Reducing Neonatal Morbidity by Discontinuing Oxytocin During the Active Phase of 1st Stage of Labor

Study Overview
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Brief Summary
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The purpose of this study is to measure the impact of a discontinuous administration of oxytocin during the active phase of the 1st stage of labor on the neonatal morbidity rate. The investigators hypothesize that discontinuation of oxytocin in the active phase of labor (from 6 cm) in women who received oxytocin in the latent phase or for an induction (before 4 cm of dilation) could reduce neonatal morbidity.

Detailed Description
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Oxytocin is effective in increasing frequency and intensity of uterine contractions and therefore in reducing the duration of labor. Nevertheless, its administration is potentially associated with fetal and maternal short-and long- term complications, such as neonatal acidosis and post-partum hemorrhage and its effectiveness in decreasing caesarean section rate has not been clearly demonstrated. The most important side effect of oxytocin infusion is uterine hyper-stimulation, which has been shown to occur in more than 30% of women induced with oxytocin. By causing uterine hyper-stimulation, oxytocin infusion may lead to or aggravate abnormal fetal heart rate, contributing to neonatal acidosis. Acidosis is a major part of neonatal morbidity due to related complications such as hospitalization in neonatal intensive care units, but also neonatal death or cerebral palsy in the most severe cases. The first stage of labor is divided into two phases, a latent phase where cervical dilation is relatively slow until 5-6 cm and an active phase until full dilatation, where cervical dilation accelerates. Currently in France, when oxytocin administration has been initiated during the latent phase, the standard care is to continue it during the whole duration of labor. One assumption is that, once women requiring oxytocin during the latent phase enter the active phase, natural oxytocin takes over from synthetic oxytocin. Thus, in the active phase, oxytocin could be discontinued, reducing exposure duration and therefore reducing the risk of complications, in particular neonatal complications, without compromising the chances of vaginal delivery. It can therefore be hypothesized that discontinuation of oxytocin in the active phase of labor (from 6 cm) in women who received oxytocin in the latent phase or for an induction (before 4 cm of dilation) could reduce neonatal morbidity. Several small trials attempting to evaluate this practice have been published, but their design and small population did not allow evaluating the impact of discontinuation of oxytocin on neonatal morbidity. Thus, the investigators propose to conduct a large randomized controlled trial, STOPOXY, aiming to reduce oxytocin exposure and its adverse effects. The investigators expect an improvement of child health at birth, with less severe neonatal morbidity that may cause neurologic damages and less moderate neonatal morbidity that may be associated with the need of resuscitation and hospitalization. The investigators plan to conduct a multicenter, randomized, open-label, controlled trial comparing neonatal and maternal outcomes among term singleton neonates after discontinuation or continuation of oxytocin infusion during the active phase of the 1st stage of labor. Two arms: Experimental group: discontinuation of oxytocin administration at the beginning of the active phase of the 1st stage of labor, i.e. oxytocin infusion will be stopped beyond a cervical dilatation of 6cm. In the experimental group, oxytocin can be re-started, if necessary, after 2 hours of arrest of labor. Control group: standard care in France, i.e. when oxytocin is started during the latent phase of the 1st stage, administration of oxytocin is continued during the active 1st stage and during the 2nd stage if the fetal heart rate is reassuring. The open-label design was chosen for several reasons. The main reason is that in case of a blinded trial, the need for un-blinding would be too frequent as the investigators estimate it from the previous published trials at 30 to 40%. The second reason is feasibility. Indeed, in case of non-reassuring fetal heart rate, it is important for the obstetrician to be able to stop the oxytocin infusion to reduce the uterine contractility.

