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C-reactive protein: a limited test for managing patients with preterm labor or preterm rupture of membranes?

C-reactive protein has been used to identify patients at high risk for infectious morbidity with preterm labor or preterm rupture of membranes. In this article we report on 104 patients with preterm labor symptoms (n = 45) or preterm rupture of the membranes (n = 59) and serial evaluations of C-reactive protein measured by latex agglutination and laser nephelometry. The simple, inexpensive latex method appears comparable to the laser method in predicting infectious morbidity and can be used clinically. Elevated C-reactive protein values before delivery predict infectious morbidity in only 8% to 29% of patients, and up to 18% of patients with serious infections may be misdiagnosed as having normal C-reactive protein values before delivery.

C-Reactive Protein↗

Barusiban, a new highly potent and long-acting oxytocin antagonist: pharmacokinetic and pharmacodynamic comparison with atosiban in a cynomolgus monkey model of preterm labor.

Preterm labor (PTL) represents a significant unmet clinical need that affects up to 20% of all pregnancies and is a leading cause of preterm delivery and associated neonatal morbidity and mortality. Therapeutic options are limited, with existing drug therapy (tocolytics) compromised by side effects and limited efficacy. Because oxytocin (OT) is likely to be involved causally in PTL, this study compared two OT receptor antagonists, barusiban and atosiban, for their tocolytic effects. OT was given to instrumented pregnant cynomolgus monkeys to induce contractions and simulate PTL. Barusiban or atosiban was then given iv (bolus or infusion) to evaluate inhibitory effects on uterine contractions, measured by telemetric recording of intrauterine pressure. Both antagonists had high efficacy (96-98% inhibition of intrauterine pressure) and rapid onset of action (0.5-1.5 h). Barusiban was three to four times more potent than atosiban, which was attributed to its higher affinity and selectivity for the OT receptor. Barusiban also had a much longer duration of action (>13-15 h, compared with 1-3 h for atosiban). The inhibitory effects of barusiban were reversible within 1.5-2.5 h by high-dose OT infusion. Overall, barusiban's improved potency, long duration of action, and reversibility may provide an improved tocolytic for treatment of PTL.

Animals↗

Regulation of uterine contraction: mechanisms in preterm labor.

Preterm labor (PTL) is defined as uterine irritability accompanied by cervical dilation and/or effecement that occurs before 37 weeks gestation. In most cases, PTL becomes preterm delivery (PTD), accounting for 8% to 10% of births in the United States. Fetuses born before 37 weeks' gestation are at risk for a multitude of health and developmental problems. Most perinatal morbidity and mortality in the United States are caused by PTL. It is a costly problem, in both monetary and human terms. Although some risk factors have been identified, they by no means identify, in advance, every case of PTL and PTD. Despite the understandable emphasis on attempts to find and test risk factors that predict PTL, the ultimate benefit--preventing PTD--will come only from an understanding of the physiologic mechanisms of parturition and how to halt those processes when they occur too early. This article reviews current approaches to preventing PTD, describes the biology of myometrial contraction, and discusses recent progress from several laboratories including the authors' that may shed light on approaches to inhibit uterine contractility in the setting of PTL.

Female↗

Preterm labor and preterm premature rupture of the membranes. Diagnosis and management.

Preterm delivery due to preterm labor and pPROM is responsible for most infant morbidity and mortality in the United States. The patient who presents with suspicious symptoms should undergo a thorough evaluation to confirm the diagnosis of either entity and identify a treatable cause. Determination of gestational age, fetal well-being, and the presence of intrauterine infection is a crucial step in subsequent management. Corticosteroid therapy has been demonstrated to be one of the most effective antenatal interventions to reduce infant morbidity and should be administered to patients with preterm labor, if feasible, when fetal pulmonary maturity is absent or undocumented. We recommend a similar protocol regarding gravidas with pPROM remote from term but recognize the need for further study in this area. Acute tocolytic therapy has been demonstrated to offer short-term benefit to enhance corticosteroid effect. However, all of the available tocolytic agents carry significant risks to the mother and fetus. As such, administration of these agents should be given only when the potential benefits outweigh the risks of administration. Evaluation for fetal pulmonary maturity and intrauterine infection, in concert with evaluation of gestational age-dependent risks of prematurity, may be helpful in determining whether tocolysis should be attempted. Adjunctive antibiotic administration has not been shown to reduce maternal or infant morbidity in the face of preterm labor. However, such treatment offers a reduction of chorioamnionitis, prolongation of latency, and a possible reduction of neonatal infectious and gestational age-dependent morbidity in the setting of pPROM remote from term. Finally, current guidelines recommend the administration of intrapartum GBS prophylaxis when preterm birth or prolonged membrane rupture is anticipated if GBS carrier status is unknown or positive. Intrapartum treatment with intravenous penicillin or ampicillin is appropriate.

