Nifedipine maintenance tocolysis and perinatal outcome: an individual participant data meta‐analysis

Vliet, Eog van; Dijkema, GH; Schuit, Ewoud; Heida, KY; Roos, Carolien; Post, Joris A. M. van der; Parry, EC; McCowan, Lesley; Lyell, DJ; El-Sayed, Y.Y.; Carr, DB; Clark, AL; Mahdy, Zaleha Abdullah; Uma, M.; Sayın, N. Cenk; Varol, GF; Mol, BW; Oudijk, Martijn A.

doi:10.1111/1471-0528.14249

Cited by 32 publications

(16 citation statements)

References 31 publications

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“…Other issues related to pregnancy outcomes of women discharged after admission for threatened preterm labor, such as the lack of an effective maintenance treatment [28,29] or characteristics of the neonates finally delivered at term [30][31][32], are out of the scope of this study; indeed, they are still under debate and need further evaluation.…”

Section: Discussionmentioning

confidence: 99%

Uterine Cervical Length Measurement to Reduce Length of Stay in Patients Admitted for Threatened Preterm Labor: A Randomized Trial

et al. 2017

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Objective: To study whether knowledge of cervical length (CL) is useful in reducing the length of hospital stay in women admitted because of threatened preterm labor. Methods: We performed a single-center, parallel, randomized trial at the Hospital Clínic of Barcelona. Inclusion criteria were single pregnancy, gestational age (GA) between 24⁺⁰ and 35⁺⁶ weeks, Bishop score <6, no parturition within 24-48 h after admission, and no clinical signs of chorioamnionitis, vaginal bleeding, or nonreassuring fetal status. CL measurement was performed 24-48 h after admission. In the control group, the patient and the physician in charge were blinded. In the study group, this information was given; if CL was >25 mm, early discharge within 12-24 h from randomization was recommended. Length of hospital stay was the main outcome. Results: After randomization, 149 patients had complete follow-up (control group, n = 74; study group, n = 75). The mean (SD) length of stay was significantly shorter - 3.0 (2.2) vs. 4.0 (2.0) days (p = 0.004) - in the study group, with a higher proportion of women remaining hospitalized ≤3 days (relative risk [95% confidence interval] 0.43 [0.26-0.70]), with no differences in GA at delivery or preterm birth rate. Conclusions: Knowledge of CL in women admitted because of threatened preterm labor is useful in reducing length of stay, with no impact on GA at delivery or preterm birth rate.

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Section: Discussionmentioning

confidence: 99%

Uterine Cervical Length Measurement to Reduce Length of Stay in Patients Admitted for Threatened Preterm Labor: A Randomized Trial

et al. 2017

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“…Different types of β2-adrenergic agonists, Ca 2+ channel blocker, oxytocin receptor antagonist and nonsteroidal antiinflammatory drugs are also used as tocolytics, but their insufficient effectiveness and side effects compromise their preliminary use [13,14]. Therefore, agents with potential tocolytic characteristics are still needed, and they could include calcium antagonists, potassium channel openers and other vasodilators [15].…”

Section: Introductionmentioning

confidence: 99%

The role of potassium channels and calcium in the relaxation mechanism of magnesium sulfate on the isolated rat uterus

Sokolović

Drakul

Oreščanin-Dušić

et al. 2019

ARCH BIOL SCI BELGRA

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MgSO 4 is used as a tocolytic agent. It is considered to be a calcium channel antagonist, but a different mechanism of its action might be involved. The aim of this study was to examine the contribution of calcium concentrations and potassium channels in the mechanism of MgSO 4 -mediated uterine relaxation. Isolated uteri from female Wister rats were treated with increasing MgSO 4 concentrations (0.1-30 mM). MgSO 4 induced dose-dependent inhibition of spontaneous activity. Addition of Ca 2+ (6 mM and 12 mM) stimulated uterine contractile activity and attenuated the inhibitory activity of MgSO 4 . In order to analyze the role of different subtypes of potassium channels, Ca 2+ -stimulated uteri were pretreated with glibenclamide (Glib), a selective ATP-sensitive potassium channel inhibitor (K ATP ), tetraethylammonium (TEA), a non-specific inhibitor of large conductance calcium-activated potassium channels (BK Ca ), and 4-aminopyridine (4-AP), a voltage-sensitive potassium channel inhibitor (Kv), at concentrations that had no effect per se. Pretreatment with 4-AP had no effect on MgSO 4 -mediated relaxation of Ca 2+ -stimulated uteri. The relaxing effect of MgSO 4 was potentiated by pretreatment with glibenclamide. Pretreatment with TEA attenuated the MgSO 4 -mediated decrease in frequency. Our results suggest that MgSO 4 acts as a general calcium antagonist that influences Ca 2+ -mediated potassium channels. Furthermore, it seems that MgSO 4 uterine relaxation activity is partially mediated by selective ATP-sensitive potassium channels, suggesting an ATP-dependent role.

