Relationship between prolonged gestation and nifedipine pharmacokinetics in long-term tocolysis.

In this study, we examined the pharmacokinetics of nifedipine and investigated the maternal and foetal background factors that prolong pregnancy in pregnant women undergoing long-term tocolysis. This prospective observational study included 38 pregnant women hospitalised for threatened preterm labour and treated with nifedipine extended-release tablets in combination with an intravenous ritodrine infusion. Maternal plasma nifedipine concentrations were determined using high-performance liquid chromatography. All patients were administered 20 or 40 mg/dose of nifedipine every 6 h at the time of blood sampling. The plasma trough concentration (Ctrough ) was 22.6 ± 17.3 ng/mL, the maximum plasma concentration (Cmax ) was 30.9 ± 15.3 ng/mL and the time to maximum concentration (Tmax ) was 1.70 ± 1.10 h, as determined using noncompartmental analysis (NCA). The area under the curve for drug concentration (AUCtau ) was 152.3 ± 91.8 mg/L・h, and oral clearance (CL/F) was 0.17 ± 0.08 L/h. Using logistic regression analyses, we identified the factors that predicted term delivery from 37 weeks to <42 weeks of gestation. Gestational age at admission and the AUCtau of nifedipine can predict term delivery. The AUCtau of nifedipine is a valuable regulatory predictor of term delivery in pregnant women undergoing long-term tocolysis.

Maintenance tocolysis, tocolysis in preterm premature rupture of membranes and in cervical cerclage - a Germany-wide survey on the current practice after dissemination of the German guideline.

OBJECTIVES: To investigate the adherence of German perinatal specialist units and those of basic obstetric care to the national guideline we compared data from a nation-wide survey on the practice of maintenance tocolysis, tocolysis in preterm premature rupture of membranes and in the perioperative setting of cervical cerclage, and bedrest during and after tocolysis with recommendations from the current German Guideline 015/025 "Prevention and Treatment of Preterm Birth". METHODS: A total of 632 obstetric clinics in Germany were approached and received a link to an online questionnaire. Data were descriptively analyzed by performing measures of frequency. To compare two or more groups Fisher's exact test was used. RESULTS: The response rate was 19%; 23 (19.2%) of respondents did not perform maintenance tocolysis, while 97 (80.8%) conducted maintenance tocolysis; 30 (25.0%) of obstetric units performed cervical cerclage without tocolysis and 90 (75.0%) combined cervical cerclage with tocolysis; 11 (9.2%) of respondents did not use tocolytics in patients with preterm premature rupture of membranes, while 109 (90.8%) conducted tocolysis in these patients; 69 (57.5%) of obstetric units did not recommend bed rest during tocolysis, whereas 51 (42.5%) favored bedrest. Perinatal care centers of basic obstetric care recommend bed arrest during tocolysis statistically significant more often to their patients than those of higher perinatal care levels (53.6 vs. 32.8%, p=0.0269). CONCLUSIONS: The results of our survey are in accordance to others from different countries and reveal considerable discrepancies between evidence-based guideline recommendations and daily clinical practice.

Progestogens for maintenance tocolysis in symptomatic women. A systematic review and meta-analysis.

