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The incidence of preterm labor and specific risk factors.

A retrospective review of patients at high risk for preterm delivery because of twin gestation, uterine malformation, incompetent cervix, or previous preterm delivery was carried out to assess the rates of preterm labor and spontaneous preterm birth. Among the 119 patients with multifetal gestation, 46% had preterm labor and 36% delivered before 37 weeks' gestation. In the 58 patients with an anomalous uterus, the rate of preterm labor was 19%, and 14% had early deliveries. Of those with incompetent cervices (115), one-fourth had preterm labor and 17% had an early birth. When a history of one or more preterm deliveries was present, the preterm labor rate ranged from 41-68%, with an early delivery rate of 30-47%. Prophylactic tocolytic therapy did not prolong gestations significantly. Maternal smoking did not have an adverse effect on the incidence of preterm labor except in twin pregnancies, for which early delivery was more likely. The percentages for preterm delivery are slightly lower than those found in the literature; this may be attributable to improvement in preterm birth prevention efforts including patient education, more frequent examinations, home uterine activity monitoring, and daily nursing contact.

Female↗

The value of cervical length and plasma proMMP-9 levels for the prediction of preterm delivery in pregnant women presenting with threatened preterm labor.

OBJECTIVE: To assess the value of plasma proMMP-9 levels in predicting the progress of threatened preterm labor to true preterm labor and delivery within 7 days of presentation, along with the ultrasonographic measurement of cervical length. STUDY DESIGN: The study included sixty two pregnant women presented in the 2nd Department of Obstetrics and Gynecology of University of Athens at Aretaieion Hospital with threatened preterm labor. On subjects' presentation, cervical length was evaluated with transvaginal ultrasonography, plasma proMMP-9 levels were measured with the use of a solid phase enzyme immunoassay, and maternal characteristics (smoking, history of preterm delivery and parity) as well as the use of tocolytics were recorded. Subjects were followed up for premature delivery within 7 days. ROC analysis for plasma proMMP-9 levels was performed and logistic regression analysis was used for the evaluation of the prognostic effect of the parameters. RESULTS: The only significant predictors for establishment of true preterm labor and delivery within 7 days of presentation were cervical length (with cutoff value 15 mm: odds ratio=0.022, 95% CI=0.002-0.243, p=0.002) and plasma proMMP-9 (with cutoff value 67.15 ng/ml: odds ratio=0.035, 95% CI=0.003-0.388, p=0.006). The combination of the adopted proMMP-9 and cervical length cutoff values was characterized by a sensitivity of 90.9% and a specificity of 98.3% for predicting the progress to true preterm labor and delivery. CONCLUSION: Plasma proMMP-9 levels could possibly serve as a predictive factor for the progress of threatened preterm labor to true preterm labor and delivery within 7 days of presentation, along with the ultrasonographic evaluation of cervical length.

Adult↗

Resolving the uncertainty of preterm symptoms: women's experiences with the onset of preterm labor.

OBJECTIVE: To describe expectant women's experiences with the onset of preterm labor. DESIGN: Qualitative, using grounded theory methods. SETTING: Southwestern tertiary women's hospital. PARTICIPANTS: Thirty pregnant women who were less than 35 weeks gestation, had experienced preterm labor within the past 7 days, and had no previous experience with preterm labor. DATA SOURCE: Taped and transcribed interviews. RESULTS: Themes that emerged from the interview data included the following: recognition and naming of sensations, a consistent pattern of attribution of symptoms, the threat or risk inferred by the attributed cause of the symptom pattern, the associated certainty or uncertainty about these attributions, the process of interpreting and verifying symptom meaning, and the decision to self-manage the symptoms or engage health care assistance. The core process of women experiencing the onset of preterm labor symptoms was identified as "resolving the uncertainty of preterm labor symptoms: recognizing and responding to the possibilities." CONCLUSIONS: Preterm labor often is not within expectant women's consciousness. They may attribute the symptoms to nonthreatening causes, which results in delays in seeking care for preterm labor. Education about symptom patterns at the onset of preterm labor will increase the probability that women and their health care providers will recognize and interpret the early, subtle symptoms that herald the onset of preterm labor. Uncertainty in illness theory and attribution theory offer frameworks for understanding women's experiences with the onset of preterm labor.

