Management of preterm labor: atosiban or nifedipine?

Preterm birth is strongly associated with neonatal death and long-term neurological morbidity. The purpose of tocolytic drug administration is to postpone threatening preterm delivery for 48 hours to allow maximal effect of antenatal corticosteroids and maternal transportation to a center with specialized neonatal care facilities. There is uncertainty about the value of atosiban (oxytocin receptor antagonist) and nifedipine (calcium channel blocker) as first-line tocolytic drugs in the management of preterm labor. For nifedipine, concerns have been raised about unproven safety, lack of placebo-controlled trials, and its off-label use. The tocolytic efficacy of atosiban has also been questioned because of a lack of reduction in neonatal morbidity. This review discusses the available evidence, the pros and cons of either drug and aims to provide information to support a balanced choice of first-line tocolytic drug: atosiban or nifedipine

Pregnant women's willingness to participate in a randomized trial comparing induction of labor at 39 weeks versus expectant management: A survey in the Netherlands

IntroductionA randomized controlled trial (RCT) in the United States, the ARRIVE trial, has indicated that induction of labor (IOL) in low-risk nulliparous women with a gestational age (GA) of 39 weeks compared to expectant management (EM) resulted in a significant lower rate of cesarean deliveries. The Dutch maternity care system is different compared to the United States with, among other factors, an overall significantly lower percentage of caesarean sections (CS). To investigate whether IOL has a favorable outcome in the Dutch maternity care system, a new trial is advised. In this questionnaire-based study we aim to evaluate whether Dutch low-risk pregnant women would be willing to participate in an RCT comparing IOL at 39 weeks to EM. Materials and methodsWe conducted an online survey in 2020 in the Netherlands. Respondent recruitment took place both in outpatient clinics at hospitals and midwife practices and via social media. Inclusion criteria were pregnant women with singleton gestation, GA ≤ 39 weeks, age 18 years or older and residency in the Netherlands. Exclusion criteria were multiple gestation, a history of a CS, planned IOL or CS in current pregnancy and GA > 39 weeks. A subgroup was formed of low risk (receiving primary care) nulliparous women with a gestational age between 34 and 39 weeks, comparable with the ARRIVE trial. ResultsThree hundred eighty respondents participated. Of all respondents (nulli- and multiparous), 47 (12.4%) would be willing to participate in the hypothetical RCT and 70 (18.4%) might be willing to participate. Amongst the 70 women in the subgroup 11 women (15.7%) would be willing to participate and 17 (24.3%) might be willing to participate. Discussion and conclusionCalculating sample size in a country with a low CS rate, in relation to 69.2% of women are not willing to participate in an RCT comparing IOL at 39 weeks with EM, would require >18.000 women to be counselled for participation. We believe such a study is a challenge in the Netherlands

Adverse drug reactions to tocolytic treatment for preterm labour: Prospective cohort study

Objective To evaluate the incidence of serious maternal complications after the use of various tocolytic drugs for the treatment of preterm labour in routine clinical situations. Design Prospective cohort study. Setting 28 hospitals in the Netherlands and Belgium. Participants 1920 consecutive women treated with tocolytics for threatened preterm labour. Main outcome measures Maternal adverse events (those suspected of being causally related to treatment were considered adverse drug reactions) leading to cessation of treatment. Results An independent panel evaluated the recorded adverse events, without knowledge of the type of tocolytic used. Of the 1920 women treated with tocolytics, 1327 received a single course of treatment (69.1%), 282 sequential courses (14.7%), and 311 combined courses (16.2%). Adverse drug reactions were categorised as serious or mild in 14 cases each. The overall incidence of serious adverse drug reaction was 0.7%. Compared with atosiban, the relative risk of an adverse drug reaction for single treatment with a (3 adrenoceptor agonist was 22.0 (95% confidence interval 3.6 to 138.0) and for single treatment with a calcium antagonist was 12 (1.9 to 69). Multiple drugtocolysis led to five serious adverse drug reactions (1.6%). Multiple gestation, preterm rupture of membranes, and comorbidity were not independent risk factors for adverse drug reactions. Conclusions The use of (3 adrenoceptor agonists or multiple tocolytics for preventing preterm birth is associated with a high incidence of serious adverse drug reactions. Indometacin and atosiban were the only drugs not associated with serious a

Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study

Objective To evaluate the incidence of serious maternal complications after the use of various tocolytic drugs for the treatment of preterm labour in routine clinical situations

Induction of labor with Foley catheter and risk of subsequent preterm birth: follow-up study of two randomized controlled trials (PROBAAT-1 and -2)

Objective: To evaluate the rate of preterm birth (PTB) in a subsequent pregnancy in women who had undergone term induction using a Foley catheter compared with prostaglandins. Methods: This was a follow-up study of two large randomized controlled trials (PROBAAT-1 and PROBAAT-2). In the original trials, women with a term singleton pregnancy with the fetus in cephalic presentation and with an indication for labor induction were randomized to receive either a 30-mL Foley catheter or prostaglandins (vaginal prostaglandin E2 in PROBAAT-1 and oral misoprostol in PROBAAT-2). Data on subsequent ongoing pregnancies > 16 weeks’ gestation were collected from hospital charts from clinics participating in this follow-up study. The main outcome measure was preterm birth 16 weeks' gestation in the Foley catheter and prostaglandin groups, respectively. There were no differences in baseline characteristics between the groups. The overall rate of PTB in a subsequent pregnancy was 9/251 (3.6%) in the Foley catheter group vs 10/258 (3.9%) in the prostaglandin group (relative risk (RR), 0.93; 95% CI, 0.38–2.24), and the rate of spontaneous PTB was 5/251 (2.0%) vs 5/258 (1.9%) (RR, 1.03; 95% CI, 0.30–3.51). Conclusion: In women with term singleton pregnancy, induction of labor using a 30-mL Foley catheter is not associated with an increased risk of PTB in a subsequent pregnancy, as compared to induction of labor using prostaglandins

Acute tocolysis for intrapartum nonreassuring fetal status: how often does it prevent cesarean delivery? A systematic review and meta-analysis of randomized controlled trials

OBJECTIVE: This study aimed to evaluate the effectiveness of intrapartum acute tocolysis for nonreassuring fetal heart rate tracing in decreasing the incidence of cesarean delivery. Secondary outcomes included modes of delivery other than cesarean delivery, successful acute tocolysis, time-to-delivery interval, and short-term perinatal outcomes. DATA SOURCES: Searches were performed in MEDLINE/PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials and Reviews, ClinicalTrials.gov, and the International Clinical Trials Registry Platform from the inception of each database until February 2022. STUDY ELIGIBILITY CRITERIA: Selection criteria included randomized controlled trials of laboring patients with singleton gestations randomized to receive intrapartum acute tocolysis for nonreassuring fetal heart rate tracing, as defined by the original trial. METHODS: All analyses were done using an intention-to-treat approach, evaluating women according to the treatment group to which they were randomly allocated in the original trials. A frequentist network-meta-analysis was performed. RESULTS: Four randomized clinical trials were eligible, including 605 patients with nonreassuring fetal heart rate tracing and singleton gestations at gestational ages >32 weeks. The cesarean delivery rate was similar among patients managed with different types of acute tocolysis. Acute tocolysis, compared with emergency delivery, was associated with improved neonatal acid-base status (notably decreasing the prevalence of base deficit >12 mmol/L [beta-2 agonists odds ratio, 0.61; 95% confidence interval, 0.37–0.99] and the rate of neonatal intensive care unit admission [beta-2 agonists odds ratio, 0.42; 95% confidence interval, 0.22–0.78]) and with an increase in the time-to-delivery interval (beta-2 agonists mean difference, 17.62 minutes; 95% confidence interval, 15.66–19.58); there was no reduction of cesarean delivery rate, showing an increased rate with atosiban and beta-2 agonists. CONCLUSION: The cesarean delivery rate was not reduced by acute tocolysis when used for nonreassuring fetal heart rate tracing during labor. Acute tocolysis is associated with improved short-term fetal outcomes and safely increases the time-to-delivery interval

Acute tocolysis for intrapartum non-reassuring fetal status: how often does it prevent cesarean delivery? A systematic review and meta-analysis of randomized controlled trials