OBJECTIVE: Prevention of preterm birth (PTB) with progestogens after an episode of threatened preterm labour is still controversial. As different progestogens have distinct molecular structures and biological effects, we conducted a systematic review and pairwise meta-analysis to investigate the individual role played by 17-alpha-hydroxyprogesterone caproate (17-HP), vaginal progesterone (Vaginal P) and oral progesterone (Oral P). METHODS: The search was performed in MEDLINE, ClinicalTrials.gov and the Cochrane Central Register of Controlled Trials (CENTRAL) up to 31 October 2021. Published RCTs comparing progestogens to placebo or no treatment for maintenance tocolysis were considered. We included women with singleton gestations, excluding quasi-randomized trials, studies on women with preterm premature rupture of membrane, or receiving maintenance tocolysis with other drugs. Primary outcomes were preterm birth (PTB) < 37 weeks' and < 34 weeks'. We assessed risk of bias and evaluated certainty of evidence with the GRADE approach. RESULTS: Seventeen RCTs including 2152 women with singleton gestations were included. Twelve studies tested vaginal P, five 17-HP, and only 1 oral P. PTB < 34 weeks' did not differ among women receiving vaginal P (RR 1.21, 95%CI 0.91 to 1.61, 1077 participants, moderate certainty of evidence), or oral P (RR 0.89, 95%CI 0.38 to 2.10, 90 participants, low certainty of evidence) as opposed to placebo. Instead, 17-HP significantly reduced the outcome (RR 0.72, 95% CI 0.54 to 0.95, 450 participants, moderate certainty of evidence). PTB < 37 weeks' did not differ among women receiving vaginal P (RR 0.95, 95%CI 0.72 to 1.26, 8 studies, 1231 participants, moderate certainty of evidence) or 17-HP (RR 0.86, 95%CI 0.60 to 1.21, 450 participants, low certainty of evidence) when compared to placebo/no treatment. Instead, oral P significantly reduced the outcome (RR 0.58, 95% CI 0.36 to 0.93, 90 participants, low certainty of evidence). CONCLUSIONS: With a moderate certainty of evidence, 17-HP prevents PTB < 34 weeks' gestation among women that remained undelivered after an episode of threatened preterm labour. However, data are insufficient to generate recommendations in clinical practice. In the same women, both 17-HP and vaginal P are ineffective in the prevention of PTB < 37 weeks'.

Long-term vs short-term tocolysis with ritodrine hydrochloride: Propensity score-matched analysis.

OBJECTIVE: To investigate whether the short-term tocolysis protocol is as effective as the traditional long-term tocolysis protocol with intravenous ritodrine hydrochloride for preterm labour. STUDY DESIGN: This single-centre, retrospective, observational study was conducted at Kitano Hospital, Osaka, Japan between April 2016 and July 2021. At the study hospital, the management protocol for preterm labour after 26 weeks of gestation was changed from the long-term tocolysis protocol to the short-term tocolysis protocol in November 2019. This study compared patients managed with the two protocols, using propensity score analysis to overcome the potential weaknesses of a retrospective study. The primary outcome was the frequency of preterm birth before 34 weeks of gestation before and after the protocol was revised. The secondary outcomes were frequency of neonatal intensive care unit admission and frequency of neonatal chronic lung disease. RESULTS: The study population consisted of 82 patients managed by the long-term tocolysis protocol and 56 patients managed by the short-term tocolysis protocol. After propensity score-weighted adjustment, the median durations of intravenous ritodrine administration in the long-term and short-term protocols were 18 days and 3 days, respectively. Differences were not detected between the long-term and short-term protocols in terms of the frequency of preterm delivery before 34 weeks of gestation [23.7 % vs 21.6 %, risk ratio (RR) 0.91, 95 % confidence interval (CI) 0.47-1.77], frequency of neonatal intensive care unit admission due to preterm birth (49.5 % vs 39.3 %, RR 0.79, 95 % CI 0.53-1.19) and frequency of neonatal chronic lung disease (4.4 % vs 9.2 %, RR 2.07, 95 % CI 0.51-8.48). CONCLUSION: Using propensity score analysis, changing from the long-term tocolysis protocol to the short-term tocolysis protocol for the management of preterm labour after 26 weeks of gestation did not have a negative effect on the frequency of preterm birth or neonatal prognosis.

Terbutaline for acute tocolysis prior to emergency caesarean delivery for suspected foetal compromise.

