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Fetal fibronectin in cervical and vaginal secretions as a predictor of preterm delivery.

BACKGROUND: Preterm delivery is the leading cause of neonatal mortality in the United States, but efforts to address the problem are hampered by the inability to predict accurately which pregnancies are at risk. We postulated that damage to the fetal membranes may release fetal fibronectin into the cervix and vagina, giving rise to a biochemical marker for preterm delivery. METHODS: We measured fetal-fibronectin concentrations in cervical and vaginal secretions, amniotic fluid, and maternal plasma with a sensitive immunoassay using the monoclonal antibody FDC-6. Immunohistochemical studies were used to determine the distribution of fetal fibronectin in the placenta and amniochorionic membranes and to ascertain its cell of origin. RESULTS: Women with uncomplicated pregnancies (n = 163) who delivered at term rarely had cervicovaginal fetal-fibronectin concentrations above 0.05 micrograms per milliliter between 21 and 37 weeks of gestation (11 of 267 cervical samples [4 percent] and 9 of 267 vaginal samples [3 percent]. High levels of fetal fibronectin were detected in amniotic fluid and in the cervical or vaginal secretions of 93.8 percent of the women with preterm rupture of membranes (n = 65). Cervical or vaginal fetal fibronectin was also present in 50.4 percent of the women with preterm uterine contractions and intact membranes (n = 117), and its presence identified the women who delivered before term (n = 60) with a sensitivity of 81.7 percent and a specificity of 82.5 percent. In the placenta and membranes, fetal fibronectin was found at points of contact with the uterine wall. CONCLUSIONS: The presence of cervicovaginal fetal fibronectin in the second and third trimesters of pregnancy identifies a subgroup of women who are at high risk for preterm delivery. This phenomenon may reflect the separation of the chorion from the decidual layer of the uterus, with the release of intact or degraded chorionic components of the extracellular matrix into the cervical and vaginal secretions.

Amniotic Fluid↗

The influence of gestational age and smoking habits on the risk of subsequent preterm deliveries.

BACKGROUND: Previous preterm delivery and maternal smoking are associated with increased risks of preterm delivery. It is not known whether gestational age at the time of a preterm delivery is correlated with gestational age in successive preterm deliveries and whether changes in smoking habits influence the subsequent risk of preterm delivery. METHODS: We studied the associations among smoking habits, previous very preterm or moderately preterm delivery (before 32 weeks and at 32 to 36 weeks, respectively), and the risk of a subsequent very preterm or moderately preterm delivery in a population-based cohort of 243,858 women in Sweden between 1983 and 1993. The results were adjusted for covariates known to be associated with preterm delivery. RESULTS: The odds ratios for very or moderately preterm delivery in a subsequent pregnancy among women with a previous very preterm delivery, as compared with women who had a previous term delivery, were 12.4 (95 percent confidence interval, 9.1 to 17.0) and 7.1 (95 percent confidence interval, 6.0 to 8.4), respectively. Among women with a previous moderately preterm delivery, the corresponding odds ratios were 2.3 (95 percent confidence interval, 1.9 to 3.0) and 5.9 (95 percent confidence interval, 5.5 to 6.3), respectively. The odds ratios for a very preterm second delivery among the women who smoked 1 to 9 cigarettes per day and those who smoked 10 or more cigarettes per day, as compared with nonsmokers, were 1.4 (95 percent confidence interval, 1.1 to 1.7) and 1.6 (95 percent confidence interval, 1.3 to 2.0), respectively. The corresponding odds ratios for moderate preterm delivery were 1.3 (95% confidence interval, 1.2 to 1.4) and 1.5 (95 percent confidence interval, 1.4 to 1.6). The women who quit smoking between pregnancies were not at increased risk for very or moderately preterm delivery, whereas the women who started to smoke in the second pregnancy had the same risk as those who continued to smoke. CONCLUSIONS: The risk of a very preterm delivery in successive pregnancies is increased primarily among women with a previous very preterm delivery. Changes in smoking habits influence the risk of preterm delivery as well.

Adult↗

[Organizational possibilities of reducing the incidence of preterm deliveries].

Preventing preterm deliveries and reducing their incidence are priority issues important to reduce infant mortality and morbidity. Organizational possibilities of reducing the incidence of preterm deliveries are associated mainly with identifying risk factors, primary prevention, intensifying secondary prevention and regionalization of perinatal care.

Female↗

Preterm delivery in patients admitted with preterm labor: a prediction study.

