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PubMed1993

Effect of intravenous beta-sympathomimetic tocolysis on human fetal serum erythropoietin levels.

OBJECTIVE: The major stimulus for erythropoietin production is tissue hypoxia. We sought to investigate the relationship of beta-sympathomimetic administration for tocolysis and fetal serum erythropoietin. STUDY DESIGN: Umbilical cord blood was obtained from infants whose mothers received intravenous beta-sympathomimetic tocolysis and who were delivered at < or = 34 weeks' gestation. Serum erythropoietin was measured by radioimmunoassay. On the basis of the presumed 2- to 4-hour half-life of fetal erythropoietin, the infants were divided into two groups. In group 1 (n = 16) beta-sympathomimetic therapy was discontinued < 24 hours before delivery; in group 2 (n = 11) it was discontinued > or = 24 hours before delivery. RESULTS: Group 1 fetuses had significantly higher erythropoietin levels than did group 2 fetuses (37.3 vs 13.9 mU/ml, p = 0.02). The duration of beta-sympathomimetic tocolysis and the maximum infusion rate were not different. The two groups did not differ in gestational age, birth weight, route of delivery, presence of labor, or duration of first or second stage of labor. CONCLUSIONS: We speculate that intravenous beta-sympathomimetic tocolytic therapy stimulates fetal erythropoietin production by decreasing fetal oxygenation as a result of the reversible fetal metabolic effects of the tocolysis. These data suggest that beta-sympathomimetic tocolysis should be undertaken cautiously if fetal compromise is suspected, fetal well-being should be assessed carefully if tocolysis is undertaken, and treatment should be discontinued promptly if a clear benefit is not realized.

Erythropoietin↗
PubMed1985

Maternal paralytic ileus as a complication of magnesium sulfate tocolysis.

Beta-adrenergic agonists tocolysis is currently the most popular treatment modality in the United States. However, magnesium sulfate is receiving increasing attention as an alternating tocolytic agent in the presence of various clinical situations, such as the treatment of insulin-dependent diabetes. While there is an abundance of information about the maternal and fetal side effects associated with beta-adrenergic tocolysis, little information is available about maternal adverse side effects of magnesium sulfate treatment for preterm labor. Side effects such as pulmonary edema, respiratory depression, hypocalcemia, and hypermagnesemia have been reported in patients receiving this agent for either tocolysis or pre-eclampsia, though their occurrence is quite rare. One of the infrequent complications of beta-adrenergic agonist tocolysis is the occurrence of a paralytic ileus, which to our knowledge has not yet been reported in association with magnesium sulfate tocolysis. This article therefore concerns the development of a paralytic ileus in a patient receiving parenteral magnesium sulfate for tocolysis. The clinical features are described and the possible mechanisms involved discussed.

Adult↗
PubMed2005

Maintenance tocolysis.

BACKGROUND: Women who are undelivered after 48 hours of tocolysis remain at increased risk of preterm labour, but it is not clear whether prolonged treatment is effective. OBJECTIVE: To review the current evidence for the effectiveness of maintenance tocolysis. METHODS: The results of published systematic reviews were summarised. RESULTS: Four systematic reviews and two trials published too recently for inclusion were identified. Maintenance tocolysis with beta-agonists and magnesium sulphate was ineffective in prolonging gestation or reducing any adverse fetal outcomes. One trial of maintenance tocolysis with nifedipine was underpowered to rule out an effect on prolonging gestation. One trial using the oxytocin receptor blocker, atosiban, showed that this drug used as maintenance tocolysis does prolong gestation, but the trial was too small to demonstrate any reduction in substantive fetal outcomes. CONCLUSIONS: There is insufficient evidence to justify the routine use of maintenance tocolysis in preterm labour. It remains plausible that prolongation of gestation might be beneficial in selected cases of very preterm labour where fetal compromise and infection have been ruled out. The only tocolytic that has been shown to prolong gestation when used as maintenance therapy is atosiban.

Adrenergic beta-Antagonists↗
PubMed2001

Effect of maternal tocolysis on the incidence of severe periventricular/intraventricular haemorrhage in very low birthweight infants.

