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Risk factors for preterm premature rupture of fetal membranes: a multicenter case-control study.

To assess the association between women with preterm premature rupture of membranes and 41 potential risk factors, we conducted a case-control study in six United States tertiary perinatal centers. The study involved completion of a comprehensive questionnaire for 341 women with preterm premature rupture of membranes in singleton pregnancies from 20 to 36 weeks' gestation and 253 control women matched for maternal age, gestational age, parity, clinic or private patient status, and previous vaginal or cesarean delivery. Univariate analysis revealed 11 variables associated with a significantly (p less than 0.05) increased risk of preterm premature rupture of membranes. After multiple logistic regression analysis, three variables remained in the model as independent risk factors: antepartum vaginal bleeding in more than one trimester (odds ratio 7.4; 95% confidence interval, 2.2, 25.6), current cigarette smoking (odds ratio, 2.1; 95% confidence interval, 1.4, 3.1), and previous preterm delivery (odds ratio, 2.5; 95% confidence interval, 1.4, 2.5). Cessation of cigarette smoking by pregnant women may reduce the risk of preterm premature rupture of membranes. Further study is necessary to determine the nature of the relationship between antepartum vaginal bleeding and preterm premature rupture of membranes.

Case-Control Studies↗

Gap junction formation in human myometrium: a key to preterm labor?

OBJECTIVE: The purpose of this study was to determine if gap junctions are a necessary component of the human laboring uterus and if their presence in myometrium is a prerequisite for both term and preterm labor. STUDY DESIGN: We obtained 27 human myometrial samples at cesarean section or nongravid hysterectomy. Gap junction formation was analyzed in a blind fashion by freeze fracture and indirect immunofluorescence. Six samples were obtained from term patients with no labor, six from term patients in labor, six from preterm patients with no labor, six from patients in preterm labor, and three from nongravid hysterectomy specimens. RESULTS: Gap junction structures were identified in the human myometrium of patients in term and in preterm labor but not in the other patient samples. In addition, evidence was obtained for the expression of (alpha 1) gap junction ribonucleic acid and (alpha 1) gap junction protein in term samples of human myometrium. CONCLUSION: Gap junctions are a necessary component of the human myometrium during term and preterm labor. The formation of gap junctions may be a final common event for the development of labor, and inhibition of gap junction activity could be a novel approach for the treatment of preterm labor.

Connexins↗

The natural interleukin-1 receptor antagonist prevents interleukin-1-induced preterm delivery in mice.

OBJECTIVES: Interleukin-1 has been implicated in the mechanisms responsible for preterm parturition in the setting of intrauterine infection. This cytokine is produced by human decidua, stimulates prostaglandin production by intrauterine tissues, and induces preterm parturition in mice. The purpose of this study was to determine whether pretreatment with the natural interleukin-1 receptor antagonist can block interleukin-1-induced preterm parturition in mice. STUDY DESIGN: Balb/CJ female mice impregnated by B6D2 F-1 male mice were randomly allocated to one of the following treatment groups: (1) saline solution (n = 15), (2) human recombinant interleukin-1 alpha or human recombinant interleukin-1 beta (n = 12), (3) human recombinant interleukin-1 receptor antagonist (n = 13), and (4) human recombinant interleukin-1 receptor antagonist plus human recombinant interleukin-1 (n = 24). RESULTS: An interleukin-1 dose of 10 micrograms per mouse induced preterm parturition in all cases. Pretreatment with interleukin-1 receptor antagonist (dose 1 mg per animal) prevented interleukin-1-induced preterm parturition. Interleukin-1 receptor antagonist administration was not associated with demonstrable side effects including behavioral changes, vaginal bleeding, duration of pregnancy, and pregnancy outcome. CONCLUSION: Our results suggest that interleukin-1-induced preterm delivery in mice is mediated by the interleukin-1 receptor.

Animals↗

A multicenter study of preterm birth weight and gestational age-specific neonatal mortality.