Adrenal Cortex Hormones↗

Pharmacotherapy of preterm labor.

Preterm labor is defined as the onset of uterine contractions in a woman who has completed less than 37 weeks of pregnancy. It may be due to maternal, placental, fetal, or idiopathic causes, and it is associated with a number of risk factors. Nondrug measures such as bedrest and hydration have been used alone or in combination with drug therapy to treat the disorder. Pharmacologic (tocolytic) agents include ethanol, progesterone, indomethacin, nifedipine, beta-adrenergic agonists, and magnesium salts. The three most commonly used drugs are ritodrine, terbutaline, and magnesium.

Clinical Trials as Topic↗

Activation of coagulation system in preterm labor and preterm premature rupture of membranes.

OBJECTIVE: Thrombin, originally discovered as a coagulation factor, is a multifunctional protease capable of inducing myometrial contractions in vitro and in vivo. This enzyme has been implicated in the mechanisms of premature labor. Plasma concentrations of thrombin-antithrombin (TAT) complexes are an index of in vivo thrombin generation. The purpose of this study was to determine whether patients with premature labor and preterm premature rupture of membranes (PROM) have evidence of increased thrombin generation in maternal blood, as determined by the TAT complex concentrations. METHODS: A cross-sectional study was designed to determine plasma concentrations of TAT complexes in 110 women in the following groups: non-pregnant women (n = 20); normal pregnant women (n = 30); women in preterm labor with intact membranes (n = 30); and women with preterm PROM (n = 30). TAT complex concentrations were determined with a sensitive and specific immunoassay. Statistical analysis was conducted with non-parametric statistics. RESULTS: Patients with preterm labor and intact membranes had a significantly higher median plasma TAT complex concentration than normal pregnant women (women in preterm labor, median 19.1 microg/l; range 7.4-406 vs. normal pregnant women, median 15 microg/l; range 6.8-32.5; p = 0.03). Patients with preterm PROM had a higher median TAT complex concentration than normal pregnant women (preterm PROM, median 19.1 microg/l; range 4.7-738.6 vs. normal pregnant women, median 15 microg/l; range 6.8-32.5; p = 0.03). Normal pregnancy was associated with a higher median plasma TAT complex concentration than the non-pregnant state (normal pregnant women, median 15 microg/l; range 6.8-32.5 vs. non-pregnant women, median 2.7 microg/l; range 0.9-14.2; p < 0.001). CONCLUSION: Preterm labor and preterm PROM are associated with an excess generation of thrombin.

Adolescent↗

A systematic approach to the management of preterm labor.

Preterm birth occurs in 7% to 12% of all deliveries, but accounts for over 85% of all perinatal morbidity and mortality. Although the ability of obstetric care providers to identify women at risk for preterm delivery has improved, the overall incidence of preterm birth has remained unchanged for the past 30 years. Preterm birth remains the single greatest challenge for physician-researchers in the field of maternal-fetal medicine in the 21st century. This article reviews in detail the current state of the literature as regards the etiology, pathophysiology, prevention, and treatment of premature labor and preterm birth. A better understanding of the molecular mechanisms responsible for the process of labor, both at term and preterm, will improve our ability to identify and manage women at risk of premature delivery.

Animals↗

Expression of bone morphogenetic protein 2 in normal spontaneous labor at term, preterm labor, and preterm premature rupture of membranes.