Objective: The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to evaluate the effectiveness of intrapartum acute tocolysis for non-reassuring fetal heart rate tracing (NRFHT) in decreasing the incidence of cesarean delivery (CD). Secondary outcomes were considered other modes of delivery than CD, successful acute tocolysis, time to the delivery interval, and short-term perinatal outcomes. Data sources: Searches were performed in MEDLINE/PubMed, EMBASE, Scopus, the Cochrane Central Register of Controlled Trials and Reviews, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) from the inception of each database until February 2022. Study eligibility criteria: Selection criteria included RCTs of laboring singleton gestations randomized to receive intrapartum acute tocolysis for NRFHT, as defined by the original trial. Study appraisal and synthesis methods: All analyses were done using an intention-to-treat approach, evaluating women according to the treatment group to which they were randomly allocated in the original trials. A frequentist network-meta-analysis was performed. Results: Four randomized clinical trials were eligible, including 605 patients with NRFHT and singleton gestation at a gestational age more than 32 weeks. The CD rate was similar in patients managed with different types of acute tocolysis. Acute tocolysis, compared with emergency delivery, was associated with improved neonatal acid-base status (notably decreasing the prevalence of base deficit > 12 mmol/L (beta-2 agonists OR 0.61 CI.95 0.37-0.99) and the rate of neonatal intensive care unit admission (beta-2 agonists OR 0.42 CI.95 0.22-0.78)) and with an increase in the time interval to delivery (beta-2 agonists MD 17.62 minutes CI.95 15.66-19.58); there was no reduction of the CD rate showing an increased rate in atosiban and beta-2 agonists. Conclusions: The CD rate was not reduced by acute tocolysis when used for NRFHT during labor. Acute tocolysis is associated with improved short-term fetal outcomes and safely increases the interval to delivery

First-trimester Placental Vascular Development in Multiparous Women differs from that in Nulliparous Women

Objective: Multiparas differ from nulliparas by delivering larger babies with larger placentas and by having a lower risk of developing placental syndromes. We postulate that these differences result from a different initial course of placental vascular development. Study design: We measured placental flow index (FI), vascularization index (VI) and placental volume by 3D power Doppler and obtained blood samples at 8, 10 and 12 weeks pregnancy in 34 healthy nulliparous and 16 multiparous women with an uneventful pregnancy. Results: Between 8 and 12 weeks multiparas differed from nulliparas in a more rapid initial rise in FI, a higher angiopoietin-2 (ang2) level at eight weeks and no decline in the VEGF/sVEGF-R ratio. Nevertheless, at 12 weeks the FI and placental volume were indistinguishable between both study groups. Conclusions: These results combining serially measured placental vascularization, placental volume and circulating angiogenetic factors show initial differences in placental development, that howeve, did not maintain till the end of first trimester. The results support the concept that early placental vascular development differs between nulliparas and multiparas. Nevertheless, it is unclear whether these differences contribute to the development later on in pregnancy of intergroup differences in birthweight and incidence of placental syndromes

Pregnancy and ischemic stroke : A practical guide to management

Purpose of review Ischemic stroke during pregnancy or the puerperium is a devastating disease during a crucial period in life and warrants a specific approach. To date, current practice is mainly based on expert opinion because of a lack of randomized controlled trials and high-quality observational studies. The present review is intended as a practical guide to (acute) management of ischemic stroke during pregnancy and puerperium. Recent findings Recent findings showed that the incidence of stroke during pregnancy is rising. In 2014, the first guideline for the prevention of stroke in women was released, however on many (pregnancy) related topics the evidence was too scarce to make clear evidence-based recommendations. Summary The risk of ischemic stroke is elevated especially from the third trimester until 6 weeks postpartum. MRI is the most accurate and well tolerated diagnostic option but low-dose CT-head is a valid alternative. Reperfusion therapies should not be withheld from a pregnant woman with moderate-To-severe stroke when benefits outweigh the risk. Aspirin up to 150 mg daily is considered well tolerated during pregnancy and lactation period. Multidisciplinary care is essential when counseling these women in the acute and later stages