When to make the diagnosis of failed induction of labor after Oxytocin and Rupture of membranes?

Clinical Pearls:

• In Nulliparous women 12 hours of Oxytocin and Rupture of membranes is optimum before diagnosing an unsuccessful induction. The neonates of women who remained in latent phase past 12 hours have increased rate of NICU admissions.
• In Multiparous women 15 hours of Oxytocin and Rupture of membranes is optimum before diagnosing an unsuccessful induction. The neonates of women who remained in latent phase past 15 hours have increased rate of NICU admissions.
• The longer women remained in latent phase with Oxytocin and Rupture of Membranes, the risk of maternal and neonatal complication increased.

According to CDC between 1990 and 2011 the rate for labor induction have more than doubled rising from 9.5% to 23.2%. About 762,000 induction of labor were performed making it one of the most commonly performed obstetric procedure in US.[1]

There is no accepted definition of “failed induction of labor”, although the ACOG in its statement to bring down the cesarean section rate does quote “cesarean deliveries for failed induction of labor in the latent phase can be avoided by... requiring that oxytocin be administered for at least 12–18 hours after membrane rupture before deeming the induction a failure.”[2] However this recommendation by ACOG is based on limited studies with very small study population. [3] In the two studies on which the recommendation is based 17- 60% of the women had vaginal delivery after still being in latent phase after 12 hours. [4] [5]

A Joint statement issued by Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, and American College of Obstetricians and Gynecologists Workshop quotes that “The diagnosis of failed induction should only be made after an adequate attempt. Failed induction is defined as failure to generate regular (eg, every 3 minutes) contractions and cervical change after at least 24 hours of oxytocin administration with artificial membrane rupture if feasible.”[6] But, with the latent phase extending long, maternal and neonatal safety concerns are constantly raised.

A recent retrospective cohort study published in Journal of Obstetrics and Gynecology compared neonatal and maternal outcome in relation to oxytocin induction and rupture of membranes before the active phase of labor (Cervical dilatation > 6 cm). This large study used the data from Consortiumon Safe Labor (CSL) which is a consortium of 12 clinical institutions providing data on labor and newborn to create a perinatal database with more than 200,000 deliveries. The de-identified database is than used for secondary data analysis to answer several obstetrics questions.

The study data included 9,763 nulliparous and 8,379 multiparous women, carrying singleton term pregnancies, with unfavorable cervix. In all these women labor was induced at 2 cm dilatation or less to 6 cm dilatation with rupture of membrane.  6 cm was taken as cut-off because women entered into active phase of labor once they crossed the 6 cm dilatation. No cervical ripening agent was used in the women included in the study.

The clinical outcomes evaluated included vaginal delivery rates, maternal and neonatal morbidity including NICU admissions. Women were assessed at fixed intervals of 6, 9, 12, 15, and 18 hours post oxytocin and rupture of membranes in regards to cervical dilatation, contraction, vaginal delivery or cesarean delivery. Time was marked zero hour when oxytocin and rupture of membrane both were present.

Hypertensive disorders of pregnancy were the most common indication for induction of labor in nulliparous (21.8%) and multiparous patients (10.7%) followed by post-date pregnancy.

At the end of 12 hours most of the nulliparous women have entered the active phase or have delivered with only 6.5% still in the latent phase, while at 15 hours only .6% multiparous women were still in the latent phase.

Eventually, out of this group 36.6% of the nulliparous and 50.0% of multiparous women had vaginal birth.  Those nulliparous women who still were in latent phase of labor at the end of 12 or 15 hours had high rates of maternal and neonatal complications. For multiparous patients who were still laboring at the end of 15 hours had increased maternal complications but the rate of NICU admission were not statistically significant.

The longer the patients remained in the latent phase with rupture of membranes and oxytocin, chances of vaginal delivery decreased proportionately and maternal and neonatal complications increased as time progressed. Maternal complications include chorioamnionitis, PPH and endometritis while neonatal complications include neonatal sepsis and NICU admissions.

The large cohort of patient’s data drawn from diverse population powered the study sufficiently to study a variety of outcomes including neonatal morbidity and NICU admission associated with longer duration of oxytocin and rupture of membranes. It also increased the generalizability of the study. Labor management is not standardized across the hospitals which may have led to cesarean deliveries in latent phase without waiting longer.

It was seen that the longer women remained in latent phase with Oxytocin and Rupture of Membranes, the risk of maternal and neonatal complication increased. Because of the retrospective nature of the data, diagnosis of failed induction cannot be made but 12 hours of Oxytocin and rupture of membranes in Nulliparous and 15 hours in Multiparous patient is a reasonable cutoff, because neonatal morbidity rises after that.