OBJECTIVE: This analysis was performed to present updated neonatal mortality data by age and birth weight for preterm newborns and to demonstrate the influence of plurality, ethnicity, and infant sex on mortality. STUDY DESIGN: Preterm birth weight and gestational age-specific mortality rates were compiled from the five centers that participated in the March of Dimes Multicenter Preterm Birth Prevention Project. In each center gestational age was assessed by standardized methods. A birth weight and gestational age-specific mortality chart for preterm births was created with live-birth data. RESULTS: In each birth weight group mortality decreased as the gestational age advanced; for each gestational age group heavier infants had less mortality. Female infants < 29 weeks survived better than male infants, and singletons < 29 weeks survived better than twins. Survival for black preterm newborns was better than that of whites but differences were not significant. Mortality for black term infants was significantly higher. The largest improvement in survival occurred between 25 and 26 weeks. At 30 weeks survival was > 90% and improved < 1% per week thereafter. CONCLUSIONS: When compared with rates in previous reports, mortality rates appear to have improved, especially at gestational ages < 29 weeks. These data may be useful in decision-making and in counseling patients at risk for preterm delivery.

Black or African American↗

A prospective random trial of home uterine activity monitoring in pregnancies at increased risk of preterm labor.

In a prospective trial we enrolled 157 women at increased risk of preterm birth, randomly assigning women in a ratio of 1:2 to receive either frequent (greater than or equal to 5 days/wk) nursing contact, education in preterm labor symptoms, and self-palpation of uterine activity (group E, n = 50), or daily nursing contact, preterm labor education, and the Term Guard home uterine activity monitor (group EM, n = 107). Comparison of the rate of preterm birth, the incidence of preterm labor and successful tocolysis, and the mean birth weight and gestational age revealed no significant differences and suggested that beneficial effects previously attributed to monitored contraction data may in fact be the result of frequent (five or more times per week) nursing contact and careful attention to preterm labor symptoms and perceived contractions.

Clinical Trials as Topic↗

The value of amniotic fluid interleukin-6 determination in patients with preterm labor and intact membranes in the detection of microbial invasion of the amniotic cavity.

OBJECTIVES: Our purpose was to (1) determine the value of amniotic fluid interleukin-6 determination in the detection of microbial invasion of the amniotic cavity and (2) compare interleukin-6 to other rapid tests in the evaluation of preterm labor. STUDY DESIGN: Amniotic fluid interleukin-6 was determined quantitatively by enzyme-linked immunosorbent assay in 91 amniotic fluid specimens obtained by amniocentesis in 89 patients with preterm labor. Amniotic fluid cultures for aerobes, anaerobes, and mycoplasma species were performed. Receiver-operator characteristic curve analysis, logistic regression analysis, and Cox's proportional-hazards model were used to explore the relationship between several explanatory and outcome variables. Diagnostic index values of interleukin-6, glucose level, Gram stain, leukocyte esterase, and limulus amebocyte lysate assay for prediction of a positive amniotic fluid culture, preterm delivery, clinical infection, and neonatal sepsis were calculated. RESULTS: The prevalence of positive amniotic fluid cultures was 13% (12/89). The median interleukin-6 concentration in patients with positive cultures was 241.8 ng/ml, in contrast to 0.291 ng/ml in patients with negative cultures (p. < 0.005). Sensitivity and specificity of an interleukin-6 level > or = 6.17 ng/ml was 75% and 79%, in contrast to that of glucose, < or = 12 mg/dl (83% and 86%) for a positive amniotic fluid culture and sensitivity (p = 0.26, z test). All patients with an interleukin-6 level > 6.17 ng/ml were delivered preterm, in contrast to 85.2% of patients with a glucose level < or = 12 mg/dl. When all rapid tests and clinical parameters were considered simultaneously in the logistic model, only interleukin-6 maintained a significant relationship to preterm birth (odds ratio 35, p = 0.003). Cox's proportional analysis demonstrated a strong relationship between interleukin-6 and the amniocentesis-to-delivery interval after clinical variables were controlled for (hazard ratio 3.01, p < 0.00001). CONCLUSION: Amniotic fluid interleukin-6 determination may be a useful adjunct to our armamentarium of rapid tests to exclude infection and predict delivery in patients with preterm labor and intact membranes.

Amniocentesis↗

A prospective, randomized, placebo-controlled trial of penicillin in preterm premature rupture of membranes.