INTRODUCTION: Terbutaline has been used as a foetal resuscitation measure to improve the intrapartum foetal heart rate abnormalities and neonatal outcome for suspected foetal compromise. Unfortunately, till date, the available data are limited to draw any recommendation. MATERIAL AND METHODS: This was a double-blind, placebocontrolled trial conducted among women planned for emergent caesarean delivery for suspected foetal compromise where 100 were randomised to receive subcutaneous terbutaline or placebo. The primary outcomes were the neonatal acid-base status, while the 5- minute Apgar score, admission to the intensive care unit and the maternal outcomes were recorded as secondary outcomes. RESULTS: Data from a total of 96 women were analysed and showed a lower incidence of neonatal acidemia (4.4% vs 10.4%) and fewer neonates born with umbilical artery pH of less than 7.20 (12.5% vs 27.1%) and 7.10 (4.2% vs 6.2%) after terbutaline injection. However, the difference in the incidence of neonatal acidaemia, mean cord pH and base excess, Apgar score or admission to the intensive care unit did not differ significantly. No difference was seen in the maternal mean arterial pressure, estimated blood loss or haematocrit after the surgery between the study groups. The only significant maternal effect was tachycardia which was more common after terbutaline injection (54.2% vs 25.0 %, p=0.003). CONCLUSION: The study shows that acute tocolysis with subcutaneous terbutaline prior to caesarean delivery has the potential to improve the neonatal outcome in suspected intrauterine foetal compromise and should be further investigated.

Tocolysis with nifedipine versus atosiban and perinatal outcome: an individual participant data meta-analysis.

BACKGROUND: Worldwide, nifedipine and atosiban are the two most commonly used tocolytic agents for the treatment of threatened preterm birth. The aim of this study was to evaluate the effectiveness of nifedipine and atosiban in an individual participant data meta-analysis (IPDMA). METHODS: We investigated the occurrence of adverse neonatal outcomes in women with threatened preterm birth by performing an IPDMA, and sought to identify possible subgroups in which one treatment may be preferred. We searched PubMed, Embase, and Cochrane for trials comparing nifedipine and atosiban for treatment of threatened preterm birth between 240/7 and 340/7 weeks' gestational age. Primary outcome was a composite of perinatal mortality and neonatal morbidities including respiratory distress syndrome, intraventricular haemorrhage, periventricular leucomalacia, necrotising enterocolitis, and sepsis. Secondary outcomes included NICU admission, prolongation of pregnancy and GA at delivery. For studies that did not have the original databases available, metadata was used. This led to a two-stage meta-analysis that combined individual participant data with aggregate metadata. RESULTS: We detected four studies (N = 791 women), of which two provided individual participant data (N = 650 women). The composite neonatal outcome occurred in 58/364 (16%) after nifedipine versus 69/359 (19%) after atosiban (OR 0.76, 95%CI 0.47-1.23). Perinatal death occurred in 14/392 (3.6%) after nifedipine versus 7/380 (1.8%) after atosiban (OR 2.0, 95%CI 0.80-5.1). Nifedipine results in longer prolongation of pregnancy, with a 18 days to delivery compared with 10 days for atosiban (HR 0.83 (96% CI 0.69-0.99)). NICU admission occurred less often after nifedipine (46%) than after atosiban (59%), (OR 0.32, 95%CI 0.14-0.75). The sensitivity analysis revealed no difference in prolongation of pregnancy for 48 hours (OR 1.0, 95% CI 0.73-1.4) or 7 days (OR 1.3, 95% CI 0.85-5.8) between nifedipine and atosiban. There was a non-significant higher neonatal mortality in the nifedipine-exposed group (OR 1.4, 95% CI 0.60-3.4). CONCLUSIONS: In this IPDMA, we found no differences in composite outcome between nifedipine and atosiban in the treatment of threatened preterm birth. However, the non-significant higher mortality after administering nifedipine warrants further investigation of the use of nifedipine as a tocolytic drug. STUDY REGISTRATION: We conducted this study according to a prospectively prepared protocol, registered with PROSPERO (the International Prospective Register of Systematic Reviews) under CRD42016024244.

[Tocolysis during External Cephalic Version (ECV): A retrospective before/after study in a type III maternity hospital]. / Tocolyse lors des Versions par Manœuvres Externes (VME) : étude rétrospective avant/après dans une maternité de type III.

