“Nature is a terrible obstetrician.” – Norwitz, quoted in Margulies 2016

“When nature does work, it cannot be improved. Technology does not enhance a natural process that is working. It can only mar or destroy it.” – Stewart, 1998

It seemed like all anyone in the birth world could talk about last week was the ARRIVE trial (A Randomized Trial of Induction Versus Expectant Management) that was shared as an abstract at the Society for Maternal-Fetal Medicine conference.  The big takeaway point seemed to be that inducing healthy, low-risk people at 39 weeks resulted in a lower cesarean rate than waiting for the pregnancy to continue and spontaneous labor.  The ARRIVE trial has been ongoing and many people have been waiting for its publication.  Author and evidence-based maternity care expert Henci Goer, a frequent Science & Sensibility contributor, has done a deep dive on the abstract (the only published material from the study available at this time) and shares with S&S readers her careful examination of the study's conclusions. What are you hearing about the ARRIVE trial in your professional community? - Sharon Muza, Community Manager, Science & Sensibility.

Introduction 

Exploding across the internet is news of a study that should give pause to anyone who champions physiologic care in childbirth. The ARRIVE study claims to overturn the dogma that electively inducing 1st-time mothers increases the likelihood of cesarean delivery and adverse outcomes, finding, in fact, reduced cesarean rates and improved perinatal and maternal outcomes with induction. Since it’s a large (6106 women), multicenter (41 hospitals) randomized controlled trial, its conclusions have enormous potential to impact birth management. Is this study incontrovertible evidence for medical- model management or spin doctoring by real doctors? Let’s start with what we know about the study and then pull back to look at the overall elective induction landscape.

What Does the Study Say?

According to the study abstract, which is all we have at present, investigators randomly allocated “low- risk” 1st-time mothers in week 38 either to induction between 39 wk 0 days and 39 wk 4 days or to “forgo elective delivery” before 40 wk 5 days. The management plan was adhered to in 94% of the intervention group and 95% of the control group. Outcomes did not differ by race/ethnicity, maternal age > 34 yr, BMI > 30, or Bishop score < 5 at time of allocation.

Women in the intervention group (the induction group) delivered significantly (meaning the difference is unlikely to be due to chance) earlier (39 wk 3 days; interquartile range 39 wk 1 day – 39 wk 6 days) than the control group (40 wk 0 days; interquartile range 39 wk 3 days – 40 wk 7 days), although, as you can see, there was considerable overlap. Women in the intervention group were significantly less likely to deliver by cesarean (19% vs. 22%) and to experience preeclampsia/gestational hypertension (9% vs. 14%).

Babies were significantly less likely to require respiratory support (3% vs. 4%). The text also states that babies were less likely to experience the primary perinatal outcome (5% vs. 4%), a composite of adverse events, but omits that this difference didn’t achieve statistical significance, a fact that must be gleaned from the accompanying table. The composite consisted of perinatal death, respiratory support, Apgar ≤ 3 at 5 min, hypoxic ischemic encephalopathy, seizures, infection, meconium aspiration syndrome, birth trauma, intracranial or subgaleal hemorrhage, and hypotension requiring pressor support. All but two of the adverse outcomes making up the composite occurred at rates of 6 per 1000 or less. The two exceeding that rate were meconium aspiration syndrome at 6 vs. 9 per 1000 and need for respiratory support at 3.0 vs. 4.2 per 100.

It isn’t possible to evaluate a study properly from its abstract alone, but even the abstract raises red flags:

Did clinicians refrain from electively delivering control group women before 40 wk 5 days? The interquartile range is the middle 50% of the group. Among control-group women, the middle 50% were delivered by 40 wk 7 days, which means 75% of the group overall had their babies by that day. A study on median pregnancy duration (50% delivered before and 50% after) in uncomplicated pregnancy in 1st-time mothers reaching term reported a median length of 41 wk 1 day (Mittendorf 1990). In the ARRIVE trial, 75%, not 50%, of control-group women had delivered by a day earlier than that, which raises the question of what percentage of control- group women were induced? Observational studies consistently find that inducing labor in healthy 1st-time mothers roughly doubles their odds of cesarean, amounting to an absolute difference of 3 to 31 more women per 100, even after adjusting for factors such as birth weight and gestational age and despite treatment to ripen the cervix (Baud 2013; Boulvain 2001; Cammu 2002; Davey 2016; Dublin 2000; Ehrenthal 2010; Glantz 2005; Jaquemyn 2012; Le Ray 2007; Luthy 2004; Macer 1992; Maslow 2000; Seyb 1999; Vahratian 2005; Van Gemmund 2003; Vardo 2011; Vrouenaets 2005; Yeast 1999). If, as seems likely, sizeable percentages of control- group women were being induced, this would have diminished differences between them and the intervention group.