OBJECTIVE: Preterm premature rupture of the fetal membranes is common and frequently results in infectious complications. A prospective, randomized, controlled trial of penicillin versus placebo in preterm premature rupture of membranes is reported. The aim of the study was to determine if prophylactic antibiotics after preterm premature rupture of membranes would reduce infectious complications in the mother or neonate. STUDY DESIGN: Patients with preterm premature rupture of membranes between 21 and 37 weeks' gestation were randomized into a penicillin group that received 1 million units of benzylpenicillin intravenously every 4 hours followed by 250 mg of potassium phenoxymethyl penicillin (Pen-Vee K, Wyeth-Ayerst) orally twice daily or a placebo group before delivery. Latency period, infectious complications, and neonatal outcomes were studied. RESULTS: Patients with preterm premature rupture of membranes who received prophylactic penicillin had fewer infectious complications, including intraamniotic infection and postpartum endometritis (4 vs 11, p < 0.03), without adverse effects on the mother or fetus. CONCLUSION: Prophylactic penicillin in patients with preterm premature rupture of membranes reduces maternal infectious complications without adversely affecting the mother or newborn.

Chorioamnionitis↗

The West Los Angeles Preterm Birth Prevention Project. I. Program impact on high-risk women.

OBJECTIVE: The primary objective of this prospective study was to test whether preterm birth prevention education plus increased clinic visits and selected prophylactic interventions reduce preterm birth. STUDY DESIGN: Eight West Los Angeles prenatal county clinics, comparable with respect to selected demographics, were randomized to be either experimental or control clinics. High-risk patients in all clinics were identified with a risk scoring system derived from a similar population. High-risk patients (N = 1774) in experimental clinics were offered a program of education and more frequent visits and were randomized to receive various secondary intervention protocols in addition to the basic interventions of education and more frequent visits. Control clinic patients (N = 880) received standard county care. RESULTS: Preterm birth rates were 19% lower among the experimental high-risk patients (7.4% vs 9.1%), and differences were significant (p < 0.05) when preterm risk was taken into account. There was no evidence to suggest that the secondary interventions provided added benefit over the primary intervention protocol of preterm birth prevention education and increased visits. CONCLUSION: The 19% reduction in preterm birth rate observed in the experimental clinics suggest an overall program benefit from a protocol that offered education, more frequent visits, and greater attention given to patients while the selected interventions were applied.

Adult↗

A promoter mutation that increases transcription of the tumor necrosis factor-alpha gene is not associated with preterm delivery.

OBJECTIVE: Increased amniotic fluid concentrations of tumor necrosis factor-alpha are observed in women with preterm labor and subsequent preterm birth. We tested whether a mutation in the promoter region of tumor necrosis factor-alpha gene, TNF T2, which increases transcription of the gene, is more frequent in a preterm delivery cohort. STUDY DESIGN: Deoxyribonucleic acid was extracted from whole blood of 203 women and 44 fetuses delivered at < 37 weeks of estimated gestational age. The polymerase chain reaction was used to amplify the promoter region of the tumor necrosis factor-alpha gene. The resulting polymerase chain product was subjected to allele-specific enzymatic digestion with Nco I. Fragments were size fractionated on a 3% Metaphor agarose gel stained with ethidium bromide. Results were analyzed with use of a chi 2 contingency table. RESULTS: No statistically significant differences for either the TNF T1 or TNF T2 allele frequencies were found between women or fetuses delivered preterm compared with a control group or previously published allele frequencies. CONCLUSIONS: The frequency of this tumor necrosis factor-alpha promoter mutation, TNF T2, is not increased in either women or fetuses delivered at < 37 weeks' gestation. Basal levels of tumor necrosis factor-alpha are unlikely to affect a woman's risk of preterm delivery. Tumor necrosis factor-alpha variants should not be used as a predictive test for preterm delivery.

Adolescent↗

A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition.

