Combination of labor induction agents almost halves the time to delivery.

The cascade of spontaneous events that sets the wheels of labor in motion has remained a mystery despite all the recent advances in the field of maternal and fetal medicine. Researchers hypothesize that it’s blend of physiology and magic that sets the ball rolling. Maternal and fetal signals both play a part in starting the process.

The history of labor induction dates to time of Hippocrates' when mammary stimulation and mechanical cervical dilatation was used to bring about uterine contraction.[1]

Induction of labor for singleton births has seen a slight decline from 23.8% in 2010 and 23.3% in 2012 after seeing a steady increase in past 20 years. [2]  This translate to 932,000 women undergoing induction of labor for various maternal and fetal indication.

Various mechanical and chemical methods singly or in combination have been in use since long. The choice of method depends on state of cervix, previous obstetric history, indication of induction and gestational age at induction. Foley’s balloon catheter, Prostaglandin E2 and misoprostol are common methods used for cervical ripening. Amniotomy and oxytocin are used when the cervix is already ripened.[3]

A recent paper published on November 03, 2016 in Journal of Obstetrics & Gynecology evaluated the effectiveness of the four most commonly used method. [4] The paper was also presented at the Pregnancy Meeting, the 2016 Annual Meeting of the Society for Maternal-Fetal Medicine (SMFM).

Dr. Lisa Levine, MD, University of Pennsylvania’s Perelman School of Medicine, Philadelphia, Pennsylvania, and colleagues said in their presentation “This randomized trial is one of the first of its kind to compare 4 different induction methods in a head-to-head trial. We found that combination induction methods resulted in delivery in half the amount of time as single agents with no difference in caesarean delivery rates.”

The study called as Foley or Misoprostol for the Management of Induction (FOR MOMI) trial was a 4-armed randomized trial conducted between May 2013 and June 2015. The study recruited 492 women with singleton full-term pregnancy (37 weeks of gestation or greater), vertex-presentation, with no contraindication to vaginal delivery, intact membranes, Bishop score 6 or less, and cervical dilation 2 cm or less. These women were assigned to receive either misoprostol alone; or Foley catheter alone; Foley catheter and Pitocin concurrently or misoprostol and cervical Foley catheter concurrently.

The primary outcome measured was reduction in time to delivery with a reduction of more than 4 hours considered significant. Numerous secondary outcomes like time to vaginal delivery, rate of caesarean deliveries, time in active labor, defined as cervical dilation of 5 cm or more, delivery within 12 or 24 hours, and maternal length of stay were also looked at.

The demographics and clinical characteristics of the study participants were quite similar with a mean age of 27 years, 72% being nullipara, mean gestational age at induction being 39 weeks with mean bishop score 3 and mean cervical dilatation 1.

The median time to delivery for nulliparous and multiparous women in various arms of the study are (P<.001):

misoprostol–Foley group       13.1 hours

oxytocin–Foley group            14.5 hours

misoprostol only                    17.6 hours

Foley-only group                   17.7 hours

When the data was adjusted for parity and only vaginal deliveries analyzed, women in the misoprostol-Foley group where twice as likely to deliver earlier (HR=1.92) with reference to misoprostol only or Foley-only group.

  

Women in the combination arms of the study also had the maximum chance of delivering in 24 hours. (88% of women in the misoprostol/Foley group and 84% in the oxytocin/Foley group).

Rates of cesarean section and other maternal morbidities like perineal lacerations, endometritis, wound infection and dehiscence, readmission or length of stay were comparable in all the groups. No significant difference was found in neonatal morbidities too.

The authors opined that “This study has significant clinical implications for obstetric care. The ability to shorten the length of time women spend in labor without increasing morbidity has large clinical and financial implications given the cost and known maternal–neonatal risks associated with both prolonged labor and cesarean delivery."

The only study limitation was lack of blinding, because women had to be examined for application of different methods in 4 study arms. Also, individual arm lacked the statistical power to compare the cesarean section, maternal and neonatal morbidities across different groups.

In all, the findings could help millions of women and shorten thousands of hours in labor across the world. It is estimated that nearly 20% or 932,000 women undergo induction of labor in USA. If combination method is used in all of them, then there would be more than 3 million fewer hours, or more than 125,000 fewer days that women spend in labor in the United States alone. 

This has huge financial and health care utilization implications.

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[1] www.glowm.com/section_view/heading/Induction%20of%20Labor/item/130

[2] http://www.cdc.gov/nchs/data/databriefs/db155.pdf

[3] https://sogc.org/wp-content/uploads/2013/08/September2013-CPG296-ENG-Online_REV-D.pdf

[4] http://journals.lww.com/greenjournal/Abstract/publishahead/Mechanical_and_Pharmacologic_Methods_of_Labor.98564.aspx

Is outpatient preinduction cervical ripening an option at term? News from ACOG Annual Clinical and Scientific Meeting 2016.

Outpatient preinduction cervical ripening has always been debated. With nearly 1 in 4 pregnancies scheduled for induction of labor and  50% of these women having unfavorable cervix interest in this has grown. Those clinician and researchers in favor of it vouch that it offers many advantage like decreased hospitalization time, conserving resources due to decreased labor room staffing, and improving patient satisfaction.  

While clinicians against it advocate its use only in specific, well planned situation with valid indication. The reason behind it is lack of large scale data reporting experience behind it. There are also no large scale trials to back up the regime. Studies found in literature involve term pregnancies of living fetuses with some means of continuous monitoring of uterine activity and the fetal heart rate for the first few hours. Also there exist no studies comparing the mechanical vs various drug therapies for cervical ripening.

Samuel A. Cosgrove Memorial Lecture on May 17, 2016 took a detailed look at doing cervical ripening on an outpatient basis for low-risk patients.