Why was the elective induction threshold set at 40 wk 5 days rather than 41 wk 0 days? Even if 41 weeks has become the new 42, why weren’t control-group women given the full 41 weeks? To repeat, if inducing labor increases the risk of cesarean, then control-group women were handicapped by not having an extra two days to start labor on their own.

Was the population actually low risk? The abstract tells us that 14% of control-group women had preeclampsia or gestational hypertension as did 9% of women in the intervention group. But these were all “low-risk” women at the time of group allocation in week 38. It seems extremely unlikely that 9 women per 100 developed new hypertension in the following week and an additional 5 per hundred did so in the ensuing days after that, and, in fact, a study of 31,000 U.S. 1st-time mothers found that only 5% of women developed hypertension with ongoing pregnancy beginning at week 39 (Bailit 2015). If women in the ARRIVE trial could have medical indications for induction at trial entry, then was the ARRIVE trial truly studying elective induction?

Perhaps there is another explanation for 1 in 7 control-group women being diagnosed with hypertension: “You can always find a reason to do what you want to do.” Clark et al. (2009) write that among women having planned delivery for hypertension, in only 3 of 27 facilities was the mean admission systolic pressure > 145 mm Hg, and in only 1 was the mean diastolic pressure > 90 mm Hg. If control-group women were being labeled hypertensive to justify inducing them, it calls into question the trustworthiness of the data.

Could control-group management have contributed to their excess risk of cesarean? It’s a safe bet that control-group women underwent antenatal fetal surveillance testing. Fetal surveillance testing does a poor job of discriminating fetuses at risk (Grivell 2015; Lalor 2009). Almost all positive tests will be false positives, but they will lead to inducing labor, and, what’s more, to inducing labor under the worst circumstances: with a nervous practitioner ready to call for a cesarean at the slightest deviation from normal.

In short, control-group women weren’t playing on a level playing field, and a case can be made that investigators were interpreting the data to fit their pre-conceived notions. But we have broader issues to consider: the trial’s findings apparently support routinely inducing labor at 39 weeks. This raises two more questions:

Would we expect to see the same results if elective induction of 1st-time mothers at 39 weeks became widespread? The California Maternal Quality Care Collaborative (CMQCC) has published a commentary on the ARRIVE trial questioning whether trial results can be generalized. The commentary points out that cesarean rates in low-risk 1st-time mothers undergoing induction in California’s 240 hospitals averages 32% and ranges as high as 60%. CMQCC attributes the low rate in induced women in the ARRIVE trial to using a common definition of failed induction: “Cesarean delivery should not be undertaken during the latent phase prior to at least 15 hours after rupture of membranes have occurred with concurrent oxytocin administration,” at which point the decision to continue labor was individualized. Active phase was defined as beginning at 6 cm dilation, and ACOG/SMFM guidelines were followed for diagnosing labor progress and descent disorders in active labor and second stage. Failure to adhere to the trial’s protocol would surely result in substantially increasing cesarean rates if elective induction of 1st-time mothers became common.

Does a 19% cesarean rate in healthy 1st-time mothers represent optimal care? Home birth and birth center studies of 1st-time mothers qualified for out-of-hospital birth report cesarean rates ranging from 8% to 13% (Bailey 2017; Birthplace in England 2011; Bovbjerg 2017; Hutton 2015; Janssen 2009; Johnson 2005; Jolles 2017; van der Hulst 2004). Physiologic care, therefore, would have resulted in anywhere from 6 to 11 fewer healthy 1st-time mothers per 100 having cesarean surgery than in the intervention arm of the ARRIVE trial.

What’s Wrong with This Picture?

The ARRIVE trial is the capstone of a decades-long effort to demonstrate that awaiting labor has no benefits and that inducing labor doesn’t increase cesareans or adverse outcomes and, in fact, that the reverse is true. The argument runs like this: We now know that waiting for labor to start on its own has no advantages over inducing labor, so why risk the baby outgrowing its mother’s pelvis or something going wrong with the baby, which can happen without warning even in healthy women? Is that argument sound?