AIM: To examine the relation between grade III-IV periventricular/intraventricular haemorrhage (PVH/IVH) and antenatal exposure to tocolytic treatment in very low birthweight (VLBW) premature infants. STUDY DESIGN: The study population consisted of 2794 infants from the Israel National VLBW Infant Database, of gestational age 24-32 weeks, who had a cranial ultrasound examination during the first 28 days of life. Infants of mothers with pregnancy induced hypertension or those exposed to more than one tocolytic drug were excluded. Of the 2794 infants, 2013 (72%) had not been exposed to tocolysis and 781 (28%) had been exposed to a single tocolytic agent. To evaluate the effect of tocolysis and confounding variables on grade III-IV PVH/IVH, the chi(2) test, univariate analysis, and a logistic regression model were used. RESULTS: Of the 781 infants (28%) exposed to tocolysis, 341 (12.2%) were exposed to magnesium sulphate, 263 (9.4%) to ritodrine, and 177 (6.3%) to indomethacin. The overall incidence of grade III-IV PVH/IVH was 13.4%. In the multivariate logistic regression analysis, the following factors were related significantly and independently to grade III-IV PVH/IVH: no prenatal steroid treatment, low gestational age, one minute Apgar score 0-3, respiratory distress syndrome, patent ductus arteriosus, mechanical ventilation, and pneumothorax. Infants exposed to ritodrine tocolysis (but not to the other tocolytic drugs) were at significantly lower risk of grade III-IV PVH/IVH after adjustment for other variables (odds ratio = 0.3; 95% confidence interval 0.2 to 0.6). CONCLUSION: This study suggests that antenatal exposure of VLBW infants to ritodrine tocolysis, in contrast with tocolysis induced by magnesium sulphate or indomethacin, was associated with a lower incidence of grade III-IV PVH/IVH.

Anti-Inflammatory Agents↗
PubMed1986

[Indications for tocolysis. A prospective study].

In a prospectively randomised group of pregnant patients showing signs of prematurity, who had undergone long-term tocolysis between the 28th and 38th week of gestation--mainly with Fenoterol--the interval between the end of the tocolytic therapy and the delivery is noted. According to the duration of the end of tocolysis to delivery interval (TEDI) the indication for tocolysis can be retrospectively investigated. In patients where the TEDI was 72 hours or less, tocolysis is regarded as being necessary, and in patients with TEDI of longer than 72 hours, tocolysis is regarded as questionable or unnecessary. In this study in 49% of the cases tocolysis was necessary, whereby the primapara had a shorter TEDI on the average than the multipara. Both groups with short and long TEDI are compared with reference to obstetrical parameters, whereby virtually only the greater anamnestic strain of the patients with short TEDI emerged. There is not easily recognizable uniform criterion which can identify prospectively those patients whose baby is born within 72 hours after the tocolytic therapy has been discontinued. The results are discussed under the aspect of unsolved problems in the indication for tocolytic treatment.

Aspirin↗
PubMed1982

[Studies of the clinical effectiveness of intravenous long-term tocolysis].

Possible retardation of delivery following different periods of intravenous Partusisten tocolysis was studied in 701 premature births, between the 28th and 36th weeks of pregnancy. The studies were conducted separately, for all probands together and by gestational age groups. Various symptoms of imminent premature birth were not weighed. The rate of failure amounted to 23 per cent, that is delivery occurred within 24 hours from beginning of treatment. Extension of pregnancy by something between two and seven days was achieved in 45 per cent of the probands or by more than seven days in 32 per cent. Growing length of intravenous tocolysis was followed by significant rise in the number of women with genuine prolongation of pregnancy (between eight and 28 days or even more), however, without any unambiguous evidence to differentiation between gestational age groups with regard to therapeutic responsiveness. Significant percentual rise in prematurity between the 34th and 36th weeks of pregnancy by almost 30 per cent (with 20 per cent in the 36th week of pregnancy alone) seems to indicate a measurable clinical benefit of intravenous long-term tocolysis in terms of higher life expectancy and better survival quality. --The above findings were compared with results that had been obtained from 1,037 prematurely born infants of the same gestational age groups without preceding tocolysis. The conclusion was that intravenous tocolysis in general and long-term tocolysis in particular failed to have the slightest negative impact in terms of acidosis and RDS morbidity, average birth weight, hypotrophy, and survival chance. The need for properly timed detection of prematurity as part of routine care may be seen from the great number of untreated premature births, that is cases beyond any possibility of treatment. The point is made that the effectiveness of tocolytic therapy can be measured only by those premature newborns who had received treatment rather than by the totality of premature newborns.

