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Background: Preterm birth is a major cause of perinatal mortality and morbidity. Cyclo-oxygenase (COX) inhibitors inhibit uterine contractions, are easily administered and appear to have few maternal side effects. However, adverse effects have been reported in the fetus and newborn as a result of exposure to COX inhibitors., Objectives: To assess the effects on maternal and neonatal outcomes of COX inhibitors administered as a tocolytic agent to women in preterm labour when compared with (i) placebo or no intervention and (ii) other tocolytics. In addition, to compare the effects of non-selective COX inhibitors with COX-2 selective inhibitors., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (24 August 2014). We also contacted recognised experts and searched reference lists of retrieved studies., Selection Criteria: All published and unpublished randomised trials in which COX inhibitors were used for tocolysis for women in labour between 20 and 36 completed weeks' gestation., Data Collection and Analysis: Two review authors independently evaluated methodological quality and extracted data. We sought additional information from study authors. Results are presented using risk ratio (RR; dichotomous data) and mean difference (MD; continuous data) with 95% confidence interval (CI). The number needed to treat for benefit (NNTB) and the number needed to treat for harm (NNTH) were calculated for statistically different categorical outcomes., Main Results: With the addition of seven studies with a total of 684 women, this review now includes outcome data from 20 studies including 1509 women. The non-selective COX inhibitor indomethacin was used in 15 studies. The overall quality of the included studies was considered moderate to low.Three small studies (102 women), two of which were conducted in the 1980's, compared COX inhibition (indomethacin only) with placebo. No difference was shown in birth less than 48 hours after trial entry (average RR 0.20, 95% CI 0.03 to 1.28; two studies with 70 women). Indomethacin resulted in a reduction in preterm birth (before completion of 37 weeks of gestation) in one small study (36 women) (RR 0.21, 95% CI 0.07 to 0.62; NNTB 2, 95% CI 2 to 4); and an increase in gestational age at birth (average MD 3.59 weeks, 95% CI 0.65 to 6.52; two studies with 66 women) and birthweight (MD 716.34 g, 95% CI 425.52 to 1007.16; two studies with 67 infants). No difference was shown in measures of neonatal morbidity or neonatal mortality.Compared with betamimetics, COX inhibitors resulted in a reduction in birth less than 48 hours after trial entry (RR 0.27, 95% CI 0.08 to 0.96; NNTB 7, 95% CI 6 to 120; two studies with 100 women) and preterm birth (before completion of 37 weeks of gestation) (RR 0.53, 95% CI 0.28 to 0.99; NNTB 6, 95% CI 4 to 236; two studies with 80 women) although no benefit was shown in terms of neonatal morbidity or mortality. COX inhibition was also associated with fewer maternal adverse affects compared with betamimetics (RR 0.19, 95% CI 0.11 to 0.31; NNTB 3, 95% CI 2 to 3; five studies with 248 women) and maternal adverse effects requiring cessation of treatment (average RR 0.09, 95% CI 0.02 to 0.49; NNTB 5, CI 95% 5 to 9; three studies with 166 women).No differences were shown when comparing COX inhibitors with magnesium sulphate (MgSO4) (seven studies with 792 women) or calcium channel blockers (CCBs) (two studies with 230 women) in terms of prolonging pregnancy or for any fetal/neonatal outcomes. There were also no differences in very preterm birth (before completion of 34 weeks of gestation) and no maternal deaths occurred in the one study that reported on this outcome. However COX inhibitors resulted in fewer maternal adverse affects when compared with MgSO4 (RR 0.39, 95% CI 0.25 to 0.62; NNTB 11, 95% CI 9 to 17; five studies with 635 women).A comparison of non-selective COX inhibitors versus any COX-2 inhibitor (two studies with 54 women) did not demonstrate any differences in maternal, fetal or neonatal outcomes.No data were available to assess COX inhibitors compared with oxytocin receptor antagonists (ORAs). Further, no data were available on extremely preterm birth (before 28 weeks of gestation), longer-term infant outcomes or costs., Authors' Conclusions: In this review, no clear benefit for COX inhibitors was shown over placebo or any other tocolytic agents. While some benefit was demonstrated in terms of postponement of birth for COX inhibitors over placebo and betamimetics and also maternal adverse effects over betamimetics and MgSO4, due to the limitations of small numbers, minimal data on safety, lack of longer-term outcomes and generally low quality of the studies included in this review, we conclude that there is insufficient evidence on which to base decisions about the role of COX inhibition for women in preterm labour. Further well-designed tocolytic studies are required to determine short- and longer-term infant benefit of COX inhibitors over placebo and other tocolytics, particularly CCBs and ORAs. Another important focus for future studies is identifying whether COX-2 inhibitors are superior to non-selective COX inhibitors. All future studies on tocolytics for women in preterm labour should assess longer-term effects into early childhood and also costs.