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“…The current first‐line tocolytic therapy consists of the L‐type calcium channel blocker nifedipine and the oxytocin‐receptor antagonist atosiban. A recent meta‐analysis showed that nifedipine maintenance tocolysis is not associated with improved perinatal outcome or pregnancy prolongation . Another meta‐analysis showed that atosiban is less effective than pan–prostaglandin synthesis inhibitors, calcium channel blockers, MgSO 4 , or beta‐mimetics in delaying labor .…”

mentioning

confidence: 99%

“…A recent meta-analysis showed that nifedipine maintenance tocolysis is not associated with improved perinatal outcome or pregnancy prolongation. 3 Another meta-analysis showed that atosiban is less effective than pan-prostaglandin synthesis inhibitors, calcium channel blockers, MgSO 4 , or beta-mimetics in delaying labor. 4 Thus, a requirement for a new class of tocolytic persists.…”

mentioning

confidence: 99%

Confirmation of the Cardiac Safety of PGF_2αReceptor Antagonist OBE022 in a First‐in‐Human Study in Healthy Subjects, Using Intensive ECG Assessments

Täubel

Lorch²,

Coates³

et al. 2018

Clinical Pharm in Drug Dev

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OBE022, a new orally active prostaglandin F2α receptor antagonist (OBE022) with myometrial selectivity is being developed to reduce uterine contractions during preterm labor. This first‐in‐human study evaluated the effect of OBE022 following multiple doses on the QT interval in 23 healthy postmenopausal women, using the effect of a meal on QTc to demonstrate assay sensitivity. We report the cardiac safety outcome performed during the multiple ascending part of this trial. OBE022 was administered after a standardized breakfast on day 1 and in the fasted state from day 3 to day 9 wth a standardized lunch 4 hours after administration. Concentration–effect modeling was used to assess the effect of prodrug OBE022 and parent OBE002 on QTc after a single dose (days 1 and 3) and multiple doses (day 9). The concentration–response analysis showed the absence of QTc prolongation at all doses tested. Two‐sided 90% confidence intervals of the geometric mean Cmax for estimated QTc effects of OBE022 and OBE002 of all dose groups were consistently below the threshold of regulatory concern. The sensitivity of this study to detect small changes in the QTc was confirmed by a significant shortening of the QTc on days 1, 3, and 9 after standardized meals. This study establishes that neither prodrug OBE022 nor parent OBE002 prolong the QTc interval. The observed food effect on the QT interval validated the assay on all assessment days. Both the change from predose, premeal and the change from premeal, postdose demonstrated the specificity of the method.

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Nifedipine maintenance tocolysis and perinatal outcome: an individual participant data meta‐analysis

Abstract: Nifedipine maintenance tocolysis is not associated with improved perinatal outcome or pregnancy prolongation.

Cited by 32 publications

References 31 publications

Uterine Cervical Length Measurement to Reduce Length of Stay in Patients Admitted for Threatened Preterm Labor: A Randomized Trial

Uterine Cervical Length Measurement to Reduce Length of Stay in Patients Admitted for Threatened Preterm Labor: A Randomized Trial

The role of potassium channels and calcium in the relaxation mechanism of magnesium sulfate on the isolated rat uterus

Confirmation of the Cardiac Safety of PGF_2αReceptor Antagonist OBE022 in a First‐in‐Human Study in Healthy Subjects, Using Intensive ECG Assessments

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Nifedipine maintenance tocolysis and perinatal outcome: an individual participant data meta‐analysis

Abstract: Nifedipine maintenance tocolysis is not associated with improved perinatal outcome or pregnancy prolongation.

Cited by 32 publications

References 31 publications

Uterine Cervical Length Measurement to Reduce Length of Stay in Patients Admitted for Threatened Preterm Labor: A Randomized Trial

Uterine Cervical Length Measurement to Reduce Length of Stay in Patients Admitted for Threatened Preterm Labor: A Randomized Trial

The role of potassium channels and calcium in the relaxation mechanism of magnesium sulfate on the isolated rat uterus

Confirmation of the Cardiac Safety of PGF2αReceptor Antagonist OBE022 in a First‐in‐Human Study in Healthy Subjects, Using Intensive ECG Assessments

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Product

Resources

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Confirmation of the Cardiac Safety of PGF_2αReceptor Antagonist OBE022 in a First‐in‐Human Study in Healthy Subjects, Using Intensive ECG Assessments