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.

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.

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.

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.

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.

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..

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.

Tocolysis in the management of preterm prelabor rupture of membranes at 22-33 weeks of gestation: study protocol for a multicenter, double-blind, randomized controlled trial comparing nifedipine with placebo (TOCOPROM).

BACKGROUND: Preterm prelabor rupture of membranes (PPROM) before 34 weeks of gestation complicates 1% of pregnancies and accounts for one-third of preterm births. International guidelines recommend expectant management, along with antenatal steroids before 34 weeks and antibiotics. Up-to-date evidence about the risks and benefits of administering tocolysis after PPROM, however, is lacking. In theory, reducing uterine contractility could delay delivery and reduce the risks of prematurity and its adverse short- and long-term consequences, but it might also prolong fetal exposure to inflammation, infection, and acute obstetric complications, potentially associated with neonatal death or long-term sequelae. The primary objective of this study is to assess whether short-term (48 h) tocolysis reduces perinatal mortality/morbidity in PPROM at 22 to 33 completed weeks of gestation. METHODS: A randomized, double-blind, placebo-controlled, superiority trial will be performed in 29 French maternity units. Women with PPROM between 220/7 and 336/7 weeks of gestation, a singleton pregnancy, and no condition contraindicating expectant management will be randomized to receive a 48-hour oral treatment by either nifedipine or placebo (1:1 ratio). The primary outcome will be the occurrence of perinatal mortality/morbidity, a composite outcome including fetal death, neonatal death, or severe neonatal morbidity before discharge. If we assume an alpha-risk of 0.05 and beta-risk of 0.20 (i.e., a statistical power of 80%), 702 women (351 per arm) are required to show a reduction of the primary endpoint from 35% (placebo group) to 25% (nifedipine group). We plan to increase the required number of subjects by 20%, to replace any patients who leave the study early. The total number of subjects required is thus 850. Data will be analyzed by the intention-to-treat principle. DISCUSSION: This trial will inform practices and policies worldwide. Optimized prenatal management to improve the prognosis of infants born preterm could benefit about 50,000 women in the European Union and 40,000 in the United States each year. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03976063 (registration date June 5, 2019).

The effectiveness of nifedipine/indomethacin combination therapy and nifedipine monotherapy for postponing preterm birth (25-34 weeks of gestation) in Sudanese women: a randomized clinical trial study protocol.

BACKGROUND: Preterm birth is the most common cause of neonatal morbidity and mortality. Tocolytics are considered a standard treatment for women with threatened preterm delivery to allow time for maternal steroid administration and transfer to referral centers with neonatal intensive care units. However, there is controversy about the best tocolytic therapy to be considered as the first choice. The aim of this study is to compare the tocolytic effectiveness and tolerability of combination therapy with nifedipine and indomethacin versus nifedipine monotherapy among Sudanese women with preterm labor (PTL) as well as to compare the possible neonatal outcomes associated with each drug. METHODS/DESIGN: This is a randomized controlled clinical trial to be conducted in the Medani Maternity Hospital, Sudan. Women aged 18-40 years that are diagnosed with preterm labor and have a gestational age between 25 and 34 weeks will be eligible to participate in this trial. The diagnosis of threatened PTL is defined as persistent uterine contractions "(four contractions every 20 min or eight contractions every 60 min)" with cervical changes "(cervical effacement ≤80% or cervical dilatation >two cm)". Patients will be eligible regardless of the presentation of the fetus. It will be randomly decided whether participants receive nifedipine/indomethacin combination therapy or nifedipine monotherapy. The primary outcome is the number of women who do not deliver and do not need alternative tocolytic drug (terbutaline). The secondary outcome is an estimated association with neonatal morbidity and mortality. The sample size will be 117 subjects in each arm of the study, according to a type I error of 0.05 and a study power of 80%. DISCUSSION: We expect higher effectiveness of the combination indomethacin/nifedipine tocolytic therapy compared with nifedipine monotherapy. We plan to suggest this combination therapy as the best option for postponing PTL. TRIAL REGISTRATION: Clinical trial registration: PACTR202004681537890 , date of registration: March 8, 2020.

Umbilical cord prolapse: revisiting its definition and management.