OBJECTIVE: On January 2020, the French College of Gynecologists and Obstetricians (CNGOF) issued new Clinical Practice Guidelines (CPG) "Breech Presentation". Since then, it is recommended to use a tocolytic agent to improve the success rate of External Cephalic Version (ECV). The aim of this study, one year after these CPG, is to compare ECV without (before CPG) and with (after CPG) tocolysis in a type III maternity hospital. We intend to assess its effects on immediate success rate of ECV and obstetrical and neonatal outcomes. MATERIALS AND METHODS: This is a single-center retrospective study conducted in Nantes University Hospital. We collected patient characteristics, immediate success rate, and maternal and neonatal outcomes at delivery of all ECV over two periods: the first one during 2019 (before CPG) and the second one from June 2020 to June 2021 (after CPG). RESULTS: We included 253 patients: 126 in the first period and 127 in the second period. Immediate success rate of ECV was significantly higher since the use of tocolysis: 38.6 % (period 2) vs 23.8 % (period 1) (P=0.011). However, there was not significant difference found for cephalic presentation at birth, mode of delivery or obstetrical and neonatal outcomes. CONCLUSION: The immediate success rate is significantly improved with the widespread use of tocolysis during ECV, with no change in obstetrical and neonatal outcomes.

A Cohort Comparison Study on Women in Threatened Preterm Labor Given Nifedipine or Nifedipine and Salbutamol Tocolysis in Air Medical Retrieval.

OBJECTIVE: Women with threatened preterm labor in remote Australia often require tocolysis in the prevention of in-flight birth during air medical retrieval. However, debate exists over the tocolytic choice. METHODS: A retrospective analysis was undertaken on data containing women who required air medical retrieval for threatened preterm labor within Western Australia between the years 2013 and 2018. RESULTS: A total number of 236 air medical retrievals were deemed suitable for inclusion; 141 received nifedipine, and 95 women received salbutamol + nifedipine. Tocolytic efficaciousness was reported in 151 cases, proportionally more (P < .05) from the women who received salbutamol + nifedipine (n = 68, 71.6%) compared with the women who received nifedipine only (n = 83, 58.9%). Those receiving salbutamol + nifedipine were more likely to suffer maternal tachycardia (n = 87 [91.6%] vs. n = 62 [44.0%]), fetal tachycardia (n = 26 [27.4%] vs. n = 13 [9.2%]), nausea (n = 17 [17.9] vs. n = 5 [3.55%]), and vomiting (n = 12 [12.6%] vs. n = 2 [1.4%]). Three women who received salbutamol + nifedipine had serious side effects including echocardiographic changes, chest pain, and metabolic and lactic acidosis. CONCLUSION: Salbutamol + nifedipine tocolysis was proven to be more effective than nifedipine only. Although salbutamol + nifedipine had increased temporary side effects, most were nonsevere and managed in-flight.

Tocolytic Treatment for the Prevention of Preterm Birth from a Taiwanese Perspective: A Survey of Taiwanese Obstetric Specialists.

Preterm birth represents a great burden to the healthcare system, resulting in the consideration for the use of tocolytic therapy to provide a "better time" for delivery in order to buy time to accelerate fetal lung maturity, thereby minimizing prematurity-related morbidity and mortality. However, the benefits and potential side effects and risks of tocolytic treatment for preterm birth should be carefully balanced. Although many countries and societies provide guidelines or consensuses for the management for preterm birth, there is no standardized national guideline or consensus in Taiwan. As such, great heterogeneity is suspected in preterm labor management, contributing to the uncertainty of attitudes and practice patterns of obstetric specialists in Taiwan. This study attempts to understand the attitudes and practice patterns regarding tocolytic therapy in Taiwan. A paper-based survey was conducted at the 2020 Taiwan Society of Perinatology Conference on 8 December 2020, exploring how obstetric specialists would use tocolytics under nine different clinical scenarios, such as a short cervix, preterm labor, maintenance tocolysis, preterm premature rupture of membranes, etc. Three hundred ten specialists attended the conference, and 77 responded to the survey with a response rate of 24.8%. According to the survey, many of these specialists would prescribe tocolytics for less evidence-based indications, including 22% for abdominal tightness, 46% for a short cervix, 60% for maintenance tocolysis, and 89% for repeat tocolysis, with the preferred first line medication being ritodrine and nifedipine. We concluded that tocolysis is widely accepted and practiced in Taiwan. More research is needed to include Taiwan-specific economic and cultural factors as well as associated adverse effects and patients' outcomes.