Are there benefits to waiting for labor to start on its own? Yes. Inducing labor disrupts a complex set of hormonal interactions that prepare the baby for life in the outside world, orchestrate the birth process, help mother and baby cope with the stress of labor, promote successful breastfeeding, and foster attachment between mother and child (Buckley 2015).

How likely are babies to outgrow their mothers’ ability to birth them with the ongoing pregnancy at term? Not very. The percentage of macrosomic babies (≥ 4000 g) changes very little over the last few weeks of pregnancy. A study reported that the percentage of macrosomic babies went from 11% in week 38 to 14% in week 40—and this data comes from a population exclusively of high BMI women, who are more likely to have bigger babies than the population at large (Lee 2016).

More importantly, the inability to birth larger babies largely originates in doctors’ heads, not women’s bodies. Every study that has ever looked at the issue has found that when doctors suspect the baby is going to be big, the odds of cesarean delivery go up markedly regardless of whether the baby is actually on the large side (Blackwell 2009; Levine 1992; Melamed 2010; Parry 2000; Peleg 2014; Sadeh- Mestechkin 2008; Scifres 2015; Weeks 1995; Weiner 2002). The reverse is also true: unsuspected big babies have much lower cesarean rates than babies correctly suspected.

The fear that the baby will be too big for the woman to deliver becomes a self-fulfilling prophecy. It leads to inducing labor to prevent the baby growing even bigger, and induced labors are more likely to end in cesarean. It leads to more diagnoses of failure to progress (Blackwell 2009) and failed induction, especially in early labor, before this diagnosis can legitimately be made (Weeks 1995). Typical medical management practices and policies also load the dice against vaginal birth. Women, in general, are often held to rigid expectations of how rapidly they should progress. Policies that inhibit mobility such as continuous fetal monitoring, routine IVs, encouragement to have epidurals, and requiring women to push and give birth on their backs prevent women from finding activities and positions that promote progress, create more space in the pelvis, and get gravity to work for instead of against them. While this handicaps all women, it hits women with bigger babies the hardest. Finally, requiring women to birth on their backs increases the potential for shoulder dystocia, and when one occurs, doctors are likely to become even more anxious about vaginal birth with a suspected big baby the next time.

How likely are healthy 1st-time mothers to develop a complication with an ongoing pregnancy at term? Not very. As we saw above, Bailit et al. (2015) reported that 5% of healthy 1st-time mothers developed hypertension with continuing pregnancy beginning at 39 weeks. That same study found that even fewer (4%) would develop oligohydramnios (reduced amniotic fluid volume), and only 3% of babies would test positive for non-reassuring fetal status. What is more, these numbers are likely to be high. As we also saw, one way to get around hospital restrictions on elective induction is to code women with mildly elevated blood pressure as “hypertensive” (Clark 2009), and we saw that almost all positive fetal testing results are false-positives, and the baby is actually fine (Grivell 2012; Lalor 2009). In addition, low amniotic fluid volume in the absence of other symptoms predicts adverse outcomes poorly (Morris 2014), which means isolated oligohydramnios isn’t of much concern. In any case, that some women develop complications after reaching term doesn’t argue for preventive induction, only for induction when a problem arises.

How likely is stillbirth with an ongoing pregnancy at term? Not very.

*Calculated by dividing the number of fetal deaths at a given gestational age by the number of live births and fetal deaths at or beyond that gestational age.

The odds of fetal death with ongoing pregnancy in any given week at term are very low, and the change from week to week is clinically insignificant until 42 weeks, when the odds are still quite low (Alimena 2017 [U.S.]; MacDorman 2015 [U.S.]; Morken 2014 [Norway]; Weiss 2014 [Germany]). Moreover, the risk of fetal death varies according to factors such as race, marital status, and extremes of maternal age (Flenady 2011; Getahun 2007; MacDorman 2015; Reddy 2010), characteristics that may be markers for other factors such as poverty, substandard care, or prior cesarean (Moraitis 2015). If none of these factors apply to an individual woman, then her risk is at the low end or lower than these numbers. While the German and Norwegian database analyses excluded some risk factors that would increase the risk of stillbirth, they didn’t exclude all of them, and the U.S. statistics didn’t exclude any of them, including whether the baby had genetic abnormalities or congenital malformations. In the sole analysis of low-risk U.S. women, investigators reported rates 10 times higher than the other three studies (Alimena 2017), which suggests that they misplaced the decimal points. The study’s authors didn’t respond to a query about this possibility. If there was a typo, the risk of stillbirth is very low indeed in healthy women carrying healthy babies.

