Study design

The EOLE study is designed as a randomised, controlled, non-blinded multicentre superiority trial with two parallel groups, comparing directed closed-glottis pushing with directed open-glottis pushing during the active phase of the second stage of labour. Randomisation is being performed with a 1:1 allocation.

Study setting

There are four centres, all in France: two university hospitals and two general hospitals.

Eligibility criteria

Women of any parity are eligible for inclusion if they: have taken an antenatal class that includes training in the types of pushing, have planned a vaginal delivery, are admitted at 37–42 weeks of gestation for spontaneous or induction of labour, with cervical dilation ≥7 cm, a singleton pregnancy in cephalic presentation, and provide written consent, and speak and write French. Women will be excluded if they are younger than 18 years, have had a previous caesarean delivery or other uterine surgery (that leaves a scar), have a disease contraindicating expulsive efforts or that may justify emergency delivery (HELLP syndrome, pre-eclampsia, abruptio placentae, etc), or severe genital haemorrhage, or major fetal malformation and/or hydramnios or oligohydramnios, and/or intrauterine growth restriction diagnosed in utero (ie, below the 5th centile for gestational age and sex), or a fetal heart rate anomaly or an in utero fetal death before randomisation.

Interventions

In the intervention group, directed open-glottis pushing (with prolonged exhalation) must be explained to the women and professionals as follows: ‘After inhaling deeply, the woman will exhale while pulling in her stomach in such a way that she can use the contraction of her abdominal muscles to help the fetus descend through the birth canal. She should push as long as possible’.

In the control group, directed closed-glottis pushing (pushing while holding one's breath) should be explained to the women and professionals as follows: ‘After inhaling deeply, the woman should push very hard downwards to the perineum, while holding the inhaled breath in her lungs. She should push as hard and as long as possible’.

The pregnant women receive information about the study and instruction about the types of pushing between 29 and 37 weeks of gestation. To be sure that the intervention is standardised in all participating centres, the women receive specific instruction in these breathing techniques. During one session of antenatal classes, pregnant women see a video specifically created for them, describing and illustrating both types of directed pushing. Those who have completed this instruction receive a card attesting to this instruction, which they are asked to keep with their blood group cards (to minimise the possibility of losing it).

Both techniques are coached by the midwife managing the delivery. This study is not assessing spontaneous pushing. Women in both groups are coached to push three times per contraction, as usual in France, if possible. Elsewhere, all participating staff—that is, all professionals teaching antenatal classes who agree to support the study and the midwives-investigators who include the women and then manage the delivery—are trained in advance in both pushing techniques so that they can teach and support the women. A video intended specifically for professionals has been produced for the study to standardise the information provided to patients.

Co-interventions

The co-interventions (analgesia, maternal position, use of oxytocin to augment labour, etc) associated with labour and its monitoring are identical to the usual management in the participating maternity units. The midwife managing the delivery determines the moment that active labour and thus bearing down and pushing efforts begin. The fetal heart rate and the frequency of uterine contractions are monitored continuously, after randomisation, with an external tocodynamometer, throughout labour and expulsive efforts.

Investigators who determine after 20 min that the type of pushing used appears ineffective can ask mothers to switch to the other type, if they think it useful. In the latter case, the women will remain in their initial group. If fetal heart rate abnormalities or other obstetric emergencies occur, the midwife and/or the supervising obstetrician will be the sole decision-makers, jointly with the mother, to the extent possible, for the ensuing medical management (change in pushing technique, instrumental or caesarean delivery).

Outcomes

The principal end point is a composite criterion: spontaneous delivery with no perineal lesion (no episiotomy or second-degree, third-degree or fourth-degree lacerations).

