[Clinical practice recommendations. Risk of premature birth with intact membranes. Conclusions (2002)].
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Biomedical subjects
Publications and source records attributed to B Carbonne.
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The objective of intrapartum fetal monitoring is to prevent fetal asphyxia and fetal death during labor. Although a large proportion of neurologic sequelae are of antepartum origin, criteria have been defined to relate cerebral palsy to an intrapartum event, including fetal asphyxia. Since the introduction of fetal heart rate monitoring, no changes in the cerebral palsy rate have been observed. Several other methods of fetal surveillance have been more or less recently developed: fetal scalp blood pH and lactates, fetal pulse oximetry and fetal electrocardiogram. The benefits and limits of these new tools are analyzed in this review.
BACKGROUND: Preterm birth is a major contributor to perinatal mortality and morbidity and affects approximately six to seven per cent of births in developed countries. Tocolytics are drugs used to suppress uterine contractions. The most widely tested tocolytics are betamimetics. Although they have been shown to delay delivery, betamimetics have not been shown to improve perinatal outcome, and they have a high frequency of unpleasant and even fatal maternal side effects. There is growing interest in calcium channel blockers as a potentially effective and well tolerated form of tocolysis. OBJECTIVES: To assess the effects on maternal, fetal and neonatal outcomes of calcium channel blockers, administered as a tocolytic agent, to women in preterm labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's specialised register of controlled trials, the Cochrane Controlled Trials Register (February 2002), MEDLINE, EMBASE, and Current Contents. We also contacted recognised experts and cross referenced relevant material. SELECTION CRITERIA: All published and unpublished randomised trials in which calcium channel blockers were used for tocolysis for women in labour between 20 and 36 weeks gestation. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group were used. Evaluation of methodological quality and trial data extraction were undertaken independently by three authors. Additional information was sought to enable assessment of methodology and conduct of intention-to-treat analyses. Meta-analysis was conducted assessing the effects of calcium channel blockers compared with any other tocolytic agent. Results are presented using relative risk for categorical data and weighted mean difference for continuous data. MAIN RESULTS: Eleven randomised controlled trials involving 870 women were included. When compared with any other tocolytic agent (mainly betamimetics), calcium channel blockers reduced the number of women giving birth within 48 hours (relative risk (RR) 0.73; 95% confidence interval (CI) 0.54, 0.98) and within seven days (RR 0.76; 95% CI 0.59, 0.99). Calcium channel blockers also reduced the requirement for women to have treatment ceased for adverse drug reaction (RR 0.15; 95% CI 0.06, 0.43), the frequency of neonatal respiratory distress syndrome (RR 0.64; 95% CI 0.45, 0.91) and neonatal jaundice (RR 0.73; 95% CI 0.57, 0.93). REVIEWER'S CONCLUSIONS: When tocolysis is indicated for women in preterm labour, calcium channel blockers are preferable to betamimetic agents. Further research should address the effects of different dosage regimens and formulations of nifedipine on maternal and neonatal outcomes.
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Because criteria used for the prediction of preterm labor are poorly effective, many patients receive tocolytic therapy in excess during pregnancy. Beta-mimetic agonists are the reference tocolytic drugs in most countries. Their efficacy in prolonging pregnancy compared to a placebo is proven although no benefit in neonatal morbidity or mortality has been demonstrated. Beta-mimetics have many contraindications, and side-effects are frequent. Serious complications such as pulmonary edema and maternal deaths, though rare, have been reported. Recent research has focused on tocolytic drugs with similar efficacy to beta-mimetics but with less side effects. Calcium-channel-blockers and oxytocin antagonists have been compared with beta-agonists in randomized trials. Both have demonstrated similar efficacy in the prolongation of pregnancy for at least 48 hours. Contrary to beta-mimetics, very few interruptions of treatment have been observed with these treatments. Other tocolytic drugs such as cyclooxygenase inhibitors, although effective in prolonging pregnancy, have unacceptable fetal side effects. Progesterone, antispasmodic drugs and magnesium sulfate have been widely used but their efficacy has not been demonstrated. More recent treatments such as NO-donors and cyclooxygenase-II specific antagonists are not sufficiently evaluated. In conclusion, three main classes may be used as first line tocolytic therapy, beta-adrenergic agonists, calcium-channel-blockers, and oxytocin antagonists. The choice among these treatments may be based on contraindications to beta-mimetics, side-effects of the treatment, or even economic reasons.
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OBJECTIVE: To clarify the relative efficacy of nifedipine and beta-agonists for tocolysis. DATA SOURCES: The literature was searched in the following databases: MEDLINE 1965-1998, Embase 1988-1998, Current Contents 1997-1998, and the Cochrane Database for 1998. We also sought unpublished trials and abstracts submitted to major international congresses. Search terms were: "tocolysis," "nifedipine," "calcium channel blocker," "ritodrine," "terbutaline," and "salbutamol." METHODS OF STUDY SELECTION: Randomized controlled trials comparing tocolysis with nifedipine and beta-adrenergic agonists during preterm labor were reviewed. In cases with postrandomization exclusions, authors were contacted to obtain intent-to-treat results and to avoid analytical bias. We identified 11 published and two unpublished randomized trials. TABULATION, INTEGRATION, AND RESULTS: Data were extracted by two reviewers and analyzed by a blinded biostatistician with RevMan 3.1 software from the Cochrane Collaboration. We analyzed nine relevant randomized controlled trials that included 679 patients. Meta-analysis showed that nifedipine was more effective than the beta-agonists in delaying delivery at least 48 hours [odds ratio (OR) 1.52, 95% confidence interval (CI) 1.03, 2.24], or over 34 weeks (OR 1.87, 95% CI 1.11, 3.15). The agents did not differ as to the incidence of deliveries after 37 weeks (OR 1.29, 95% CI 0.85, 1.96) or the neonatal mortality rate (OR 1.51, 95% CI 0.63, 3.65). Treatment with nifedipine was interrupted significantly less often because of side effects (OR 0.12, 95% CI 0.05, 0.29) and led to better neonatal outcomes (fewer infants with respiratory distress syndrome: OR 0.57, 95% CI 0.37, 0.89) or transferred to neonatal intensive care units (OR 0.65, 95% CI 0.43, 0.97). CONCLUSION: With respect to neonatal outcome, nifedipine appears to be more effective than beta-agonists for tocolysis and should be considered for use as a first-line tocolytic agent.
