Cervilenz assessment of cervical length compared to fetal fibronectin in the prediction of preterm delivery in women with threatened preterm labor

Objective.?To determine whether cervical length (CL) measured by the Cervilenz? measuring device is an effective screening tool for the prediction of preterm delivery (PTD) compared to fetal fibronectin (fFN).

Methods.?We evaluated fFN and CL among women who enrolled into a randomized control trial (RCT) comparing management algorithms for threatened preterm labor between 24 and 34 weeks' gestation. In all subjects, fFN was collected, with CL determined in blinded fashion. The sensitivity, specificity, and positive and negative predictive values (NPV) for fFN or Cervilenz in prediction of PTD within 7 days or prior to 37 weeks were determined.

Results.?Fifty-two subjects were evaluated. CL?<30?mm correlated with PTD?<7 days (r?=?0.31, p?=?0.04) and fFN positivity (r?=?0.43, p?=?0.006). CL?<30?mm and fFN had excellent NPV for PTD?<7 days (97.1 vs. 97.3%), and the area under the receiver operator characteristic curves were similar for prediction of PTD?<7 days (76.6 vs. 75.2%, p?=?0.71) or?<37 weeks (56.7 vs. 55.2%, p?=?0.71).

Conclusions.?Measurement of CL with Cervilenz appears to be equivalent to fFN in screening symptomatic women for PTD within 7 days or prior to 37 weeks. Given cost and turnaround time with fFN testing, Cervilenz represents a promising new tool for real time, clinically useful results in the management of women with threatened preterm labor.     

Prediction of delivery among women with early preterm labor by means of clinical characteristics alone

OBJECTIVE: This study was undertaken to assess whether individual clinical factors or combinations thereof could be used to accurately predict the risk of delivery within 1 week of admission among women with preterm labor and minimal cervical dilatation. STUDY DESIGN: We performed a case-control study of patients admitted to our institution with preterm labor and minimal cervical dilatation. A case patient was a patient who sought treatment with uterine contractions between 24 and 34 weeks' gestation with cervical dilatation 70 potential predictors was recorded. Statistical analysis consisted of bivariate and multivariable methods. We also generated a multivariable clinical predictive model with the purpose of detecting a proportion as high as possible of those destined to be delivered within 1 week (high sensitivity). We estimated that we would need 50 case patients and 150 control subjects to detect an odds ratio of 2.5 for risk factors with a prevalence of 20%, an alpha error of.05, a beta error of.20, and a control subject/case patient ratio of 3:1. RESULTS: Three variables were eligible for inclusion in our logistic models according to the bivariate analyses-bleeding on admission, substance abuse, and admission white blood cell count >/=14,000 cells/microL. The simplest and most favorable model included only 2 variables, bleeding and substance abuse, and yielded a sensitivity of 46% and a specificity of 76%. The full 3-variable model had similar test characteristics. For no model were we able to achieve a sensitivity >/=50%. CONCLUSION: The results of this case-control study suggest that combinations of clinical factors do not yield an adequate level of discrimination to be used alone for predicting the likelihood of delivery within 1 week among patients with minimal degrees of cervical dilatation.     

Presentation to delivery interval in women with early preterm delivery presenting with preterm labor: the effect of gestational age

Background: To evaluate the association between gestational age at presentation and interval to delivery in women with early spontaneous preterm delivery (PTD).

Methods: A retrospective cohort study of women who presented with threatened preterm labor (tPTL) and intact membranes and had a spontaneous PTD <34 weeks in a university-affiliated hospital (2009–2015). The interval from presentation to delivery was compared between different gestational age subgroups.

Results: Of 67 550 deliveries during the study period, 252 met inclusion criteria. This cohort was divided to three gestational age subgroups at presentation: 24–28^6/7 weeks (n?=?83), 29–31^6/7 weeks (n?=?61) and 32–33^6/7 weeks (n?=?108). Median time from presentation to delivery was 24.5?h. An inverse relation was observed between gestational age at presentation and admission–delivery interval (group A: 74.7?h, group B: 21.0?h, group C: 14.0?h, p?Conclusion: Gestational age at presentation is inversely related to admission–delivery interval in women with tPTL and intact membranes.     

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.     