OBJECTIVE: There is no evidence for the participation of the human fetus in the mechanisms responsible for the onset of preterm labor. We propose that preterm labor in the setting of infection results from the actions of proinflammatory cytokines secreted as part of the fetal and/or maternal host response to microbial invasion. The objective of this study was to determine whether a systemic fetal inflammatory response, defined as an elevation of fetal plasma interleukin-6 concentrations, has a temporal relationship with the commencement of labor. STUDY DESIGN: After informed consent was obtained, amniocentesis and cordocentesis were performed in 41 patients with preterm premature rupture of membranes who were not in labor on admission. Amniotic fluid was cultured for both aerobic and anaerobic bacteria, as well as for mycoplasmas. Fetal plasma interleukin-6 was assayed by a sensitive and specific immunoassay. Statistical analyses included contingency tables and survival analysis with time-dependent Cox regression hazard modeling. RESULTS: Microbial invasion of the amniotic cavity was present in 58.5% (24/41) of patients. Fetuses with fetal plasma interleukin-6 concentrations > 11 pg/mL had a higher rate of spontaneous preterm delivery within 48 and 72 hours of the procedure than those with fetal plasma interleukin-6 levels < or = 11 pg/mL (88% vs 29% and 88% vs 35%, respectively; P < .05 for all comparisons). Moreover, patients with initiation of labor and delivery within 48 hours of the procedure had a higher proportion of fetuses with plasma interleukin-6 values > 11 pg/mL than patients delivered > 48 hours (58% [7/12] vs 8% [1/13], respectively; P < .05). Survival analysis indicated that fetuses with elevated fetal plasma interleukin-6 levels had a shorter cordocentesis-to-delivery interval than those without elevated fetal plasma interleukin-6 concentrations (median 0.8 days [range 0.1 to 5] vs median 6 days [range 0.2 to 33.6], respectively; P < .05). Time-dependent Cox regression hazard modeling indicated that fetal plasma interleukin-6 level was the only covariate significantly associated with the duration of pregnancy after we adjusted for gestational age, amniotic fluid interleukin-6 level, and the microbiologic state of the amniotic cavity (P < .01). CONCLUSION: A systemic fetal proinflammatory cytokine response is followed by the onset of spontaneous preterm parturition in patients with preterm premature rupture of membranes.

Acute-Phase Reaction↗

Oral nicardipine versus intravenous magnesium sulfate for the treatment of preterm labor.

OBJECTIVE: The aim of this study was to compare the efficacy and safety of oral nicardipine in acute therapy for preterm labor with those of parenteral magnesium sulfate. STUDY DESIGN: Patients between 24 and 34 weeks' gestation with documented preterm labor were randomly assigned to receive oral nicardipine (n = 57) or intravenous magnesium sulfate (n = 65) as initial tocolytic therapy. Patients in the nicardipine group received a 40-mg loading dose and then 20 mg every 2 hours as needed to stop contractions (total 80 mg). Patients in the magnesium sulfate group received a 6-g bolus followed by 2 to 4 g/h to provide uterine quiescence. Patients could be switched to another tocolytic regimen if they continued to have contractions after 6 hours of therapy. The main outcome variables examined were time to uterine quiescence, time gained in utero, recurrence of preterm labor, failure of tocolysis, and pertinent maternal and neonatal outcomes. RESULTS: There were no significant differences in maternal demographic characteristics between the groups. Among patients who responded with uterine quiescence within 6 hours, there was a significant decrease in the time to uterine quiescence in the nicardipine group (P <.01). Patients in the magnesium sulfate group were more likely to have recurrence of preterm labor necessitating further tocolytic attempts (P =.048). The patients in the magnesium sulfate group had more adverse side effects, mainly nausea and vomiting (P =.004). There were no differences in birth weight, estimated gestational age at delivery, or neonatal complications between the 2 groups. CONCLUSIONS: Oral nicardipine is an effective, safe, and well-tolerated tocolytic agent. In this prospective clinical trial patients randomly assigned to receive oral nicardipine had arrest of preterm labor more rapidly than did those randomly assigned to receive parenteral magnesium sulfate. Patients who received magnesium sulfate were more likely to have adverse medication effects and recurrent preterm labor.

Administration, Oral↗

Maternal plasma corticotropin-releasing hormone associated with stress at 20 weeks' gestation in pregnancies ending in preterm delivery.