Ethanolamines↗
PubMedDate not supplied

Diltiazem for maintenance tocolysis of preterm labor: comparison to nifedipine in a randomized trial.

The objective of this study was to compare the safety and efficacy of maintenance tocolysis with oral diltiazem to oral nifedipine in achieving 37 weeks gestation. After successful intravenous tocolysis with magnesium sulfate, 69 women with preterm labor at <35 weeks gestation were randomly assigned to nifedipine (20 mg orally every 4-6 hr), or diltiazem (30-60 mg orally every 4-6 hr). The primary outcome was the percentage of patients achieving 37 weeks gestation. Maternal cardiovascular alterations and neonatal outcomes were also assessed. Sixty-nine patients were available for final analysis. Less patients on diltiazem as compared to nifedipine achieved 37 weeks (15.1% vs. 41.7%, P = 0.019). Gestational age at delivery was also less for patients receiving diltiazem (35.5 +/- 3.5 weeks vs. 33.4 +/- 3.9 weeks, P = 0.022). There were fewer days gained in utero from randomization to delivery with diltiazem as compared to nifedipine; however, this difference was not statistically significant (22.4 +/- 16.3 days vs. 31.2 +/- 24.4 days, P = 0.084). Maternal blood pressure and pulse during tocolysis did not differ significantly between groups. Despite the theoretical advantages of diltiazem tocolysis, maintenance tocolysis with diltiazem offered no benefit over nifedipine in achieving 37 weeks gestation. The cardiovascular alterations with either drug in normotensive, pregnant patients appear minimal.

Amniotic Fluid↗
PubMed2006

Tocolysis in women with preterm labor between 32 0/7 and 34 6/7 weeks of gestation: a randomized controlled pilot study.

OBJECTIVE: The purpose of this study was to determine whether intravenous magnesium sulfate (MgSO4) followed by oral nifidepine tocolysis in women with preterm labor between 32 0/7 and 34 6/7 weeks' gestation reduces neonatal hospital stay. STUDY DESIGN: Fifty-four women between 32 0/7 and 34 6/7 weeks with preterm labor were randomized to receive either MgSO4 and oral nifidepine (n = 24) or no tocolysis (n = 30). All women received betamethasone and prophylactic antibiotics. The primary outcome was total neonatal hospital stay. Data were analyzed using Chi-square and Mann Whitney U test. RESULTS: The 2 groups had similar mean cervical dilation and gestational age at enrollment. There were no statistically significant differences in total neonatal hospital stay (5.8 +/- 7.2 days; median of 3 days in the no tocolysis vs. 7.5 +/- 8.6 days; median of 3 days in the tocolysis group), rate of preterm delivery (57% vs. 75%) or need for oxygen supplementation (7% vs. 21%, p < 0.23). The neonatal complications were similar in each group. CONCLUSION: Tocolysis after 32 weeks gestation does not reduce neonatal hospital stay.

Adult↗
PubMed1995

Tocolysis in advanced preterm labor: impact on neonatal outcome.

Chart review of 73 patients with 3.5 cm or more dilation, intact membranes, and regular contractions at less than 36 weeks. Forty-four (group A) received tocolysis with magnesium sulfate, and 13 of the 44 also received indomethacin. Twenty-nine (group B) received no tocolysis. Obstetric and neonatal outcomes were compared. Demographic factors and admission gestational age, cervical dilation, effacement, and uterine activity were similar. Twenty-one of the 44 in group A versus 3 of 29 in group B had delivery delayed by more than 48 hours (p = 0.002). Group A had a lower incidence of severe respiratory distress syndrome; 4 of 48 babies in group A versus 9 of 32 in group B (p = 0.04; RR = 0.47; confidence interval [CI], 0.2, 1.0). Tocolysis in advanced preterm labor delays delivery by more than 48 hours in 50% of patients. The neonatal benefits of aggressive tocolysis in cases with advanced cervical dilation may outweigh the potential maternal risks of tocolysis, particularly in the setting of extreme prematurity. Delay in delivery enabling steroid enhancement of pulmonary maturity reduces the severity of respiratory distress syndrome.