Background: Preterm birth, defined as birth between 20 and 36 completed weeks, is a major contributor to perinatal morbidity and mortality globally. Oxytocin receptor antagonists (ORA), such as atosiban, have been specially developed for the treatment of preterm labour. ORA have been proposed as effective tocolytic agents for women in preterm labour to prolong pregnancy with fewer side effects than other tocolytic agents., Objectives: To assess the effects on maternal, fetal and neonatal outcomes of tocolysis with ORA for women with preterm labour compared with placebo or any other tocolytic agent., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 December 2013)., Selection Criteria: We included all randomised controlled trials (published and unpublished) of ORA for tocolysis of labour between 20 and 36 completed weeks' gestation., Data Collection and Analysis: Two review authors independently evaluated methodological quality and extracted trial data. When required, we sought additional data from trial authors. Results are presented as risk ratio (RR) for categorical and mean difference (MD) for continuous data with the 95% confidence intervals (CI). Where appropriate, the number needed to treat for benefit (NNTB) and the number needed to treat for harm (NNTH) were calculated., Main Results: This review update includes eight additional studies (790 women), giving a total of 14 studies involving 2485 women.Four studies (854 women) compared ORA (three used atosiban and one barusiban) with placebo. Three studies were considered at low risk of bias in general (blinded allocation to treatment and intervention), the fourth study did not adequately blind the intervention. No difference was shown in birth less than 48 hours after trial entry (average RR 1.05, 95% CI 0.15 to 7.43; random-effects, (two studies, 152 women), perinatal mortality (RR 2.25, 95% CI 0.79 to 6.38; two studies, 729 infants), or major neonatal morbidity. ORA (atosiban) resulted in a small reduction in birthweight (MD -138.86 g, 95% CI -250.53 to -27.18; two studies with 676 infants). In one study, atosiban resulted in an increase in extremely preterm birth (before 28 weeks' gestation) (RR 3.11, 95% CI 1.02 to 9.51; NNTH 31, 95% CI 8 to 3188) and infant deaths (up to 12 months) (RR 6.13, 95% CI 1.38 to 27.13; NNTH 28, 95% CI 6 to 377). However, this finding may be confounded due to randomisation of more women with pregnancy less than 26 weeks' gestation to atosiban. ORA also resulted in an increase in maternal adverse drug reactions requiring cessation of treatment in comparison with placebo (RR 4.02, 95% CI 2.05 to 7.85; NNTH 12, 95% CI 5 to 33). No differences were shown in preterm birth less than 37 weeks' gestation or any other adverse neonatal outcomes. No differences were evident by type of ORA, although data were limited.Eight studies (1402 women) compared ORA (atosiban only) with betamimetics; four were considered of low risk of bias (blinded allocation to treatment and to intervention). No statistically significant difference was shown in birth less than 48 hours after trial entry (RR 0.89, 95% CI 0.66 to 1.22; eight studies with 1389 women), very preterm birth (RR 1.70, 95% CI 0.89 to 3.23; one study with 145 women), extremely preterm birth (RR 0.84, 95% CI 0.37 to 1.92; one study with 244 women) or perinatal mortality (RR 0.55, 95% CI 0.21 to 1.48; three studies with 816 infants). One study (80 women), of unclear methodological quality, showed an increase in the interval between trial entry and birth (MD 22.90 days, 95% CI 18.03 to 27.77). No difference was shown in any reported measures of major neonatal morbidity (although numbers were small). ORA (atosiban) resulted in less maternal adverse effects requiring cessation of treatment (RR 0.05, 95% CI 0.02 to 0.11; NNTB 6, 95% CI 6 to 6; five studies with 1161 women).Two studies including (225 women) compared ORA (atosiban) with calcium channel blockers (CCB) (nifedipine only). The studies were considered as having high risk of bias as neither study blinded the intervention and in one study it was not known if allocation was blinded. No difference was shown in birth less than 48 hours after trial entry (average RR 1.09, 95% CI 0.44 to 2.73, random-effects; two studies, 225 women) and extremely preterm birth (RR 2.14, 95% CI 0.20 to 23.11; one study, 145 women). No data were available for the outcome of perinatal mortality. One small trial (145 women), which did not employ blinding of the intervention, showed an increase in the number of preterm births (before 37 weeks' gestation) (RR 1.56, 95% CI 1.13 to 2.14; NNTH 5, 95% CI 3 to 19), a lower gestational age at birth (MD -1.20 weeks, 95% CI -2.15 to -0.25) and an increase in admission to neonatal intensive care unit (RR 1.70, 95% CI 1.17 to 2.47; NNTH 5, 95% CI 3 to 20). ORA (atosiban) resulted in less maternal adverse effects (RR 0.38, 95% CI 0.21 to 0.68; NNTB 6, 95% CI 5 to 12; two studies, 225 women) but not maternal adverse effects requiring cessation of treatment (RR 0.36, 95% CI 0.01 to 8.62; one study, 145 women). No longer-term outcome data were included., Authors' Conclusions: This review did not demonstrate superiority of ORA (largely atosiban) as a tocolytic agent compared with placebo, betamimetics or CCB (largely nifedipine) in terms of pregnancy prolongation or neonatal outcomes, although ORA was associated with less maternal adverse effects than treatment with the CCB or betamimetics. The finding of an increase in infant deaths and more births before completion of 28 weeks of gestation in one placebo-controlled study warrants caution. However, the number of women enrolled at very low gestations was small. Due to limitations of small numbers studied and methodological quality, further well-designed randomised controlled trials are needed. Further comparisons of ORA versus CCB (which has a better side-effect profile than betamimetics) are needed. Consideration of further placebo-controlled studies seems warranted. Future studies of tocolytic agents should measure all important short- and long-term outcomes for women and infants, and costs.

Background: Preterm birth is a major contributor to perinatal mortality and morbidity, affecting around 9% of births in high-income countries and an estimated 13% of births in low- and middle-income countries. Tocolytics are drugs used to suppress uterine contractions for women in preterm labour. The most widely used tocolytic are the betamimetics, however, these are associated with a high frequency of unpleasant and sometimes severe maternal side effects. Calcium channel blockers (CCBs) (such as nifedipine) may have similar tocolytic efficacy with less side effects than betamimetics. Oxytocin receptor antagonists (ORAs) (e.g. atosiban) also have a low side-effect profile., Objectives: To assess the effects on maternal, fetal and neonatal outcomes of CCBs, administered as a tocolytic agent, to women in preterm labour., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (12 November 2013)., Selection Criteria: All published and unpublished randomised trials in which CCBs were used for tocolysis for women in labour between 20 and 36 completed weeks' gestation., Data Collection and Analysis: Two review authors independently assessed trial eligibility, undertook quality assessment and data extraction. Results are presented using risk ratio (RR) for categorical data and mean difference (MD) for data measured on a continuous scale with the 95% confidence interval (CI). The number needed to treat to benefit (NNTB) and the number needed to treat to harm (NNTH) were calculated for categorical outcomes that were statistically significantly different., Main Results: This update includes 26 additional trials involving 2511 women, giving a total of 38 included trials (3550 women). Thirty-five trials used nifedipine as the CCB and three trials used nicardipine. Blinding of intervention and outcome assessment was undertaken in only one of the trials (a placebo controlled trial). However, objective outcomes defined according to timing of birth and perinatal mortality were considered to have low risk of detection bias.Two small trials comparing CCBs with placebo or no treatment showed a significant reduction in birth less than 48 hours after trial entry (RR 0.30, 95% CI 0.21 to 0.43) and an increase in maternal adverse effects (RR 49.89, 95% CI 3.13 to 795.02, one trial of 89 women). Due to substantial heterogeneity, outcome data for preterm birth (less than 37 weeks) were not combined; one placebo controlled trial showed no difference (RR 0.96, 95% CI 0.89 to 1.03) while the other (non-placebo controlled trial) reported a reduction (RR 0.44, 95% CI 0.31 to 0.62). No other outcomes were reported.Comparing CCBs (mainly nifedipine) with other tocolytics by type (including betamimetics, glyceryl trinitrate (GTN) patch, non-steriodal anti inflammatories (NSAID), magnesium sulphate and ORAs), no significant reductions were shown in primary outcome measures of birth within 48 hours of treatment or perinatal mortality.Comparing CCBs with betamimetics, there were fewer maternal adverse effects (average RR 0.36, 95% CI 0.24 to 0.53) and fewer maternal adverse effects requiring discontinuation of therapy (average RR 0.22, 95% CI 0.10 to 0.48). Calcium channel blockers resulted in an increase in the interval between trial entry and birth (average MD 4.38 days, 95% CI 0.25 to 8.52) and gestational age (MD 0.71 weeks, 95% CI 0.34 to 1.09), while decreasing preterm and very preterm birth (RR 0.89, 95% CI 0.80 to 0.98 and RR 0.78, 95% CI 0.66 to 0.93); respiratory distress syndrome (RR 0.64, 95% CI 0.48 to 0.86); necrotising enterocolitis (RR 0.21, 95% CI 0.05 to 0.96); intraventricular haemorrhage (RR 0.53, 95% CI 0.34 to 0.84); neonatal jaundice (RR 0.72, 95% CI 0.57 to 0.92); and admissions to neonatal intensive care unit (NICU) (average RR 0.74, 95% CI 0.63 to 0.87). No difference was shown in one trial of outcomes at nine to twelve years of age.Comparing CCBs with ORA, data from one study (which did blind the intervention) showed an increase in gestational age at birth (MD 1.20 completed weeks, 95% CI 0.25 to 2.15) and reductions in preterm birth (RR 0.64, 95% CI 0.47 to 0.89); admissions to the NICU (RR 0.59, 95% CI 0.41 to 0.85); and duration of stay in the NICU (MD -5.40 days,95% CI -10.84 to 0.04). Maternal adverse effects were increased in the CCB group (average RR 2.61, 95% CI 1.43 to 4.74).Comparing CCBs with magnesium sulphate, maternal adverse effects were reduced (average RR 0.52, 95% CI 0.40 to 0.68), as was duration of stay in the NICU (days) (MD -4.55, 95% CI -8.17 to -0.92). No differences were shown in the comparisons with GTN patch or NSAID, although numbers were small.No differences in outcomes were shown in trials comparing nicardipine with other tocolytics, although with limited data no strong conclusions can be drawn. No differences were evident in a small trial that compared higher- versus lower-dose nifedipine, though findings tended to favour a high dose on some measures of neonatal morbidity., Authors' Conclusions: Calcium channel blockers (mainly nifedipine) for women in preterm labour have benefits over placebo or no treatment in terms of postponement of birth thus, theoretically, allowing time for administration of antenatal corticosteroids and transfer to higher level care. Calcium channel blockers were shown to have benefits over betamimetics with respect to prolongation of pregnancy, serious neonatal morbidity, and maternal adverse effects. Calcium channel blockers may also have some benefits over ORAs and magnesium sulphate, although ORAs results in fewer maternal adverse effects. However, it must be noted that no difference was shown in perinatal mortality, and data on longer-term outcomes were limited. Further, the lack of blinding of the intervention diminishes the strength of this body of evidence. Further well-designed tocolytic trials are required to determine short- and longer-term infant benefit of CCBs over placebo or no treatment and other tocolytics, particularly ORAs. Another important focus for future trials is identifying optimal dosage regimens of different types of CCBs (high versus low, particularly addressing speed of onset of uterine quiescence) and formulation (capsules versus tablets). All future trials on tocolytics for women in preterm labour should employ blinding of the intervention and outcome assessment, include measurement of longer-term effects into early childhood, and also costs.

Background: In some women, an episode of preterm labour settles and does not result in immediate preterm birth. Subsequent treatment with tocolytic agents such as oxytocin receptor antagonists may then have the potential to prevent the recurrence of preterm labour, prolonging gestation, and preventing the adverse consequences of prematurity for the infant., Objectives: To assess the effects of maintenance therapy with oxytocin antagonists administered by any route after an episode of preterm labour in order to delay or prevent preterm birth., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2013), sought ongoing and unpublished trials by contacting experts in the field and searched the reference lists of relevant articles., Selection Criteria: Randomised controlled trials comparing oxytocin antagonists with any alternative tocolytic agent, placebo or no treatment, used for maintenance therapy after an episode of preterm labour., Data Collection and Analysis: We used the standard methods of The Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group. Two review authors independently undertook evaluation of methodological quality and extracted trial data., Main Results: This review includes one trial of 513 women. When compared with placebo, atosiban did not reduce preterm birth before 37 weeks (risk ratio (RR) 0.89; 95% confidence intervals (CI) 0.71 to 1.12), 32 weeks (RR 0.85; 95% CI 0.47 to 1.55), or 28 weeks (RR 0.75; 95% CI 0.28 to 2.01). No difference was shown in neonatal morbidity, or perinatal mortality., Authors' Conclusions: There is insufficient evidence to support the use of oxytocin receptor antagonists to inhibit preterm birth after a period of threatened or actual preterm labour. Any future trials using oxytocin antagonists or other drugs as maintenance therapy for preventing preterm birth should examine a variety of important infant outcome measures, including reduction of neonatal morbidity and mortality, and long-term infant follow-up. Future research should also focus on the pathophysiological pathways that precede preterm labour.

