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This systematic review aimed to identify the benefits and possible harms of tocolytic therapy for preterm labour management in the context of pregnant women with extremely preterm birth, multiple gestations, or growth-restricted foetuses. A comprehensive search using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, CINAHL, and the WHO Global Index Medicus databases was conducted from 10 to 15 July 2021. We included randomized controlled trials and non-randomized studies that assessed the effects of tocolysis compared with placebo or no treatment. We found 744 reports and, finally, nine studies (three randomized controlled trials and six cohort studies) pertaining to women with <28 weeks of gestation were included. No eligible studies were identified among women with a multiple pregnancy or a growth-restricted foetus. A meta-analysis of the trial data showed that there were no clear differences in perinatal death nor for a delay in birth. Non-randomized evidence showed that tocolysis delayed birth by 7 days, though there was no clear difference for preterm birth. In summary, it remains unclear whether tocolytic therapy for inhibiting preterm labour is beneficial for these subgroups of women and their newborns. Further well-designed randomized controlled trials and observational studies are needed to address the lack of evidence regarding tocolytic agents in these populations.

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.

Preterm birth is the leading cause of death in newborns and the survivors are prone to health complications. Threatened preterm labor (TPL) is the most common cause of hospitalization in the second half of pregnancy. The current methods used in clinical practice to diagnose preterm labor, the Bishop score or cervical length, have high negative predictive values but not positive ones. In this work we analyzed the performance of computationally efficient classification algorithms, based on electrohysterographic recordings (EHG), such as random forest (RF), extreme learning machine (ELM) and K-nearest neighbors (KNN) for imminent labor (<7 days) prediction in women with TPL, using the 50th or 10th-90th percentiles of temporal, spectral and nonlinear EHG parameters with and without obstetric data inputs. Two criteria were assessed for the classifier design: F1-score and sensitivity. RF F1&#95;2 and ELM F1&#95;2 provided the highest F1-score values in the validation dataset, (88.17 ± 8.34% and 90.2 ± 4.43%) with the 50th percentile of EHG and obstetric inputs. ELM F1&#95;2 outperformed RF F1&#95;2 in sensitivity, being similar to those of ELM Sens (sensitivity optimization). The 10th-90th percentiles did not provide a significant improvement over the 50th percentile. KNN performance was highly sensitive to the input dataset, with a high generalization capability.

Threatened preterm labor (TPL) is the most common cause of hospitalization in the second half of pregnancy and entails high costs for health systems. Currently, no reliable labor proximity prediction techniques are available for clinical use. Regular checks by uterine electrohysterogram (EHG) for predicting preterm labor have been widely studied. The aim of the present study was to assess the feasibility of predicting labor with a 7- and 14-day time horizon in TPL women, who may be under tocolytic treatment, using EHG and/or obstetric data. Based on 140 EHG recordings, artificial neural networks were used to develop prediction models. Non-linear EHG parameters were found to be more reliable than linear for differentiating labor in under and over 7/14 days. Using EHG and obstetric data, the <7- and <14-day labor prediction models achieved an AUC in the test group of 87.1 ± 4.3% and 76.2 ± 5.8%, respectively. These results suggest that EHG can be reliable for predicting imminent labor in TPL women, regardless of the tocolytic therapy stage. This paves the way for the development of diagnostic tools to help obstetricians make better decisions on treatments, hospital stays and admitting TPL women, and can therefore reduce costs and improve maternal and fetal wellbeing.

Objective: To study the tocolytic action of nifedipine combined with sildenafil citrate (SC) and if the combination is superior to nifedipine alone in inhibiting threatened preterm labour (PTL)., Design: Prospective randomised study., Setting: An Egyptian university hospital., Population: Women with threatened PTL who received either nifedipine with SC or nifedipine alone., Methods: Patients were randomly allocated to receive either (1) nifedipine 20 mg orally (stat dose), followed by 10 mg orally every 6-8 hours at the same time as vaginal administration of SC (25 mg at 8-hourly intervals) or (2) nifedipine alone. Medications were continued for 48-72 hours., Main Outcome Measures: The percentage of women who remained undelivered during hospitalisation., Results: From January 2015 to November 2016, 239 women were randomised. The baseline characteristics of participants were similar. Nifedipine combined with SC was associated with more women remaining undelivered (81.8 versus 68.6%; P = 0.018) during hospitalisation. Regarding secondary outcomes, the addition of SC was also associated with fewer deliveries within 7 days of admission (9.1 versus 20.3%; P = 0.014), prolonged latency (29 versus 7 days; P = 0.002), fewer admissions to neonatal intensive care units (31.4 versus 44.1%; P = 0.043), fewer very preterm deliveries (from 28 to <32 weeks, 20.7 versus 38.1%; P = 0.043), and increased neonatal birthweight (1900 versus 1500 g; P = 0.018)., Conclusions: Vaginal SC combined with nifedipine is an effective option for tocolytic therapy during threatened PTL., Tweetable Abstract: Vaginal SC enhances the tocolytic effect of nifedipine., (© 2018 Royal College of Obstetricians and Gynaecologists.)

As one of the main aims of obstetrics is to be able to detect imminent delivery in patients with threatened preterm labor, the techniques currently used in clinical practice have serious limitations in this respect. The electrohysterogram (EHG) has now emerged as an alternative technique, providing relevant information about labor onset when recorded in controlled checkups without administration of tocolytic drugs. The studies published to date mainly focus on EHG-burst analysis and, to a lesser extent, on whole EHG window analysis. The study described here assessed the ability of EHG signals to discriminate imminent labor (< 7 days) in women with threatened preterm labor undergoing tocolytic therapy, using both EHG-burst and whole EHG window analyses, by calculating temporal, spectral, and non-linear parameters. Only two non-linear EHG-burst parameters and four whole EHG window analysis parameters were able to distinguish the women who delivered < 7 days from the others, showing that EHG can provide relevant information on the approach of labor, even in women with threatened preterm labor under the effects of tocolytic therapy. The whole EHG window outperformed the EHG-burst analysis and is seen as a step forward in the development of real-time EHG systems able to predict imminent labor in clinical praxis. Graphical abstract The ability of EHG recordings to predict imminent labor (< 7 days) was analyzed in preterm threatened patients undergoing tocolytic therapies by means of EHG-burst and whole EHG window analysis. The non-linear features were found to have better performance than the temporal and spectral parameters in separating women who delivered in less than 7 days from those who did not.

Introduction: Tocolytics may cause changes in fetal heart rate (HR) pattern, while fetal heart rate variability (HRV) is an important marker of fetal well-being. We aim to systematically review the literature on how tocolytic drugs affect fetal HRV., Materials and Methods: We searched CENTRAL, PubMed and EMBASE up to June 2016. Studies published in English, using computerized or visual analysis to describe the effect of tocolytics on HRV in human fetuses were included. Studies describing tocolytics during labor, external cephalic version, pre-eclampsia and infection were excluded. Eventually, we included six studies, describing 169 pregnant women., Results: Nifedipine, atosiban and indomethacin administration show no clinically important effect on fetal HRV. Following administration of magnesium sulfate decreased variability and cases of bradycardia are described. Fenoterol administration results in a slight increase in fetal HR with no changes in variability. After ritodrine administration increased fetal HR and decreased variability is seen. The effect of co-administration of corticosteroids should be taken into account., Conclusion: In order to prevent iatrogenic preterm labor, the effects of tocolytic drugs on fetal HRV should be taken into account when monitoring these fetuses.