Four kinds of tocolytic therapy for preterm delivery: Systematic review and network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Premature birth affects more than 15 million infants, as well as mothers and families around the world. With the relaxation of the two-child policy, the problem of premature birth has become relatively prominent in China. According to statistics, China had a birth population of 15.23 million in 2018, with a considerably large number of premature births. This study aims to evaluate the efficacy and safety of tocolysis in the treatment of preterm delivery, provide clinical evidence for medical staff and promote the self-management of patients with premature births. METHODS: Four English databases (PubMed, Embase, Cochrane Library and Web of Science) were retrieved by computer, the retrieval time was from the establishment of each database to November 2021, and the randomized controlled trials for the treatment of preterm delivery were screened according to the pre-set natriuretic exclusion criteria. After literature screening, data selection and risk of bias evaluation were independently conducted by two researchers. R 4.1.1 and Stata 17.0 software were used for statistical analysis. RESULTS AND DISCUSSION: A total of 44 RCTs were included, including 6939 patients. The results of network meta-analysis reveal that in terms of effectiveness, indomethacin was the most effective intervention measure, followed by nifedipine, and the difference was statistically significant; regarding safety, nifedipine was the safest intervention measure, followed by indomethacin, and the difference was statistically significant; and in respect of adverse reactions, ritodrine had the highest probability, and the difference was statistically significant. WHAT IS NEW AND CONCLUSION: Nifedipine may be better for delayed delivery and less likely to produce adverse pregnancy outcomes, followed by indomethacin. Limited by the number and quality of recipient studies, the aforementioned conclusions need to be verified through more high-quality studies. At the same time, the focus should be on patients with twin pregnancy and patients with clinical manifestations of extreme preterm delivery.

A comparative study of transdermal nitroglycerine patch and oral nifedipine in preterm labor.

Background: Currently, the main goal for the use of tocolytic therapy is to delay the birth so as to allow the use of corticosteroids for accelerating fetal lung maturity and maternal transfer to a tertiary care center and thereby reducing neonatal morbidity and mortality. Aims and Objectives: The aims amd objectives were to compare the safety and efficacy of transdermal nitroglycerine patch with oral nifedipine as a tocolytic agent to arrest preterm labor and prevent preterm birth. Materials and Methods: Based on the selection criteria, 50 patients were selected randomly in Group A and Group B. Group A women were given transdermal nitroglycerin patch, which delivered 10 mg Nitroglycerin (NTG) over 24 h and it was applied to the woman's abdomen followed by another patch of 10 mg after 1 h if contractions persisted. After 24 h, it was replaced by a fresh patch. Group B women were given an oral loading dose of nifedipine 20 mg followed by a similar dose if contractions persisted after 1 h. A maintenance dose of 10 mg thrice daily was given if contractions were suppressed. Patients were monitored from the time of admission to the time of discharge. Results: The mean duration of prolongation of pregnancy in Group B (3.68 ± 1.91 days) was significantly more than Group A (2.78 ± 1.39 days). Headache was seen significantly more in Group A (42%) than group B (6%). Tachycardia, hypotension, and palpitation showed no statistically significant difference between them. There was no statistically significant difference in the birth weight of the babies in both the groups. Conclusion: Nifedipine is a safe and effective drug in prolonging preterm labor and has minimal maternal and neonatal side effects.