OBJECTIVE: Genome-wide screening studies of the chorioamniotic membranes unexpectedly identified an increase in the expression of bone morphogenetic protein 2 in spontaneous labor at term. The objective of this study was to determine whether bone morphogenetic protein 2 messenger RNA and protein expression are altered in the chorioamniotic membranes of patients with term labor, preterm labor, and preterm premature rupture of membranes. STUDY DESIGN: Chorioamniotic membranes were obtained from patients at term (with and without labor), with preterm labor (with and without histologic chorioamnionitis), and with preterm premature rupture of membranes (with and without histologic chorioamnionitis). The expression of bone morphogenetic protein 2 was studied by real-time quantitative reverse transcriptase-polymerase chain reaction (n = 88) and immunohistochemistry (n = 124). Nonparametric statistics were used for analysis. Primary amnion cells obtained from women at term not in labor were treated with bone morphogenetic protein 2 to examine whether there was increased prostaglandin E2 expression. RESULTS: The median bone morphogenetic protein 2 messenger RNA and protein expression were significantly higher in the membranes of patients with spontaneous labor at term than in those of patients not in labor at term (P < .001 for both). Bone morphogenetic protein 2 messenger RNA and protein expression were increased in patients with preterm labor with histologic chorioamnionitis than in those without histologic chorioamnionitis (P < .05 and P < .001, respectively). There was no difference in bone morphogenetic protein 2 messenger RNA and protein expression in patients with preterm premature rupture of membranes, regardless of chorioamnionitis (P = .13 and P = .08, respectively). There was a correlation between bone morphogenetic protein 2 and cyclooxygenase 2 protein expression in chorioamniotic membranes (R = .34; P < .001). CONCLUSION: Bone morphogenetic protein 2 messenger RNA and protein expression are increased in the chorioamniotic membranes of patients with spontaneous labor at term and patients with preterm labor associated with histologic chorioamnionitis. Its expression pattern and biologic effects strongly suggest that bone morphogenetic protein 2 is involved in human parturition.

Amnion↗

Terbutaline pump maintenance therapy after threatened preterm labor for preventing preterm birth.

BACKGROUND: Women with preterm labor that is arrested with tocolytic therapy are at increased risk of recurrent preterm labor. Terbutaline pump maintenance therapy has been given to such women to decrease the risk of recurrent preterm labor, preterm birth, and its consequences. OBJECTIVES: To determine the effectiveness and safety of terbutaline pump maintenance therapy after threatened preterm labor in preventing preterm birth and its complications. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (searched May 2002) and the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2002). SELECTION CRITERIA: Randomized trials comparing terbutaline pump maintenance therapy with alternative therapy, placebo, or no therapy after threatened preterm labor. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the studies for inclusion and then extracted data from eligible studies. MAIN RESULTS: We included two studies. Terbutaline pump maintenance therapy did not appear to offer any advantages over the saline placebo pump or oral terbutaline maintenance therapy in preventing preterm births by prolonging pregnancy or its complications among women with arrested preterm labor. The weighted mean difference (WMD) for gestational age at birth was -0.1 weeks (95% confidence interval (CI) -1.7 to 1.4) for terbutaline pump therapy compared with saline placebo pump for both trials combined and 1.4 weeks (95% CI -1.1 to 3.9) for terbutaline pump versus oral terbutaline therapy for the first trial. The second trial reported a relative risk (RR) of 1.17 (95% CI 0.79 to 1.73) of preterm birth (less than 37 completed weeks) and a RR of 0.97 (95% CI 0.51 to 1.84) of very preterm birth (less than 34 completed weeks) for terbutaline pump compared with saline placebo pump. Terbutaline pump therapy also did not result in a higher rate of therapy continuation or a lower rate of infant complications. No data were reported on long-term infant outcomes, costs, or maternal assessment of therapy. REVIEWER'S CONCLUSIONS: Terbutaline pump maintenance therapy has not been shown to decrease the risk of preterm birth by prolonging pregnancy. Furthermore, the lack of information on the safety of the therapy, as well as its substantial expense, argues against its role in the management of arrested preterm labor. Future use should only be in the context of well-conducted, adequately powered randomized controlled trials.

Drug Administration Schedule↗

[Nifedipine first choice in management of threatening preterm labor].

Preterm birth is the most important cause of perinatal mortality in Europe and North America. Tocolytic agents named beta 2-sympathicomimetics postpone delivery for 24-48 hours, but do not reduce perinatal mortality or morbidity. Calcium antagonists, in particular nifedipine, are more effective tocolytic agents than beta 2-sympathicomimetics in terms of delaying delivery. Meta-analyses have found that calcium antagonists statistically significantly reduced perinatal morbidity and that the number of maternal side effects was statistically significantly lower compared with beta 2-sympathicomimetics. Nifedipine also has the benefit of oral administration, in contrast with beta 2-sympathicomimetics which are administered intravenously. Nifedipine is therefore the first choice in the management of threatening preterm labour.

Administration, Oral↗

New strategies for preterm labor.