Umbilical cord prolapse is an unpredictable obstetrical emergency with an incidence ranging from 1 to 6 per 1000 pregnancies. It is associated with high perinatal mortality, ranging from 23% to 27% in low-income countries to 6% to 10% in high-income countries. In this review, we specifically addressed 3 issues. First, its definition is not consistent in the current literature, and "occult cord prolapse" is a misnomer because the cord is still above the cervix. We proposed that cord prolapse, cord presentation, and compound cord presentation should be classified according to the positional relationship among the cord, the fetal presenting part, and the cervix. All of them may occur with either ruptured or intact membranes. The fetal risk is highest in cord prolapse, followed by cord presentation, and lastly by compound cord presentation, which replaces the misnomer "occult cord prolapse." Second, the mainstay of treatment of cord prolapse is urgent delivery, which means cesarean delivery in most cases, unless vaginal delivery is imminent. The urgency depends on the fetal heart rate pattern, which can be bradycardia, recurrent decelerations, or normal. It is most urgent in cases with bradycardia, because a recent study showed that cord arterial pH declines significantly with the bradycardia-to-delivery interval at a rate of 0.009 per minute (95% confident interval, 0.0003-0.0180), and this may indicate an irreversible pathology such as vasospasm or persistent cord compression. However, cord arterial pH does not correlate with either deceleration-to-delivery interval or decision-to-delivery interval, indicating that intermittent cord compression causing decelerations is reversible and less risk. Third, while cesarean delivery is being arranged, different maneuvers should be adopted to relieve cord compression by elevating the fetal presenting part and to prevent further cord prolapse beyond the vagina. A recent study showed that the knee-chest position provides the greatest elevation effect, followed by filling of the maternal urinary bladder with 500 mL of fluid, and then the Trendelenburg position (15°) and other maneuvers. However, each maneuver has its own advantages and limitations; thus, they should be applied wisely and with great caution, depending on the actual clinical situation. Therefore, we have proposed an algorithm to guide this acute management.

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.

Effectiveness and Safety of Isoxsuprine Hydrochloride as Tocolytic Agent in Arresting Active/Threatened Preterm Labor and Its Role in Maintenance Tocolysis: A Prospective, Open-Label Study.

OBJECTIVE: The aim of the study is to obtain insights on the short and long-term safety and effectiveness of isoxsuprine hydrochloride as a tocolytic agent in the management of PTL. STUDY DESIGN: In this prospective, single-center, noncomparative study, patients (with preterm labor at gestational age of 24-37 weeks) were administered intravenous (IV) infusion of 40-mg isoxsuprine hydrochloride until uterine quiescence, followed by intramuscular (IM) injection of isoxsuprine hydrochloride 10 mg/4-hourly for first 24 hours and maintained with retard 40-mg sustained release capsule (two times a day) till the time of delivery or 37 completed weeks of pregnancy. RESULTS: All patients (n = 50) achieved successful tocolysis in 24 hours and 48 hours postadministration of isoxsuprine hydrochloride (IV/IM/oral). Mean (±SD) gestation age at the time of delivery was 39.8 ± 2.1 weeks, with latency period of 58.5 ± 18.7 days. Pregnancy outcomes were normal in all the patients and no congenital anomaly/fetal infection was reported. Mean (±SD) fetal birth weight was 2.7 ± 0.3 kg; mean (±SD) Apgar score at 1 and 5 minutes were 7.5 ± 0.6 and 9.2 ± 0.4, respectively. Maternal tachycardia and vomiting (8.0% each) were the commonly reported adverse drug reactions, which were resolved with dose adjustment. CONCLUSION: Isoxsuprine was found to be an effective and well-tolerated tocolytic agent in arresting PTL, in turn resulting in the overall improvement in maternal and perinatal outcomes.

Tocolytic Therapy in Preterm Premature Rupture of Membranes.

"Trials evaluating tocolytic use in preterm premature rupture of membranes (PPROM) have been small and lacked adequate power to evaluate uncommon outcomes. There still is much controversy on the benefit, length of use, route, and drug of choice among clinicians treating patients with PPROM. Most professional medical societies would propose to consider the use of tocolytics for 48 hours to allow for corticosteroid administration or to allow for maternal transfer to a higher level of care. Longer treatment regimens may lead to adverse maternal and perinatal outcomes. Insufficient data are available to make stronger and more definitive recommendations."