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.

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.

Association between hospitals' cesarean delivery rates for breech presentation and their success rates for external cephalic version.

INTRODUCTION: Success rates of external cephalic version (ECV) are heterogenous in the published literature. Some individual factors are already known to be associated with ECV success but probably do not fully explain the differences. The objective of this review is to assess the association between hospitals' cesarean delivery rates for breech presentations after ECV failure and their ECV success rates. MATERIAL AND METHODS: We performed a review of the literature using the Medline and Cochrane Library computer databases and by searching on clinicaltrials.gov, from 1985 through 2020. This analysis included all studies reporting ECV success rates and cesarean delivery rates for breech presentations. The prognostic factors for successful ECV, such as rates of nulliparity, gestational age at ECV, BMI, and tocolysis use, were also collected and analyzed. Median ECV success rates from the included studies were compared according to these factors. The cesarean rate for persistent breech presentation after ECV failure reported in these studies was considered a proxy indicator of the unit's policy for breech presentations. The correlation between ECV success rates and cesarean delivery rates was analyzed and is presented as a scatter plot. RESULTS: This analysis included 22 studies reporting rates of both successful ECV and cesarean deliveries for persistent breech presentation after ECV failure. The ECV success rates ranged from 16.3% to 82.5% with a median of 48.8% (interquartile range: 36.9-62.9). The median ECV success rate was higher in the studies that used tocolysis than in those that did not (51.3% versus 22.0%, P = .001) and in the studies with the highest cesarean rates for breech presentations than in those with the lowest cesarean rates (57.9% versus 36.2%, P = .006). The ECV success rates were significantly correlated with cesarean delivery rates for persistent breech presentations (R = 0.67; P = .001). CONCLUSION: The likelihood of successful ECV appears higher in hospitals with policies that generally result in cesarean delivery for persistent breech presentation.

Do obstetric units adhere to the evidence-based national guideline? A Germany-wide survey on the current practice of initial tocolysis.

OBJECTIVES: Current international guidelines recommend tocolytic treatment by at least 48 h to complete fetal lung maturation and to ensure in-utero transfer to a perinatal center before 34 weeks of gestation in patients with threatened preterm birth. According to the results of former surveys, significant differences between daily clinical practice patterns and evidence-based guideline recommendations regarding tocolytic treatment have been demonstrated. We compared data from a nation-wide survey on the practice of initial tocolysis with recommendations from the current German Guideline 015/025 "Prevention and Treatment of Preterm Birth". STUDY DESIGN: 632 obstetric units in Germany received a link to an online questionnaire between January 20th and March 31st 2020, which was developed according to national and international recommendations and guidelines. Collected data was descriptively analyzed by performing measures of frequency. RESULTS: The response rate was 19%; 51 (42.5%) of the respondents consider CTG tracing with ≥ 4 contractions within 20 min, 49 (40.8%) cervical length measurement of ≤ 25 mm and 13 (10.9%) subjective contractions as the most significant decision-making criteria for tocolysis; 47 (39.2%) of obstetric units initiate tocolysis earliest at 23 + 0, 34 (28.3%) at 22 + 0, 26 (21.7%) at 23 + 5 and 13 (10.8%) at 24 + 0 weeks of gestation; 104 (86.7%) stop tocolysis latest at the 34 + 0 weeks of gestation, 42 (35.0%) obstetric units administer antenatal corticosteroids at 23 + 5, 16 (13.3%) at 22 + 0, and 13 (10.8%) at 24 + 0 weeks of gestation. Calcium channel blockers are the first-line tocolytic drug used by 59 (49.1%) of the obstetric units, followed by intravenous betamimetics as bolus (n = 26, 21.7%) and atosiban (n = 20, 16.7%). Severe side-effects were observed by 105 (70%) of the respondents in association with the use of betamimetics, 14 (9.3%) with the use of nifedipine and 30 (20.0%) with nitroglycerine patches. The German guideline was considered the most important decision-making support by 78 (65%) of the obstetric units, followed by hospital specific SOPs/algorithms (n = 31, 25.8%). CONCLUSION: Our survey highlights a considerable discrepancy between evidence-based guideline recommendations and daily clinical practice.