Adult↗

Serum magnesium levels in pregnancy and preterm labor.

Pregnancy is marked by a state of hypomagnesemia. The serum magnesium level shows no gestational dependence (mean, 1.79 +/- 0.44 mg/dl) until 33 weeks, at which point it continuously declines. Serum magnesium is not depressed further with the onset of labor at term. Patients in preterm labor have a significantly depressed serum magnesium level (mean, 1.60 +/- 0.46 mg/dl; 21 to 33 weeks; p less than 0.0005). This level was not dependent on whether the etiology for the preterm labor was premature rupture of the membranes (PROM), twin gestation, abruption, placenta previa with bleeding, or chorioamnionitis. With PROM, the serum magnesium level was not depressed prior to the initiation of preterm labor. However, observation of hypomagnesemia for this and other etiologies just prior to the initiation of preterm labor were not available. Possible mechanisms by which hypomagnesemia induces uterine irritability are explored, including inhibition of adenyl cyclase with resultant increase in cytoplasmic calcium levels. Patients with diabetes mellitus appeared to have slightly reduced serum magnesium levels, but the results were not statistically significant. Magnesium levels in patients with preeclampsia were not significantly different from controls. Hypomagnesemia (magnesium 1.4 mg/dl or less) may be a marker for true preterm labor.

Calcium↗

[Management of threatening preterm labor with intact membranes: indications for antibiotics].

OBJECTIVE: To analyse the benefits and disadvantages of systematic antibiotic therapy in patient presenting a preterm labor with intact membranes. METHODS: We reviewed French and English reports on Medline using to the following key words: "antibiotic therapy and preterm labor, preterm labor, streptococcus B, vaginose, mycoplasma, antenatal infection". RESULTS: The systematic prescription of antibiotics is not recommended for patients presenting preterm labor who have intact membranes and no symptoms of infection. The benefit of antibiotics is small and shows a tendency to prolong the pregnancy and the reduction of maternal infection. No benefit has been shown for neonatal results. When early-onset neonatal sepsis develops in a case in which antepartum chemoprophylaxis was used, the isolated bacteria will present an increasing risk of bacterial drug resistance. Local treatment (cream or pessary) do not belong in the treatment of threatening preterm labor and are not recommended for the prevention of prematurity or materno fetal infection. Risk groups of patients who present a positive vaginal colonization are subject to discussion. Studies do not allow us to ascertain that antibiotics have a beneficial effect on prematurity in these groups. Antibiotics are recommended for the treatment of asymptomatic bacteriuria. This treatment reduces prematurity and maternal infections. Despite poor consensus criteria, if threatening preterm labor is associated with a bacteriuria, experts usually recommend treatment.

Anti-Bacterial Agents↗

Treatment of preterm labor with the beta-adrenergic agonist ritodrine.

BACKGROUND: Beta-adrenergic agonists are commonly used to arrest premature labor. Although treatment of preterm labor with these agents can delay delivery by 24 to 48 hours, the potential risks and benefits to the mother and infant before and after delivery have not been adequately assessed. METHODS: We randomly assigned 708 women with preterm labor at six hospitals to receive an intravenous infusion of either the beta-adrenergic agonist ritodrine (n = 352) or placebo (n = 356). Assignment was made with stratification according to four categories of gestational age (20 to 23 weeks, 24 to 27 weeks, 28 to 31 weeks, and 32 to 35 weeks). The primary objective was to assess the effect of ritodrine on perinatal mortality. Secondary objectives were the evaluation of the causes of perinatal death, the extent to which delivery was delayed with ritodrine, and the effects on birth weight, maternal morbidity, neonatal morbidity, and infant morbidity at 18 months of postnatal age, corrected for preterm delivery. RESULTS: Among the 771 infants born to the women in the study (including 63 pairs of twins), there were 23 deaths (6.1 percent) in the ritodrine group and 25 deaths (6.4 percent) in the placebo group (event-rate difference, -0.3 percent; 95 percent confidence interval, -3.7 percent to 3.1 percent). There was no difference between the groups in the extent of delay of delivery, the incidence of delivery before 37 weeks' gestation, the proportion of babies weighing less than 2500 g, or measures of neonatal morbidity. Maternal morbidity (such as chest pain and cardiac arrhythmias) occurred more frequently but not exclusively in the ritodrine group. One infant born to a woman in the ritodrine group and five infants born to women in the placebo group had cerebral palsy (P = 0.09). There was a slight but not significant trend toward an improved score on the Bayley Psychomotor Development Index at 18 months of age among the infants of the ritodrine-treated women. CONCLUSIONS: We found that the use of ritodrine in the treatment of preterm labor had no significant beneficial effect on perinatal mortality, the frequency of prolongation of pregnancy to term, or birth weight.