Effects of nifedipine on fetal cardiac function in preterm labor.

Objectives To evaluate the effects of nifedipine treatment on fetal hemodynamics and cardiac function during preterm labor. This prospective study assessed several quantitative parameters of fetal cardiac circulation and function, and found no significant changes at 48 h after nifedipine treatment. These findings suggest that tocolytic nifedipine may be safe for fetuses. It supports clinicians to use nifedipine treatment for tocolysis without any cardiac effect on the fetus. Methods A prospective cohort study was conducted at a tertiary hospital between January 2016 and October 2017. A total of 45 pregnant women who required nifedipine for preterm labor were included in this study. Fetal Doppler ultrasound was performed and fetal systolic and diastolic function was measured prior to, and 48 h after, the first nifedipine treatment. Conventional Doppler parameters were used to evaluate fetal heart function and hemodynamic changes. Tricuspid annular plane systolic excursion, mitral annular plane systolic excursion and the sphericity index were also evaluated to assess changes in fetal cardiac morphology. Results No significant changes in fetal Doppler parameters were observed following nifedipine tocolysis. There was no significant difference in the fetal cardiac function parameters of both ventricles before vs. after nifedipine treatment. Tricuspid annular plane systolic excursion, mitral annular plane systolic excursion, and sphericity index values were unchanged following nifedipine treatment. Conclusions Oral administration of nifedipine did not to alter fetal cardiac function or morphology. Fetal cardiac parameters and various Doppler indices were unchanged following nifedipine treatment. Maternal nifedipine treatment does not appear to have any significant effect on fetal cardiac function.

Unit policies regarding tocolysis after preterm premature rupture of membranes: association with latency, neonatal and 2-year outcomes (EPICE cohort).

After preterm premature rupture of membranes (PPROM), antibiotics and antenatal steroids are effective evidence-based interventions, but the use of tocolysis is controversial. We investigated whether a unit policy of tocolysis use after PPROM is associated with prolonged gestation and improved outcomes for very preterm infants in units that systematically use these other evidence-based treatments. From the prospective, observational, population-based EPICE cohort study (all very preterm births in 19 regions from 11 European countries, 2011-2012), we included 607 women with a singleton pregnancy and PPROM at 24-29 weeks' gestation, of whom 101, 195 and 311 were respectively managed in 17, 32 and 45 units with no-use, restricted and liberal tocolysis policies for PPROM. The association between unit policies and outcomes (early-onset sepsis, survival at discharge, survival at discharge without severe morbidity and survival at two years without gross motor impairment) was investigated using three-level random-intercept logistic regression models, showing no differences in neonatal or two-year outcomes by unit policy. Moreover, there was no association between unit policies and prolongation of gestation in a multilevel survival analysis. Compared to a unit policy of no-use of tocolysis after PPROM, a liberal or restricted policy is not associated with improved obstetric, neonatal or two-year outcomes.

Maternal and fetal parameters in pregnant woman undergoing tocolysis with nifedipine / Parâmetros maternos e fetais em gestante submetida a tocólise com nifedipina

Abstract Objectives: to evaluate the effects of nifedipine with tocolysis under maternal and fetal parameters. Methods: a cohort study with 40 pregnant women admitted at a high-risk pregnancy ward to inhibit premature labor between September/2010 to May/2012. Nifedipine was used as a 20mg sublingual attack dose and maintained 20mg every six and eight hours orally. The variables of the analysis were fetal heart rate (FHR), maternal heart rate (MHR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), and amniotic fluid index (AFI). All the variables were evaluated prior to administrating nifedipine and approximately after 6 hours and every 24 hours, until hospital discharge. Results: there were no modification of the FHR (p=0.48) and the SBP (p=0.29). The MHR increased after 24 hours, but with no statistical difference (p=0.08), returning to similar levels as at admission within 48 hours. The DBP decreased at 6 (p=0.04) to 72 hours, being stable afterwards. The AFI decreased significantly at 24, 48 and 72 hours. Conclusions: the use of high doses of nifedipine with tocolysis causes a decrease of the maternal's diastolic blood pressure and consequently decreases the amniotic fluid index, but probably without any clinical repercussions.