Our secondary outcome measures are divided into three categories. For the mother, we will assess (1) immediate maternal morbidity, defined by the occurrence of perineal lesions, such as episiotomy or a severe perineal laceration (third or fourth degree) or immediate postpartum haemorrhage (blood loss >500 mL in the 24 hours after delivery); (2) intermediate-term maternal morbidity will be defined by effect on pelvic floor and urinary function (Pelvic Organ Prolapse Quantification System (POP-Q) and International Consultation on Incontinence modular Questionnaire-Short Form (ICIQ-SF)) at 2 months after delivery or at the postpartum visit,17 ,18 and (3) women's satisfaction at 4 weeks post partum (Questionnaire d'Evaluation du Vécu de l'Accouchement questionnaire). Secondary neonatal outcomes will be immediate neonatal morbidity defined by a 5-min Apgar score <7 or an umbilical artery pH<7.10 or the need for resuscitation in the delivery room (defined by one or more of the following events: aspiration by a laryngoscope, mask ventilation, oxygenation by a nasal cannula, or hood mask, tracheal intubation, endotracheal ventilation or cardiac massage) or transfer to a neonatology department. Finally, for both mother and child, a composite end point which might be considered a quality indicator, is uncomplicated birth, defined by birth without caesarean, operative intervention or obstetrical manoeuvres, without postpartum haemorrhage (500 mL), without second-degree, third-degree or fourth-degree perineal lacerations, and with a 5 min Apgar ≥9.

Participant timeline

The study schedule is described in the schedule (figure 1).

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Figure 1

Schedule of enrolment, interventions and assessments of women in the EOLE study.

Sample size

For α=0.05 and a power of 90%, based on data from the Audipog database (a French national database: Audipog: http://www.audipog.net/interro-choices.php) that women who deliver spontaneously, without any perineal lesion (ie, without episiotomy or spontaneous second-degree, third-degree or fourth-degree lacerations) account for 49.6% of all parturients, the investigators estimate that the use of a two-sided test to show an absolute difference between groups of 20% (or 49.6% vs 69.6%, a relative difference of the order of 40%) would require 125 women per group.

Recruitment

Again using information from the Audipog database (n=413 888 women), we estimate that 63.4% of women give birth without a planned caesarean to a singleton fetus at a term ≥37 weeks of gestation and have neither a uterine scar nor a utero fetal death. Among these women, 40% take a childbirth and parenting preparation class. Accordingly, 25% of the women in each maternity ward should be eligible to participate. The four participating maternity units account for 8411 deliveries per year and should thus have 2103 eligible women each year. We estimate that 70% of the women—1472—will agree to participate each year. Although it may be feasible to complete the study in 1-year, we have planned for it to last 2 years. To optimise women’s participation in this study, information posters are displayed in the healthcare facilities where antenatal care, preparation for delivery and deliveries take place and in the offices of the midwives in private practice supporting the study. Brochures have also been made available to pregnant women. They were also informed about the study during childbirth preparation and parenthood classes and during antenatal care visits with midwives or obstetricians. These obstetric professionals have been made aware of the value of supporting this study during meetings at and outside the hospital.

Allocation and blinding

A computer program designed by an independent group of the clinical research centre is creating the randomisation list, in blocks of four to six (randomly chosen by the electronic system and well balanced by centre) and stratified by maternity ward and within maternity wards by both parity (nulliparous vs multiparous) and epidural analgesia use at randomisation. The randomisation and the data collection will be performed at a website available 24 hours a day.

After the midwives-investigators have verified the inclusion and exclusion criteria and collected the signed informed consent, the randomisation will take place. There is no conceivable way to conduct this study on either a double-blinded or single-blinded basis.

Data collection, management and analysis

Most of the information required for the study is recorded in women's computerised medical files at each centre; it was thus collected before randomisation. The other data are collected either after delivery by the investigator (compliance, station of the descending fetus at the beginning of expulsive efforts), or at a postnatal visit by a well-trained gynaecologist obstetrician or a midwife to collect the woman’s perception of pelvic floor function, determined by a self-administered questionnaire (ICIQ-SF)18 and a less subjective assessment with the POP-Q.17 All data will be entered in an electronic research case file for each woman.

