Tocolytic therapy for preterm delivery: systematic review and network meta-analysis

Haas, David M.; Caldwell, Deborah M; Kirkpatrick, Page R.; McIntosh, Jennifer; Welton, Nicky J

doi:10.1136/bmj.e6226

Cited by 357 publications

(272 citation statements)

References 109 publications

(68 reference statements)

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“…Our failure to replicate this finding may well be a result of our small sample size; the confidence interval includes the benefit of nifedipine seen in the meta-analysis. Two previous meta-analyses have suggested nifedipine is superior to terbutaline in terms of prevention of neonatal adverse events, although they failed to show a difference in these events between nifedipine and placebo [22,24] while the network meta-analysis [6] failed to find differences 3 Median and interquartile range. 4 Mann-Whitney U-test.…”

Section: Discussionmentioning

confidence: 91%

“…The most compelling summary of results of previous trials thus far comes from a network meta-analysis examining all the randomized trials of all agents used for tocolysis [6]. This meta-analysis found that, in comparison with terbutaline, calcium channel blockers have a higher probability of achieving delay in delivery beyond 48 hr.…”

Section: Discussionmentioning

confidence: 99%

“…Several randomized, controlled trials have compared the efficacy of calcium channel blockers, usually nifedipine and betamimetics. Although most trials had important methodological limitations, and conclusions varied regarding effectiveness (most reporting similar tocolysis [16][17][18][19][20] and some suggesting the superiority of nifedipine [21,22], all reported a better side effect profile with nifedipine with fewer women requiring cessation of therapy due to adverse events [6,[21][22][23][24].…”

mentioning

confidence: 99%

“…Delay in preterm labour therefore provides a potential opportunity for decreasing neonatal morbidity and mortality [6].…”

mentioning

confidence: 99%

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Nifedipine versus Terbutaline, Tocolytic Effectiveness and Maternal and Neonatal Adverse Effects: A Randomized, Controlled Pilot Trial

Padovani

Guyatt

Lopes

2014

Basic Clin Pharma Tox

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Although previous evidence suggests advantages of nifedipine over terbutaline as tocolytic agents, in some jurisdictions, terbutaline is approved for use and nifedipine is not. In women in preterm labour, we compared the impact of terbutaline versus nifedipine on inhibition of uterine contractions, preterm birth, neonatal sepsis, intracranial haemorrhage or necrotizing enterocolitis, death or admission to a neonatal intensive care unit and maternal adverse reactions. We randomized 32 women to nifedipine and 34 to terbutaline. We found no difference between groups in tocolysis or preterm birth. No serious maternal adverse effects or serious neonatal adverse outcome occurred in either group. Less serious maternal adverse effects less common with terbutaline included flushing (2.94% versus 43.7%) and headache (5.9% versus 31.2%). The administration of terbutaline increased tremor (76.4% versus 0%), nausea (58.8% versus 9.4%) and dizziness (29.4% versus 6.25%). The total number of side effects, and the proportion of women experiencing one or more side effects, proved greater with terbutaline. In this study, terbutaline and nifedipine performed similarly in their tocolytic effects. Each drug has specific side effects, although overall, nifedipine was associated with fewer adverse effects.Premature birth is common (over 5% and, in some countries, over 10%) [1,2] and is responsible for approximately 75% of all neonatal deaths and 50% of childhood neurological morbidities [3,4]. Preterm infants often require intensive care that is associated with emotional and economic costs to both the family and society [5].Approximately 75% of preterm birth is attributable to spontaneous preterm labour [1]. Delay in preterm labour therefore provides a potential opportunity for decreasing neonatal morbidity and mortality [6].The optimal medical management of threatened preterm labour is controversial [7]. Despite theoretical benefits of keeping the foetus in utero long enough to enable administration of a full course of corticosteroids to assist in foetal lung maturation, and to organize transfer to an appropriate neonatal care unit, no agent has been shown to improve neonatal outcome [2,7]. Thus, the choice of therapy has focused on delay in delivery and minimization of adverse effects.The drugs registered for tocolysis include the b adrenoceptor agonist ritodrine (United States and Europe), terbutaline (Brazil) and the oxytocin receptor antagonist atosiban (Europe) [8]. Calcium channel blockers (nifedipine) and cyclooxygenase inhibitors (indomethacin) are also used for inhibiting preterm labour although, in many countries, they are not currently registered for this indication [9].Betamimetics (isoxsuprine, ritodrine, terbutaline, fenoterol and salbutamol) delay labour [10][11][12], but their use has been limited by a high incidence of maternal adverse effects [10,13,14]. Many centres use nifedipine, which also has established effectiveness in delaying labour [15] and has advantages of oral administration and relatively low...

