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Meta-Analysis
. 2018 Aug 20;8(8):CD012274.
doi: 10.1002/14651858.CD012274.pub2.

Discontinuation of intravenous oxytocin in the active phase of induced labour

Sidsel Boie  1 , Julie Glavind, Adeline V Velu, Ben Willem J Mol, Niels Uldbjerg, Irene de Graaf, Jim G Thornton, Pinar Bor, Jannet Jh Bakker
Affiliations
Meta-Analysis

Discontinuation of intravenous oxytocin in the active phase of induced labour

Sidsel Boie et al. Cochrane Database Syst Rev. .

Abstract

Background: In most Western countries, obstetricians and midwives induce labour in about 25% of pregnant women. Oxytocin is an effective drug for this purpose, but associated with serious adverse effects of which uterine tachysystole, fetal distress and the need for immediate delivery are the most common. Various administration regimens such as reduced or pulsatile dosing have been suggested to minimise these. Discontinuation in the active phase of labour, i.e. when contractions are well-established and the cervix is dilated at least 5 cm is another method which may reduce adverse effects.

Objectives: To assess whether birth outcomes can be improved by discontinuation of intravenous (IV) oxytocin, initiated in the latent phase of induced labour, once active phase of labour is established.

Search methods: We searched Cochrane Pregnancy and Childbirth's Trials Register (31 January 2018), Scopus, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) (23 January 2018) together with reference checking, citation searching, and contact with study authors to identify additional studies.

Selection criteria: Randomised controlled trials (RCTs) comparing discontinued IV with continuous IV oxytocin in the active phase of induced labour.No exclusion criteria were applied in terms of parity, maternal age, ethnicity, co-morbidity status, labour setting, gestational age, and prior caesarean delivery.Studies comparing different dosage regimens are outside the scope of this review.

Data collection and analysis: We used standard Cochrane methods.

Main results: We found 10 completed RCTs involving 1888 women. One additional trial is ongoing. The included trials were conducted in hospital settings between February 1998 and January 2016, two in Europe (Denmark, and Greece), two in Turkey, and one each in Israel, Iran, USA, Bangladesh, India, and Thailand. Most trials included full-term singleton pregnancies with a fetus in vertex presentation. Some excluded women with cervical priming prior to induction and some excluded women with a history of prior caesarean delivery. When reported, the average age of the women ranged from 22 to 31 years, nulliparity from 45% to 68%, and pre-pregnancy body mass index from 22 to 32.Many of the included trials had design limitations and were judged to be at either high or unclear risk of bias across a number of 'Risk of bias' domains.Four trials included a Consort flow diagram. In three, this gave details of participants delivered before the active phase of labour, and treatment compliance for those who reached that stage. One Consort diagram only provided the latter information. The data in many of the trials without such a flow diagram were implausibly compliant with treatment allocation, suggesting that there had been silent post randomisation exclusions of women delivered before the active phase of labour. We therefore conducted a secondary analysis (not in our protocol) of caesarean section among women who reached the active phase of labour and were therefore eligible for the intervention.Our analysis by 'intention-to-treat' found that, compared with continuation of IV oxytocin stimulation, discontinuation of IV oxytocin may reduce the caesarean delivery rate, risk ratio (RR) 0.69, 95% confidence interval (CI) 0.56 to 0.86, 9 trials, 1784 women, low-level certainty. However, restricting our analysis to women who reached the active phase of labour (using 'reached active phase' as our denominator) suggests there is probably little or no difference between groups (RR 0.92, 95% CI 0.65 to 1.29, 4 trials, 787 women, moderate-certainty evidence).Discontinuation of IV oxytocin probably reduces the risk ofuterine tachysystole combined with abnormal fetal heart rate (FHR) compared with continued IV oxytocin (RR 0.15, 95% CI 0.05 to 0.46, 3 trials, 486 women, moderate-level certainty). We are uncertain about whether or not discontinuation increases the risk of chorioamnionitis (average RR 2.32, 95% CI 0.99 to 5.45, 1 trial, 252 women, very low-level certainty). Discontinuation of IV oxytocin may have little or no impact on the use of analgesia and epidural during labour compared to the use of continued IV oxytocin (RR 1.04 95% CI 0.95 to 1.14, 3 trials, 556 women, low-level certainty). Intrapartum cardiotocography (CTG) abnormalities (suspicious/pathological CTGs) are probably reduced by discontinuing IV oxytocin (RR 0.65, 95% CI 0.51 to 0.83, 7 trials, 1390 women, moderate-level certainty). Compared to continuing IV oxytocin, discontinuing IV oxytocin probably has little or no impact on the incidence of Apgar < 7 at five minutes (RR 0.78, 95% CI 0.27 to 2.21, 4 trials, 893 women, low-level certainty), or and acidotic cord gasses at birth (arterial umbilical pH < 7.10), (RR 1.03, 95% CI 0.50 to 2.13, 4 trials, 873 women, low-level certainty).Many of this review's maternal and infant secondary outcomes (including maternal and neonatal mortality) were not reported in the included trials.

Authors' conclusions: Discontinuing IV oxytocin stimulation after the active phase of labour has been established may reduce caesarean delivery but the evidence for this was low certainty. When restricting our analysis to those trials that separately reported participants who reached the active phase of labour, our results showed there is probably little or no difference between groups. Discontinuing IV oxytocin may reduce uterine tachysystole combined with abnormal FHR.Most of the trials had 'Risk of bias' concerns which means that these results should be interpreted with caution. Our GRADE assessments ranged from very low certainty to moderate certainty. Downgrading decisions were based on study limitations, imprecision and indirectness.Future research could account for all women randomised and, in particular, note those who delivered before the point at which they would be eligible for the intervention (i.e. those who had caesareans in the latent phase), or because labour was so rapid that the infusion could not be stopped in time.Future trials could adopt the outcomes listed in this review including maternal and neonatal mortality, maternal satisfaction, and breastfeeding.