Birth Weight↗

Preterm labor: emerging role of genital tract infections.

Preterm birth complicates 8-10% of all pregnancies in the United States and is the leading cause of infant morbidity and mortality. Neonatal morbidity and mortality is concentrated among very low-birthweight and extremely premature infants, particularly those delivered prior to 30 weeks' gestational age. In addition to the contribution of preterm birth to neonatal morbidity and mortality, the economic costs associated with this pregnancy complication are staggering. Efforts to reduce the preterm birth rate have been largely focused on prevention and early intervention with treatment for preterm labor. Mixed results regarding the success of prematurity prevention programs have been reported, and controversy continues to surround the efficacy of tocolytic therapy in the treatment of preterm labor. Although neonatal survival for infants born at early gestational ages has steadily improved in recent years, survival of infants delivered prior to 24 weeks' gestation remains very poor. Additionally, despite this decline in neonatal mortality, the United States still lags behind most industrialized nations in infant mortality, and no change in the rate of low birthweight has occurred in recent decades. Multiple lines of evidence support a role for infection as an etiologic factor in preterm labor. Although this association has been well known for many years, a wealth of new data is emerging, linking subclinical genital tract infection with spontaneous preterm birth, particularly among pregnancies that result in birth prior to 30 weeks' gestational age as a result of spontaneous preterm labor or preterm, premature rupture of membranes. Conversely, preterm birth that occurs closer to term is less likely to be associated with genital tract infection. Improved understanding of the link between genital tract infection and preterm birth now provides an exciting potential for the development of sensitive new markers to identify women at risk and effective interventions to prevent preterm birth. A review and comment on this growing literature is provided.

Biomarkers↗

Distinct molecular events suggest different pathways for preterm labor and premature rupture of membranes.

OBJECTIVE: On a clinical level, the etiologies associated with premature rupture of the membranes and preterm labor are virtually identical, though these conditions end in distinctly different events. This study was designed to determine differences between preterm labor and preterm premature rupture of membranes by using molecular markers of extracellular matrix degradation and apoptosis. STUDY DESIGN: Amniochorion and amniotic fluid samples were collected from gestational age-matched groups of women undergoing cesarean delivery before term. Samples were collected from 2 groups of women, women with premature rupture of membranes and women with preterm labor with no rupture of membranes. Changes in the expression pattern of messenger ribonucleic acid for matrix metalloproteinases (MMP), tissue inhibitor of metalloproteinases (TIMP), and pro-apoptotic (p53 and Bax) and anti-apoptotic (Bcl-2) proteins were identified by quantitative polymerase chain reaction. Enzyme-linked immunosorbent assay was used to determine the levels of these proteins in the amniotic fluid. Multiplex polymerase chain reaction was performed to study the expression of Fas-Fas ligand-associated pro-apoptotic genes. Unpaired nonparametric, 2-tailed Mann-Whitney U test was used to determine statistical significance of quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (P <.05 was considered significant). RESULTS: Quantitative polymerase chain reaction results demonstrated an increased mRNA expression for MMP2, MMP9, and MT1-MMP and a decreased expression for TIMP2 in prematurely ruptured membranes compared with preterm labor membranes. Enzyme-linked immunosorbent assay documented increases in the amniotic fluid concentrations of immunoreactive and bioactive MMP2 and MMP9 and immunoreactive MMP3 and a decreased TIMP2 concentration in fluids obtained from the premature rupture of membranes group compared with the preterm labor group. The pro-apoptotic genes p53 and bax were up-regulated in premature rupture of membranes when compared with preterm labor. Anti-apoptotic gene (Bcl-2 ) expression was increased in preterm labor membranes compared with prematurely ruptured membranes. Interleukin-18 (a pro-apoptotic cytokine) was increased in the amniotic fluid during premature rupture of membranes compared with preterm labor. Prematurely ruptured membranes also demonstrated fragmented deoxyribonucleic acid and expression of Fas and caspase 8 (apoptosis initiator), which were all absent in preterm labor membranes. CONCLUSIONS: We have begun to delineate 2 divergent molecular pathways for premature rupture of membranes and preterm labor. Most likely, this is the beginning of the identification of differences that will become evident with the use of molecular biology.