RésuméContexte: Actuellement, le principal objectif de l'utilisation de la thérapie tocolytique est de retarder la naissance afin de permettre l'utilisation de corticostéroïdes pour accélérer la maturité pulmonaire fœtale et le transfert maternel vers un centre de soins tertiaires et ainsi réduire la morbidité et la mortalité néonatales. Buts et objectifs: Les buts et objectifs étaient de comparer l'innocuité et l'efficacité du timbre transdermique de nitroglycérine avec la nifédipine par voie orale comme agent tocolytique pour arrêter le travail prématuré et prévenir l'accouchement prématuré. Matériel et méthodes: Sur la base des critères de sélection, 50 patientes ont été sélectionnées au hasard dans les groupes A et B.Les femmes du groupe A ont reçu un patch transdermique de nitroglycérine, qui a administré 10 mg de NTG en 24 h et appliqué sur l'abdomen de la femme suivi d'un autre patch de 10 mg après 1 h si les contractions ont persisté. Après 24 h, il a été remplacé par un nouveau patch. Les femmes du groupe B ont reçu une dose de charge orale de 20 mg de nifédipine suivie d'une dose similaire si les contractions persistaient après 1 h. Une dose d'entretien de 10 mg trois fois par jour était administrée si les contractions étaient supprimées. Les patients ont été suivis du moment de l'admission au moment de la sortie. Résultats: La durée moyenne de prolongation de la grossesse dans le groupe B (3,68 ± 1,91 jours) était significativement plus élevée que dans le groupe A (2,78 ± 1,39 jours). Les céphalées étaient significativement plus observées dans le groupe A (42%) que dans le groupe B (6%). La tachycardie, l'hypotension et les palpitations n'ont montré aucune différence statistiquement significative entre elles. Il n'y avait pas de différence statistiquement significative du poids à la naissance des bébés dans les deux groupes. Conclusion: La nifédipine est un médicament sûr et efficace pour prolonger le travail prématuré et a des effets secondaires maternels et néonatals minimes.

Cumulative Risk of the Oxytocin Receptor Gene Interacts with Prenatal Exposure to Oxytocin Receptor Antagonist to Predict Children's Social Communication Development.

Compelling evidence for the far-reaching role of oxytocin (OT) in social cognition and affiliative behaviors set the basis for examining the association between genetic variation in the OT receptor (OXTR) gene and risk for autism spectrum disorder (ASD). In the current study, gene-environment interaction between OXTR and prenatal exposure to either OT or OXTR antagonist (OXTRA) in predicting early social communication development was examined. One hundred and fifty-three children (age: M = 4.32, SD = 1.07) were assigned to four groups based on prenatal history: children whose mothers prenatally received OXTRA and Nifedipine to delay preterm labor (n = 27); children whose mothers received Nifedipine only to delay preterm labor (n = 35); children whose mothers received OT for labor augmentation (n = 56), and a no intervention group (n = 35). Participants completed a developmental assessment of intelligence quotient (IQ), adaptive behavior, and social communication abilities. DNA was extracted via buccal swab. A genetic risk score was calculated based on four OXTR single nucleotide polymorphisms (rs53576, rs237887, rs1042778, and rs2254298) previously reported to be associated with ASD symptomatology. OXTRrisk-allele dosage was associated with more severe autism diagnostics observation schedule (ADOS) scores only in the OXTRA group. In contrast, in the Nifedipine, OT, and no intervention groups, OXTRrisk-allele dosage was not associated with children's ADOS scores. These findings highlight the importance of both genetic and environmental pathways of OT in signaling early social development and raise the need for further research in this field. Autism Res 2019, 12: 1087-1100. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In the current study, we examined if the association between prenatal exposure to an oxytocin receptor antagonist (OXTRA) and autism spectrum disorder (ASD) related impairments are dependent on an individual's genetic background for the oxytocin receptor gene (OXTR). Children who carried a greater number of risk alleles for the OXTR gene and whose mothers received OXTRA to delay preterm labor showed more ASD-related impairments. The results highlight the importance of both genetic and environmental pathways of oxytocin in shaping early social development.

The Association between Prenatal Yoga and the Administration of Ritodrine Hydrochloride during Pregnancy: An Adjunct Study of the Japan Environment and Children's Study.

INTRODUCTION: While the beneficial effects of prenatal yoga have been reported in recent years, little is known about its effectiveness in pregnant Japanese women. Despite several adverse effects, ritodrine hydrochloride is frequently prescribed to suppress preterm labor in Japan, and its usage may therefore indicate cases of preterm labor. This study aimed to clarify the association between prenatal yoga and ritodrine hydrochloride use during pregnancy. METHODS: An observational study was conducted as an adjunct study by the Hokkaido unit of the Japan Environment and Children's Study. Information on prenatal yoga practice was collected using a self-questionnaire between March 21, 2012, and July 7, 2015, targeting women who had recently delivered. Ritodrine hydrochloride use was identified from medical records. A total of 2,692 women were analyzed using logistic regression models that adjusted for possible confounders. RESULTS: There were 567 (21.1%) women who practiced prenatal yoga, which was associated with a lower risk of ritodrine hydrochloride use (adjusted odds ratio [OR] 0.77; 95% CI 0.61-0.98). This was especially evident in women with a total practice duration that exceeded 900 minutes throughout their pregnancy (adjusted OR 0.54; 95% CI 0.38-0.76). A sensitivity analysis that excluded patients with threatened abortion during the study period produced similar results. CONCLUSIONS: Prenatal yoga was associated with a lower risk of ritodrine hydrochloride use, particularly in women with more than 900 minutes of practice time over the course of their pregnancy. Prenatal yoga may be a beneficial option for pregnant women in the selection of alternative therapies.