OBJECTIVE: To develop a model for prediction of preterm delivery in patients treated with parenteral tocolysis using combinations of maternal demographic and clinical factors. METHODS: We performed a retrospective cohort study using a perinatal database to identify women admitted with preterm labor and treated with parenteral tocolysis from 1980 to 1994. We developed an explanatory model using multiple logistic regression to determine the effect of four variables (prior preterm delivery, substance abuse, maternal complications and third-trimester care) on the likelihood of preterm delivery. For the prediction model, we initially included these four variables and then removed them in a stepwise fashion to determine the combination of the variables that offered the greatest model sensitivity and specificity. RESULTS: A total of 900 women were identified for the study and 247 (27%) had a preterm delivery. In the explanatory model, prior preterm delivery (OR 2.4; 95% CI 1.5-3.6), substance abuse (OR 2.2; 95% CI 1.2-5.1), initiation of care in the third trimester (OR 2.0; 95% CI 1.3-2.8) and medical complications of pregnancy (OR 1.8; 95% CI 1.2-2.6) increased the likelihood of preterm delivery. For the prediction tool, a three-variable model (prior preterm delivery, substance abuse and initiation of care in the third trimester) had high specificity (98%) and modest negative predictive value (73%). CONCLUSIONS: A simple three-variable model can correctly identify 98% of women with preterm labor treated with parenteral tocolysis who will not deliver preterm. Patients with no prior history of preterm delivery, no substance abuse and initiation of prenatal care before the third trimester have a 73% probability of not delivering preterm.

Adult↗

Selective use of fetal fibronectin detection after cervical length measurement to predict spontaneous preterm delivery in women with preterm labor.

OBJECTIVE: The purpose of this study was to determine whether selective use of fetal fibronectin detection after ultrasound measurement of cervical length predicts preterm delivery in symptomatic patients better than either indicator alone. STUDY DESIGN: This prospective blinded study performed both tests on 359 women hospitalized for preterm labor between 18 and 34 completed weeks' gestation. The primary outcome was preterm delivery before 35 weeks'gestation. RESULTS: Among the 359 women included, 48 (13.4%) delivered before 35 weeks' gestation. The sensitivity, specificity, and positive and negative predictive values of cervical length < or = 25 mm were 75%, 63%, 24%, and 94%, respectively, and of fetal fibronectin > or = 50 ng/mL, 63%, 81%, 33%, and 93%. Fetal fibronectin detection was significantly (P < .001) more specific than cervical length measurement. For selective use of fetal fibronectin detection after cervical length measurement, the test was considered positive if cervical length was < or = 15 mm or if cervical length was between 16 and 30 mm with fetal fibronectin > or = 50 ng/mL. The predictive values of this test were not significantly different from those of fetal fibronectin detection (67%, 81%, 36%, and 94%). This strategy could have avoided 200 fibronectin tests. CONCLUSION: Selective use of fetal fibronectin detection after cervical length measurement is more specific than cervical length and as effective as fetal fibronectin assays in the entire population of women in preterm labor for predicting preterm birth.

Adult↗

Epidemiologic characteristics of preterm delivery: etiologic heterogeneity.

Preterm delivery (less than 37 weeks completed gestation) is known to result from diverse etiologic pathways, which can be grouped into idiopathic preterm labor, preterm premature rupture of the membranes, and medical complications. Data from publications providing sufficient detail to subdivide preterm delivery cases into these groups were tabulated. In spite of inconsistent terminology and incomplete reporting, patterns were identified. Black women have a markedly higher risk of preterm delivery, which is especially pronounced for preterm premature rupture of the membranes. Idiopathic preterm labor is predominant in lower-risk, white populations. These observations encourage consideration of subcategories of preterm delivery in studies of etiology and prevention.

Abortion, Induced↗

Preterm delivery: an overview.