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[1] http://www.cdc.gov/nchs/fastats/obstetrical-procedures.htm

[2] Safe prevention of the primary cesarean delivery. Obstetric Care Consensus No. 1. American College of Obstetricians and Gynecologists. Obstet Gynecol 2014;123:693–711

[3] http://www.acog.org/Resources-And-Publications/Obstetric-Care-Consensus-Series/Safe-Prevention-of-the-Primary-Cesarean-Delivery

[4] Rouse DJ, Owen J, Hauth JC. Criteria for failed labor induction: prospective evaluation of a standard protocol. Obstet Gynecol 2000;96:671–7

[5] Simon CE, Grobman WA. When has an induction failed? Obstet Gynecol 2005;105:705–9

[6] http://journals.lww.com/greenjournal/Fulltext/2012/11000/Preventing_the_First_Cesarean_Delivery__Summary_of.26.aspx

Moderate intensity physical activity for an hour mitigates the risk of death associated with sedentary lifestyle: A Meta-analysis.

Clinical Pearls:

• Intense to moderate physical activity for 60-75 minutes’ can eliminate the effects of prolonged sitting (> 8 hours).
• This equals to brisk walking at 5.6 km/h or cycling for pleasure at 16 km/h.

The association of sedentary lifestyle and many chronic conditions and colorectal cancer is well known and physical inactivity is an important modifiable risk factors in the causation of many chronic condition.  Prolonged sitting is one of the important cause of premature mortality.

But, according to a Meta-analysis involving about a million people, intense to moderate physical activity for 60-75 minutes’ can undermine the effects of prolonged sitting. This study was published online in the Lancet on July 27, 2016.[1] Examples of physical activity were brisk walking at 5.6 km/h or cycling for pleasure at 16 km/h.

This is a second in the series of articles published on physical inactivity by Lancet, the first was published in 2012, sending a message that physical inactivity is a global pandemic killer-responsible for 5.3 million premature deaths worldwide. The number equals the deaths caused by smoking and twice the deaths caused by obesity.

This is the first harmonized meta-analysis that compares the relationship between all-cause mortality and sedentary life style and different levels of physical inactivity.

A systematic review of literature identified about 16 studies out of which 13 were identified by the researchers as providing data on sitting time and all-cause mortality.

The combined study data generated data on pool of 1,005,791 individuals from different countries, who were followed up for 2-18 years.

The study participants were divided into quartiles according to the time spent being physically active and ranged from less than 5 minutes/day to 60-75 minutes/day. The daily sitting and TV viewing time was also divided into 4 standardized protocol.

It was seen that those who very active (60-75 minutes/day), the amount of sitting time does not increase the mortality. But, the risk of death increases as the activity time decreases. WHO guidelines also recommends at least 150 minutes of physical activity per week, which is far less than what the study recommends.[2]

"A clear dose-response association was observed, with an almost curvilinear augmented risk for all-cause mortality with increased sitting time in combination with lower levels of activity," the researchers noted.

For the purpose of estimating the hazard ratio(HR), the most active individuals were used as the reference group. (HR=1).

People who exercised the least (less than 5 min/day) were at highest risk, even if they did not spend much time sitting (less than 4 h/day). In this group the hazard of premature death was 1.27. This was way higher than those group of individuals who were most active physically (60-75 min/day) but also spent more than 8 hours sitting (HR=1.04). This was very close to the referent group, which led the researchers to conclude that physical inactivity is the root cause of premature deaths, independent of the hours of sitting.

The findings of this study emphasized the importance of physical activity, even if you have a job that demands prolonged sitting.

The study also draws attention towards relationship with TV watching and premature death. Watching TV for more than 3 hours per day is associated with premature death regardless of physical activity except in the most active quartile. In this group the mortality was only increased if you watch more than 5 hours of TV. The benefit of physical activity is not very strong in people watching TV because of “residual confounding”. Dr. Ekelund points that perhaps these people have unhealthy life- style that include snacking or drinking that increases the risks.

Ekelund pointed out in a London press conference [3]  that the average amount of time adults in the United Kingdom spend watching TV is three hours and six minutes. “I don’t know if it’s too much to ask that maybe a little of those three hours be devoted to physical activity,” he said. The general rule of thumb, as Ekelund succinctly advised: “Sit less and move more, and the more the better.”

He also emphasized the message about "moving more," suggesting that people should walk as much as they can and that if they do need to sit for prolonged periods, they should break up those periods with short bursts of activity, such as walking for 5 minutes every hour.