Changing Tocolytic Exposures among Neonatal Intensive Care Unit Admitted Preterm Infants.

OBJECTIVE: Since 2010, the American College of Obstetrics and Gynecology have released three committee opinions to recommend and reaffirm the utility of magnesium sulfate for neuroprotection and later for tocolysis to achieve antenatal steroid course completion in preterm labor. We sought to determine changes in antenatal magnesium sulfate exposure and other tocolytic agents for pregnancies resulting in neonatal intensive care unit (NICU)-admitted preterm infants. STUDY DESIGN: Using the Pediatrix Clinical Data Warehouse, we evaluated all inborn infants delivered between 22 and 33 weeks' gestation and admitted to the intensive care units from 2009 to 2018. We classified patients based on antenatal exposure to tocolytic medications: calcium channel blockers (nifedipine and amlodipine), betamimetics (terbutaline, theophylline, and ritodrine), prostaglandin inhibitors (indomethacin), and magnesium sulfate. RESULTS: A total of 229,781 patients met inclusion criteria. During the study period, magnesium sulfate exposure increased from 27.6 to 57.7% of births while betamimetic exposure decreased from 10.2 to 5.2%. Increasing magnesium sulfate exposure over time was seen at all gestational ages examined and magnesium exposure was most common between 23 and 31 weeks' gestation. By 2017 to 2018, 70.5% of 24 to 29 weeks' gestation NICU infants received exposure to at least one tocolytic agent while this remained at 53.7% of 32 to 33 weeks' NICU admitted infants. Antenatal steroid exposure increased from 74.8 to 87.4% during the study period. CONCLUSION: For NICU-admitted preterm infants, prenatal exposure patterns to tocolytic agents has shifted since 2009 with prenatal magnesium sulfate exposure increasing significantly. Antenatal steroid exposure has risen concurrently. Exposure to tocolytic agents is the highest among preterm infants born between 24 and 29 weeks' gestation. KEY POINTS: · Exposure to magnesium sulfate significantly increased from 2009 to 2018 for NICU admitted infants.. · Concurrently, the use of other tocolytics decreased significantly.. · The use of antenatal steroids has been rising over time..

The Charité external cephalic version for leading twin breech without regional anesthesia and tocolysis. A prospective study on feasibility, sonographic assessment and outcomes.

OBJECTIVES: To assess the feasibility of external cephalic version (ECV) for the leading twin (twin A) in breech presentation in dichorionic and diamniotic twin pregnancies without the use of regional anesthetics and tocolysis and to characterize the sonographic parameters, maternal and neonatal outcomes. STUDY DESIGN: Prospective study performed in the Charité University Hospital outpatient obstetric department in Berlin, Germany. A total of 23 women from the 35th completed week of pregnancy with confirmed dichorionic-diamniotic twin pregnancy were recruited. ECVs were performed by the lead consultant for the breech and ECV clinic. Ethical approval provided by the Charité Ethics Commission (EA2/241/18). Demographic data were recorded. Fetal sonographic parameters were assessed. The success rate of ECV, duration of the ECV, gestational age at delivery, mode of delivery for both fetuses, maternal and neonatal outcomes were analyzed. RESULTS: Our main finding showed that ECV for twin A breech in dichorionic-diamniotic twins is successful in 56% (10/18) of cases without the need for regional anesthesia and without tocolysis. There is a significant increase in the spontaneous vaginal delivery rate for both twins of 95% (19/20) vs 12.5% (2/16) (p < 0.001). There is also a significant reduction in blood loss at delivery of 300 ml vs 500 ml (p = 0.034) in successful cases. CONCLUSIONS: We show that ECV for twin A in breech is feasible and in 56% (10/18) successful without regional anesthesia and tocolysis. The option of ECV for twin A breech should be offered to women.

