Table 5 Impact of drugs for cervical ripening and induction of labour on stillbirth and perinatal outcomes

Kelly et al. 2003 [90]

UK, Austria, New Zealand, Singapore, USA, Pakistan, Canada.

Meta-analysis (Cochrane). 8 RCTs included (N = 3648 women).

To compare the effects of vaginal prostaglandins E2 (all regimens) for third trimester cervical ripening or induction of labour (intervention) vs. placebo/no treatment (controls).

PMR: RR = 0.56 (95% CI: 0.14–2.22) [NS].

[2/1833 vs. 4/1815 in the intervention and control groups, respectively].

Boulvain et al. 2008 [62]

USA, Europe, Africa, UK, Italy.

Meta-analysis (Cochrane). 4 RCTs included (N = 1081 women).

Compared the impact on perinatal mortality of intracervical prostaglandin (prostaglandin E2) (intervention) vs. placebo/no treatment (controls) for third trimester cervical ripening and induction of labour.

PMR: RR = 0.20 (95% CI: 0.01–4.05) [NS].

[0/587 vs. 2/494 in intervention and control groups, respectively].

Hutton et al. 2001 [92]

2 RCTs. Zimbabwe, Australia.

Cochrane review. 2 RCTs included (N = 25 women).

To assess the effects of extra-amniotic prostaglandin (PGF2 alpha) (intervention) for third trimester cervical ripening or induction of labour vs. extra amniotic placebo gel (controls).

PMR: RR = 2.06 (95% CI: 0.09–46.11) [NS].

[1/15 vs. 0/10 in intervention and control groups, respectively].

Hofmeyr et al. 2003 [79]

Chile, Zimbabwe, USA, Canada, Jamaica, Malaysia.

Meta-analysis (Cochrane). 7 RCTs included (N = 268 women).

To assess the effects of vaginal misoprostol for third trimester cervical ripening or induction of labour (intervention) vs. vaginal prostaglandin (controls).

PMR: RR = 2.85 (95% CI: 0.12–68.95) [NS].

[1/136 vs. 0/132 in intervention and control groups, respectively].

Neilson 2000 [94]

France, Sweden.

Meta-analysis (Cochrane). 2 RCTs included (N = 68 women).

To assess the effects of mifepristone (all doses) for third trimester cervical ripening or induction of labour (intervention) vs. placebo/no treatment (controls).

PMR: RR not estimable.

[0/40 vs. 0/28 in intervention and control groups, respectively].

French 2001 [89]

India, Denmark.

Cochrane review. 2 RCTs included (N = 35 women).

To assess the effects of oral prostaglandin E2 for third trimester induction of labour (intervention) vs. intravenous oxytocin (controls) on perinatal mortality.

PMR: RR not estimable.

[0/15 vs. 0/20 in intervention and control groups, respectively].

Luckas et al. 2000 [93]

USA, UK, Denmark, Belgium and Netherlands.

Meta-analysis (Cochrane). 11 RCTs included (N = 990 women).

To assess the effects of intravenous prostaglandin for third trimester cervical ripening or induction of labour (intervention) vs. IV oxytocin (controls).

PMR: RR = 3.59 (95% CI: 0.60–21.53) [NS].

[4/499 vs. 0/491 in intervention and control groups, respectively].

Alfirevic 2006 [75]

Hong Kong, Switzerland, South Africa, UK, Spain, Canada, USA.

Meta-analysis (Cochrane). 17 RCTs included (N = 1508 women).

To assess the effectiveness and safety of oral misoprostol used for labour induction in women with a viable fetus in the third trimester of pregnancy (intervention) vs. vaginal prostaglandin (controls).

PMR: RR = 0.60 (95% CI: 0.08–4.50) [NS].

[data from 4 RCTs; 1/756 vs. 2/752 in intervention and control groups, respectively].

Intervention studies

Elhassan et al. 2005 [85]

Sudan.

Non-blinded RCT. N = 140 patients (N = 70 intervention, N = 70 controls).

Assessed the impact of vaginal misoprostol, 50 μg, six hourly until initiation of labour or maximum of 4 doses (intervention) vs. IV infusion of oxytocin at 2 mU/min, doubled at 30-minute intervals until the appropriate contraction pattern obtained or dose increased to a maximum of 20 mU/minute and maintained as such (controls).

Neonatal outcomes (birth weight, Apgar score and SBR): [NS]

Garry et al. 2003 [80]

USA.

RCT. Singleton gestations (N = 200) with an indication for cervical ripening and induction of labour.

Compared the impact of 50 μg of vaginal misoprostol every 3 h (intervention) vs. a 10-mg prostaglandin E2 vaginal insert every 12 h for a maximum of 24 h (controls).

Neonatal outcomes: [NS]

Vaginal delivery <12 hr: 44% vs. 12% in misoprostol vs. prostaglandin E2 group, respectively (P < 0.0001)

Vaginal delivery <24 hr: 68% vs. 38 in misoprostol vs. prostaglandin E2 group, respectively (P < 0.001).

Caesarean delivery for fetal distress: 71.4% (20/28) vs. 40% (14/35) in misoprostol group vs. prostaglandin E2 group (P = 0.03).