Amniotic Fluid↗

Strategies women engage in when managing preterm labor at home.

Despite widespread efforts to prevent preterm birth in the United States, greater than 10% of the more than 4 million births that occur each year are preterm. Up to 75% of morbidity and mortality in infants is linked to preterm labor and birth. Bed rest, which may have adverse physical and psychologic effects, is commonly prescribed to manage preterm labor. This study describes the experience of women in programs of home management for preterm labor. Interview data from 25 women treated at home for preterm labor were analyzed with the grounded theory method. Findings from this study indicate that the process of home management of preterm labor involves managing activity restriction. Women employed certain strategies when demands from relationships, households, and careers competed with the prescription of bed rest. These strategies included cheating, piggybacking, and testing the limits of their activity restriction. Implications for research and practice are suggested.

Activities of Daily Living↗

Women's views of the preterm labor experience.

This study used a naturalistic approach to describe the childbearing woman's views of her preterm labor and delivery experience. Specifically, the aim was to identify how women describe, interpret, and manage preterm labor and subsequent preterm or term delivery. The views of 20 women who were hospitalized for preterm labor (before 37 weeks) were documented with semistructured, tape-recorded, in-depth interviews during their hospitalization for preterm labor and after delivery. Qualitative data analysis focused on the process of becoming a preterm labor patient and on living with a diagnosis of preterm labor. Women either waited for a period of time before seeking care or sought care immediately for the symptoms they were experiencing. Women interpreted the experience by identifying causes of preterm labor and by worrying about the outcome for the baby. Managing preterm labor required extensive, moderate, or limited changes in their lives. Women who delivered at term appeared to have more tangible help than those who delivered preterm. A better understanding of women's preterm labor experiences will provide clues to nurses on how to improve the care they provide.

Adolescent↗

Review on prostaglandin and oxytocin activity in preterm labor.

The principal difference between term and preterm labor is how they are activated. It has been proposed that term labor results from physiological activation of the common terminal pathway, whereas preterm labor is a pathological condition caused by multiple etiologies that activate one or more of the components of this pathway. Increased uterine contractility at preterm labor results from activation and stimulation of the myometrium. Myometrium is stimulated by increased concentrations ofprostaglandins and oxytocin. Increased production of stimulatory prostaglandins by intrauterine tissues is generally considered a central component of the cascade of events leading to preterm parturition. Prostaglandins act to mediate cervical ripening and to stimulate uterine contractions and indirectly to increase fundally dominant myometrial contractility by up regulation of gap junctions, oxytocin and arginine vasopressin receptors and synchronizations of contractions. The authors tried to explain the role and influence of oxytocin in human parturition, as well as the novel therapy in inhibiting the contractions in preterm labor. The selective oxytocin inhibitor was tested in vitro on human myometrium and decidua by the author of this article among the first in the world.

Adult↗

Antibiotics and preterm labor.