The use of vaginal progesterone as a maintenance therapy in women with arrested preterm labor: a double-blind placebo-randomized controlled trial.

BACKGROUND: The efficacy of maintenance tocolytic therapy after successful arrest of preterm labor remains controversial. The purpose of this study was to evaluate the efficacy of 400 mg of daily vaginal progesterone (cyclogest) after successful parenteral tocolysis to increase latency period and improvement of neonatal outcomes in women with threatened preterm labor. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled trial, 85 participants were randomly allocated to either 400 mg daily of vaginal progesterone (n = 45) or placebo (n = 40) until 34 weeks of gestation. The primary outcomes were the time until delivery (latency period) and cervical length after 1 week of treatment. Secondary outcome were GA on delivery, type of delivery, incidence of low birth weight, perinatal morbidity and mortality. RESULTS: Longer mean latency until delivery (53.6 ± 16.8 versus 34.5 ± 12.9) days p = .0001; longer mean of gestational age on delivery (37.5 ± 2.2 versus 34.2 ± 2.1) weeks p = .0001; cervical length after 1 week of treatment (27.5 ± 5.5 versus 20.7 ± 3.1) mm p = .0001; low birth weight 12 (29.3%) versus 19 (57.6%) p = .01; and NICU admission 9 (22%) versus 15 (45.5%), were significantly different between the two groups. No significant differences were found between neonatal death 1 (2.4%) versus 2 (6.1%), p = .43; RDS 5 (12.2%) versus 8 (24.2%), p = .17; and need to mechanical ventilator 2 (5.4%) versus 6 (18.2%) p = .136, for the progesterone and placebo groups, respectively. CONCLUSION: Daily administration of 400 mg vaginal progesterone after successful parenteral tocolysis may increase latency preceding delivery and improves cervical shortening and neonatal outcome in women with preterm labor. Further confirmatory studies are warranted.

Pessary use in patients diagnosed with short cervix and cervical insufficiency.

OBJECTIVE: The aim was to evaluate the effectiveness of Arabin pessary use in patients with cervical insufficiency or short cervix before the 24th week of gestation and the impact of cervical examination findings prior to pessary application on the outcome in terms of the gestational week. MATERIALS AND METHODS: In our study, among the pregnancies between the 12th and 24th gestational weeks, 60 pregnant women with a preterm delivery history and/or cervical length less than 25 mm were included. Among these 60 patients, 43 of them had a short cervix, 17 of them had cervical insufficiency. Routine medical and obstetric history was obtained. In the vaginal examination, the cervix was evaluated in terms of patency, dilatation, and position. Cervical length, presence of debris, and funneling were evaluated by transvaginal ultrasound. After receiving patients' approval a cervical pessary was applied to patients. Pessaries of pregnant women with 37 weeks of gestation were removed. Before reaching the 37th gestation week, pessaries were withdrawn in patients who had ongoing vaginal bleeding, premature rupture of membranes, and preterm contractions unresponsive to tocolytic treatment. RESULTS: Thirty-one pregnant women (51.7%) out of 60 pregnant women who underwent pessary, delivered at 37 weeks and below. Delivery rates in the short cervical measurement group and cervical insufficiency group at ≤28 weeks, ≤34 weeks and ≤37 weeks were respectively (n = 21) 34.8% vs 36.3% (p = 0.976), (n = 29) 41.8% vs 64.7% (p = 0.111), (n = 31) 44.2% vs 70.6% (p = 0.888). The presence of cervical funneling before pessary application shows a statistically significant difference in terms of patient's giving birth before or after 28 weeks (p = 0.033). In patients with cervical funneling, there was a significant increase in a birth before 28 weeks. Depending on whether or not patients applying with pain need for tocolysis, it shows the statistically meaningful difference in terms of the patients giving birth before or after 34 weeks (p = 0.001) (OR 7, 61, 95% GA 2.4-24.6). In the group without the need for tocolysis, there is a meaningful increase in birth after 34 weeks. CONCLUSIONS: Our findings showed that, alongside the defined cervical risk factors, cervical funneling and the need for tocolysis are remarkable prognostic variables in pessary application.