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Conflict of interest statement

Sidsel Boie is co‐author on one of the included trials (Bor 2016) and primary investigator of an ongoing double‐blind multicentre randomised controlled trial (RCT) on the topic (NCT02553226). She has/will not be involved in any decisions relating to this review ‐ assessment for inclusion, risk of bias, data extraction and GRADE quality assessments has been/will be carried out by other members of the team who are not directly involved in the trial.

Adeline V Velu: none known.

Julie Glavind: Trygfonden Denmark provided postdoctoral salary support at Aarhus University Hospital from April‐September 2014. She currently receives salary support (as a registrar) from Central Denmark Region. She is an investigator of an ongoing double‐blind multicentre RCT on the topic (NCT02553226). She will not be involved in any decisions relating to this review ‐ assessment for inclusion, risk of bias, data extraction and GRADE quality assessments will be carried out by other members of the team who are not directly involved in the trial.

Ben Willem J Mol and his institution have received payment for consultancy from ObsEva Geneva. Ben has also received payment for review preparation from European Journal of Obstetrics & Gynecology from ESHRE Munich and Prebic Geneva in respect of travel/accommodation/meeting expenses for various non‐commercial scientific meetings

Niels Uldbjerg is an investigator on the ongoing randomised trial, the CONDISOX trial (NCT02553226) that may be considered for inclusion in a future update of this review. He will not be involved in any decisions relating to this review ‐ assessment for inclusion, risk of bias, data extraction and GRADE quality assessments will be carried out by other members of the team who are not directly involved in the trial.

Irene de Graaf: none known.

Pinar Bor is principle investigator on one of the included trials (Bor 2016), and an investigator on a ongoing double‐blind multicentre RCT on the topic (NCT02553226). She has/will not be involved in any decisions relating to this review ‐ assessment for inclusion, risk of bias, data extraction and GRADE quality assessments has been/will be carried out by other members of the team who are not directly involved in the trial.

Jannet JH Bakker is one of the authors of the ongoing randomised trial, the CONDISOX trial (NCT02553226) that may be considered for inclusion in a future update of this review. She will not be involved in any decisions relating to this review ‐ assessment for inclusion, risk of bias, data extraction and GRADE quality assessments will be carried out by other members of the team who are not directly involved in the trial.

JIm Thornton is the chair of the trial steering committee for the ongoing randomised trial, the CONDISOX trial (NCT02553226) that may be considered for inclusion in a future update of this review. He will not be involved in any decisions relating to this review ‐ assessment for inclusion, risk of bias, data extraction and GRADE quality assessments will be carried out by other members of the team who are not directly involved in the trial.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Continued versus discontinued oxytocin stimulation in the active phase, Outcome 1 Caesarean delivery.
1.2
1.2. Analysis
Comparison 1 Continued versus discontinued oxytocin stimulation in the active phase, Outcome 2 Duration of the active phase of labour.
1.3
1.3. Analysis
Comparison 1 Continued versus discontinued oxytocin stimulation in the active phase, Outcome 3 Postpartum haemorrhage of 500 mL or more.
1.4
1.4. Analysis
Comparison 1 Continued versus discontinued oxytocin stimulation in the active phase, Outcome 4 Uterine tachysystole combined with abnormal fetal heart rate.
1.5
1.5. Analysis
Comparison 1 Continued versus discontinued oxytocin stimulation in the active phase, Outcome 5 Uterine tachysystole.
1.6
1.6. Analysis
Comparison 1 Continued versus discontinued oxytocin stimulation in the active phase, Outcome 6 Chorioamnionitis.
1.7
1.7. Analysis
Comparison 1 Continued versus discontinued oxytocin stimulation in the active phase, Outcome 7 Use of analgesia and epidural during labour.
1.8
1.8. Analysis
Comparison 1 Continued versus discontinued oxytocin stimulation in the active phase, Outcome 8 Third‐ and fourth‐degree perineal tear.
1.9
1.9. Analysis
Comparison 1 Continued versus discontinued oxytocin stimulation in the active phase, Outcome 9 Vaginal instrumental delivery.
1.10
1.10. Analysis
Comparison 1 Continued versus discontinued oxytocin stimulation in the active phase, Outcome 10 Caesarean delivery after the active phase of labour has begun.
1.11
1.11. Analysis
Comparison 1 Continued versus discontinued oxytocin stimulation in the active phase, Outcome 11 Caesarean delivery after active phase begun using "reached active phase" as denominator.
1.12
1.12. Analysis
Comparison 1 Continued versus discontinued oxytocin stimulation in the active phase, Outcome 12 Intrapartum cardiotocography (CTG) abnormalities (suspicious/pathological CTGs).
1.13
1.13. Analysis
Comparison 1 Continued versus discontinued oxytocin stimulation in the active phase, Outcome 13 Apgar score at five minutes below seven.
1.14
1.14. Analysis
Comparison 1 Continued versus discontinued oxytocin stimulation in the active phase, Outcome 14 Acidotic cord gasses at birth (arterial umbilical pH < 7.10).
1.15
1.15. Analysis
Comparison 1 Continued versus discontinued oxytocin stimulation in the active phase, Outcome 15 Neonatal admission to the neonatal intensive care unit.
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Update of

References

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Boie 2016
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