OBJECTIVE: This study tested the hypothesis that maternal stress is associated with elevated maternal levels of corticotropin releasing hormone and activation of the placental-adrenal axis before preterm birth. STUDY DESIGN: In a behavior in pregnancy study, 524 ethnically and socioeconomically diverse women were followed up prospectively and evaluated at 3 gestational ages: 18 to 20 weeks, 28 to 30 weeks, and 35 to 36 weeks. Maternal variables included demographic data, medical conditions, perceived stress level, and state anxiety. Maternal plasma samples were collected at each gestational age. Eighteen case patients with spontaneous onset of preterm labor were matched against 18 control subjects who were delivered at term, and their samples were assayed for corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol by means of radioimmunoassay. Statistical tests were used to examine mean differences in these hormones. In addition, the relationship between stress level and each hormone was tested with a Pearson correlation coefficient and hierarchic multiple regressions in each group. RESULTS: Patients who had preterm delivery had significantly higher plasma corticotropin-releasing hormone levels than did control subjects at all 3 gestational ages (P <.0001). Analyses did not find any differences in reported levels of stress between 18 to 20 weeks' gestation and 28 to 30 weeks' gestation. A hierarchic multiple regression indicated that maternal stress level at 18 to 20 weeks' gestation and maternal age accounted for a significant amount of variance in corticotropin-releasing hormone at 28 to 30 weeks' gestation, after controlling for corticotropin-releasing hormone at 18 to 20 weeks' gestation (P <. 001). In addition, patients who were delivered preterm had significantly elevated plasma levels of adrenocorticotropic hormone at all 3 gestational ages (P <.001) and significantly elevated cortisol levels at 18 to 20 weeks' gestation and 28 to 30 weeks' gestation (P <.001). CONCLUSION: Maternal plasma levels of corticotropin-releasing hormone are significantly elevated at as early as 18 to 20 weeks' gestation in women who are subsequently delivered preterm. Changes in corticotropin-releasing hormone between 18 to 20 weeks' gestation and 28 to 30 weeks' gestation are associated with maternal age and stress level at 18 to 20 weeks' gestation. Maternal stress and corticotropin-releasing hormone levels may be potential markers for the patient at risk for preterm birth. Activation of the placental maternal pituitary-adrenal axis is consistent with the classic endocrine response to stress.

Adult↗

A new model for inflammation-induced preterm birth: the role of platelet-activating factor and Toll-like receptor-4.

Preterm birth is a leading cause of neonatal morbidity and mortality. Despite a growing body of evidence correlating inflammation with preterm birth, the signal transduction pathways responsible for the emptying of the uterus in the setting of intrauterine inflammation has not been elucidated. We now report a unique, reproducible mouse model of localized intrauterine inflammation. This model results in 100% preterm delivery with no maternal mortality. Using our model, we also show that platelet-activating factor is a crucial mediator of both inflammation-induced preterm birth and fetal demise. Using C3H/HeJ mice, we demonstrate that toll-like receptor-4 (TLR-4) plays a role in lipopolysaccharide-induced preterm birth but not in inflammation-induced fetal death. Immunohistochemistry studies demonstrate the presence of the platelet-activating factor receptor in both endometrial glands and smooth muscle in uterine tissues. Molecular studies demonstrate the differential expression of platelet-activating factor receptor and TLR-4 in uterine and cervical tissue throughout gestation. Quantitative polymerase chain reaction revealed an up-regulation of TLR-4 in the fundal region of the uterus in response to intrauterine inflammation. The use of this model will increase our understanding of the significant clinical problem of inflammation-induced preterm birth and will elucidate signal transduction pathways involved in an inflammatory state.

Animals↗

Preterm low birth weight and periodontal disease among African Americans.

African Americans consistently experience higher rates of preterm and low birth weight (LBW) deliveries than do whites. LBW and preterm infants are more likely to die before their first birthday and survivors may suffer from a number of health problems. Therefore, identification of modifiable risk factors for preterm deliveries and LBW has considerable public health significance. Pregnant women's poor periodontal healtlh is emerging as one such factor. Maternal clinical periodontal status and bacteriologic and immunologic profiles related to periodontal disease have been associateted with risk of fetal growth and preterm LBW, and periodontal treatment during pregnancy has reduced the incidence of preterm deliveries. This article reviews the literature on the above association and presents data from a previously published prospective study of predominantly African Americans to show that preterm LBW deliveries are associated with higher midtrimester maternal serum antibody levels against Porphyromonas gingivalis.

Black or African American↗

Transvaginal ultrasonography of the uterine cervix in hospitalized women with preterm labor.

