictor of spontaneous preterm delivery in the patient with cervical cerclage.

OBJECTIVE: The purpose of this study was to assess the validity of vaginal fetal fibronectin as a screening test for spontaneous preterm birth in patients with cervical cerclage. STUDY DESIGN: A historic cohort of 117 patients who underwent cervical cerclage placement between 1996 and 2002 were identified. All patients were followed up in a maternal-fetal medicine faculty practice in a university setting. Serial fetal fibronectin samples of vaginal secretions were collected every 2 to 3 weeks, starting at 22 weeks of gestation and continuing until 32 weeks or delivery, whichever came first. RESULTS: There were 81 singleton, 23 twin, 12 triplet, and 1 quadruplet pregnancies. There were 61 ultrasound-indicated, 47 prophylactic, and 9 emergency cerclages that were placed. Most cerclages were of the modified Shirodkar type (95%) with a median gestational age at cerclage placement of 16.6 weeks. Overall, 33.3% of gestations were delivered spontaneously before 37 weeks of gestation; 17.1% of gestations were delivered spontaneously before 34 weeks. For deliveries within 2 weeks and 3 weeks of a single fetal fibronectin assessment, the test had a sensitivity of 50% and 48.3%, a specificity of 90% and 91.1%, a positive predictive value of 16.3% and 28.6%, and a negative predictive value of 97.9% and 96%, respectively. Subgroup analysis by number of fetuses (singleton, twin, and higher order multiple gestations) revealed similar values. For delivery before 34 weeks of gestation, fetal fibronectin had a sensitivity of 50%, a specificity of 78.4%, a positive predictive value of 33.3%, and a negative predictive value of 88%. CONCLUSION: This study is the first to evaluate the use of vaginal fetal fibronectin assessments to screen for preterm birth in patients who had undergone cervical cerclage procedures. We conclude that this test has similar validity to predict spontaneous preterm delivery in these high-risk pregnancies, as in previously published cohorts.