Effects of acute tocolysis using ritodrine hydrochloride on foetal heart rate patterns in intrauterine foetal resuscitation: a retrospective, single-centre observational study.

No consistent recommendations concerning the preferred tocolytic agents for intrauterine foetal resuscitation are available. We evaluated the effects of acute tocolysis (AT) using ritodrine hydrochloride on foetal heart rate (FHR) patterns and neonatal outcomes. We retrospectively analysed the data of patients undergoing emergency caesarean section because of non-reassuring foetal status indicated by foetal scalp electrodes. Patients were classified into AT (ritodrine hydrochloride approximately 500 µg/min) and control groups with 15 and 12 participants, respectively. FHR patterns, Apgar scores, umbilical arterial analysis, and neonatal admission were compared. All participants had FHR category II; decelerations disappeared in all foetuses in the AT group, with no significant difference in neonatal outcomes. The AT group had a higher baseline FHR and lower short-term FHR variability than the control group, indicating foetal autonomic responses. Further studies are needed to clarify the effects of AT on FHR patterns, neonatal outcomes, and foetal and neonatal autonomic responses.Impact statementWhat is already known on this subject? The usefulness of acute tocolysis using ritodrine hydrochloride has been well-documented in several studies; however, such an application often induces side effects, such as maternal tachycardia, palpitations, and tremors.What the results of this study add? The short-term administration of ritodrine hydrochloride eliminated decelerations, with no significant difference in neonatal outcomes in pregnant women with foetal heart rate category II. Meanwhile, there were higher foetal heart rate and lower short-term foetal heart rate variability in pregnant women administered with ritodrine hydrochloride, indicating foetal autonomic responses.What the implications are of these findings for clinical practice and/or further research? Ritodrine hydrochloride administration, even for short-term, appears to be associated with foetal autonomic responses. Further studies with stratification of patient groups based on the severity and aetiology of non-reassuring foetal status, including pregnant women with foetal category III, would elucidate the risk and benefit of acute tocolysis using ritodrine hydrochloride, based on foetal heart rate patterns, neonatal outcomes, and foetal and neonatal autonomic responses.

Association between the prolonged use of magnesium sulfate for tocolysis and fracture risk among infants.

ABSTRACT: In 2013, the U.S. Food and Drug Administration issued a safety warning that cautioned against using magnesium sulfate (MgSO4) injections for more than 5 to 7 days to stop preterm delivery due to the bone problems subsequently observed in infants. However, the warning was mainly based on case reports, and further investigation is necessary to determine whether prolonged MgSO4 use increased infant fractures.To evaluate whether prolonged MgSO4 use for tocolysis increased the risk of subsequent fractures among infants.A retrospective population-based cohort study was conducted with a new-user study design using the National Health Insurance Database in Taiwan. We included pregnant women aged between 12 and 55 years old who delivered a live-born singleton. The enrollment period was from January 1, 2012 to December 31, 2014. The exposure group was defined as pregnant women who received MgSO4 injection for >5 days during pregnancy, while those not receiving any tocolytics were the reference group. The outcome was any bone fracture among the infants during the 2-year follow-up period. Propensity score matching and Cox proportional hazards regression models were used to estimate the hazard of fractures. We further studied the effect of MgSO4 treatment with varied dosages and durations of treatment in the sensitivity analyses.Among the 4092 pregnant women in the database, 693 (16.9%) of them were included in the exposure group. The hazard ratio of infant fractures among prolonged MgSO4 users was not significantly different from that of tocolytic nonusers in adjusted models (adjusted hazard ratio (aHR) = 1.48; 95% confidence interval (CI) = 0.59-3.71). A similar lack of significance was found in the sensitivity analyses (aHR = 1.45; 95% CI = 0.40-5.28 for larger treatment dosage; aHR = 2.52; 95% CI = 0.49-12.98 for longer treatment duration).Prolonged MgSO4 tocolysis use did not increase the risk of infant fractures. Our findings reconfirmed the safety of MgSO4 as a tocolytic treatment.