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…Delay in preterm labour therefore provides a potential opportunity for decreasing neonatal morbidity and mortality [6].…”

mentioning

confidence: 99%

See 2 more Smart Citations

Nifedipine versus Terbutaline, Tocolytic Effectiveness and Maternal and Neonatal Adverse Effects: A Randomized, Controlled Pilot Trial

Padovani

Guyatt

Lopes

2014

Basic Clin Pharma Tox

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“…7 The commonly used tocolytics are Beta-2 agonists (isoxsuprine hydrochloride, terbutaline sulfate and ritodrine hydrochloride), calcium channel blockers (nifedipine), oxytocin receptor antagonists (atosiban), prostaglandin synthetase inhibitors, magnesium sulfate and nitric oxide donors. [8][9][10] They act through various mechanisms to decrease the availability of intracellular calcium ions, leading to inhibition of actin-myosin interaction. 5 Pertinently, the management of PTL has been plagued by a low success rate along with the incidence of serious side-effects arising from the use of therapeutic approaches, more so with beta-mimetic tocolytics.…”

Section: Introductionmentioning

confidence: 99%

Practice patterns in the management of preterm labor in India: a multi-centric, retrospective study

Jaju

Sood

Chavan

et al. 2017

Int J Reprod Contracept Obstet Gynecol

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Background: Preterm labor (PTL) is considered as one of the leading cause of perinatal morbidity and mortality. Preterm labor refers to the onset of uterine contractions of sufficient strength and frequency to effect progressive dilatation and effacement of cervix between 22 and 37 weeks of gestation. Methods: In this study, 285 patients of PTL admitted/treated (during the period of 1 st January 2014 to 31 st December 2016) across 5 centres in India were enrolled. Adult women with PTL, receiving oral or intravenous regime of tocolytic drugs were screened based on eligibility criteria. Results: We evaluated the practice patterns in the management of PTL in India. The pharmacological management (n=193) was preferred over nonpharmacological management (n=92) in the present study. Amongst the pharmacological agents, isoxsuprine (60.10%) was more frequently used followed by nifedipine (23.83%). Prolongation of delivery for at least 48 hours was observed in 57.76% patients receiving isoxsuprine compared to 34.78% patients receiving nifedipine. The mean latency period (36.77±28.09 vs. 1.44±1.33 days), birthweight (2.25±1.34 vs. 1.07±0.34 kg) and Apgar score at 5 mins (7.56±2.36 vs. 4.87±2.10) was higher for isoxsuprine compared to nifedipine group patients, with mean gestational age of <32 weeks (extreme to very PTL cases; p<0.0001). Similar results were observed in latency period and Apgar score between isoxsuprine and nifedipine groups in late PTL cases (>32 weeks). Conclusions: Pharmacological treatment was preferred for the management of PTL in India. Among pharmacological agents, isoxsuprine was preferred over other tocolytics. Significant improvement in mean latency period, prolongation of delivery beyond 48 hours and perinatal outcomes were noted amongst patients on isoxsuprine versus other pharmacological agents.

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Magnesium sulphate for preventing preterm birth in threatened preterm labour

Crowther

Brown

McKinlay

et al. 2014

Cochrane Database of Systematic Reviews

132

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Tocolytic therapy for preterm delivery: systematic review and network meta-analysis

Cited by 357 publications

References 109 publications

Nifedipine versus Terbutaline, Tocolytic Effectiveness and Maternal and Neonatal Adverse Effects: A Randomized, Controlled Pilot Trial

Nifedipine versus Terbutaline, Tocolytic Effectiveness and Maternal and Neonatal Adverse Effects: A Randomized, Controlled Pilot Trial

Practice patterns in the management of preterm labor in India: a multi-centric, retrospective study

Magnesium sulphate for preventing preterm birth in threatened preterm labour

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