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OBJECTIVE: To determine whether there is an association between early recurrent miscarriage (before 10 weeks of pregnancy) and Factor V Leiden and G20210A prothrombin mutations. DESIGN: A prospective study. SETTING: Department of Gynaecology and Obstetrics, Saint Antoine Hospital, Paris, France. POPULATION: Two groups of women: those with early unexplained recurrent miscarriage before 10 weeks of pregnancy (n = 260) and control healthy women without a previous history of thromboembolism (n = 240). METHODS: Screening for defects in the protein C anticoagulant pathway was performed using the anticoagulant response to agkistrodon confortrix venom (ACV test). Protein C and Factor V Leiden mutation testing was performed for each low ACV level. Each sample was tested for the G20210A prothrombin mutation. RESULTS: Factor V Leiden and G20210A mutations were found to be associated with early recurrent spontaneous miscarriage before 10 weeks of pregnancy, the odds ratios being 2.4 (95% CI 1-5) and 2.7 (95% CI 1-7), respectively. Similar results were found whether or not women had had a previous live birth. CONCLUSIONS: Early recurrent miscarriage before 10 weeks of pregnancy is significantly associated with Factor V or G20210A prothrombin mutations. These results indicate a possible role for anticoagulant prevention in these early miscarriages.
Beta-mimetics are the gold standard tocolytic treatment but raise several problems. Despite their recognized efficacy in prolonging pregnancy, the neonatal benefit remains to be proven. There are several contraindications and frequent adverse effects, with a risk of fatal maternal accidents. The lack of reliable criteria for the prediction of preterm birth leads to giving unnecessary treatments to two-thirds of the patients. In this context, obstetrical practices have tended to prefer tocolytics which, with the same efficacy, would have fewer side effects than beta-mimetics and which would not raise a risk of severe complications. Calcium-channel blockers belonging to the dihydropyridin family and ocytocin antagonists would appear to meet the new requirements. In randomized trials versus beta-mimetics, they have been found to have a comparable effect in prolonging pregnancy by 48 hours. Tolerance is better than with beta-mimetics and treatment interruption due to side effects can be avoided. Finally, a meta-analysis of trials comparing calcium inhibitors versus beta-mimetics demonstrated a decrease in respiratory distress syndrome in the neonates and a reduction in the number of transfers to neonatal intensive care. The data accumulated on these new compounds would appear to suggest that they should be used as the first line treatment and not as an alternative to beta-mimetics. Other compounds including NO donors and cyclo-oxygenase 2 inhibitors are under evaluation.
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OBJECTIVE: To evaluate the use of calcium-channel-blockers (CCBs) for tocolysis. METHODS: We reviewed the literature retrieved from the Medline database from 1967 to 200 dealing with fetal toxicity and efficacy of CCBs compared with beta-adrenergic agonists. RESULTS: Data on fetal toxicity in animals were inconsistent. A teratologic effect has been observed during early pregnancy at supratherapeutic dosage. At usual therapeutic dosage, no fetal abnormalities have been observed. The efficacy of CBs for tocolysis is superior to that of beta-adrenergic drugs and allows a reduction of neonatal morbidity. Calcium channel blockers are better tolerated than beta-adrenergic agonists. CONCLUSION: Published data suggest that CCBs could be used a first line tocolytic agents. Although use of CCBs is extremely simple, they should not be prescribed in low-risk outpatients.
The law on voluntary pregnancy termination has been modified in France. Many questions are currently raised concerning its application. We provide a review discussing available elements needed to answer these questions.
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OBJECTIVE: To evaluate the benefits and indications for amniocentesis in cases of preterm labor with or without preterm rupture of membranes. METHOD: A review of the literature on amniocentesis in cases of intra-amniotic infection. RESULTS: Amniocentesis is an invasive method that allows the diagnosis of intra-amniotic infection. However, no randomized trials have been performed from which we can assess the benefits and complications of amniocentesis in preterm labor. CONCLUSION: The published data do not justify the routine practice of amniocentesis in preterm labor. More data are needed to evaluate the benefits and complications of this practice. Only randomized trials of patients in preterm labor, comparing those who undergo amniocentesis with those who do not, will clarify the indications for this procedure.
We have developed a simple mathematical model with three physiologically significant states to describe the changes in intrauterine pressure associated with a contraction during human parturition. The myometrium is modelled as a set of smooth muscle cells, each of which is in one of three states (quiescent, contracted, refractory) at a given time. These states are occupied according to a cycle governed by three temporal parameters. The solutions of the equations describing the model show an oscillatory behavior for particular values of these parameters, which is very similar to the time dependent development of intrauterine pressure during labor. Due to its non-linear terms, our model could lead to chaotic oscillations (in the mathematical sense), whose clinical counterpart may occur in cases of dystocia. Despite its simplicity, this model appears to be a useful guide to further investigations of the oscillatory behavior of the myometrium, or other smooth muscles, in normal and pathological situations.