Evaluation of the ability of cervical length and fetal fibronectin measurement to predict preterm delivery in asymptomatic women with risk factors

Objective: To evaluate the power of transvaginal ultrasound cervical length (CL) and fetal fibronectin (fFN) measurement for the prediction of preterm delivery (PTD) in asymptomatic women with risk factors.

Methods: Between January 2010 and October 2012, 218 women with singleton pregnancies and a high risk for PTD (i.e. prior history of PTD, cervical surgeries, late miscarriages, uterine abnormalities or premature rupture of the membranes) were selected. CL was measured by transvaginal ultrasonography between 14 and 22 weeks, and a CL?+0 and <37⁺⁰ weeks, and the PTD rate was analyzed by either of two methods alone or combined.

Results: There were 213 cases included in the analysis, and 47 women (22.1%) had positive fFN. The average CL of women with positive fFN (2.3?±?0.9?cm) was significantly shorter than that of women with negative fFN (3.1?±?0.8?cm; p?=?0.02). There were 25 (11.7%) and 38 (18.8%) cases with PTD at <34⁺⁰ and <37⁺⁰ weeks, respectively. By individual analyses, the highest PTD rate was 51.2% in women with positive fFN at <37⁺⁰ weeks. The sensitivity and diagnostic efficiency values for PTD prediction by CL were low at <34⁺⁰ and <37⁺⁰ weeks. The values of diagnostic efficiency by fFN were >80% at <34⁺⁰ and <37⁺⁰ weeks. In the combined analysis, the highest PTD rate was 57.1% in women with CL?≤?2.5?cm and positive fFN at <37⁺⁰ weeks. The Kaplan–Meier curve indicated that there were significant differences among the four groups (χ^2?=?54.261; p?=?0.000).

Conclusions: These results indicate a significant correlation between fFN and PTD prediction. The PTD prediction could be enhanced by combined CL and fFN measurement.     

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.     

Risk factors for spontaneous preterm delivery after arrested episode of preterm labor

Introduction: We aimed to identify specific risk factors for spontaneous preterm delivery (PTD) among women with arrested preterm labor (PTL).

Method: A retrospective study of women admitted due to imminent PTL and intact membranes, which did not progress to PTD within 24?h from admission. Eligibility was limited to singleton gestations at 24?+?0/7–33?+?6/7 weeks of gestations with no known chromosomal or structural anomalies. All women were treated with corticosteroids and tocolysis. Comparison was made between those who delivered at <37?+?0/7 weeks of gestation (study group) to women who delivered at ≥37?+?0/7 weeks of gestation (controls).

Results: Overall, 301 women were recruited, of which 85 (28.2%) delivered before 37?+?0/7 weeks and 216 (71.8%) delivered at term. Advanced cervical dilatation was found to be an independent risk factor for PTD [for women with no past PTD: adjusted odds ratio (aOR) 1.66, 95% CI: 1.06–2.61 for each 1?cm dilatation; for women with past PTD: aOR 2.81, 95% CI: 1.02–7.73 for each 1?cm dilatation]. Among women without past PTD, additional independent risk factors for PTD were earlier gestational week at admission (OR: 1.20, 95% CI: 1.09–1.32 for each earlier week) and short cervical length (OR: 1.04, 95% CI: 1.01–1.08 for each decrease of 1?mm in cervical length).

Conclusion: Advanced cervical dilatation, earlier gestational age at the episode of arrested PTL, and short cervical length are specific risk factors for PTD in women with arrested PTL. These findings may assist in counseling women and direct further investigation.     

The impact of fetal fibronectin testing for women with symptoms of preterm labour in routine clinical practice within a New Zealand population

AIMS: To perform a comparative analysis of antenatal management received according to the results of cervico-vaginal fetal fibronectin (fFN) testing, and to review preterm delivery rates and fFN predictive values within a New Zealand population of women presenting with threatened preterm labour. METHODS: Case note review of all fFN tests performed at Middlemore Hospital, South Auckland from August 2003 to March 2005 (n = 199). Data collected included risk factors for preterm delivery, signs and symptoms at presentation, antenatal management received after fFN test and outcome and delivery details. Positive and negative fFN results were compared. RESULTS: Women with a positive fFN were more likely to receive antenatal corticosteroids (96.4 vs 4.7% RR 8.74 (95% CI 5.40-14.17)) and tocolysis (71.4 vs 2.4% RR 8.10 (95% CI 4.49-14.59)) and to be admitted antenatally (96.4 vs 54.4% RR 1.77 (95% CI 1.50-2.10)) with a higher mean cost of treatment (967.47 NZ dollars vs 335.27 NZ dollars P < 0.05). Rates of delivery < 34 weeks were higher in those with a positive fFN (41.9 vs 0.7% RR 62.06 (95% CI 8.43-457.14)). CONCLUSION: Women with a positive fFN result received different treatment to those with a negative fFN. Use of fFN test in routine clinical practice allows management and resources to be targeted more appropriately and may limit unnecessary interventions.     

