Discontinuation of intravenous oxytocin used to stimulate uterine contractions in the active phase of induced labour

What is the issue?

Oxytocin is a natural hormone, which causes the uterus (womb) to have regular, painful contractions and labour to start. It is available as an intravenous (into a vein (IV)) drug and infused slowly to artificially stimulate labour if doctors or midwives feel that it is necessary to accelerate the birth of the baby, or if the mother requests it. In Western countries, about one in four pregnant women have labour induced, usually with prostaglandin drugs either alone or in combination with oxytocin.

Risks associated with using IV oxytocin to stimulate uterine contractions include the woman having contractions that are too long or too frequent (uterine hyperstimulation), which can lead to changes in the baby’s heart rate and the need for emergency caesarean. This review examines whether stopping IV oxytocin once labour is well-established (i.e. the cervix is dilated more than halfway) reduces the associated risks for mother and baby compared to continuing with IV oxytocin.

Why is this important?

Stopping oxytocin infusion once active labour has started could result in a more natural childbirth, particularly if the risk of uterine overstimulation and need for immediate caesarean section is reduced. Also, the overall total dose of oxytocin the mother received would be reduced, which could lead to fewer adverse effects (e.g. maternal nausea, vomiting and headache, or changes to the baby's heart rate).

What evidence did we find?

We searched for evidence (January 2018) and found 10 randomised controlled studies (1888 women and their babies) conducted between February 1998 and January 2016 at hospitals in Denmark, Greece, Turkey, Israel, Iran, USA, Bangladesh, India, and Thailand. We cannot be confident in the results because of study design limitations and how the findings were reported.

Stopping IV oxytocin during active labour may reduce the number of women who have a caesarean section (nine trials, 1784 women). However, when we performed another analysis including only those women who were actually in active labour, we found that there is probably little or no difference between the two groups (four trials, 787 women).

Discontinuing IV oxytocin probably reduces the risk of women having contractions that become too long or too strong resulting in changes to the baby’s heart rate (three trials, 486 women). We are uncertain about whether stopping IV oxytocin or not affects the risk of having a bacterial infection of the membranes or sac inside the womb) (one trial, 252 women). Stopping IV oxytocin during labour may have little or no impact on women’s use of analgesia and epidural compared to women who continued to receive IV oxytocin (three trials, 556 women).

There were probably fewer babies in the discontinued IV oxytocin group with abnormal cardiotocography results (an electronic method of measuring both the women’s contractions and the baby’s heartbeat) compared to women who continued to receive IV oxytocin (seven trials, 1390 women).

Compared to continued IV oxytocin, discontinuing IV oxytocin probably has little or no impact on the number of babies with a low score on a standard test of well-being for newborn babies (Apgar), five minutes after being born (four trials, 893 women), or another other measure of infant well-being involving analysing blood taken from the umbilical cord once (four trials, 873 women).

The included trials did not report on many of this review's outcomes, including death of the mother or her baby.

What does this mean?

Stopping oxytocin after the active phase of labour has started may reduce the number of women with contractions that become too long or too strong resulting in changes to the baby’s heart rate, and the risk of having a caesarean. However, the possible reduction in the risk of caesarean may be an artefact of poor study design.

Better quality trials are needed. These could include in the analysis those women who did not reach the active phase of labour because their babies were delivered earlier by caesarean, and those whose labour was so rapid that the oxytocin could not be stopped in time, i.e. analysis should be by 'intention-to-treat".

Future studies could include the outcomes listed in this review, including women's satisfaction.

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.

Read the full 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 strategy: 

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 of uterine 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.

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