The safety of tocolytics used for the inhibition of preterm labour.

INTRODUCTION: Preterm birth is the major cause of neonatal mortality and morbidity worldwide and a huge cost burden on healthcare. Between 22 and 26 completed weeks of gestation, for every day that delivery is delayed, survival increases by 3%. AREAS COVERED: Following a systematic review of the literature, we have provided an overview of the use of tocolytics for the prevention of preterm birth and have examined the fetal and maternal adverse effects of the various tocolytic agents currently in use. EXPERT OPINION: No tocolytic currently in use was developed specifically to treat preterm labour so most have multi-organ side effects. ß2-agonists are relatively safe for the fetus but have rare and potentially serious maternal adverse effects. In contrast, prostaglandin synthetase inhibitors have potentially serious side effects for the fetus and neonate but have mild maternal gastrointestinal side effects. In Europe, the choice of first line therapy is either atosiban or nifedipine. The evidence base for atosiban is much more robust than for nifedipine. While their efficacy is similar, atosiban has placebo level side effects and is safer than nifedipine but is much more expensive.

Retained placenta: will medical treatment ever be possible?

The standard treatment for retained placenta is manual removal whatever its subtype (adherens, trapped or partial accreta). Although medical treatment should reduce the risk of anesthetic and surgical complications, they have not been found to be effective. This may be due to the contrasting uterotonic needs of the different underlying pathologies. In placenta adherens, oxytocics have been used to contract the retro-placental myometrium. However, if injected locally through the umbilical vein, they bypass the myometrium and perfuse directly into the venous system. Intravenous injection is an alternative but exacerbates a trapped placenta. Conversely, for trapped placentas, a relaxant could help by resolving cervical constriction, but would worsen the situation for placenta adherens. This confusion over medical treatment will continue unless we can find a way to diagnose the underlying pathology. This will allow us to stop treating the retained placenta as a single entity and to deliver targeted treatments.

Different treatment regimens of magnesium sulphate for tocolysis in women in preterm labour.

