Induction of labour with an unfavourable cervix and a Bishop score lower than five relies on a very different mechanism and time scale than induction of labour with intravenous oxytocin when the woman has a ripe cervix and ruptured membranes. The primary goal of use of prostaglandins is to ripen the cervix which makes it possible to artificially rupture the membranes and induce contractions. Therefore, we reported the outcomes of these two comparisons separately.
Comparison 1. Morning versus evening start of induction with prostaglandins
Two trials with a total of 746 women contributed to this comparison (Dodd 2006a; Oei 2000). The study by Oei 2000 included women with a unfavourable cervix and a Bishop's score of ≤ five; and primed with PGE2 (0.5 mg) endocervical gel, second administration when needed was after 10 hours and third administration after 48 hours. The trial by Dodd 2006a included women with a Bishops' score ≤ 6 who consented to the Milo trial (Dodd 2006b); a randomised controlled trial that compared oral misoprostol (20 mcg at two-hour intervals with a maximum of six doses) with PGE2 gel at six-hour intervals with a maximum of six doses. Both trials included women with a vital singleton pregnancy, a gestational age greater than 36+6 weeks, cephalic presentation and a fetus in good condition. Women with any contraindication to vaginal birth, previous uterine surgery (including caesarean section), or ruptured membranes were excluded. Since misoprostol is an E1 prostaglandin analogue we judged it appropriate to combine both trials in the analysis.
The primary outcome of this review was perinatal mortality, defined as intrauterine deaths plus newborn deaths in the first week of life. No such adverse events were reported in the included trials.
Secondary neonatal outcomes
Birth asphyxia was defined by trialists in both included trials as an Apgar score below seven at five minutes. There was no statistical difference between study groups; only one of the trials contributed estimable data (Dodd 2006a) (risk ratio (RR) 0.20, 95% confidence interval (CI) 0.02 to 1.67) Analysis 1.1.
Admission to neonatal intensive care was reported in both trials, there was no statistical difference between study groups. There was estimable data for only one of the trials (Dodd 2006a) (RR 0.40, 95% CI 0.04 to 3.87) Analysis 1.2.
The following prespecified secondary neonatal outcomes of this review were not reported: convulsions, encephalopathy, use of anticonvulsants, neonatal admissions, meconium aspiration syndrome, pneumonia and neurodevelopment at childhood follow-up.
Secondary maternal outcomes
Mode of delivery: rates of caesarean section and vaginal instrumental delivery were reported in both trials. Because these variables can interfere with each other and there was substantial heterogeneity (I²: 51% for caesarean section and 86% for instrumental vaginal delivery), we decided not to pool these variables. Possibly, the different basic intervention rates between the Australian population in the study of Dodd 2006a, (24.4% caesarean sections), and the Dutch population in the study of Oei 2000, (15.1% caesarean sections) partly accounts for this heterogeneity. There was no evidence of a difference in the risk for caesarean section between study groups in either of these studies Oei 2000 (RR 1.61, 95% CI 0.70 to 37.4) and Dodd 2006a (RR 0.85, 95% CI 0.64 to 1.12) Analysis 1.3. Although the risk for a instrumental vaginal delivery was statistically significantly higher in the evening group in the trial of Oei 2000 (RR 0.25, 95% CI 0.10 to 0.63), this was not confirmed by the outcome in the larger trial of Dodd 2006a (RR 0.92, 95% CI 0.65 to 1.30) (Analysis 1.4).
In the study by Dodd 2006a, use of epidural anaesthesia was much more common, more than 64% versus 13.5% of the women in the study by Oei 2000. This is in concordance with the difference in daily practices in obstetrics between Australia and the Netherlands. Because of substantial statistical heterogeneity (I² 61%), we decided not to pool results for this outcome; there was no evidence of a difference in the studies between the morning and the evening group (Oei 2000 (RR 0.49, 95% CI 0.18 to 1.31), Dodd 2006a (RR 1.10, 95% CI 0.98 to 1.24)) Analysis 1.5.
Perineal trauma was not reported in either of the trials.
Need for blood transfusion was only reported in the study by Dodd 2006a, and there was no strong evidence of any difference between groups (RR 0.91, 95% CI 0.32 to 2.59) Analysis 1.6.
Use of antibiotics because of signs of intrauterine infection was not reported in either of these trials.
Duration of labour was not reported in these two studies. Because the primary outcome measure of the Dodd 2006a trial was "vaginal birth not achieved within 24 hours", we decided to report this non-prespecified outcome here. There was no evidence of a difference between study groups; in the subgroup of primiparae (RR 1.00, 95% CI 0.84 to 1.20), and in multiparae (RR 0.92, 95% CI 0.60 to 1.43) Analysis 1.7. The study of Oei 2000 chose "delivery outside office hours" (08:00 to 18:00) as a primary outcome. The number of deliveries outside office hours was similar for women in both groups (RR 1.17, 95% CI 0.83 to 1.65) Analysis 1.8. In this study the authors reported that in nulliparous women, the chance of delivery at night was slightly reduced when endocervical prostaglandin E2 was administered in the evening (RR 0.65, 95% CI 0.29 to 1.5), while in multiparous women the chance of delivery in the evening was significantly reduced (RR 0, 95% CI 0 to 0.71) with no effect on the probability to deliver at night (data not shown in data and analyses tables). Delivery outside office hours was not reported by Dodd 2006a.