Background: In some women, an episode of preterm labour settles and does not result in immediate preterm birth. Subsequent treatment with tocolytic agents such as oxytocin receptor antagonists may then have the potential to prevent the recurrence of preterm labour, prolonging gestation, and preventing the adverse consequences of prematurity for the infant., Objectives: To assess the effects of maintenance therapy with oxytocin antagonists administered by any route after an episode of preterm labour in order to delay or prevent preterm birth., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (June 2008), sought ongoing and unpublished trials by contacting experts in the field and searched the reference lists of relevant articles., Selection Criteria: Randomised controlled trials comparing oxytocin antagonists with any alternative tocolytic agent, placebo or no treatment, used for maintenance therapy after an episode of preterm labour., Data Collection and Analysis: Standard methods of the Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group were used. Two review authors independently undertook evaluation of methodological quality and extracted trial data., Main Results: This review includes one trial of 513 women. When compared with placebo, atosiban did not reduce preterm birth before 37 weeks (risk risk (RR) 0.89; 95% confidence intervals (CI) 0.71 to 1.12), 32 weeks (RR 0.85; 95% CI 0.47 to 1.55), or 28 weeks (RR 0.75; 95% CI 0.28 to 2.01). No difference was shown in neonatal morbidity, or perinatal mortality., Authors' Conclusions: There is insufficient evidence to support the use of oxytocin receptor antagonists to inhibit preterm birth after a period of threatened or actual preterm labour. Any future trials using oxytocin antagonists or other drugs as maintenance therapy for preventing preterm birth should examine a variety of important infant outcome measures, including reduction of neonatal morbidity and mortality, and long-term infant follow up. Future research should also focus on the pathophysiological pathways that precede preterm labour.

Background: Preterm birth, defined as birth before 37 completed weeks, is the single most important cause of perinatal mortality and morbidity in high-income countries. Oxytocin receptor antagonists have been proposed as effective tocolytic agents for women in preterm labour to postpone the birth, with fewer side-effects than other tocolytic agents., Objectives: To assess the effects on maternal, fetal and neonatal outcomes of tocolysis with oxytocin receptor antagonists for women with preterm labour compared with placebo or no intervention and compared with any other tocolytic agent., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2004), CENTRAL (The Cochrane Library, Issue 3, 2004), MEDLINE (1965 to June 2004), EMBASE (1988 to June 2004)., Selection Criteria: Randomised trials of oxytocin receptor antagonists for tocolysis in the management of women in labour between 20 and 36 weeks' gestation., Data Collection and Analysis: Two authors independently evaluated methodological quality and extracted trial data. We sought additional information from trial authors., Main Results: Six trials (1695 women) were included. Compared with placebo, atosiban did not reduce incidence of preterm birth or improve neonatal outcome. In one trial (583 infants), atosiban was associated with an increase in infant deaths at 12 months of age compared with placebo (relative risk (RR) 6.15; 95% confidence intervals (CI) 1.39 to 27.22). However, this trial randomised significantly more women to atosiban before 26 weeks' gestation. Use of atosiban resulted in lower infant birthweight (weighted mean difference -138.31 gm; 95% CI -248.76 to -27.86) and more maternal adverse drug reactions (RR 4.02; 95% CI 2.05 to 7.85, 2 trials, 613 women).Compared with betamimetics, atosiban increased the numbers of infants born under 1500 gm (RR 1.96; 95% CI 1.15 to 3.35, 2 trials, 575 infants). Atosiban was associated with fewer maternal drug reactions requiring treatment cessation (RR 0.04; 95% CI 0.02 to 0.11, number needed to treat 6; 95% CI 5 to 7, 4 trials, 1035 women)., Authors' Conclusions: This review failed to demonstrate the superiority of atosiban over betamimetics or placebo in terms of tocolytic efficacy or infant outcomes. The finding of an increase in infant deaths in one placebo controlled trial warrants caution. A recent Cochrane review suggests that calcium channel blockers (mainly nifedipine) are associated with better neonatal outcome and fewer maternal side-effects than betamimetics. However, a randomised comparison of nifedipine with placebo is not available. Further well-designed randomised controlled trials of tocolytic therapy are needed. Such trials should incorporate a placebo arm.