Women will complete the satisfaction questionnaire directly online a month after delivery, after receiving an email asking them to do so and including a link, personal log-in name and password to enter the website.

The primary analysis will be by intention to treat and a secondary analysis per protocol. The baseline characteristics of the women and children (age, weight, parity, etc), the women's satisfaction and pelvic floor function in the two groups will be compared with a χ² test (or Fisher's exact test, as appropriate) for the qualitative variables and by Student's t-test for the quantitative variables. The principal results will be reported as crude relative risks (RRs) with their 95% CIs. Simple descriptive statistics will be used to report some relatively infrequent data (such as transfer to the neonatal intensive care unit (ICU)). A multivariate analysis will be performed to take prognostic and confounding factors (parity, analgesia, maternal position, operative delivery, etc) into account to obtain adjusted RRs. A centre effect will be sought and handled with a Cochran-Mantel Haenszel test, to compare the efficacy of the type of pushing in each group. An analysis according to parity is planned.

An interim analysis will be planned after half of the planned women have been included. Adherence to the type of pushing in France is currently unknown. To preserve an overall threshold of 5% for the final analysis, the interim analysis will use a threshold of 0.1%.

The missing data will be treated as missing.

Monitoring

A data monitoring committee met at the study launch and will continue to meet throughout the study, on its own initiative or at the request of the sponsor (Clermont-Ferrand University Hospital Centre). It will also issue a general report about the course of the study procedures and may contribute to decisions in the following circumstances: opinion about early stopping of the study; opinion about significant modifications of the protocol or taking new scientific data into account. This committee is composed of two physicians, two midwives and a biostatistician, all independent of the study investigators and methodological advisors. The trial sponsor has no role in the design of the trial, the collection, analysis or interpretation of the data, or the future writing of the manuscript.

No serious adverse events directly associated with the study intervention are expected. Nonetheless, the following complications must be reported: death or transfer to adult or neonatal ICU. Any serious adverse event in the first 8 weeks post partum must be reported to the principal investigator and the study sponsor within 24 hours by the investigator, on a special form. The institutional review board must also be informed no later than 7 days after the event. The investigator shall make a determination about the existence of any causal relation between the serious adverse event and the study. When a serious adverse event persists at the end of the study, the investigator shall continue the follow-up of the woman until the event is considered resolved.

According to the French Law and the French research quality guideline, an external audit is not requested for this low-risk trial.

Protocol amendments

Any modifications to the protocol must be characterised as substantial or minor. Substantial modifications must be approved de novo by the Patient Protection Committee and/or the ANSM (National Agency for the Drug and Medical Product Safety).

Consent

The women will be informed completely and fairly of the objectives and constraints of the study, of any possible risks, of their right to refuse to participate and of their right to withdraw their consent and end their participation at any time. All of this information will be included on the information and consent form provided to the woman (see online supplementary files 1 and 2). The investigator shall collect each woman's free and informed consent in writing.

Confidentiality

In compliance with French regulations, persons with direct access to the data will take all precautions necessary to ensure the confidentiality of the data concerning women participating in this study. Moreover, the storage of data collected for this study must comply with French guidelines issued by the competent agency (CNIL: National Data Protection Authority—http://www.cnil.fr).

The study documents shall be archived on the premises of the PEPRADE research team until the end of their practical utility and then stored in the sponsor’s central archives for 15 years.

Access to data

At the conclusion of the research, the data collected about the participants will be anonymised before the statistical analysis. Access to the anonymised data will be limited to the two principal investigators and to the statisticians accredited by the sponsor.

Dissemination policy

The data will be divulged only after the joint accord of the principal investigator and the sponsor. The results will be the subject of scientific communications and publications. The authorship eligibility will follow the Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals, 2015 (http://www.icmje.org).