Cohort Studies↗
PubMed2005

Assessing the neonatal safety of indomethacin tocolysis: a systematic review with meta-analysis.

OBJECTIVE: To systematically review and summarize the medical literature regarding the effects of tocolysis with indomethacin on neonatal outcome. DATA SOURCES: We supplemented a search of entries in electronic databases with references cited in original studies and review articles to identify studies pertaining to indomethacin tocolysis and neonatal outcome. METHODS OF STUDY SELECTION: We evaluated, abstracted data, and performed quantitative analyses in studies assessing the neonatal outcomes of patients undergoing tocolysis with indomethacin. Observational studies and randomized trials were included in this systematic review. TABULATION, INTEGRATION, AND RESULTS: Forty-six studies were identified, 28 of which met criteria for systematic review and meta-analysis. These 28 studies included 6,008 infants. Of these infants, 1,621 were exposed to indomethacin for tocolysis antenatally; 4,387 infants not exposed to indomethacin served as the comparison group. An estimate of pooled odds ratios with 95% confidence intervals was calculated for dichotomous outcomes using random- and fixed-effects models. Observational studies and randomized trials were analyzed separately. Pooled estimates from observational studies and randomized trials revealed no significant differences in the rates of intraventricular hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, or neonatal mortality between infants exposed to indomethacin antenatally and those not exposed. Meta-analysis of randomized trials revealed increased risk of bronchopulmonary dysplasia. However, the meta-analysis included only 3 randomized clinical trials, one of which showed increased risk. An association of bronchopulmonary dysplasia and indomethacin use was not noted in our analysis of observational studies. CONCLUSION: Although our pooled results did not identify significantly increased risks of adverse effects, the limited statistical power of published randomized trials does not allow us to exclude the possibility that indomethacin tocolysis increases the risk of adverse neonatal outcomes.

Adult↗
PubMed2003

Behaviour of beta 2-adrenoceptors on lymphocytes under continuous and pulsatile tocolysis with Fenoterol.

The present study investigates the population of beta 2-receptors on lymphocytes in pregnant women with premature labor between the 29th and 34th week of pregnancy. The population of receptors on lymphocytes correlates with that on the myometrium, which is not accessible for study during pregnancy. Fourteen patients received a pulsatile tocolysis, while ten women received a continuous tocolysis with Fenoterol. Assuming an equal population of receptors in both groups before commencement of therapy, the numbers of receptors in the patients with continuous tocolysis fell to about 35% of the initial value after 72 hours. Under pulsatile tocolysis, the numbers of receptors remained unchanged for a period of three days and was still only just below 70% of the initial value by the seventh day. Our data demonstrate that continuous administration of the short-acting beta 2-agonist Fenoterol resulted in a substantial loss of beta 2-adrenoceptors on lymphocytes. In contrast, intermittent administration of the same beta 2-adrenergic agonist prevented the onset of receptor down-regulation in pregnant women with preterm labor. Further studies are required to investigate the impact of the decreased loss of beta 2-adrenoceptor density on the good clinical experience with intermittent tocolysis.

Dose-Response Relationship, Drug↗
PubMed2002

[Tocolysis: indications and contraindications. When to start and when to stop].