BACKGROUND: Magnesium sulphate has been used to inhibit preterm labour to prevent preterm birth. There is no consensus as to the safety profile of different treatment regimens with respect to dose, duration, route and timing of administration. OBJECTIVES: To assess the efficacy and safety of alternative magnesium sulphate regimens when used as single agent tocolytic therapy during pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials comparing different magnesium sulphate treatment regimens when used as single agent tocolytic therapy during pregnancy in women in preterm labour. Quasi-randomised trials were eligible for inclusion but none were identified. Cross-over and cluster trials were not eligible for inclusion. Health outcomes were considered at the level of the mother, the infant/child and the health service. INTERVENTION: intravenous or oral magnesium sulphate given alone for tocolysis.Comparison: alternative dosing regimens of magnesium sulphate given alone for tocolysis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and quality and extracted data. MAIN RESULTS: Three trials including 360 women and their infants were identified as eligible for inclusion in this review. Two trials were rated as low risk of bias for random sequence generation and concealment of allocation. A third trial was assessed as unclear risk of bias for these domains but did not report data for any of the outcomes examined in this review. No trials were rated to be of high quality overall.Intravenous magnesium sulphate was administered according to low-dose regimens (4 g loading dose followed by 2 g/hour continuous infusion and/or increased by 1 g/hour hourly until successful tocolysis or failure of treatment), or high-dose regimens (4 g loading dose followed by 5 g/hour continuous infusion and increased by 1 g/hour hourly until successful tocolysis or failure of treatment, or 6 g loading dose followed by 2 g/hour continuous infusion and increased by 1 g/hour hourly until successful tocolysis or failure of treatment).There were no differences seen between high-dose magnesium sulphate regimens compared with low-dose magnesium sulphate regimens for the primary outcome of fetal, neonatal and infant death (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.12 to 1.56; one trial, 100 infants). Using the GRADE approach, the evidence for fetal, neonatal and infant death was considered to be VERY LOW quality. No data were reported for any of the other primary maternal and infant health outcomes (birth less than 48 hours after trial entry; composite serious infant outcome; composite serious maternal outcome).There were no clear differences seen between high-dose magnesium sulphate regimens compared with low-dose magnesium sulphate regimens for the secondary infant health outcomes of fetal death; neonatal death; and rate of hypocalcaemia, osteopenia or fracture; and secondary maternal health outcomes of rate of caesarean birth; pulmonary oedema; and maternal self-reported adverse effects. Pulmonary oedema was reported in two women given high-dose magnesium sulphate, but not in any of the women given low-dose magnesium sulphate.In a single trial of high and low doses of magnesium sulphate for tocolysis including 100 infants, the risk of respiratory distress syndrome was lower with use of a high-dose regimen compared with a low-dose regimen (RR 0.31, 95% CI 0.11 to 0.88; one trial, 100 infants). Using the GRADE approach, the evidence for respiratory distress syndrome was judged to be LOW quality. No difference was seen in the rate of admission to the neonatal intensive care unit. However, for those babies admitted, a high-dose regimen was associated with a reduction in the length of stay in the neonatal intensive care unit compared with a low-dose regimen (mean difference -3.10 days, 95% confidence interval -5.48 to -0.72).We found no data for the majority of our secondary outcomes. AUTHORS' CONCLUSIONS: There are limited data available (three studies, with data from only two studies) comparing different dosing regimens of magnesium sulphate given as single agent tocolytic therapy for the prevention of preterm birth. There is no evidence examining duration of therapy, timing of therapy and the role for repeat dosing.Downgrading decisions for our primary outcome of fetal, neonatal and infant death were based on wide confidence intervals (crossing the line of no effect), lack of blinding and a limited number of studies. No data were available for any of our other important outcomes: birth less than 48 hours after trial entry; composite serious infant outcome; composite serious maternal outcome. The data are limited by volume and the outcomes reported. Only eight of our 45 pre-specified primary and secondary maternal and infant health outcomes were reported on in the included studies. No long-term outcomes were reported. Downgrading decisions for the evidence on the risk of respiratory distress were based on wide confidence intervals (crossing the line of no effect) and lack of blinding.There is some evidence from a single study suggesting a reduction in the length of stay in the neonatal intensive care unit and a reduced risk of respiratory distress syndrome where a high-dose regimen of magnesium sulphate has been used compared with a low-dose regimen. However, given that evidence has been drawn from a single study (with a small sample size), these data should be interpreted with caution.Magnesium sulphate has been shown to be of benefit in a wide range of obstetric settings, although it has not been recommended for tocolysis. In clinical settings where health benefits are established, further trials are needed to address the lack of evidence regarding the optimal dose (loading dose and maintenance dose), duration of therapy, timing of therapy and role for repeat dosing in terms of efficacy and safety for mothers and their children. Ongoing examination of different regimens with respect to important health outcomes is required.

[MEDICAL THERAPY FOR THE MANAGEMENT OF PRETERM LABOR: IS THERE A FIRST LINE AGENT?].

Preterm birth is defined as delivery before 37 weeks. It is the leading cause of perinatal morbidity and mortality. Spontaneous preterm birth accounts for approximately 70% of all preterm births. Postponing delivery for 48 hours in order to allow administration of corticosteroids, magnesium for neuroprotection and in order to transfer women to a center with neonatal intensive care unit are the goals of tocolytic therapy. The benefits of tocolytic therapy between 24.0 and 34.0 weeks of gestation outweigh the risk of maternal and fetal complications and it should be initiated provided no contraindications exist. Tocolytic agents that have been used are: prostaglandin synthetase inhibitors, calcium channel antagonists, B-adrenergic agonists, magnesium and oxytocin receptor antagonists. All drugs have demonstrated limited benefit that consists mainly of prolonging the gestational age for 48 hours, without a reduction in the incidence of perinatal mortality and morbidity. Additionally, most available tocolytic agents carry inherent risks of adverse effects. According to the American College of Obstetricians and Gynecologists recommendations, there is no clear first line tocolytic drug to manage preterm labor. Other subjects of debate related to the use of tocolytic therapy include: The effectiveness of combination therapy, the use of tocolytic therapy in multiple pregnancies and the use of progesterone as an adjuvant therapy. We will address the efficacy and tolerability of the tocolytic agents available, the issue of maintenance therapy and debates mentioned above, and try to suggest a first line tocolytic agent based on a study performed at our institution.