In summary, a definite association has been demonstrated between preterm labor and genital tract infection. Conclusions regarding the true benefits of antibiotics as adjunctive therapy in treatment of preterm labor are inconsistent. Whereas some of the studies were able to demonstrate significant prolongation of pregnancy, no consistent reduction in either maternal or neonatal morbidity has been demonstrated. However, because the actual incidental morbidity rate is low in the populations studied, the power of this finding is also low. The potential risks for using antimicrobials has yet to be adequately addressed. It has been shown that bacterial resistance can develop when antibiotics are used without specific aim or when a specific bacteria is undertreated. It has been recently shown that prenatal and intrapartum antibiotic use is associated with an increased risk for antibiotic resistant neonatal sepsis if infection occurs. Because of these reasons, we discourage the administration of antibiotic treatment to women in preterm labor for the purpose of pregnancy prolongations. Treatment should be directed towards those with specific indications for treatment (e.g., intrapartum, group B streptococci prophylaxis, urinary tract infection, etc). The primary flaw in these many evaluations of preterm labor is the true incidence of preterm birth. The clinical diagnosis of preterm labor is a difficult one. Approximately one-half of those individuals with preterm contractions will not deliver until term. So, the use of antibiotics for all women in idiopathic preterm labor is destined to treat many women who are unlikely to benefit. If we were able to truly identify those who were in "true" labor, perhaps we could be more selective in determining who may benefit from antibiotics. Biochemical markers such as onco-fetal fibronectin could well-be a helpful marker. Goldberg et al evaluated FFN in vaginal and cervical secretions while attempting to better-predict who would have upper genital tract infection. In this large, multicenter trial, patients were tested for FFN every 2 weeks from 23 to 30 weeks gestation. In those patients who proceeded to deliver before 32 weeks gestation, increased levels of cervical FFN (> 50 ng/ml) were identified in approximately one-quarter. Fetal fibronectin was positive in 4% of their samples and was found to be twice as likely in one with bacterial vaginosis. They showed that the presence of increased FFN was associated with upper genital tract infection (clinical and histologic chorioamnionitis) as a main reason for preterm labor and delivery (increased risk 16-20-fold). Those with increased FFN levels were also shown to have an increased incidence of neonatal sepsis as well. Peaceman et al used FFN to attempt to identify those at risk for preterm delivery among women with contractions between 24 and 34 6/7 weeks gestation. Those with negative FFN were less likely to deliver within 7 days of the test. The negative predictive value was 99.7%, suggesting that this test may be helpful in identifying women who would not benefit from antibiotic treatment. However, if in the absence of prospective clinical trials demonstrating the efficacy of this approach, we discourage the use of FFN screening for this indication.

Anti-Bacterial Agents↗

Amniotic fluid interleukin 6 in preterm labor. Association with infection.

To evaluate whether IL-6 participates in the host response to intrauterine infection, we studied IL-6 bioactivity and isoforms in amniotic fluid (AF). Two different assays for IL-6 were used: the hepatocyte stimulating factor assay (in Hep3B2 cells) and the SDS-PAGE/immunoblot assay. IL-6 determinations were performed in 205 AF samples. Samples were obtained from patients in the midtrimester of pregnancy (n = 25), at term with no labor (n = 31), at term in active labor (n = 40), and from patients in preterm labor (n = 109). Higher AF IL-6 levels were observed in women in preterm labor with intraamniotic infection than in women in preterm labor without intraamniotic infection (median = 375 ng/ml, range = 30-5000 ng/ml vs. median = 1.5 ng/ml, range = 0-500, respectively, P less than 0.0001). The 23-25- and 28-30-kD IL-6 species could be readily detected in SDS-PAGE immunoblots performed directly on 10-microliters aliquots of AF from patients with intraamniotic infection. Among women in preterm labor with culture-negative AF, those who failed to respond to subsequent tocolytic treatment had higher AF IL-6 concentrations than those who responded to therapy (median = 50 ng/ml vs. median = 1.2 ng/ml, respectively, P less than 0.05). Only low levels of IL-6 were detected in AF obtained from normal women in the midtrimester and third trimester of pregnancy. Decidual tissue explants obtained from the placentas of women undergoing elective cesarean section at term without labor (n = 11) produced IL-6 in response to bacterial endotoxin. In a pilot study, AF IL-6 was determined in 56 consecutive women admitted with preterm labor. All patients (n = 10) with elevated AF IL-6 (cutoff = 46 ng/ml) delivered a premature neonate. 4 of these 10 patients had positive AF cultures for microorganisms. These studies implicate IL-6 in the host response to intrauterine infection and suggest that evaluation of AF IL-6 levels may have diagnostic and prognostic value in the management of women in preterm labor.

Adult↗

Spontaneous preterm labor and premature rupture of membranes at late preterm gestations: to deliver or not to deliver.