Preterm delivery is the leading factor causing neonatal mortality and morbidity. We have conducted a PubMed literature search to obtain an update on the etiology, diagnostic problems and therapeutic considerations of preterm delivery. Approximately 5-10% of all births are premature. Preterm labor is associated with preterm rupture of membranes, cervical incompetence, polyhydramnion, fetal and uterine anomalies, infections, social factors, stress, smoking, heavy work and other risk factors. The diagnosis is made on the patients presenting symptoms, clinical findings and of progressive effacement and dilatation of the cervix. Biochemical markers of preterm delivery are of minor importance in daily clinical work. Measurement of the cervix, however, is a practical and valuable tool to predict preterm delivery. Cervical cerclage can be useful in selected cases. Antibiotics may help to prevent preterm labor in cases of known etiologic agents (e.g. preterm rupture of membranes and urinary infection). The use of tocolytic agents such as beta-sympathetic receptor stimulators can be advocated for a few days. There is evidence that their long-term use is not beneficial and could even be harmful to the fetus. Calcium channel blockers (nifedipine) and a new selective oxytocin receptor antagonist, atosiban, appear to be as effective as beta-sympathomimetic drugs on uterine contractions with fewer side-effects. Prostaglandin synthetase inhibitors such as indomethacin may prevent uterine contractions and can be used prior to the 32nd week of pregnancy. A single course of corticosteroid treatment in two doses of 12 mg betamethasone or 6 mg of dexamethasone is important for the prevention of respiratory distress between the 24th and 34th weeks of pregnancy. Multiple doses may be harmful and should be avoided. In these cases management should depend on gestation age (fetal maturity). Uterine contractions after 34 weeks' gestation are not an indication for tocolytic treatment.

Female↗

Maternal weight gain and preterm delivery: differential effects by body mass index.

We examined associations between weight gain (kg) per week of pregnancy and net weight gain per week of pregnancy (weight gain - birth weight/weeks of gestation at delivery) and preterm delivery in a population of 266,172 low-income women. Risk of preterm delivery was lowest among women with intermediate weight gain (0.35 to <0.46 kg/week) and net weight gain (0.27 to <0.37 kg/week). Both lower and higher weight gains and net weight gains per week were associated with an increased risk for preterm delivery. Associations, however, were not uniform across body mass index categories. Compared with women gaining 0.35 to <0.46 kg/week, preterm risk differences (95% confidence limits) for women gaining <0.10 kg/week were +9.5% (+6.5, +12.4) for underweight women, +6.7% (+5.6, +7.9) for average-weight women, +3.5% (+2.0, +4.9) for overweight women, and +0.4% (-0.4, +1.2) for obese women. The opposite pattern was observed with high weight gain. Preterm risk differences for weight gains >0.65 kg/week ranged from +0.8% (-0.7, +2.1) for underweight women, to +2.5% (+1.3, +3.9) for obese women. We also evaluated weight gain per week in the latter part of pregnancy (from week 14 to delivery). The same basic patterns were observed; however, variation in the associations across body mass index groups was not as marked.

Adult↗

Change in prostaglandin E synthases (PGESs) in microsomal PGES-1 knockout mice in a preterm delivery model.

Most preterm deliveries are associated with infection and inflammation. Prostaglandin E2 (PGE2) is one of the most important mediators in the processes of inflammation, and is converted from PGH2 by various kinds of PGE synthases (PGESs). Among PGESs, microsomal PGES-1 (mPGES-1) is known to be the most important subtype in the processes of inflammation. To evaluate the role of PGESs in preterm delivery, we used mPGES-1 knockout mice in a lipopolysaccharide (LPS)-induced preterm labor model. Unexpectedly, the duration of labor after LPS treatment was not statistically different between C57BL6 wild-type mice and mPGES-1 knockout mice. In wild-type mice, mPGES-1 mRNA and protein expression increased in the myometrium and fetal membrane after LPS treatment. In contrast, the expression of mPGES-2 or cytosolic PGES was not changed by LPS treatment. On mPGES-1 knockout mice, mPGES-2 increased by LPS treatment in myometrium. The present data indicate that mPGES-1 may be involved in LPS-induced preterm labor, but inhibition of mPGES-1 alone may not prevent preterm delivery, because mPGES-2 might compensate for the role of mPGES-1.

Animals↗

Pathologic analysis of preterm delivery placentas.

198 preterm delivery placentas of 28 weeks to less than 37 weeks pregnancy were analyzed. Gross examination revealed that the differences of placenta previa and low implantation (2.91%), bipartate placenta and rupture of marginal sinus (0.97% respectively), large placenta (2.91%), short cord (4.85%), velamentous insertion of cord (3.88%), etc in comparison with those of term delivery placentas were statistically significant. Microscopic examination of 165 placentas showed that in 19 cases (11.52%) of infection of membranes and umbilical vessels, 11 were due to premature rupture of membranes or cervical interventions and 8 to preterm delivery. Among 72 cases of PIH, 65 (90.28%) had arteriopathy of decidua capsularis. 18 cases (25%) which had not been diagnosed clinically as PIH were found to be neglected after discovery of arteriopathy of decidua capsularis by pathologic examination. Placental examinations showed that preterm delivery may be attributable to the factors of placenta, amniotic fluid and umbilicus. 20 cases (27.78% of total PIH) of premature rupture of membranes were complicated by PIH. Whether the cases of decidual arteropathy are liable to have rupture of membranes awaits further investigation.