[Tocolysis with nifedipin; its use in current practice].

AIM: The aim of the study is to establish the safety and efficacy of calcium channel blocker- Nifedipin as tocolytic agents. A wide range of tocolytics have been utilized for the management of preterm labor Calcium channel blockers, namely nifedipine, gained popularity as tocolytics due to the oral route of administration, availability of immediate- and slow-release preparations, the low incidence of maternal adverse effects associated with their use, and the fact that they are inexpensive. METHODS: 88 pregnant women in preterm labor participated in a prospective longitudinal study Inclusion criteria were: gestational age between 24 and 34 weeks gestation; uterine contractions in 10-15 min interval; single pregnancy, lack of contraindications for tocolysis. In all cases the calcium antagonist Nifedipine was used in dosage 4 x 10 mg per os. The clinical response to tocolysis, gestational age at delivery and potential side effects were analyzed. RESULTS: 91 pregnant women participated in the study. Three were excluded because they refused to participate. 88 pregnancies were finally analyzed. In nine of them maternal contractions persisted despite of treatment. The other 79 pregnancies were delayed 48 hours to receive antenatal corticosteroids. From all these 79 pregancies 66 delayed 7 days. The most common adverse effects were tachycardia, hypotonia, headache, dizziness, but they escape soon after the first dose. CONCLUSION: Nifedipine is an effective oral tocolytic with few maternal side effects.

Tocolytics for preterm premature rupture of membranes.

BACKGROUND: In women with preterm labor, tocolysis has not been shown to improve perinatal mortality; however, it is often given for 48 hours to allow for the corticosteroid effect for fetal maturation. In women with preterm premature rupture of membranes (PPROM), the use of tocolysis is still controversial. In theory, tocolysis may prolong pregnancy in women with PPROM, thereby allowing for the corticosteroid benefit and reducing the morbidity and mortality associated with prematurity. OBJECTIVES: To assess the potential benefits and harms of tocolysis in women with preterm premature rupture of membranes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 January 2014). SELECTION CRITERIA: We included pregnant women with singleton pregnancies and PPROM (23 weeks to 36 weeks and six days). We included any tocolytic therapy compared to no tocolytic, placebo, or another tocolytic. DATA COLLECTION AND ANALYSIS: All review authors assessed the studies for inclusion. We extracted and quality assessed data. MAIN RESULTS: We included eight studies with a total of 408 women. Seven of the studies compared tocolysis to no tocolysis. One study compared nifedipine to terbutaline. Compared to no tocolysis, tocolysis was not associated with a significant effect on perinatal mortality in women with PPROM (risk ratio (RR) 1.67; 95% confidence interval (CI) 0.85 to 3.29). Tocolysis was associated with longer latency (mean difference (MD) 73.12 hours; 95% CI 20.21 to 126.03; three trials of 198 women) and fewer births within 48 hours (average RR 0.55; 95% CI 0.32 to 0.95; six trials of 354 women; random-effects, Tau² = 0.18, I² = 43%) compared to no tocolysis. However, tocolysis was associated with increased five-minute Apgar of less than seven (RR 6.05; 95% CI 1.65 to 22.23; two trials of 160 women) and increased need for ventilation of the neonate (RR 2.46; 95% CI 1.14 to 5.34; one trial of 81 women). In the subgroup analysis comparing betamimetic to no betamimetics, tocolysis was associated with increased latency and borderline significance for chorioamnionitis. Prophylactic tocolysis with PPROM was associated with increased overall latency, without additional benefits for maternal/neonatal outcomes. For women with PPROM before 34 weeks, there was a significantly increased risk of chorioamnionitis in women who received tocolysis. However, neonatal outcomes were not significantly different. There were no significant differences in maternal/neonatal outcomes in subgroup analyses comparing cox inhibitor versus no tocolysis, calcium channel blocker versus betamimetic, antibiotic, corticosteroid or combined antibiotic/corticosteroid. AUTHORS' CONCLUSIONS: Our review suggests there is insufficient evidence to support tocolytic therapy for women with PPROM, as there was an increase in maternal chorioamnionitis without significant benefits to the infant. However, studies did not consistently administer latency antibiotics and corticosteroids, both of which are now considered standard of care.