Resumo Objetivos: avaliar os efeitos da nifedipina utilizada na tocólise sobre os parâmetros maternos e fetais. Métodos: estudo de coorte incluindo 40 gestantes admitidas na enfermaria de alto risco para inibição do trabalho de parto prematuro entre setembro/2010 a maio/2012. Utilizou-se a nifedipina sublingual na dose de ataque de 20mg e uma manutenção de 20mg por via oral a cada seis e oito horas. As variáveis avaliadas foram os batimentos cardio-fetais (BCF), frequência cardíaca materna (FCM), pressão arterial sistólica (PAS) e diastólica (PAD) e índice de líquido amniótico (ILA). Todas as variáveis foram avaliadas antes da administração da nifedipina e aproximadamente após 6h e cada 24h até alta hospitalar. Resultados: não houve modificação dos BCF (p=0,48) e da PAS (p=0,29). A FCM aumentou após 24h, mas sem significância estatística (p=0,08) retornando a níveis similares ao da admissão com 48h. A PAD diminuiua partir de 6h (p = 0,04)até 72h, mantendo-se constante. O ILA diminuiu significativamente em 24h, 48h e 72h. Conclusão: a utilização de altas doses de nifedipina para tocóliseocasio na diminuição dos níveis pressóricos diastólicos maternos e consequentemente diminuição do ILA, mas provavelmente sem repercussões clínicas.

Outcomes following acute tocolysis prior to emergency caesarean section.

AIM: To determine if a policy recommending administration of terbutaline prior to emergency caesarean section improved arterial umbilical cord pH. MATERIALS AND METHODS: This was a prospective audit between February 2018 and June 2019 among women who underwent a category one or two caesarean section. Neonatal cord gas results and perinatal outcomes were compared before and after the introduction of a policy recommending subcutaneous terbutaline prior to emergency caesarean section. RESULTS: Among 423 women in the pre-policy change cohort and 253 post-policy change, there was no difference in arterial cord pH (median pH = 7.24 before the policy and median pH = 7.24 after the policy was introduced, P = 0.88). There was no statistically significant difference in any perinatal outcome, apart from the median arterial cord lactate which was higher in the post-treatment group (4.2 mmol/L vs 3.9 mmol/L, P = 0.006). Maternal heart rate was higher (median 110 vs 95, P < 0.0001) in the post-treatment group. Breastfeeding was more common in the post-treatment group (99% vs 95%, P = 0.005). There was no difference in estimated blood loss or rate of post-partum haemorrhage. A post hoc analysis according to treatment received, limited to caesarean section when the indication was suspected fetal compromise, demonstrated that among women who received terbutaline the rate of low pH (<7.1) was 3.8% (5/130) when terbutaline was given, compared with 6.6% (18/272) when terbutaline was not given (χ21  = 1.3, P = 0.26). CONCLUSION: Changing our labour ward policy to recommending terbutaline prior to all category one and category two caesarean sections did not change arterial cord pH.

Cervical pessary plus vaginal progesterone versus long-term tocolysis for the prevention of preterm birth: An observational retrospective study.

OBJECTIVE: To compare cervical pessaries plus vaginal progesterone versus long-term tocolysis for preventing preterm birth for women with a short cervix. METHODS: Retrospective evaluation of women with singleton pregnancy who received cervical pessaries plus vaginal progesterone (combined group) or ritodrine hydrochloride (tocolysis group) for short cervix (≤25 mm at 20-24 weeks, or ≤20 mm at 25-34 weeks) at a general hospital in Kagoshima, Japan, 2015-2019. The primary outcome was rate of preterm birth (<36 weeks); secondary outcomes were maternal hospital admittance and treatment complications. RESULTS: Data were evaluated from 95 women (combined group, n=43; tocolysis group, n=52). There was no significant difference in cervical length or gestational age at intervention between the groups. Overall, 3/43 (7.0%) women delivered before 36 weeks in the combined group versus 16/52 (30.8%) in the tocolysis group (relative risk, 0.56; 95% confidence interval, 0.41-0.76; P=0.004). Median maternal admittance was shorter in the combined group (6.6 vs 41.0 days, P<0.001). Although 36/43 (83.7%) women in the combined group reported increased vaginal discharge, no major complications occurred. CONCLUSION: A combination of pessaries and vaginal progesterone reduced the rate of preterm birth (<36 weeks) for women with short cervix as compared with long-term tocolysis.