Female↗

Dynamic cervical change: is real-time sonographic cervical shortening predictive of preterm delivery in patients with symptoms of preterm labor?

OBJECTIVES: To determine prospectively if dynamic cervical change (spontaneous real-time cervical shortening) is predictive of preterm delivery at < 37 weeks' gestation in patients with symptoms of preterm labor. METHODS: This was a prospective study of patients at 23-34 weeks' gestation who were symptomatic for preterm labor. Patients underwent a 10-min real-time sonographic cervical length assessment with measurements taken at 1-min intervals. The presence or absence of dynamic cervical change, defined as real-time changes in cervical length observable to the naked eye of the sonologist during the examination, was recorded. Gestational age at delivery was obtained from medical records. Preterm delivery was defined as delivery at < 37 weeks' gestation. Dynamic cervical change and initial and minimum cervical lengths were assessed for prediction of preterm delivery. RESULTS: Seventy-six patients were enrolled, and 66 were available for outcome analysis. Thirty-one patients (47%) exhibited dynamic cervical change. Patients with dynamic change had shorter initial cervical lengths (27 mm vs. 36 mm, P = 0.001), shorter minimum cervical lengths (20 vs. 33 mm, P < 0.001) and larger changes in cervical length during the examination period (10 vs. 4 mm, P < 0.001). In the subgroup of patients with an initial cervical length > 30 mm, those with dynamic change delivered earlier than did those without dynamic change (36.8 vs. 38.6 weeks, P = 0.02), and a higher percentage delivered preterm (27% vs. 11%, odds ratio (OR), 3.0 (0.5-17.0)). Multivariate analysis showed that minimum cervical length was a better predictor of preterm delivery than was initial cervical length. CONCLUSIONS: Dynamic cervical change occurs frequently in association with shortened cervical length. In patients with longer initial cervical lengths, dynamic change may increase the risk for preterm delivery. When dynamic change is noted in a patient with preterm labor symptoms, use of the minimum cervical length observed may be better compared with initial cervical length for determining preterm delivery risk.

Adult↗

Cervicovaginal fibronectin improves the prediction of preterm delivery based on sonographic cervical length in patients with preterm uterine contractions and intact membranes.

OBJECTIVE: The purpose of this study was to examine the diagnostic performance of ultrasonographic measurement of the cervical length and vaginal fetal fibronectin determination in the prediction of preterm delivery in patients with preterm uterine contractions and intact membranes. STUDY DESIGN: Ultrasound examination of the cervical length and fetal fibronectin determination in vaginal secretions were performed in 215 patients admitted with preterm uterine contractions (22-35 weeks) and cervical dilatation of </=3 cm. Outcome variables were the occurrence of preterm delivery within 48 hours, 7 days, and 14 days of admission, delivery </=32 and </=35 weeks, as well as the admission-to-delivery interval. Statistical analysis included chi-square test, receiver-operator characteristic (ROC) curve analysis, logistic regression, and survival analysis. RESULTS: The overall prevalence of preterm delivery </=35 weeks was 20% (43/215). The prevalence of spontaneous preterm delivery within 48 hours, 7 days, and 14 days of admission, and delivery </=32 and </=35 weeks were 7.9% (17/215), 13.0% (28/215), 15.8% (34/215), 8.9% (9/101), and 15.8% (34/215), respectively. ROC curve analysis and contingency tables showed a significant relationship between the occurrence of preterm delivery and both cervical length and fetal fibronectin results ( P < .01 for each). Both tests performed comparably in the prediction of spontaneous preterm delivery. However, when fetal fibronectin results were added to those of cervical length (<30 mm), a significant improvement in the prediction of preterm delivery was achieved. CONCLUSION: Fetal fibronectin adds prognostic information to that provided by sonographic measurement of the cervical length in patients with preterm uterine contractions and intact membranes.

Adult↗

Preterm delivery rate and fetal outcome in structurally affected twin pregnancies: a retrospective matched control study.

Data from 23 twin pregnancies with one structurally affected fetus were compared with data from 23 twin pregnancies with proven absence of structural fetal anomalies and matched for maternal age, parity, and year of delivery. The preterm delivery rate (< 37 weeks) was high in both groups but not significantly different (57 vs. 48 per cent). Perinatal mortality was significantly higher in the structurally affected twin pregnancies (65 vs. 9 per cent). In the affected twins, birth weight of the anomalous fetus was significantly lower than that of the normal co-twin. Since there was no difference in the incidence of maternal disease (hypertensive disorders, diabetes), it was concluded that the higher perinatal mortality was determined mainly by the nature of the anomaly and not by the preterm delivery rate.