Evaluating the side effects of treatment for preterm labor in a center that uses "high-dose" magnesium sulfate.

OBJECTIVE: To evaluate the tolerability and safety of intravenous magnesium sulfate use for tocolysis in a center that uses a "high-dose" regimen. STUDY DESIGN: We conducted a retrospective cohort study of patients treated with magnesium sulfate for preterm labor from December 2006 to June 2010. Data were abstracted from review of individual patient electronic medical records. RESULTS: The cohort consisted of 456 women. Of these, 417 (91.4%) experienced side effects. Severe side effects (pulmonary edema, respiratory arrest, intensive care unit transfer, cardiac arrest, or death) occurred in 24 (5.3%) cases, all but one due to pulmonary edema. No cases of respiratory arrest, cardiac arrest, or death occurred. Those with severe side effects were less likely to have a singleton and more likely to have a higher order multifetal gestation (p < 0.001), received more magnesium, and more often were given multiple concurrent tocolytics (p = 0.04). CONCLUSION: "High-dose" magnesium tocolysis results in side effects for 9 of every 10 patients treated, and severe side effects occur in 1 of every 20 patients. When used for tocolysis, magnesium should be used as a single agent, for less than 48 hours, and with great caution in multifetal gestations.

Atosiban and nifedipine in the suppression of pre-term labour: a comparative study.

This is a retrospective study comparing the efficacy and safety of atosiban and nifedipine in the suppression of pre-term labour. A total of 75 patients were included in this study; 34 received atosiban and 41 received nifedipine. There were no statistically significant differences in the baseline characteristics for both groups. A total of 68.3% of women in the atosiban group remained undelivered at 7 days or more, compared with 64.7% in the nifedipine group, which was not statistically significant. Average birth weight, admission to the neonatal intensive care unit and mode of delivery were similar in both groups. However, the gestational age at delivery was significantly higher in the nifedipine group. We concluded that atosiban and nifedipine are effective in delaying delivery for 7 days or more in women presenting with pre-term labour. They have the same efficacy and associated minor side-effects. However, flushing, palpitation and hypotension were significantly higher in the nifedipine group.

Tocolytics for preterm premature rupture of membranes.

BACKGROUND: In women with preterm labor, tocolysis has not been shown to improve perinatal mortality; however, it is often given for 48 hours to allow for the corticosteroid effect for fetal maturation. In women with preterm premature rupture of membranes (PPROM), the use of tocolysis is still controversial. In theory, tocolysis may prolong pregnancy in women with PPROM, thereby allowing for the corticosteroid benefit and reducing the morbidity and mortality associated with prematurity. OBJECTIVES: To assess the potential benefits and harms of tocolysis in women with preterm premature rupture of membranes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 April 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE (1966 to 6 April 2011) and EMBASE (1974 to 6 April 2011). SELECTION CRITERIA: We included pregnant women with singleton pregnancies and PPROM (23 weeks to 36 weeks and six days). We included any tocolytic therapy compared to no tocolytic, placebo, or another tocolytic. DATA COLLECTION AND ANALYSIS: All review authors assessed the studies for inclusion. We extracted and quality assessed data. MAIN RESULTS: We included eight studies with a total of 408 women. Seven of the studies compared tocolysis to no tocolysis. One study compared nifedipine to terbutaline. Compared to no tocolysis, tocolysis was not associated with a significant effect on perinatal mortality in women with PPROM (risk ratio (RR) 1.67; 95% confidence interval (CI) 0.85 to 3.29). Tocolysis was associated with longer latency (mean difference (MD) 73.12 hours; 95% CI 20.21 to 126.03; three trials of 198 women) and fewer births within 48 hours (average RR 0.55; 95% CI 0.32 to 0.95; six trials of 354 women; random-effects, T(2) = 0.18, I(2) = 43%) compared to no tocolysis. However, tocolysis was associated with increased five-minute Apgar of less than seven (RR 6.05; 95% CI 1.65 to 22.23; two trials of 160 women) and increased need for ventilation of the neonate (RR 2.46; 95% CI 1.14 to 5.34; one trial of 81 women). In the subgroup analysis comparing betamimetic to no betamimetics, tocolysis was associated with increased latency and borderline significance for chorioamnionitis. Prophylactic tocolysis with PPROM was associated with increased overall latency, without additional benefits for maternal/neonatal outcomes. For patients with PPROM before 34 weeks, there was a significantly increased risk of chorioamnionitis in women who received tocolysis. However, neonatal outcomes were not significantly different. There were no significant differences in maternal/neonatal outcomes in subgroup analyses comparing cox inhibitor versus no tocolysis, calcium channel blocker versus betamimetic, antibiotic, corticosteroid or combined antibiotic/corticosteroid. AUTHORS' CONCLUSIONS: Our review suggests there is insufficient evidence to support tocolytic therapy for women with PPROM, as there was an increase in maternal chorioamnionitis without significant benefits to the infant. However, studies did not consistently administer latency antibiotics and corticosteroids, both of which are now considered standard of care.