Aim: The aim of this study is to assess the role of progesterone in preterm birth prevention., Methods: A MEDLINE search (from 1966 to the present; date of last search January 2005) was performed - using the key words progesterone, pregnancy, preterm birth, preterm labor, and randomized, controlled trial - in order to identify randomized, controlled trials in which progesterone (either intramuscular or vaginal administration) was compared with placebo or no treatment. Data were extracted and a meta-analysis was performed., Results: Seven randomized, controlled trials were identified. Women who received progesterone were statistically significantly less likely to give birth before 37 weeks (seven studies, 1020 women, RR = 0.58, 95% CI = 0.48-0.70), to have an infant with birth weight of < or =2.5 kg (six studies, 872 infants, RR = 0.62, 95% CI = 0.49-0.78), or to have an infant diagnosed with intraventricular hemorrhage (one study, 458 infants, RR = 0.25, 95% CI = 0.08-0.82)., Conclusions: For progesterone supplementation to be advocated for women at the risk of preterm birth, the prolongation of gestation demonstrated in this meta-analysis must translate into improved infant outcomes, including a reduction in mortality. There is currently insufficient information to allow recommendations regarding the optimal dose, route, and timing of administration of progesterone supplementation.

Background: Preterm birth is a major cause of perinatal mortality and morbidity. Cyclo-oxygenase (COX) inhibitors inhibit uterine contractions, are easily administered and have fewer maternal side-effects compared to conventional tocolytics. However, adverse effects have been reported on the fetus and newborn as a result of exposure to COX inhibitors., Objectives: To assess the effects on maternal, fetal and neonatal outcomes of COX inhibitors administered as a tocolytic agent to women in preterm labour when compared with (i) placebo or no intervention and (ii) other tocolytics. In addition, to compare the effects of non-selective COX inhibitors with COX-2 selective inhibitors., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's trials register (August 2004). We also contacted recognised experts and cross referenced relevant material., Selection Criteria: All published and unpublished randomised trials in which COX inhibitors were used for tocolysis for women in labour between 20 and 36 completed weeks' gestation., Data Collection and Analysis: Three authors independently evaluated methodological quality and extracted data. We sought additional information from trial authors., Main Results: This review includes outcome data from 13 trials with a total of 713 women. The non-selective COX inhibitor, indomethacin was used in 10 trials. When compared with placebo, COX inhibition (indomethacin only) resulted in a reduction in birth before 37 weeks' gestation (relative risk (RR) 0.21; one trial, 36 women), an increase in gestational age (weighted mean difference (WMD) 3.53 weeks) and birthweight (WMD 716.34 gm; two trials, 67 women). Compared to any other tocolytic, COX inhibition resulted in a reduction in birth before 37 weeks' gestation (RR 0.53; three trials, 168 women) and a reduction in maternal drug reaction requiring cessation of treatment (RR 0.07; five trials and 355 women). A comparison of non-selective COX inhibitors versus any COX-2 inhibitor (two trials, 54 women) did not demonstrate any differences in maternal or neonatal outcomes. Due to small numbers, all estimates of effect are imprecise and need to be interpreted with caution. Potential adverse effects of COX inhibition on the fetus, newborn or mother could not be adequately assessed due to insufficient data., Authors' Conclusions: There is insufficient information on which to base decisions about the role of COX inhibition for women in preterm labour. Further well designed trials are needed.