The impact of fetal gender on preterm birth in a southern Chinese population

Objective: This study was conducted to determine whether carrying a singleton male fetus increases the risk of preterm birth (PTB) in Chinese women. Methods: A retrospective cohort study was conducted on women with singleton pregnancies and delivered in our hospital. Maternal characteristics, pregnancy outcome, and incidence of PTB, were compared between women carrying a male versus a female fetus. The independent effect of a male fetus on PTB was examined with multiple logistic regression analysis adjusting for the other confounding factors identified. Results: There were significant differences in maternal and infant characteristics between women with a male versus a female fetus. Despite similar or lower incidences of complications and labor induction, women with a male fetus had increased birth <37 weeks (7.0% versus 6.2%, p?<?0.001) and birth at 34–36 weeks (5.15% versus 4.4%, p?<?0.001), but not for birth <34 weeks (2.0% versus 1.8%, p?=?0.163). Regression analysis confirmed the association between male fetus with birth at 34–36 weeks (aOR 1.11, 95% CI 1.10–1.33) and spontaneous preterm labor (aOR 1.09, 95% CI 1.00–1.19). Conclusions: The results confirmed that carrying a male fetus is an independent risk factor for spontaneous preterm labor and PTB at 34–36 weeks gestation in southern Chinese women.     

The use of 17-hydroxy progesterone in women with arrested preterm labor: a randomized clinical trial

Abstract

Background: The use of 17-alpha-hydroxyprogesterone caproate (17?P) has been shown to reduce preterm delivery in women who have had a prior preterm birth. The role of 17?P in women with arrested preterm labor is less certain.

Aims: To compare the preterm birth rate and neonatal outcome in women with arrested preterm labor randomized to receive 17?P or placebo.

Materials and methods: Women with arrested preterm labor were randomized to weekly injections of either 17?P (250?mg) or placebo. Maternal and neonatal outcome were evaluated.

Results: Forty-five singleton pregnancies were randomized after successful tocolysis; 22 received 17?P while 23 got placebo. Gestational age at delivery (p?=?0.067) and the interval from treatment to delivery (p?=?0.233) were not affected by 17?P. Significantly less women in the 17?P group delivered at <34 weeks (14 versus 21, p?=?0.035). There was also a significant reduction in the risk of neonatal sepsis (p?=?0.047) and gr III/IV intraventricular hemorrhage (IVH) (p?=?0.022) in the 17?P group.

Conclusion: In this study, 17?P did not delay the interval to delivery after successful preterm labor, but births <34 weeks as well as neonatal sepsis and IVH were reduced by 17?P treatment.     

Evaluation of the quantitative fetal fibronectin test and PAMG-1 test for the prediction of spontaneous preterm birth in patients with signs and symptoms suggestive of preterm labor

Abstract

Objective: The objective of this study is to compare the qualitative fFN test at 50?ng/ml threshold to novel methods for assessing risk of imminent sPTB in women with symptoms of preterm labor (PTL): (1) quantitative fetal fibronectin (qfFN) at four thresholds: 10, 50, 200, and 500?ng/ml; and (2) qualitative PAMG-1 test.

Study design: Consecutive patients presenting with singleton pregnancies, signs of PTL, gestational age 23.1–34.6, intact membranes, no coitus within 24?h, and cervical dilation ≤3?cm. fFN was performed as standard of care, while clinicians were blinded to the qfFN and PAMG-1 test results. qfFN accuracy was evaluated at four thresholds of 10, 50, 200, and 500?ng/ml for its ability to predict imminent spontaneous preterm delivery (sPTD)?≤?7 and ≤14 d from the time of sample collection. The PAMG-1 test was evaluated based on its qualitative result for the same delivery endpoints.