Comparison of the efficacy and adverse effects of nifedipine and indomethacin for the treatment of preterm labor.

OBJECTIVE: To compare the effectiveness and adverse effects of nifedipine versus indomethacin in the treatment of preterm labor. METHODS: In a randomized clinical trial, 79 women with labor pain at 26-33 weeks of gestation were treated with either oral nifedipine (n=40) or rectal indomethacin (n=39). RESULTS: Twenty-three (59%) women in the indomethacin group, and 10 (25%) in the nifedipine group did not respond to treatment (P=0.002). None of the 16 and 30 women remaining in the indomethacin and nifedipine groups, respectively, delivered during the subsequent 48 hours. Of these remaining women, 1 (6.25%) in the indomethacin group and 4 (13.3%) in the nifedipine group delivered between 48 hours and 7 days (P=0.162). For the women who responded to treatment, the mean gestational age at time of delivery was 238.5±19.4 days and 246.4±15.4 days in the nifedipine and indomethacin groups, respectively (P=0.182). Seventeen (42.5%) women in the nifedipine group, and 11 (28.2%) in the indomethacin group showed adverse effects (P=0.184). CONCLUSION: Indomethacin was less effective than nifedipine for the fast treatment of preterm labor. For women who responded to treatment within 2 hours, however, the delaying of delivery by indomethacin was similar to that by nifedipine.

Nifedipine for the treatment of preterm labor in twin and singleton pregnancies.

PURPOSE: To investigate the outcomes of singleton and twin pregnancies that were complicated by spontaneous preterm labor and received nifedipine tocolysis. METHODS: We identified the following subjects from a computerized, hospital database: 58 singleton and 32 twin pregnancies that were between 24 and 34 weeks of gestation, admitted for spontaneous preterm labor without rupture of the membranes, and receiving tocolysis with nifedipine. Data were analyzed using the Chi-square test, the Mann-Whitney test, and the Kaplan-Meier survival analysis. RESULTS: Spontaneous, preterm delivery occurred in 31.1% cases of singleton and 81.3% of twin pregnancies. Although the 22% of the mothers of twins did not have cervical changes upon admission, 37% of twins were delivered within 48 h. Mean for delivery weeks from admission to 36 weeks was significantly less for twin than it was for singleton gestations (32.3 ± 1.0 vs. 35.0 ± 0.5 weeks, respectively; Mantel-Cox X (2) = 41.118; p < 0.001). The maternal side effects were not significantly different between the groups. No serious cardiovascular complication had been found in either group. CONCLUSIONS: Tocolysis with nifedipine is effective and safe for use in both singleton and twin gestations.

[Nifedipine or nicardipine in management of threatened preterm delivery: an observational population-based study]. / Utilisation de la nifédipine et de la nicardipine dans le traitement de la menace d'accouchement prématurée: données observationnelles en population.