Does inducing labor decrease cesarean rates? As we saw above, observational studies consistently find that elective induction increases the likelihood of cesarean, which means the increased risk is intrinsic to induction and not attributable to its indication. Induction proponents, however, argue that the question isn’t whether women do better with induced or spontaneous labors but whether women reaching term are better off with induction compared with continuing the pregnancy to some later date (Bailit 2015; Cheng 2012; Darney 2013; Gibson 2014; Lee 2016).

*9% vs. 13% macrosomic babies in wk 39; 14% in both groups in wk 40

Studies examining induction in any given week vs. expectant management beyond that week—which could mean either spontaneous labor onset or induction beyond that week—generally report fewer cesareans with induction. However, the wide variation in cesarean rates makes clear that management style is responsible for those results, not factors intrinsic to study participants or advancing gestation at term. For example, Rasmussen & Rasmussen (2011), a study with low cesarean rates overall, found that, contrary to the others, induction increased cesareans. Cheng et al. (2012) and Rasmussen & Rasmussen (2011), both studies of women at 39 weeks at low risk for complications, got very different cesarean rates despite having participants with similar characteristics. Darney et al. (2013), a study that included women with medical complications such as high blood pressure, reported cesarean rates similar to Cheng et al. (2012), a study of low-risk women only, and Lee et al. (2016), a study of high BMI women, reported cesarean rates ranging from 30% to 38%, although low and similar percentages of women had macrosomic babies, which is the big concern (pun intended) with high BMI women.

Furthermore, the study design is flawed. Glantz (2010) pointed out that “induction that week vs. expectant management beyond that week” leaves out the women who gave birth during that week. He took the cesarean rates week by week according to whether women were induced or began labor on their own from a New York database. He then calculated cesarean rates according to “induction that week vs. expectant management beyond that week” and compared the numbers with “induction that week vs. expectant management in or beyond that week.” After adjusting for risk factors, he found that when women giving birth during that week were included, women were more, not less, likely to have a cesarean with induction than expectant management. When Darney (2013) recalculated their data using the “in or beyond” percentages, they didn’t give the new numbers, but they reported that rates no longer favored induction. Bailit et al. (2015) analyzed data using the “in or beyond” calculation and found similar rates with induction vs. expectant management in week 39 (26% vs. 24%) and a 30%- increased likelihood of cesarean (OR 1.3) with induction in week 40 (34% vs. 27%), which, I should add, didn’t stop them from recommending routine induction at 39 weeks.

Is advancing gestational age the culprit in rising cesarean rates? No. Medical model management is to blame. How do we know?

• The largest trial that looked at routinely inducing women at 41 weeks, which at the time was considered an elective induction, reported that 26% of 1st-time mothers beginning labor on their own had cesareans (Hannah 1996). These were all healthy women carrying one, head-down, healthy baby who were admitted in labor. In other words, they had not one reason at hospital admission that would predict the possible need for a cesarean.

  Conclusion: If you find extraordinarily high cesarean rates in ultra low-risk women, then something is wrong with labor management, not the women.

• Two large U.S. studies reported that the cesarean rate was stable in healthy 1st-time mothers in weeks 37 through 40 but then leaped upward. One reported a rise from 23% in week 40 to 30% in week 41, a percent increase of 30% (Cheng 2008), and a second reported a rise from 15% to 22% between the two weeks, an astonishing 46% increase, and another leap from 22% in week 41 to 31% at 42 or more weeks (Caughey 2007), this time a 41% increase.

Conclusion: If you see an extraordinary increase in cesarean rate over a few days in healthy women, then what changed was care provider perception and management, not the woman’s health status or the size of her baby.

• A Swiss study reported similar cesarean rates in 1st-time mothers induced for medical reasons compared with women induced electively (27% medical reason vs. 29% elective) (Baud 2013), and an Australian study found substantially lower cesarean rates in women induced for medical reasons than women induced electively (18% medical reason vs. 26% elective) (Grivell 2012). You would expect that women being induced for medical problems would have higher cesarean rates than healthy women undergoing induction for non-medical reasons.

Conclusion: If women induced for medical reasons have similar or lower cesarean rates than women induced for nonmedical reasons, then we’re looking at something to do with the care provider, not the woman.