Results: Seventy-two patients were analyzed. Fifty-seven percent of patients had an fFN concentration of <10?ng/ml fFN; 75%?<?50?ng/ml; 92%?<?200?ng/ml; 97%?<?500?ng/ml. The SN, SP, PPV, and NPV for fFN at each of the four cutoffs for sPTB ≤7 d: 10?ng/ml: 67%, 58%, 6%, 98%; 50?ng/ml: 67%, 77%, 11%, 98%; 200?ng/ml: 33%, 93%, 17%, 97%; 500?ng/ml: 0%, 97%, 0%, 96%. The PAMG-1 test was positive in 7% of patients. SN, SP, PPV, and NPV for PAMG-1 for sPTD ≤7 d were 67%, 96%, 40%, and 99%, respectively.

Conclusion: Compared with qfFN, the PAMG-1 test is a better predictor of spontaneous delivery within 7 d while maintaining a very high negative predictive value. The PAMG-1 test is an easy-to-use bedside test that provides rapid results, does not require a speculum examination, can be used after vaginal exam and coitus and does not require specialized equipment to analyze results. As to be expected, compared with the conventional cutoff of fFN (50?ng/ml), a higher fFN cutoff of 200?ng/ml does seem to increase the PPV of the test, but this comes at a cost to the fFN test’s SN and NPV, rendering it of little to no advantage in clinical practice.     

Short interpregnancy interval and risk of spontaneous preterm delivery

OBJECTIVES: Short interpregnancy intervals are related to increased prevalence of adverse perinatal outcomes. However, the reported association with preterm birth might be due to confounding by factors such as previous pregnancy outcomes, socioeconomic level or lifestyles. The objective of this study was to evaluate the effect of short interpregnancy interval on the occurrence of spontaneous preterm delivery. STUDY DESIGN: The prevalence of a short interpregnancy interval, defined as six or less months between a preceding delivery or abortion and the last menstrual period before index pregnancy, was compared between 263 spontaneous preterm (<37 weeks) and 299 term (37-42 weeks) consecutive births. Separate analyses were performed for early (<34 weeks) and late (34-36 weeks) preterm deliveries. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated using unconditional logistic regression. RESULTS: There was a significant association between short interpregnancy interval and spontaneous early preterm delivery, both crude (OR=3.9; 95% CI: 1.91-8.10) and adjusted for maternal age, school education, previous birth outcomes, antenatal care, smoking habits, body mass index and gestational weight gain (adj(OR)=3.6; 95% CI: 1.41-8.98). No significant effect on spontaneous late preterm delivery was found (crude(OR)=0.8; 95% CI: 0.32-1.83). CONCLUSIONS: This study showed that short interpregnancy intervals significantly increased the risk of early spontaneous preterm birth but no such effect was evident for late preterm deliveries.     

Effect of fetal gender on induction of labor failure rates

Purpose: To evaluate gender effect on induction of labor (IoL) failure rates stratified by indication to delivery.

Methods: Retrospective cohort analysis of singleton pregnancies 34–42 weeks undergoing cervical ripening using controlled-release PGE2 vaginal insert. IoL Indications were divided into: (1) maternal; (2) hypertensive disorders; (3) premature rupture of membrane or (4) fetal (growth abnormalities, oligohydramnios, postdate, etc,). IoL failure was defined as: (1) Bishop-score ≤7 after 24?hours of PGE2; (2) cesarean delivery due to failed induction; (3) fetal distress followed by PGE2 removal and emergent cesarean. IoL failure rates were stratified by neonatal gender and indication to induction. Logistic regression analysis was utilized to control outcomes to potential confounders.

Results: Overall, 1062 pregnancies were included – 521 (49%) had male fetuses. IoL indications did not differ by gender. IoL failure rate was 20.1% (213/1062) – 76% for unfavorable Bishop-score after PGE2 removal; 5.2% for failed induction and 18.8% for fetal-distress while on PGE2. Overall, 14.3% delivered by cesarean section. There were no differences in IoL failure as a group or by indications to induction stratified by fetal gender (21.7% vs. 18.5%, male vs. females, p?Conclusions: IoL failure rate is not affected by fetal gender regardless of indication to induction.     