Preterm birth is the leading cause of perinatal mortality and morbidity despite the technological advances in neonatology and maternal-fetal medicine. Risk factors have been tabulated that can help identify the woman at risk for preterm birth. Past medical history, present pregnancy events, and demographic/environmental characteristics can help the practitioner select women who need special care to help prevent or reduce the effects of premature delivery. Recently, new concepts of risk have been identified through research, and emphasis needs to shift from intervention to prevention of the low birth weight infant. Past and present management of premature labor is discussed. New research protocols are presented. Strategies for nurses working in family planning or obstetrical areas are discussed, demonstrating areas for interventions from a prevention-oriented nursing base.

Family Planning Services↗

Does "idiopathic" preterm labor resulting in preterm birth exist?

OBJECTIVE: In an effort to elucidate possible causes of preterm labor, we undertook a prospective study of 50 patients consecutively admitted with intact membranes and preterm labor who eventually had a preterm delivery despite the use of tocolysis. STUDY DESIGN: A comprehensive evaluation plan was instituted. This included a detailed history and physical examination, targeted ultrasonography, amniocentesis for Gram stain, culture, and glucose determination, laboratory analysis for infection (complete blood cell count, urinalysis, and cervical and urine cultures) and for antiphospholipid antibody syndrome (antinuclear antibody, lupus anticoagulant, anticardiolipin antibody), pathologic examination of the placenta, and a urine toxicology screen. RESULTS: The following groups of possible causes of preterm labor were identified: (1) faulty placentation, 50% (25/50); (2) intrauterine infection 38% (19/50); (3) immunologic factors, 30% (15/50); (4) cervical incompetence, 16% (8/50); (5) uterine factors, 14% (7/50); (6) maternal factors 10% (5/50); (7) trauma and surgery, 8% (4/50); (8) fetal anomalies, 6% (3/50); and (9) idiopathic conditions, 4% (2/50). Among the 50 patients two or more possible causes were identified in 58% (29/50). CONCLUSION: We suggest that an exhaustive evaluation plan can identify possible causes in the majority (96%) of cases of "idiopathic" preterm labor that result in preterm delivery.

Female↗

Involvement of oxytocin and vasopressin in the pathophysiology of preterm labor and primary dysmenorrhea.

Important sources of oxytocin and vasopressin in the human, apart from the supraoptic and paraventricular nuclei of the brain, may be the fetus during labor as well as the endometrium and decidua of the uterus itself. The release of oxytocin and vasopressin to plasma is under influence of ovarian steroids. The two hormones stimulate uterine contractions in pregnant and non-pregnant women via myometrial oxytocin and vasopressin V1a receptors. At the onset of human labor preterm or at term no clear rise in the maternal plasma concentration of oxytocin and/or vasopressin has been demonstrated, but there may be an increased pulse frequency of the release of oxytocin to plasma with the advance of labor. Vasopressin is more potent than oxytocin on isolated myometrium from women undergoing Cesarean section at term. The myometrial concentration of the two receptors is about equal. At the onset of labor preterm and at term there is a tendency to an increase in the density of oxytocin and vasopressin V1a receptors, but there may be a heterogeneous expression of at least the former receptor between different myometrial cells. In advanced labor or after oxytocin treatment the receptors are markedly downregulated. The importance of oxytocin and vasopressin in mechanisms of preterm labor is confirmed by the therapeutic effect in the condition of the oxytocin and vasopressin V1a receptor blocking oxytocin analogue, atosiban. In women with primary dysmenorrhea the plasma concentration of vasopressin is elevated. The in vivo effect of vasopressin on uterine activity in non-pregnant women is about five times more pronounced than that of oxytocin, and it increases premenstrually. Correspondingly, the density of vasopressin V1a and oxytocin receptors vary to the same degree, and a premenstrual rise in the former receptor is seen. Atosiban and the non-peptide compound, SR 49059, which binds to the two receptors in a similar way as atosiban, are therapeutically effective in dysmenorrhea.

Dysmenorrhea↗

A review of the role of proinflammatory cytokines in labor and noninfectious preterm labor.

The prevention of preterm labor has the potential to reduce newborn morbidity and mortality by decreasing the incidence of preterm birth. Half of all preterm births occur in women with no known clinical risk factors. Labor onset and progress is multifactorial, and we are just beginning to understand the role of cytokines in uterine activity. The purpose of this article is to review the role of cytokines in labor and preterm labor not associated with infection and to provide implications for research and practice.

Cytokines↗

[Biopsychosocial predictors of preterm labor and preterm delivery? Results of a prospective study].