Dr. Anthony C. Sciscione, DO, Christiana Care Health Services, Newark, DE was in favor of outpatient cervical ripening and he mostly shared his experiences with Foleys catheter.

He stressed that outpatient ripening has a very high rate of patient satisfaction and patients were willing to make extra trip to hospital. Studies also showed that in-patients have a very high level of anxiety and outpatients were more stress free.  

A small randomized trial at Christiana care was carried out to see if patients can manage Foleys catheter in outpatient setting.   Women who were low risks, with stable vital signs, adequate amniotic fluid had a catheter placed in and randomized to 2 groups inpatient (n=50) and outpatient (n=61) and observed for 2 hours. The outpatient group was discharged with proper instructions and advised to return next day 6 AM. Dr. Sciscione did not really observed any difference between the two groups. 

While Dr. William F. Rayburn, MD, MBA, University of New Mexico, Albuquerque, NM, scrutinized it because of lack of concrete and meticulous research behind it . He urged the audience that they should not postulate that all outpatient inductions are safe. He argued that Up to Date does not recommend it except in research settings and ACOG practice bulletin and leading textbook do not mention it. A review of literature found less than 10% of literature on this subject.

He quoted “What we all would agree with here, I assume, is that whatever we do with this procedure, we want to add as little, or ideally, no additional risk to the mother and the fetus, so we’ve got to have sufficient experience to really say that.”

In researching for the debate he only found two additional clinical trial to the one conducted by Dr. Sciscione. The total number of patients receiving outpatient balloon cervical ripening was only 141.

While adverse effects were rare, no consensus was reached on what constitutes unacceptable risk. 

The studies found that compared with placebo, PGE2 (vaginal or intracervical) and misoprostol (oral or vagina) are effective. But good benefits were documented with Foleys balloon catheter too.

He also commented on the difficulties faced by patients in transporting to and from hospitals and lack of monitoring at home.

In the end he stressed the need of having large randomized trial or meta-analysis to really exclude excess risk here and determine what works and what does not.

References:

http://www.acogdailynews.com/value-of-outpatient-cervical-ripening-debated/

When and How to Induce Labor in Nulliparous Women-- News from ACOG Annual Clinical and Scientific Meeting 2016.

Induction of labor is a major component of obstetrics practice with nearly one third of multiparous women   and 43 percent of nulliparous women undergoing induction.

Mary Catherine Tolcher, MD, MS, assistant professor of obstetrics, Mayo Clinic Rochester said “Induction of labor is likely to become more common with increasing maternal age, hypertensive disorders and obesity,” at Saturday afternoon Clinical Seminar at the conference.

The leading indications for induction of labor at the Mayo Clinic are late-term pregnancy, fetal indications, PROM, gestational hypertension and diabetes.

She further added that benefits of induced labor are clear, Induced labor avoids maternal and fetal risks of continuing pregnancy, avoids risks of late-term pregnancy, allows the timing of labor to be controlled in cases where delivery in a particular facility is appropriate and may be an alternative to cesarean delivery.

The risks are equally clear too, which means prolonged hospitalization before delivery, increased likelihood of more intrusive interventions, increased risk of postpartum hemorrhage and increased likelihood of cesarean delivery.

Answering the key question of whether induction increases the risks of cesarean section she said that it is like a lot of other things in medicine, and depends on your comparison group. 

Results based on retrospective cohort data show the following conclusions.

Depending upon studies the odds ratio for undergoing a cesarean delivery was somewhere between 1.9 and 3.5 when comparing spontaneous labor and induction. 

But compared to expectant management, induction does not seem to be associated with an increased risk of cesarean delivery. 

The first randomized control trial of induction vs expectant (ARRIVE TRIAL) management is currently recruiting participants and will be completing the data collection at the end of 2016.

Since the inception of induction of labor, many methods have been in use like mechanical ripening by Foleys catheter, pharmacological use of prostaglandins and oxytocin. These are either used alone or in combination with or without amniotomy.    

According to Dr. Tolcher, clinical trials have shown all of them to be effective. Cervical ripening is definitely more effective than oxytocin alone, while prostaglandins and Foleys catheter seems to have the same outcome.  Recent data reported at annual meeting of Society for Maternal-Fetal Medicine in 2016, concluded that time to delivery is shortened by using combination methods than using each of the method alone with no increase in cesarean section rates.

Amniotomy is also effective in augmenting the labor, but when early amniotomy (Cervix < 5 cm dilated) was compared to late amniotomy (Cervix > 5 cm dilated), the latter seemed more appropriate. Early amniotomy does results in shorter labor time but it comes with higher incidences of chorioamnionitis and increased fetal cord compression.

Dr. Tolcher also said that Mayo clinic has its own protocols for induction and the cases scheduled for induction in the coming week are reviewed in a staff meeting on Friday and Labor and Delivery nurse also has a significant say to put a stop to non-indicated cases.

Current indication for inductions include advanced maternal age, cholestasis, diabetes, fetal issues, hypertensive disorders, obesity, preterm premature rupture of membranes, prolonged pregnancy, prior stillbirth and unstable presentation. Depending on the indication, the pregnancy must be in week 37 and later.

Cervical ripening is the initial step, followed by oxytocin as needed and amniotomy at the discretion of physician. A failed induction is 24 hours of oxytocin or 18 hours of oxytocin plus rupture of membranes.

Before the decision for induction is taken, the physician should have a very good discussion with patient about the procedure, the expected time to delivery and slightly higher odds of having a cesarean delivery.

References:

http://www.acogdailynews.com/when-and-how-to-induce-labor-in-nulliparous-women/

http://www.acog.org/Womens-Health/Labor-Induction