Nationwide the American College of Obstetricians and Gynecologists noted in 1995 that the survival rate for newborns at 34 weeks is within 1% of those born at or beyond 37 weeks. Newborn major morbidity is slightly but significantly increased from 34(0) to 36(6) compared with 37 or greater weeks. These data form the basis for and reflect the perinatal outcomes associated with the standardized obstetric practices of effecting delivery for women with amnion rupture and also of not attempting tocolysis for preterm labor at or beyond 34(0) weeks gestation. Pragmatically, a prospective randomized management trial of women at late preterm gestation (34(0) to 36(6)) and with spontaneous preterm labor or amnion rupture would require multi-institutional support to achieve a required study population.

Female↗

Prostaglandin endoperoxide synthase kinetics in human amnion before and after labor at term and following preterm labor.

To determine whether the kinetics of prostaglandin endoperoxide synthase (PGHS, commonly known as cyclooxygenase) in human amnion change with labor onset or between preterm and term labor, a specific enzyme assay was developed and characterized. The assay was linear for time (0-8 min) and protein concentration (5-30 micrograms/250 microliters incubation volume). The optimum pH was 8.0-8.5, and the enzyme reaction reached saturation at 10-20 microM arachidonic acid. Flufenamic acid was more efficacious than ibuprofen in the presence of 1 mM tryptophan in inhibiting enzyme activity. The Km and Vmax of PGHS were determined in 10 amnions obtained at elective caesarean section before labor onset (CS) at 39.3 +/- 0.8 wk gestational age (mean +/- SD, range = 38.5-41 wk) and 9 amnions obtained following spontaneous labor and vaginal delivery (SL) at 39.6 +/- 0.8 wk (range = 38.5-41 wk). The Km values were 1.4 +/- 1.2 mumol/l (CS) and 2.2 +/- 1.5 mumol/l (SL) (not different). However, the Vmax increased significantly (p < 0.05) from 11 +/- 8 (CS) to 19 +/- 4 (SL) pg PGE2/micrograms protein/min. In eight preterm amnions obtained following spontaneous labor and delivery at 32.9 +/- 2.1 wk (range = 29-36 wk), the Km and Vmax were 2.0 +/- 1.2 mumol/l and 17 +/- 9 pg PGE2/micrograms protein/min, respectively. Neither of these values was different from those of CS or SL amnions. None of the preterm pregnancies displayed histological evidence of infection. These results suggest that an increase in the mean amnion PGHS maximum velocity occurs in association with the onset of labor at term. The mean Vmax of PGHS in amnions obtained from idiopathic preterm spontaneous deliveries is between the CS and SL term values, reflecting, perhaps, multiple etiologies for preterm delivery.

Amnion↗

Maintenance treatment of preterm labor with the oxytocin antagonist atosiban. The Atosiban PTL-098 Study Group.

OBJECTIVES: Patients admitted with an acute episode of preterm labor who respond to early intravenously administered tocolysis remain at risk of having subsequent episodes of preterm labor and preterm delivery. Several pharmacologic agents have been used in an attempt to reduce subsequent episodes of preterm labor, and all are associated with significant side effects. Atosiban, an oxytocin receptor antagonist, is effective in the treatment of an acute episode of preterm labor. This study was designed to compare the efficacy and safety of atosiban with those of placebo maintenance therapy in women with preterm labor who achieved uterine quiescence with intravenous atosiban. STUDY DESIGN: A multicenter, double-blind, placebo-controlled trial was designed for patients in preterm labor who responded to early intravenous treatment with atosiban. Five hundred thirteen patients were randomly assigned to receive maintenance therapy, 252 to receive atosiban, and 251 to receive matching placebo. Maintenance therapy was administered as a continuous subcutaneous infusion, via pump, of 30 microg/min to the end of 36 weeks' gestation. The primary end point was the number of days from the start of maintenance therapy until the first recurrence of labor. A secondary end point was the percentage of patients receiving subsequent intravenous atosiban therapy. RESULTS: The time (median) from the start of maintenance treatment to the first recurrence of labor was 32.6 days with atosiban and 27.6 days with placebo (P =.02). At least one subsequent intravenous atosiban treatment was needed by 61 atosiban patients (23%) and 77 placebo patients (31%). Except for injection site reactions, adverse event profiles of atosiban and placebo were comparable. There were 4 neonatal deaths reported in the atosiban group and 5 in the placebo group after the start of maintenance therapy. Infant outcomes (including birth weight) were comparable between maintenance and treatment groups. CONCLUSIONS: Maintenance therapy with the oxytocin receptor antagonist atosiban can prolong uterine quiescence after successful treatment of an acute episode of preterm labor with atosiban. Treatment was well tolerated.