RESEARCH QUESTION: In addition to medical, job related, sociodemographic risk factors, and health related behavior, topics that traditionally have been less in the focus of attention in this context, such as biographic data, coping with stress, personality variables, pregnancy related attitudes, fears, and the social network were examined. PATIENTS AND METHODS: 589 women between 16(th) and 22(nd) week of pregnancy were examined using a questionnaire that was designed for the study. This resulted in 508 women pregnant with a single child, whose pregnancy and delivery were examined based on their medical records. Factor analysis and main component analysis with subsequent varimax rotation resulted in factors that were subject to a proof of reliability. Statistical analysis was based on logistic regression. RESULTS: 129 (27.7%) of women displayed signs/indices of an imminent preterm delivery, 29% (5.8%) of whom later actually had a preterm delivery before the end of the 37(th) week of pregnancy. Pregnant women who were in treatment for an imminent preterm delivery appear to have been subject to higher social stress as compared to those, who later later actually gave birth before completing the 37(th) week of pregnancy. Lack of a female network and lack of emotional understanding from the partner are correlated to both of these complications. Specifically, actual preterm delivery appears to be significantly influenced by partner relationship. Another significant predicting variable for imminent and actual preterm delivery appears to be a history of gynecological problems. A distinct risk factor for delivery before completion of the 37(th) week of pregnancy was a history of colpitis. In addition, pronounced anxieties in respect to the pregnancy, and low general anxiety were significant predicting variables for delivery before completion of the 37(th) week of pregnancy. CONCLUSIONS: Partner relationship, female networks, psychosomatic reactivity in terms of diseases/disorders of the reproductive organs, and anxieties appear to be worthwhile targets in the prevention of preterm delivery.

Female↗

The relationship between oligohydramnios and the onset of preterm labor in preterm premature rupture of membranes.

OBJECTIVE: The objective of this study was to determine whether a reduced amniotic fluid volume was associated with the onset of preterm parturition in patients with preterm premature rupture of membranes. STUDY DESIGN: An amniotic fluid index was determined before transabdominal amniocentesis in 129 patients with preterm premature rupture of membranes (gestational age < or = 35 weeks). Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas. Survival techniques were used for analysis. RESULTS: Amniotic fluid index was < or = 5 cm in 29% of patients (38/129). Patients with an amniotic fluid index of < or = 5 cm had a significantly higher rate of positive amniotic fluid culture than those with an amniotic fluid index of >5 cm (42% [16/38] vs 18% [16/91]; P<.01). Spontaneous preterm delivery within 24 hours and 48 hours was more frequent among patients with an amniotic fluid index of < or = 5 cm than those with an amniotic fluid index of >5 cm (for 24 hours, 29% vs 12%; for 48 hours, 42% vs 21%; P<.05 for each). The amniocentesis-to-delivery interval was significantly shorter in patients with an amniotic fluid index of < or = 5 cm than in patients with an amniotic fluid index of >5 cm (median, 38 hours; range, 0.2-1310 hours; vs median, 100 hours; range 0.1-2917 hours; P<.01). Moreover, Cox proportional hazards model analysis indicated that an amniotic fluid index of < or = 5 cm was a significant predictor of the duration of the pregnancy after adjustment for gestational age and the results of amniotic fluid culture (odds ratio, 2.4; 95% confidence interval, 1.4-3.9; P<.001). CONCLUSION: Patients with preterm premature rupture of membranes and an amniotic fluid index of < or = 5 cm are at increased risk for a shorter interval to delivery.

Adult↗

Bacterial isolates from patients with preterm labor with and without preterm rupture of the fetal membranes.

OBJECTIVE: The aim of this study is to describe the bacterial flora of women in preterm labor with or without premature rupture of membranes. METHODS: Retrospective studies of 239 patients with preterm labor were performed. RESULTS: One hundred and twenty-three of 239 patients with preterm labor (51.5%) had bacterial vaginosis. Seventy of the 239 patients with preterm labor (29.3%) developed premature rupture of the membranes (preterm PROM). Of the 70 patients with preterm PROM, 51 (72.9%) had bacterial vaginosis. Therefore, 51 of the 123 patients with bacterial vaginosis (41.5%) developed preterm PROM. An increased number of organisms detected from the vaginal discharge in patients with preterm labor was associated with preterm PROM by Cochran-Armitage test. An increased number of organisms detected from the vaginal discharge in patients with preterm labor complicated with bacterial vaginosis was significantly associated with preterm PROM by Cochran-Armitage test. CONCLUSIONS: In preterm labor, the number of different species detected in the vagina provide sensitive and specific prediction of preterm PROM in patients with preterm labor.

Bacteria, Aerobic↗