OBJECTIVE: For the first line tocolysis, calcium channel blockers (CCB)--oral nifedipine (Adalate®) or intravenous nicardipine (Loxen®)--are frequently used in France. No study compared nifedipine and nicardipine in management of threatened preterm delivery. From data of a French observational study, we compared factors associated with the use of nifedipine and nicardipine. Efficacy and tolerance of the two treatments were also compared. METHODS: It was a secondary analysis of EVAPRIMA study, a practice survey describing management of threatened preterm delivery in 107 French maternity units. Only women who received calcium channel blockers in their first line tocolytic therapy were included. We studied obstetrical factors associated with the choice of nifedipine or nicardipine. We also analyzed factors associated with a delivery within seven days following admission using univariate and multivariate analysis. Adverse secondary effects were compared between women who received nifedipine or nicardipine. RESULTS: Three hundred and four women received calcium channel blockers for their first line tocolytic therapy, in 73 maternity units: 93 (30.6%) women received oral nifedipine and 211 (69.4%) intravenous nicardipine. The same CCB was always prescribed in 69 maternity units. Admission after in utero transfer was less frequent among women who received nifedipine (6.5% versus 17.1%, P=0.01). Premature rupture of the membranes was also less frequent among women who received nifedipine (4.3% versus 13.7%, P=0.02), in comparison with women who received nicardipine. Median duration between admission for threatened preterm labor and delivery was longer when nifedipine was used (44 days versus 36 days, P=0.04). After adjustment on obstetrical factors, the risk to have a delivery within 7 days following admission was not significantly different between nifedipine and nicardipine groups (adjusted OR=0.5 [0.2-1.2]). Among women who received nifedipine only two cases (2.1%) of adverse event were reported with only one case needing a switch of treatment. Thirteen (6.2%) cases of adverse event were reported among women who received nicardipine (P=0.16); in three cases it motivated a switch. However, due to bias and limits inherent in such studies, our results should be interpreted cautiously. CONCLUSION: Nicardipine is the first choice for French obstetricians in management of severe threatened preterm delivery. However, intravenous nicardipine does not increase gestational duration in comparison with oral nifedipine.

[Management of pre-term labor: use of nifedipine in Conakry, Guinea]. / Menaces d'accouchement prématuré: utilisation de la nifédipine à Conakry, Guinée.

This purpose of this prospective and descriptive study was to evaluate the utility of a calcium-channel inhibitor, i.e. nifedipine, for management of preterm labor in our work setting in terms of safety and cost-effectiveness in comparison with betamimetics classically used for this indication. Study was carried out over a six-month period in the department of Gynecology-Obstetrics Department of Ignace Deen National Hospital in Conakry, Guinea. Pregnant women meeting the following criteria were included: 28 to 33 weeks of amenorrhea, six days of hospitalization either for preterm labor or for another diagnosis that was associated with the occurrence of preterm labor during hospitalization, and absence of contraindications for tocolysis using nifedipine. A total of 42 women were included. Pregnancy was extended for more than 48 hours after the first dose of nifedipine in 86.8% of cases. Administration of nifedipine failed in 5 cases including one case in which it was necessary to change the tocolytic and 4 cases in which delivery occurred less than 48 hours after the first dose of nifedipine. In 68% of cases, 90 mg of nifedipine were sufficient to stop uterine contractions within 48 hours. In 39.5% of cases, no side effects were observed. Adverse effects in the other cases were dizziness (39.5%) and headache (18.4%). The mean term of delivery was 36 weeks +/- 5 days of amenorrhea with a mean extension of 6.2 weeks. Apgar score was low in 30.5% of the newborns and normal in 69.5%. One newborn (2.8%) died. The results of this study indicate that nifedipine is an effective, economical and safe drug for tocolysis and that it can be used as an alternative to betamimetis in countries with limited resources. An information campaign is needed to promote use of nifedipine as a tocolytic in obstetrical facilities of our country.

[Tocolytic therapy in threatened preterm labor]. / Leczenie tokolityczne w zagrazajacym porodzie przedwczesnym.

The most important benefit of tocolysis is a 48-hour prolongation of gestational age in order to administer corticosteroids to reduce perinatal mortality and morbidity as well as, if necessary to gain time for "in utero" transfer to a tertiary centre with neonatal facilities. The tocolytic agents used in clinical practice can be grouped into six classes, namely: calcium channel blockers, betamimetics, magnesium sulfate, cyclooxygenase inhibitors, oxytocin receptor antagonists and nitric oxide donors. The use of them should be individualized and based on tocolytic effectiveness, safety gestational age as well as maternal, fetal and neonatal outcomes. Data from clinical trials suggests that nifedipine appears to be the drug of first choice in the management of preterm labor.