Adult↗

Tocolytic treatment for the management of preterm labor: a review of the evidence.

OBJECTIVE: Preterm labor is often a prelude to early births and the significant attendant burden of infant morbidity and mortality. Treatment consists of bedrest, hydration, pharmacologic interventions, and combinations of these. We systematically reviewed the effectiveness of tocolytics to stop uterine contractions (first-line therapy) or maintain quiescence (maintenance therapy). Our objective was to evaluate the evidence on the benefits and harms of five classes of tocolytic therapy for treating uterine contractions related to preterm labor--beta-mimetics, calcium channel blockers, magnesium, nonsteroidal anti-inflammatory agents, and ethanol. STUDY DESIGN: Reports of randomized controlled trials and other study designs in English, French, and German identified from searches of MEDLINE, EMBASE, specialized databases, bibliographies of review articles, unpublished literature, and discussions with investigators in the field were identified. Studies on women with preterm labor between 1966 and February 1999 that met our inclusion criteria were included. Through dual review, we abstracted the following information: study design and masking; definitions of preterm labor and successful tocolysis; patient inclusion/exclusion characteristics; patient demographic characteristics; drug and cointerventions; and numerous birth, maternal, and neonatal outcome measures. RESULTS: Of the 256 articles evaluated, we abstracted data from 60 first-line and 15 maintenance studies. Of these, 16 first-line and 8 maintenance studies met more stringent requirements for meta-analyses. Studies of first-line tocolysis (grade Fair) reveal a mixed outcome pattern with small improvement in pregnancy prolongation and birth at term relative to placebo. Data were insufficient to show directly a beneficial effect on neonatal morbidity or mortality. Ethanol was less beneficial than, and beta-mimetics were not superior to, other tocolytic options. Maintenance tocolytics (grade Poor) showed no improvements in birth or infant outcomes relative to placebo; these results were confirmed through meta-analysis. In contrast to other tocolytic treatments, maternal harms from beta-mimetics were rated High; all tocolytics were rated as Low risk for short-term neonatal harms. CONCLUSIONS: Management of uterine contractions with first-line tocolytic therapy can prolong gestation. Among the tocolytics, however, beta-mimetics appear not to be better than other drugs and pose significant potential harms for mothers; ethanol remains an inappropriate therapy. Continued maintenance tocolytic therapy has little or no value.

Adrenergic beta-Agonists↗

Cervical sonography in preterm labor.

OBJECTIVE: To improve the accuracy of the diagnosis of preterm labor by comparing transvaginal sonography to digital examination of the cervix. METHODS: We performed transvaginal sonography in women with preterm labor who had completed a course of parenteral tocolysis. Cervical length was measured according to criteria reported previously. Cervical sonographic findings were not used in diagnosis or management. Sonographic cervical length was compared to digital assessment of dilation and effacement to assess the risk of preterm birth after treatment for preterm labor. RESULTS: Forty-eight singleton and 12 twin gestations were studied. Thirty women were nulliparous and 30 were parous. The mean (+/- standard deviation) gestational age was 31.1 +/- 2.7 weeks (range 24-35) at the examination and 35.6 +/- 2.9 weeks (range 26-43) at delivery. Twenty-four subjects delivered before 36 weeks' gestation and 36 delivered at or after 36 weeks. Cervical sonography was distinctly superior to digital assessment of dilation and effacement as a test for delivery before 36 weeks, when compared using receiver operating characteristic curves. This analysis indicated a cervical length of 30 mm as the best cutoff to maximize sensitivity and specificity. All 24 subjects who delivered preterm had cervical lengths less than 30 mm. Cervical sonography was especially useful in selecting women with preterm labor who would not deliver prematurely, ie, a high negative predictive value. None of 15 women whose cervical length was 30 mm or more delivered spontaneously before 36 weeks. CONCLUSION. Among women treated for preterm labor, a cervical length of at least 30 mm predicted a low likelihood of preterm birth. Cervical sonography may improve the accuracy of diagnosis in women treated for preterm labor.

Adult↗