Adult↗

Does hospitalization prevent preterm delivery in the patient with a short cervix?

This study considers whether admission to the hospital of a patient diagnosed with a short cervix delayed delivery, prevented preterm delivery, and/or decreased the rate of change in the cervical length (CL) on follow-up measurements. The design was a retrospective cohort study of women carrying singleton pregnancies with cervical lengths <or= 25 mm at gestational ages 16 to 28 weeks managed expectantly from July 2002 through July 2005. Eighty-two patients met criteria for inclusion, 26 (32%) of whom were hospitalized. On univariate analysis, hospitalization correlated with delivery < 34 weeks ( p=0.027), an earlier gestational age (GA) at delivery ( p=0.046), and a shorter time from diagnosis to delivery ( p< .001). Multivariate regression analysis of significant factors (age, prior preterm births, initial CL, GA at diagnosis, and hospitalization) showed a correlation between hospitalization and increased rate of cervical shortening ( p=0.005), and a trend toward hospitalization as an independent risk factor for delivery less than 34 weeks ( p=0.066), an earlier GA at delivery ( p=0.058), and a shorter time from diagnosis to delivery ( p=0.078). There also was no benefit seen from hospitalization when the initial CL was < 15 mm, although we were underpowered for this analysis. Admission to the hospital was not associated with a decreased rate of preterm delivery and there was a trend toward hospitalization as an independent risk factor for delivery at < 34 weeks, an earlier GA at delivery, and a shorter time from diagnosis to delivery. Hospitalization was independently associated with an increased rate of cervical shortening.

Adult↗

[Prevention of preterm delivery with gestagens].

Preterm delivery with its short-term and long-term sequealae constitutes a serious problem in terms of morbidity, disability and mortality of the newborn and cost to the society. The incidence of premature deliveries persists and according to the latest national and international reports a tendency for an increase has been observed. Therefore, besides screening programmes for the detection of vaginal infections one has to look for additional therapeutic concepts. According to previous data and recent publications, progesterone vaginally and 17alpha-hydroxyprogesterone caproate intramuscularely should be considered as possible treatment options for the prevention of preterm delivery in high-risk women, with therapy starting in the second trimester.

17-alpha-Hydroxypregnenolone↗

Preterm deliveries in twin pregnancies in Aberdeen.

The incidence of preterm delivery was 28.2% of all twin deliveries. Preterm delivery was common in monozygotic twins due to a high incidence of spontaneous rupture of the membranes. In addition, preterm delivery was associated more often with boy rather than girl infants.

Female↗

[Fetal fibronectin as a predictor of preterm delivery in patients with preterm contractions and cervical changes].

OBJECTIVE: The purpose of the study was to assess the clinical value of fetal fibronectin assay in the group of women presenting with preterm contractions and cervical changes. STUDY DESIGN: We prospectively evaluated 82 patients between 23-34 weeks of gestation presenting with signs and symptoms of preterm labor, intact membranes and cervical dilatation < 3 cm. In all cases cervico-vaginal samples were collected and assayed for the presence of fetal fibronectin. The primary outcome was delivery < or = 28 days from examination. RESULTS: The rate of preterm delivery (< 37 weeks) was 25.6% (21/82) and 17.1% (14/82) of the patients delivered < or = 28 days from the examination. The mean Bishop score was significantly higher in patients delivered < 28 days (5.9 +/- 1.2 vs 4.7 +/- 1.4; p = 0.004). Positive result of fFN (> 0.05 mg/ml) was found in 71.4% of patients that were delivered < or = 28 days and in 7.4% delivered > 28 days (p < 0.001). For predicting delivery < or = 28 days the positive fFN testing had sensitivity of 71.4%, specificity of 92.7%, PPV of 66.7% and NPV of 94%. The cutoff value for Bishop's score > or = 5 had sensitivity of 85.7% and specificity of 48.5%. Performing fFN testing only in patients with Bishop score > or = 5 resulted in the sensitivity of 71.4%, specificity of 95.6%, PPV of 76.9% and NPV of 94.2%. CONCLUSIONS: Fetal fibronectin is a very good predictor of imminent preterm delivery. It needs further research whether performing of the fFN assay can be limited only to the patients with the estimated Bishop's score > or = 5.

Abortion, Spontaneous↗