OBJECTIVE: The aim of this study was to examine the relation between cervical length and the presence of funneling and the risk of preterm delivery. METHOD: This prospective blind cohort involved 200 hospitalized women with preterm labor in a tertiary care hospital. Women were recruited for a single transvaginal ultrasonography to assess cervical length and presence of funneling. The main outcome measures were: (1) relative risks (RR) and adjusted odds ratios of preterm delivery (<37 weeks' gestation); (2) time interval between the cervical ultrasonography date to 37 weeks' gestation or to-preterm birth. RESULTS: The RR of preterm delivery according to the cervical length (cut-off of <30 mm) was 2.79 (95% CI 1.70--4.59). The RR according to the presence of funneling (cut-off of >5 mm) was 1.39 (95% CI 0.99--1.95). The adjusted odds ratio was 3.92 (95% IC 1.75--8.75) for cervical length and 0.77 (95% CI 0.35--1.67) for funneling. Women with a cervical length of <30 mm had a significantly shorter interval from ultrasonography date up to 37 weeks' gestation than did women with a cervical length of >30 mm (P<0.003). CONCLUSION: Ultrasonographic mensuration of the cervix provides predictive information on the risk of preterm delivery.

Adolescent↗

Maternal serum placental leucine aminopeptidase (P-LAP)/oxytocinase and preterm delivery.

OBJECTIVE: To test the applicability of maternal serum placental leucine aminopeptidase (P-LAP) as a parameter for predicting preterm delivery. PATIENTS AND METHODS: Maternal serum P-LAP activity of 61 consecutive women with preterm labor at admission were assayed and examined to assess the relationship of levels to the incidence of preterm and term deliveries. RESULTS: When P-LAP activity of study patient serum was at or below the 10th percentile, we found a greater ratio of preterm delivery (P=0.0085) and an approximately 2.3-fold increase risk. The sensitivity, specificity, positive predictive value and negative predictive value were 29, 97, 89 and 62%, respectively. CONCLUSION: Maternal serum P-LAP activity decreases in cases with spontaneous preterm delivery and may be a clinically potential marker for some cases of preterm labor.

Adult↗

Association of the Gln27Glu polymorphism of the beta-2-adrenergic receptor with preterm labor.

OBJECTIVES: To investigate a potential association between the beta-2-adrenergic receptor (B2AR) polymorphisms occurring at amino acid positions 16 (Arg16Gly) and 27 (Gln27Glu) and preterm labor. METHODS: Eighty patients with preterm labor and 76 control subjects were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: A significant association was found between Gln27Glu substitution and preterm labor (P=0.001). The frequency of Gly16 and Glu27 alleles were found to be higher in patients than in control women (0.54 vs. 0.48 and 0.42 vs. 0.26, respectively), and the odds ratio for the occurrence of preterm labor was 2.14 (95% CI, 1.32-3.46; P=0.002) for the Glu 27 allele. An early delivery was noted in 52.5% of patients. CONCLUSION: The Gln27Glu polymorphism of the B2AR gene may have a role in molecular pathogenesis of preterm labor. Glu27 allele in patients with preterm labor might be a risk factor for deliveries before 37 weeks of gestation.

Adult↗

Fetal fibronectin as a predictor of preterm delivery in twin gestations.

OBJECTIVE: To evaluate fetal fibronectin as a predictor of premature delivery in twin pregnancies. METHOD: Cervicovaginal secretions were obtained from 52 pregnant women with twin pregnancies between 24 and 34 weeks of gestation. The secretions were analyzed to detect the presence of fetal fibronectin by immediate-reading membrane test. The correlation between the presence of fetal fibronectin and preterm birth was evaluated. In addition, cervical dilatation and effacement were evaluated with each sampling. RESULT: The sensitivity, specificity, positive predictive value and negative predictive value to predict preterm delivery were 89.3, 50.0, 67.6, and 80.0%, respectively. A positive fetal fibronectin result was associated with a relative risk (RR) for preterm birth of 3.4 (95% CI, 1.2-9.5). A positive fetal fibronectin test associated with cervical dilatation or effacement increased the RR for preterm birth to 4.3 and 7.7, respectively, when compared with those with negative test and without cervical dilatation and effacement. CONCLUSION: Fetal fibronectin in the cervicovaginal secretions of patients with twin pregnancies is a sensitive predictor of preterm delivery. However, because of its low specificity, the fetal fibronectin test should be evaluated along with cervical changes for better identification of twins likely to develop preterm labor.

Adult↗