Prolonged labour was not reported in either of the trials.
Both studies assessed patient satisfaction by asking the participating women to complete questionnaires for assessment of patient preferences. In the study by Dodd 2006a, all women completed the forms, and in the study by Oei 2000 86% of all women filled in the forms. In the morning group in the study of Oei 2000 2/48 (4.2%) of the women were dissatisfied with the timing of induction versus 12/60 (20%) of the women of the evening group. This was a statistically significant difference (RR 0.21, 95% CI 0.05 to 0.89) Analysis 1.9. Both studies questioned women about the quality of their sleep during the night before delivery. Significantly more women in the evening group reported a bad quality of sleep (average RR 0.24, 95% CI 0.04 to 1.46) Analysis 1.10. There was substantial heterogeneity (I² 69%) so we decided to use the random-effects model.
Postnatal depression was not reported in the trials.
Health service use
Lenght of maternal or neonatal admission was not reported in the included studies.
Comparison 2. Morning versus evening start of induction with intravenous oxytocin
One study Bakker 2009 with 371 women contributed to this comparison. Women beyond a gestational age of 36 weeks and with a favourable cervix (Bishop score greater than six) or ruptured membranes, with an indication for induction of labour, were randomised to either the evening group (a start of induction of labour at 21:00 hours) or the morning group (start at 07:00 hours). When the membranes were still intact, they were artificially ruptured. Oxytocin was administered by an intravenous pump infusion. The dosage was raised stepwise according to the protocol, starting with 3.3 mIU oxytocin/minute and a maximum of 33.3 mIU oxytocin/minute, until regular contractions occurred every three to four minutes. Exclusion criteria were intrauterine fetal death, non reassuring fetal status, contraindication for amniotomy (e.g. HIV positive women), maternal age below 18 years or a history of secondary caesarean section (failed vaginal delivery). Data are presented both by the authors according to the intention-to-treat principle as well as according to the on-protocol principle and for the strata primiparity and multiparity separately. For this review, we used the aggregated data of primi- and multiparae in the intention-to-treat analysis.
The primary outcome of this review was perinatal mortality; no such adverse events were reported in this trial.
Secondary neonatal outcomes
Birth asphyxia was not statistically significantly different between the study groups; 4/187 children in the morning group versus 2/184 children in the evening group (RR 1.97, 95% CI 0.36 to 10.61) Analysis 2.1.
Admission to the neonatal intensive care unit was not reported separately.
Neonatal convulsions, neonatal encephalopathy and use of anticonvulsants were not reported in the trial.
Neonatal admission (defined by trialists as neonatal admissions to the maternity ward, the neonatal medium care or neonatal intensive care) occurred statistically significantly more often when the induction of labour started in the morning; 54/187 children in the morning group versus 36/184 children in the evening group (RR 1.48, 95% CI 1.02 to 2.14 ) Analysis 2.2.
Meconiumaspiration syndrome, pneumonia and neurodevelopment at childhood follow-up were not reported in the trial.
Secondary maternal outcomes
No evidence of a difference in mode of delivery was found between study groups; 23/187 women in the morning group versus 20/184 women in the evening group gave birth with a caesarean section (RR 1.13, 95% CI 0.64 to 1.99) Analysis 2.3 and 26/187 women in the morning group had a vaginal instrumental delivery versus 23/184 women in the evening group (RR 1.11, 95% CI 0.66 to 1.88) Analysis 2.4.
Epidural anaesthesia was not different between study groups; 22/187 women in the morning group versus 25/184 women in the evening group (RR 0.87, 95% CI 0.51 to 1.48) Analysis 2.5.
Perineal trauma and need for blood transfusion were not reported in the trial.
There was no evidence of a difference in rates of use of antibiotics during labour because of signs of intrauterine infection between study groups; 4/187 women in the morning group versus 1/184 women in the evening group (RR 1.97, 95% CI 0.36 to 10.61) Analysis 2.6.
Duration of labour, defined as time between start of labour and time of birth, was the primary outcome of the only study in this comparison Bakker 2009. The intention-to-treat analysis showed no evidence of a difference in both subgroups (primiparae n = 242: morning 12 hours and eight minutes versus evening 11 hours and 22 minutes, P value 0.29; multiparae n = 129: morning seven hours and 34 minutes versus evening seven hours and 46 minutes, P value 0.70) Analysis 2.7.
Prolonged labour was not reported in the trial.
In this study patient satisfaction was measured by a postpartum questionnaire. The results showed no evidence of a difference between the study groups, all women in both groups showed signs of fatigue at the start of the induction with Likert scores of 6.6 for the morning group and 7.1 for the evening group on a scale ranging from 1 (extreme fatigue) to 10 (no fatigue at all). All other items, provision of information, level of attendance and care of nurses and staff, scored on average between 8 and 9.
Postnatal depression was not reported in the trial.
Health service use
Length of maternal or neonatal admission was not reported in this included study.