Official Title
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Reducing Neonatal Morbidity by Discontinuing Oxytocin During the Active Phase of 1st Stage of Labor: a Multicenter Randomized Controlled Trial

Conditions
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Neonatal Morbidity

Intervention / Treatment
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* Drug: discontinuation of oxytocin administration
* Drug: continuation of oxytocin administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With a term (≥37 WG) pregnancy Singleton pregnancy Fetus in cephalic presentation Women receiving oxytocin during the latent phase of the 1st stage of labor, before 4 cm of cervical dilatation, including women with an induction of labor using cervical ripening or oxytocin Speaking and reading French language Affiliated to social security Who have signed the consent form Exclusion Criteria: Women with a scarred uterus Fetus with a congenital anomaly Fetal growth retardation <3rd percentile Having an abnormal fetal heart rate at randomization Maternal age < 18 years Participating in another trial involving medication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: discontinuation of oxytocin administration<br>Discontinuation of oxytocin administration at the beginning of the active phase of the 1st stage of labor, i.e. oxytocin infusion will be stopped beyond a cervical dilatation of 6cm | Drug: discontinuation of oxytocin administration<br>* Discontinuation of oxytocin administration at the beginning of the active phase of the 1st stage of labor, i.e. oxytocin infusion will be stopped beyond a cervical dilatation of 6cm. In the experimental group, oxytocin can be re-started, if necessary, after 2 hours of arrest of labor.<br>|
| Active Comparator: continuation of oxytocin administration<br>Standard care in France, i.e. when oxytocin is started during the latent phase of the 1st stage, administration of oxytocin is continued during the active 1st stage and during the 2nd stage if the fetal heart rate is reassuring. | Drug: continuation of oxytocin administration<br>* continuation of oxytocin administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| neonatal morbidity composite measure | Neonatal morbidity will be assessed using a composite variable defined by: an umbilical arterial pH at birth <7.10 and/or a base excess >10mmol/L and/or umbilical arterial lactates>7 mmol/L and/or a 5 minutes Apgar score <7 and/or admission in neonatal intensive care unit (NICU). This composite outcome is based on pertinent and previously published thresholds to assess neonatal acidosis[16] | At birth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| umbilical cord pH<7.20 | umbilical arterial cord pH at birth less than 7.20 | At birth | 
| umbilical cord pH<7.10 | umbilical arterial cord pH at birth less than 7.10 | At birth | 
| umbilical cord pH<7.00 | umbilical arterial cord pH at birth less than 7.00 | At birth | 
| Need for hypothermia | need for hypothermia | At birth | 
| other neonatal complications: | need of resuscitation at birth | 2 hours postpartum | 
| neonatal admission | transfer to neonatal care unit | 2 hours postpartum | 
| length of the newborn's hospital stay | length of hospital stay | 0-1 month | 
| mode of delivery | cesarean rate | 0-48hours | 
| mode of delivery | cesarean rate for abnormal fetal heart rate | 0-48hours | 
| mode of delivery | instrumental vaginal delivery | 0-48hours | 
| mode of delivery | instrumental delivery for abnormal fetal heart rate | 0-48hours | 
| labor duration | labor duration (active 1st stage, passive and active 2nd stage) | 0-48hours | 
| uterine hyper-stimulation | uterine hyper-stimulation, defined by periods with more than 5 uterine contractions in 10 minutes during labor | 0-48hours | 
| fetal scalp blood testing | need for fetal scalp blood testing during labor | 0-48hours | 
| fetal occipito-posterior position | fetal occipito-posterior position | 0-48hours | 
| maternal hyperthermia | maternal fever during labor, defined by maternal temperature >38°C | 0-48hours | 
| postpartum hemorrhage | post-partum hemorrhage, defined by an estimated blood loss >500mL | 0-48hours | 
| The post-partum women's satisfaction | women's satisfaction is recorded using the labor agentry scale. Scores on the Labor Agentry Scale range from 29 to 203, with higher scores indicating greater perceived control during childbirth. | 0 5 day | 
| The post-partum women's satisfaction: labor agentry scale | women's satisfaction is recorded using the labor agentry scale[18] | at 2 months postpartum in a survey | 
| The post-partum women's satisfaction | Edinburgh Postnatal Depression Scale. Scores on the Edinburgh Postnatal Depression Scale rabge from 0 to 30, with higher score indicating mental health issues. | at 2 months postpartum in a survey | 
| The post-partum women's satisfaction | Satisfactiuon of labor and childbirth with Labor Agentry Scale | at 2 months postpartum in a survey | 
| The post-partum women's satisfaction | Birth experience and well being with EPDS at 2 months | at 2 months postpartum in a survey | 
| The post-partum women's satisfaction | Breastfeeding at 2 months | at 2 months postpartum in a survey | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multicenter, randomized, control study, Oxytocin discontinuation, Neonatal acidosis