The full Lancet podcast about the series can be heard here.

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[1] http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30370-1/fulltext

[2]  http://www.who.int/dietphysicalactivity/factsheet_recommendations/en/

[3] http://press.thelancet.com/PhysicalactivityMEDIA.mp3

Induction of labor does not hike the risk for Autism Spectrum disorders.

Clinical Pearls:

• Contrary to the findings of earlier study, Induction of labor does not increase the risk for development of Autism Spectrum disorders(ASD).

Autism Spectrum disorders(ASD) is a group of complex developmental disability that affects a person ability to interact and communicate socially. It includes several conditions that were earlier diagnosed separately and include autistic disorder, pervasive developmental disorder not otherwise specified (PDD-NOS), and Asperger syndrome.

According to CDC about 1% of world population have ASD. It is the fastest growing developmental disability in US and the current prevalence is 1 in 64 births and has increased 119.4 percent from 2000 (1 in 150) to 2010 (1 in 68).[1] An article published in JAMA Pediatric 2014 by Buescher et al. estimated that about 3.5 million people in US live with ASD.[2]

Numerous pregnancy related risk factors have been attributed in putting the children at high risk for ASD like children that were born to older parents,  were preterm or low birth weight, born with other chromosomal disorders like  Down syndrome, fragile X syndrome, tuberous sclerosis and  those delivered by cesarean section.

A study published in Annals of Epidemiology attributed three perinatal risk factors like being born too early, too small, and/or by Cesarean delivery to be responsible for 12-13% of ASD in children.[3]

Many other studies have examined the mother’s use of  serotonin uptake  inhibitors (SSRIs) and increasing use of ART as a causative factor for  sudden increase in prevalence of ASD.

Another large population based study published in JAMA pediatrics in October,2013 concluded that “Compared with children born to mothers who received neither labor induction nor augmentation, children born to mothers who were induced and augmented, induced only, or augmented only experienced increased odds of autism after controlling for potential confounders related to socioeconomic status, maternal health, pregnancy-related events and conditions, and birth year. The observed associations between labor induction/augmentation were particularly pronounced in male children.”[4]

This study sparked a widespread debate between physicians and researchers and the lead author of the study Dr. Gregory proposed the culprit to be oxytocin in induced or augmented labors, putting these children at high risk for ASD. After this controversy ACOG put out a committee opinion (597) in 2014 stating that “Current evidence does not support a conclusion that labor induction or augmentation causes autism spectrum disorder (ASD) in newborns, available evidence is inconsistent and does not demonstrate causation.”[5]

A recent study conducted by researchers at Harvard T.H. Chan School of public health in Boston and published in JAMA pediatrics online first on July 25, 2016 found no association between induction of labor and ASD. This large nationwide study performed in Sweden, followed up a cohort of 1,362,950 children born between 1992-2005. Out of which 1.6% (22077) children were diagnosed with ASD by ages 8 years through 21 years.  

In 11% of the mothers’ labor induction was done due to preeclampsia, gestational diabetes and chronic hypertension. After the statistical analysis, the study found an association between labor induction and ASD but when the analysis was performed between siblings and close relatives the association was not documented.

Siblings share many genetic, socioeconomic and maternal characteristics that may increase the risk for development of ASD, so if association is not documented when comparing with them, the association probably does not exist.

The finding of this large study suggests that if clinically indicated, decision to induce labor should not be withheld in fear of baby developing ASD. Not to induce the labor when indicated may have adverse neonatal consequences.

Dr. Bateman concludes "Overall, these findings should provide reassurance to women who are about to give birth, that having their labor induced will not increase their child's risk of developing autism spectrum disorders."

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[1] https://www.cdc.gov/ncbddd/autism/facts.html

[2] http://www.ncbi.nlm.nih.gov/pubmed/24911948

[3] Schieve LA, Tian LH, Baio J, Rankin K, Rosenberg D, Wiggins L, Maenner MJ, Yeargin-Allsopp M, Durkin M, Rice C, King L, Kirby RS, Wingate MS, Devine O. Annals of Epidemiology. January 2014. [epub ahead of print]

[4] Gregory SG, Anthopolos R, Osgood CE, Grotegut CA, Miranda M. Association of Autism With Induced or Augmented Childbirth in North Carolina Birth Record (1990-1998) and Education Research (1997-2007) Databases. JAMA Pediatr.2013;167(10):959-966. doi:10.1001/jamapediatrics.2013.2904.

[5] http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Obstetric-Practice/Labor-Induction-or-Augmentation-and-Autism