Clinical trials have demonstrated that most tocolytic agents such as beta mimetics, atosiban and indometacine -exception made for magnesium sulfate- extend the duration of pregnancy, when compared to placebo. They reduce the rate of delivery at 24 hours, 48 hours and at 7 days. There is no proof however for their beneficial effect on perinatal or neonatal outcomes. Usual obstetrical contraindications of tocolytic treatments (infection, genital haemorrhage, fetal distress and certain maternal conditions) are often determined on a case by case basis, rather than upon evidence based medicine. Tocolysis may be considered in case of maternal infection without chorioamniotitis or during moderate hemorrhage due to placenta preavia (NP 4). There is no objective argument to refute a tocolytic attempt due and in accordance with a low gestationnal age limit. The risk for neonatal respiratory distress syndrome is higher at 34 weeks compared to 35 and 36 weeks. The studies were however realized before the corticosteroid era of fetal lung maturation. There are no available randomized trials concerning the benefits of tocolysis after 34 weeks of amenorrhea. Furthermore, there are no satisfactory trials preconising a specific tocolytic agent based on amniotic liquid study of lung maturity. In case of advanced cervical dilatation, rare studies have concluded the usefulness of tocolysis to allow fetal lung maturation by corticosteroids. Most studies have evaluated the effectiveness of tocolytic treatment during 48 hours. There is no evidence for continuing tocolytic treatment after an effective tocolysis prescribed during the first 48 hours. For intermediate situations, between franc success or failure of tocolysis (such as reduction but persistent painful uterine contractions or major cervical modification at a low gestational age despite reduction of uterine contractile activity), literature guidelines are poorly contributive. The management of such patients is most often empirical.

Clinical Trials as Topic↗
PubMed1990

Tocolysis in the management of third trimester bleeding.

Fifteen patients were identified in a retrospective analysis of one institution's experience with the use of tocolysis in selected patients with an admission diagnosis of placenta previa or abruptio placentae. There were no fetal deaths after admission, and the two neonatal deaths were related to prematurity. Eight of the 15 patients receiving tocolysis had their pregnancies prolonged by 2 weeks or more, and there were no fetal or neonatal deaths in this group. Both neonatal deaths occurred in patients who underwent tocolysis but who gave birth within 1 day of admission. These data suggest the safety of tocolysis in preterm patients with the diagnosis of placenta previa or abruption who are bleeding. A prospective, randomized trial is required to evaluate whether tocolysis is superior to expectant management or to immediate delivery. The clinical difficulty in differentiating between these two diagnoses, despite liberal use of ultrasonography, is discussed.

Abruptio Placentae↗
PubMed1987

A randomized trial of ritodrine tocolysis versus expectant management in patients with premature rupture of membranes at 25 to 30 weeks of gestation.

Expectant management was compared with similar management plus ritodrine tocolysis in a randomized controlled trial in patients with premature rupture of membranes at 25 to 30 weeks of gestation. In the tocolysis group intravenously administered ritodrine was instituted at the onset of labor and then changed to the oral form if successful. Tocolysis was discontinued or not instituted after 31 weeks of gestation. Seventy-nine patients were randomized over a 4-year period, 39 in the tocolysis group and 40 in the expectant group. Twenty-three patients in the tocolysis group actually received ritodrine. No difference between the two groups was demonstrated in the interval between premature rupture of membranes and delivery or in reaching 32 weeks of gestation. No statistical difference was seen in maternal morbidity. Birth weights and gestational ages at delivery were similar between the two groups as were the incidences of neonatal morbidities caused by prematurity and infection and in the duration of neonatal hospital stays. Despite being conducted in those gestational ages in which prolongation of pregnancy might be expected to be of most benefit, no difference could be demonstrated with the addition of tocolytic therapy over expectant management alone.

Adult↗
PubMed2003

Hemodynamic and metabolic effects after nifedipine and ritodrine tocolysis.