Does labor induction have harms in addition to increasing cesarean rates? Yes. Induction deprives women of the psychological benefits of internally produced oxytocin (Buckley 2015), and it implants that women’s bodies are “lemons,” incapable of safely birthing their babies on their own timetables, which could lead to feelings of inadequacy or failure. Induction also carries the potential of life-threatening complications. These include:

• uterine rupture in women with an unscarred uterus and no predisposing factors (Al Zirqi 2009; Azem 1993; Bennett 1997; De Abajo 2004; Litwin 2003; Magann 2005; Mazzone 2006; Miller 1997; Porreco 2009; Sachs 2005; Sweeten 1995; Wagner 2004; Walsh 2007);

• severe hemorrhage and idiopathic disseminated intravascular coagulation (Al Zirqi 2009; De Abajo 2004; Helman 2015; Khireddine 2013; Magann 2005), a dire potential consequence of severe bleeding;

• anaphylactic syndrome, also known as amniotic fluid embolism (Abenhaim 2008; Knight 2010; Kramer 2006; Stolk 2012);

• umbilical cord prolapse, which undoubtedly occurs because induction frequently involves rupturing membranes, (Boyle 2005; Kahana 2004; MacDorman 2002; Roberts 1997); and cerebral palsy (Elkamil 2011).

Severe adverse outcomes are rare, but they must be taken into account when considering intervening in a healthy pregnancy that is proceeding normally.

Can we disprove the theory that routine induction produces better newborn outcomes with lower cesarean rates? We’ve dismantled the assumptions behind the theory that routine induction improves newborn outcomes without increasing the cesarean rate, but we also have evidence contradicting it. If the theory were correct, then a high induction rate should correlate with better newborn outcomes and fewer cesareans, but it doesn’t. A multi-hospital analysis found no correlation among induction rates, cesarean rates, and adverse newborn outcomes (Glantz 2011). We also have a birth center study and a home birth study reporting low induction rates (4% and 12%) and low cesarean rates (9% and 14%) in 1st-time mothers (Jolles 2017; van der Hulst 2004).

Conclusion: If physiologic care achieves low induction rates, low cesarean rates, and equivalent outcomes, then we’ve disproved the theory that routine induction is a beneficial strategy.

The Take-Away

Randomized controlled trials are based on the premise that results depend on the interaction between factors intrinsic to the participants and the treatment, in this case, that women change over a few additional days of gestation in ways that heighten the odds of cesarean and adverse newborn outcomes and that labor induction reduces those odds. But the trial wasn’t measuring anything to do with the women or the treatment. The trial was measuring care-provider propensity to perform a cesarean--or induce labor, since "expectant management" doesn't preclude that. What is more, women in both groups were managed in ways that obstruct their ability to achieve spontaneous, uncomplicated, vaginal birth. This means the trial is nothing more than a frying pan vs. fire comparison with the not surprising finding that in the hands of medical-model practitioners, the frying pan comes out slightly ahead of the fire. As Sarah Wickham (2014) put it:

"We might consider that [the research] teaches us that awaiting spontaneous labor while in the care of an obstetrician may increase the risk of being advised to have a caesarean section, which may or may not have been genuinely warranted."

To circle back to the quotation that opened this commentary, Mother Nature is, indeed, a terrible obstetrician, but that’s not a bad thing because she’s a great midwife.

Note:

Here are some public statements from maternal-infant organizations after this abstract was released:

American College of Nurse-Midwives – ACNM Recommends No Change No Change in Practice in Response to Induction Study

California Maternal Quality Care Collaborative – Comments on the ARRIVE Trial

Rebecca Dekker, Evidence Based Birth - Facebook Live Video examing this study

National Accreta Foundation - New Research on Induction Creates Controversy

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About Henci Goer

Henci Goer

Henci Goer, award-winning medical writer, and internationally known speaker, is an acknowledged expert on evidence-based maternity care. Her first book, Obstetric Myths Versus Research Realities, was a valued resource for childbirth professionals. Its successor, Optimal Care in Childbirth: The Case for a Physiologic Approach, won the American College of Nurse-Midwives “Best Book of the Year” award. Goer has also written The Thinking Woman's Guide to a Better Birth, which gives pregnant women access to the research evidence, as well as consumer education pamphlets and articles for trade, consumer, and academic periodicals; and she posts regularly on Lamaze International’s Science & Sensibility. Goer is founder and director of Childbirth U, a website offering narrated slide lectures to help pregnant women make informed decisions and obtain optimal care for themselves and their babies.