Jindal et al. 2007. [87]

India.

Quasi-RCT. N = 100 women (N = 50 intervention group, N = 50 controls).

Compared the impact of 50 μg of vaginal misoprostol 4 hourly for a maximum of six doses (intervention) vs. transcervical Foley catheter with simultaneous intravenous oxytocin (controls).

SBR: 1/50 vs. 0/50 in intervention and control groups, respectively.

Lokugamage et al. 2003 [81]

UK. Hospital based.

RCT. N = 191 patients.

Compared the impact of 50 μg vaginal misoprostol initially then a further identical dose 6 hrs later (intervention) vs. 2 mg vaginal prostaglandin E2 initially followed by 1 mg 6 hrs later, over a period of 24 hrs (controls). All participants not in labour after 24 hrs received prostaglandin E2 alone as per hospital protocol.

Neonatal outcome: [NS]

Induction-to-delivery interval: 1047 vs. 1355 min (P = 0.01) in intervention and control groups, respectively.

Delivery <12 hrs: 35.4% vs. 18.9%, (P = 0.02) in intervention and control groups, respectively.

Delivery <24 hrs: 83.3% vs. 63.3%, (P = 0.01) in intervention and control groups, respectively.

Oxytocin augmentation: [NS] (P = 0.47),

Tachysystole: [NS] (P = 0.32) and

Hyperstimulation syndrome: [NS] (P = 0.82).

Majoko et al. 2002 [151]

Zimbabwe.

RCT. N = 152 women admitted for induction of labour (N = 76 in each group).

Compared the impact of vaginal misoprostol (intervention) versus extra-amniotic prostaglandin F2α gel (controls).

SBR: 1/76 in each group due to asphyxia (both mothers induced for pre-eclampsia; deaths resulting from inadequate response to fetal distress).

Meyer et al. 2005 [86]

USA.

RCT. N = 84 patients.

Compared the impact of 0.25μg misoprostol vaginally (intervention) vs. 0.5 mg prostaglandin E2 gel intracervically (controls), the evening before oxytocin induction.

Neonatal outcome: [NS]

Caesarean rate: 9/42 vs. 8/42 in intervention and control groups, respectively [NS]

Papanikolaou et al. 2004 [84]

Greece.

RCT. Nulliparous pregnant women (N = 163) with an unfavorable cervix and > 285 days of gestation (N = 80 intervention group, N = 83 controls).

Compared the efficacy of 50 μg vaginal misoprostol (intervention) versus 3 mg prostaglandin E2 (controls), administered every 9 hrs for a maximum of three doses for elective induction of labour.

SBR or PMR: 0/80 vs. 1/83 (1.2%) in intervention and control groups, respectively [NS].

Rowlands et al. 2001 [83]

Australia.

RCT. N = 126 women recruited to the study (N = 63 in each group).

Compared the effect on neonatal outcomes of vaginal prostaglandin E2 (group 1) vs. vaginal misoprostol (controls) for cervical priming prior to induction of labour.

Neonatal outcome (low cord pH, Apgar score at delivery or admission to the neonatal special care nursery): [NS]

Sahin et al. 2002 [88]

Turkey.

RCT. N = 100 pre-eclamptic women with a modified Bishop score of = 4 (N = 50 in each group).

Compared the impact of 50 μg vaginal misoprostol 4 times at 4 hour intervals (intervention) vs. oxytocin infusion for induction of labour starting from 1 mIU/per min, increasing it every 30 min with 2 mIU/min increments up to maximum of 30 mIU/min (controls).

Intrapartum SB: 0/50 in both groups.

Sahraoui et al. 2005 [91]

Tunisia.

RCT. All uncomplicated pregnancies that reached 41 weeks'gestation with a Bishop score of < or = 4.

Compared the impact on fetal outcomes of cervical prostaglandin E2 gel for cervical ripening (intervention) vs. control.

Caesarean rates: [NS]

Rates of admission into the neonatal unit and fetal outcomes: [NS]

Van Gemud et al. 2004 [82]

The Netherlands. Labour wards of one university hospital and two teaching hospitals.

RCT. Women (N = 681) with indication for labour induction at > or = 36 weeks of gestation, singleton pregnancy and no previous Caesarean section.

Compared the impact on pregnancy outcomes of misoprostol (25 mcg, hospital-prepared capsule) in the posterior vaginal fornix, every four hours, maximum three times daily (intervention) vs. prostaglandin E2 gel every four hours (controls). Oxytocin was administered if necessary

Neonatal deaths: (excluding malformations): 0 in both groups.

Adverse neonatal outcome: 21% vs. 23% in intervention and control groups, respectively [NS].

Median induction-delivery interval: 25 vs. 19 h in intervention and control groups, respectively (P = 0.008).

Caesarean rate: RR = 0.8 (95% CI: 0.6–1.04) [NS].

[16.1% vs. 21% in intervention and control groups, respectively].

Admission to NICU: RR = 0.7 (95% CI: 0.5–0.98).

[19% vs. 26% in intervention and control groups, respectively].