OBJECTIVES: The purpose of this study is to compare the hemodynamic and metabolic changes after ritodrine and nifedipine tocolysis. METHODS: For an open randomized study, patients with preterm labor (N=185) were allocated to groups to receive ritodrine intravenously (N=90) or nifedipine orally (N=95). RESULTS: The mean diastolic blood pressure was significantly lower in the ritodrine group 24 h (65+/-12 vs. 70+/-8, P=0.001) and 48 h (65+/-12 vs. 71+/-8, P=0.004) after starting tocolysis compared with the nifedipine group. Mean maternal heart rate was significantly higher in the ritodrine group 24 h (105+/-17 vs. 86+/-13, P<0.0001) and 48 h (100+/-21 vs. 85+/-12, P<0.0001) after starting tocolysis compared with the nifedipine group. Mean fasting glucose levels were higher (6.68+/-2.53 vs. 4.93+/-1.23, P=0.0016), while mean potassium levels were lower (3.52+/-0.84 vs. 3.81+/-0.45, P=0.04) in the ritodrine group 48 h after starting tocolysis compared with the nifedipine group. CONCLUSIONS: Use of nifedipine for preterm labor is associated with a lower incidence of adverse hemodynamic and metabolic changes compared with ritodrine after 24 and 48 h of tocolysis. In our opinion nifedipine is the preferred drug of choice for the treatment of preterm labor.

Adult↗
PubMed1980

[Tocolysis with a beta-receptor stimulating compound in patients with WPW-syndrome. A casuistic report (author's transl)].

During a previous pregnancy supraventricular tachycardia complicated delivery in time in a woman with WPW-syndrome (Typ A) known since seven years. In the 34th week of the second pregnancy onset of preterm labor with a pelvic score of 7 and a tocolysis index of 5 was indication for tocolytic therapy. For protection against paroxysmal supraventricular tachycardia tocolysis with the semiselective beta 2-stimulating compound Fenoterol was started in combination with the beta 1-selective blocking compound Metoprolol. Tocolysis lasted 6 days without cardiac complications. Also during labor no tachycardia set on. The duration of tocolysis with Fenoterol/Metoprolol in this case was comparable with the duration of tocolysis reported for monotherapy with Fenoterol in similar obstetric states. In patients with WPW-syndrome the combination of a semiselective beta 2-simulating compound with a beta 1-blocking agent seems to offer a new possibility for tocolytic therapy.

Adult↗
PubMed1981

[Tocolysis in imminent premature delivery: limits of indication--assessment of success--sources of error (author's transl)].

303 imminent premature deliveries were treated from 1977 to 1978 with hexoprenaline (Gynipral) on an inpatient basis. Indication for tocolysis was obtained according to the tocolysis index (Baumgarten). Cases with an index of three and more were evaluated only. This criterion enabled accurate separation between prophylactic and therapeutic tocolysis. By means of postpartal determination of the age of gestation via the Dubowitz score, the period of gestation was controlled which had been determined at the beginning of the tocolysis. This made it possible to detect erroneous indication due to false estimation of the gestation period. Tocolysis success was assessed according to two different aspects. Pharmacodynamic success was assumed if 15 or more points were attained according to the Weidinger success score. This occurred in 56,5% of all treated patients. Clinical success, defined by delivery of a child which did not die perinatally nor suffered from the respiratory distress syndrome, was seen in 90.7% of all treated patients.

Adult↗
PubMedDate not supplied

Preterm premature rupture of membranes: aggressive tocolysis versus expectant management.

The objective of our study is to determine whether aggressive tocolysis in patients with preterm premature rupture of membranes between 24 and 34 weeks gestation improves neonatal outcome. Patients with documented preterm premature rupture of membranes between 24 and 34 weeks gestation were prospectively randomized to group I, aggressive tocolysis with intravenous magnesium sulfate, or to group II, no tocolysis. The lecithin/sphingomyelin ratio was determined upon hospital admission and every 48-96 hours until delivery. Both groups received weekly steroids and antibiotics pending culture results and were promptly delivered when chorioamnionitis, fetal stress, or an Lecithin/sphingomyelin ratio of > or = 2.0 occurred. The study group involved 145 patients. No statistically significant differences between groups I (n = 78) and II (n = 67) were observed regarding demographic characteristics, gestational age at enrollment or at delivery, latency, development of clinical chorioamnionitis, birth weight, number of days in neonatal intensive care unit, days on oxygen or ventilatory support, frequency of hyaline membrane disease, necrotizing enterocolitis, intraventricular hemorrhage, neonatal sepsis, or neonatal mortality. Our data suggest that tocolysis in patients with preterm premature rupture of membranes does not significantly improve perinatal outcome.

Adult↗