Interleukin-8 and glucose in amniotic fluid, fetal fibronectin in vaginal secretions and preterm labor index based on clinical variables are optimal predictive markers for preterm delivery in patients with intact membranes

AIM: Various predictive markers for preterm delivery have been proposed in previous studies. We investigated which marker is most reliable. METHODS: In 126 patients with preterm labor before 32 weeks of gestation and intact membranes, who had regular uterine contractions with cervical changes effaced > or =50%, we evaluated seven markers: interleukin (IL)-8, glucose, and granulocyte count in amniotic fluid (AF); fetal fibronectin (fFN) in vaginal secretions; IL-8 in cervical mucus; cervical length; and preterm labor index (PLI) based on clinical variables. The relationships of these variables to the occurrence of preterm delivery before 34 weeks were examined by logistic regression analysis. RESULTS: Values for AF IL-8, AF granulocyte count, fFN in vaginal secretions, and PLI were significantly higher, while the value for AF glucose was significantly lower, in patients delivering before 34 weeks than those in patients delivering at or following 34 weeks (P < 0.0001 for all). The most sensitive marker for predicting delivery before 34 weeks was AF IL-8 (sensitivity, 67.8%). The most specific markers were AF IL-8 (specificity, 95.5%) and PLI (specificity, 95.5%). By the logistic regression analysis, AF IL-8, AF glucose, fFN in vaginal secretions and PLI showed independent relationships with delivery before 34 weeks (P = 0.0009, P = 0.0032, P = 0.0131 and P = 0.0038, respectively). CONCLUSIONS: In preterm labor with intact membranes, AF IL-8, AF glucose, fFN in vaginal secretions and PLI were highly predictive markers for detecting preterm delivery before 34 weeks.     

Diabetes mellitus and the risk of preterm birth with regard to the risk of spontaneous preterm birth

Introduction.?It is internationally agreed that diabetes mellitus (DM) is associated with increased maternal and fetal morbidity and long-term complications. To avoid these complications, it is often necessary to induce birth before term. The impact of DM on spontaneous preterm birth (spontaneous labor, preterm premature rupture of membranes and/or cervical incompetence resulting in delivery before the completion of 37 gestation weeks) is still unexplained. Preterm birth accounts for the most neonatal deaths and infant morbidities, and therefore it still remains one of the biggest challenges in obstetrics.

Objective.?Our study determined if there is an increasing tendency towards spontaneous preterm birth in mothers with gestational and preexisting DM.

Methods.?In this retrospective cohort study, 187 pregnant women with gestational DM and preexisting DM were compared to a randomized control group consisting of 192 normoglycemic women concerning gestational age and perinatal outcome. Data were collected by the Medical University of Vienna. Multiple pregnancies and women with severe maternal diseases, such as preeclampsia, were excluded.

Results.?Women with DM tended significantly more often to preterm births (P?=?0.002). A significant difference in the incidence of spontaneous preterm birth was found (P?=?0.047).

Conclusion.?DM affects the length of gestation and incidence of spontaneous preterm birth.     

Periodontal disease and bacterial vaginosis as genetic and environmental markers for the risk of spontaneous preterm labor and preterm birth

Objective.?The aim of this study was to review the evidence associating periodontal disease, and bacterial vaginosis with preterm birth, and the link with gene polymorphism, as well as the preventions and interventions which might reduce the risk of spontaneous preterm labor and preterm births in women with periodontal disease and/or bacterial vaginosis.

Background.?Preterm birth accounts for 70% of perinatal mortality, nearly 50% of long term neurological morbidity, and a significant impact on health care costs. There is evidence that spontaneous preterm labor and preterm birth are associated with intrauterine infection due to abnormal genital and/or oral colonization. Periodontal disease and bacterial vaginosis share microbiological similarities, and both conditions are associated with spontaneous preterm labor and preterm birth. In addition, periodontal disease and bacterial vaginosis have been linked through gene polymorphism.

Methods.?A review of the literature using widely accepted scientific search engines in English language.

Results.?Studies evaluating antibiotic administration to eradicate periodontal disease and/or bacterial vaginosis responsible organisms, and minimize the risk of preterm births have yielded conflicting results. With respect to bacterial vaginosis, the timing and the choice of antibiotic administration might partly explain the conflicting results. The use of scaling and/or root planning for women with periodontal disease appears to reduce the risk of preterm birth, but routine administration of antibiotics has not demonstrated any impact on preterm birth.

Conclusion.?Prospective studies evaluating the association of gene polymorphism with preterm birth, and the contribution of periodontal disease and bacterial vaginosis are needed.