Background: Preterm birth is a major contributor to perinatal mortality and morbidity and affects approximately six to seven per cent of births in developed countries. Tocolytics are drugs used to suppress uterine contractions. The most widely tested tocolytics are betamimetics. Although they have been shown to delay delivery, betamimetics have not been shown to improve perinatal outcome, and they have a high frequency of unpleasant and even fatal maternal side effects. There is growing interest in calcium channel blockers as a potentially effective and well tolerated form of tocolysis., Objectives: To assess the effects on maternal, fetal and neonatal outcomes of calcium channel blockers, administered as a tocolytic agent, to women in preterm labour., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's specialised register of controlled trials (June 2002), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2002), MEDLINE (1965 to June 2002), EMBASE (1988 to June 2002), and Current Contents (1997 to June 2002). We also contacted recognised experts and cross referenced relevant material., Selection Criteria: All published and unpublished randomised trials in which calcium channel blockers were used for tocolysis for women in labour between 20 and 36 weeks' gestation., Data Collection and Analysis: Standard methods of the Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group were used. Evaluation of methodological quality and trial data extraction were undertaken independently by three authors. Additional information was sought to enable assessment of methodology and conduct of intention-to-treat analyses. Meta-analysis was conducted assessing the effects of calcium channel blockers compared with any other tocolytic agent. Results are presented using relative risk for categorical data and weighted mean difference for continuous data., Main Results: Twelve randomised controlled trials involving 1029 women were included. When compared with any other tocolytic agent (mainly betamimetics), calcium channel blockers reduced the number of women giving birth within seven days of receiving treatment (relative risk (RR) 0.76; 95% confidence interval (CI) 0.60 to 0.97) and prior to 34 weeks' gestation (RR 0.83; 95% CI 0.69 to 0.99). Calcium channel blockers also reduced the requirement for women to have treatment ceased for adverse drug reaction (RR 0.14; 95% CI 0.05 to 0.36), the frequency of neonatal respiratory distress syndrome (RR 0.63; 95% CI 0.46 to 0.88), necrotising enterocolitis (RR 0.21; 95% CI 0.05 to 0.96), intraventricular haemorrhage (RR 0.59 95% CI 0.36 to 0.98) and neonatal jaundice (RR 0.73; 95% CI 0.57 to 0.93)., Reviewer's Conclusions: When tocolysis is indicated for women in preterm labour, calcium channel blockers are preferable to other tocolytic agents compared, mainly betamimetics. Further research should address the effects of different dosage regimens and formulations of calcium channel blockers on maternal and neonatal outcomes.

Background: Preterm birth is a major contributor to perinatal mortality and morbidity and affects approximately six to seven per cent of births in developed countries. Tocolytics are drugs used to suppress uterine contractions. The most widely tested tocolytics are betamimetics. Although they have been shown to delay delivery, betamimetics have not been shown to improve perinatal outcome, and they have a high frequency of unpleasant and even fatal maternal side effects. There is growing interest in calcium channel blockers as a potentially effective and well tolerated form of tocolysis., Objectives: To assess the effects on maternal, fetal and neonatal outcomes of calcium channel blockers, administered as a tocolytic agent, to women in preterm labour., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's specialised register of controlled trials, the Cochrane Controlled Trials Register (February 2002), MEDLINE, EMBASE, and Current Contents. We also contacted recognised experts and cross referenced relevant material., Selection Criteria: All published and unpublished randomised trials in which calcium channel blockers were used for tocolysis for women in labour between 20 and 36 weeks gestation., Data Collection and Analysis: Standard methods of the Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group were used. Evaluation of methodological quality and trial data extraction were undertaken independently by three authors. Additional information was sought to enable assessment of methodology and conduct of intention-to-treat analyses. Meta-analysis was conducted assessing the effects of calcium channel blockers compared with any other tocolytic agent. Results are presented using relative risk for categorical data and weighted mean difference for continuous data., Main Results: Eleven randomised controlled trials involving 870 women were included. When compared with any other tocolytic agent (mainly betamimetics), calcium channel blockers reduced the number of women giving birth within 48 hours (relative risk (RR) 0.73; 95% confidence interval (CI) 0.54, 0.98) and within seven days (RR 0.76; 95% CI 0.59, 0.99). Calcium channel blockers also reduced the requirement for women to have treatment ceased for adverse drug reaction (RR 0.15; 95% CI 0.06, 0.43), the frequency of neonatal respiratory distress syndrome (RR 0.64; 95% CI 0.45, 0.91) and neonatal jaundice (RR 0.73; 95% CI 0.57, 0.93)., Reviewer's Conclusions: When tocolysis is indicated for women in preterm labour, calcium channel blockers are preferable to betamimetic agents. Further research should address the effects of different dosage regimens and formulations of nifedipine on maternal and neonatal outcomes.