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Traditionally nonmedically indicated induction of labor has been thought to increase cesarean delivery and thus maternal complications, especially in nulliparous patients.1 However, many of the studies that have led to this conclusion have compared women who undergo induction with those in spontaneous labor.2, 3 and 4 Unfortunately, spontaneous labor is not the actual alternative to induction that is available to physicians, and the appropriate comparison group should be composed of women who undergo expectant treatment.5

 

Previous studies that have compared expectant management with nonmedically indicated induction of labor have used administrative data or have been from single centers.5, 6 and 7 The coding of labor induction indication is known to be inaccurate within administrative data,8 and 9 which makes these data sets suboptimal for these types of studies. Single-center studies have been hampered by a sample size that is either too small to detect meaningful differences or a time frame that is so long that relevance to contemporary practice is uncertain.

 

The Assessment of Perinatal Excellence (APEX) study, which was conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, used direct chart abstraction by trained research personnel to collect information on intrapartum care from 25 geographically dispersed hospitals. This database provides a resource that can provide the information necessary to help evaluate the consequence of nonmedically indicated induction. The present study is a secondary analysis of the APEX data that compares maternal and neonatal outcomes for nulliparous women who undergo nonmedically indicated induction of labor with those of nulliparous women who are expectantly treated.

 

Methods

From 2008-2011, we assembled a cohort of women and their neonates who were born in any of the 25 hospitals in the Maternal-Fetal Medicine Units Network. This APEX study was designed to develop quality measures for intrapartum obstetric care. The APEX study was approved by the institutional review board at each participating institution under a waiver of informed consent. This article is a planned secondary analysis of the data that were collected during APEX.

 

A full description of the methods of data collection has been described previously.10 In short, any patient who delivered at a hospital, was at least 23 weeks of gestation, and had a live fetus on admission was included. Data were collected on randomly selected days, chosen by computer-generated random selection, that occurred over a 3-year period (March 2008 to February 2011). The medical records for all eligible women and babies were abstracted by trained and certified research personnel and entered into a web-based data entry system. Data that were recorded included demographic characteristics, details of the medical and obstetric history, information about intrapartum and postpartum events, and maternal and neonatal outcomes. Maternal data were collected until discharge, and neonatal data were collected up until discharge or until 120 days of age, whichever came first.

 

The present analysis includes nulliparous women with singleton, vertex, nonanomalous gestations who delivered from 38 0/7 to 41 6/7 weeks. We excluded women who delivered at >41 6/7 weeks of gestation because postdated pregnancies, by definition, is an indication for induction. Additionally, women in our analysis did not have a scheduled nonmedically indicated cesarean delivery. Additionally, they did not have any of the following problems: pregestational or gestational diabetes mellitus, placenta accreta, placenta previa, placental abruption, use of anticoagulation, previous myomectomy, cocaine/methamphetamine use, chronic hypertension, or preeclampsia diagnosed at <38 weeks of gestation. This was done to ensure that we had a low-risk cohort that was eligible for a nonmedically indicated induction as opposed to an indicated induction. Women were classified as having had a nonmedically indicated induction if they were coded as having had an elective induction or if an induction was performed without any other medical indication apparent in the chart. The study group assignment to nonmedically indicated vs expectantly treated was assigned after the entire data set was collected.

 

Maternal outcomes that were chosen a priori were postpartum hemorrhage, third- and fourth-degree lacerations, peripartum infection, mode of delivery, time from admission to delivery, and delivery to discharge. Neonatal outcomes chosen a priori were neonatal intensive care unit (NICU) admission, hyperbilirubinemia that required treatment, an adverse respiratory outcome composite (respiratory distress syndrome, continuous positive airway pressure, or ventilator support started within 24 hours of birth on ≥1 days delivery), and an adverse neonatal outcome composite (5-minute Apgar score <4, skeletal fracture other than of the clavicle, facial nerve palsy, brachial plexus palsy, subgaleal hemorrhage, ventilator support within 24 hours on ≥2 days, hypoxic ischemic encephalopathy, stillbirth after hospital admission, or neonatal death).

 

Maternal and neonatal outcomes for women who underwent nonmedically indicated induction within each week of gestation were compared with those of women who reached that week and were treated expectantly (ie, they did not undergo a nonmedically indicated induction). For example, women who underwent a nonmedically indicated induction at 38 weeks of gestation were compared with those who did not undergo a nonmedically indicated induction at 38 weeks of gestation and thus were expectantly treated from gestational week 38. Women in the expectantly treated group could go on to go into labor or to have an indication for delivery. Women who had an indication for induction and were delivered while in the expectant treatment group remained in the expectant treatment group. Multivariable regression was used to adjust for hospital, maternal age, race/ethnicity, body mass index, cigarette use, and insurance status. Odds ratios, adjusted means, and 95% confidence intervals are presented. All tests were 2-tailed, and a probability value of < .05 was used to define statistical significance. No imputation for missing data was performed. Analyses were performed with SAS software (SAS Institute Inc, Cary, NC).

 

Results

Data were collected from 115,502 women, of whom 31,169 women met our inclusion criteria. Most of the eligible women were in their twenties, were non-Hispanic white, and were nonsmokers. Most women had a body mass index of >25 kg/m2. Women who underwent nonmedically indicated induction were more likely to have private insurance, be of older maternal age, and be obese (Table 1).

 

 

Neonatal complications were either less frequent or not different in association with nonmedically indicated induction (Table 2, Table 3 and Table 4). In particular, NICU admission (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.47–0.93) and the respiratory composite (OR, 0.62; 95% CI, 0.41–0.94) were lower among women who underwent nonmedically indicated induction at 39 and at 40 weeks of gestation, respectively.

 

 

Peripartum infections were less frequent in association with nonmedically indicated induction at 38 and 39 weeks of gestation. In addition, those women who underwent nonmedically indicated induction at 39 weeks of gestation were less likely to have a third- and fourth-degree laceration. Nonmedically indicated induction was associated with a significantly higher frequency of cesarean delivery at 38 and 40 weeks of gestation, with an odds ratio of 1.50 (95% CI, 1.08–2.08) and 1.30 (95% CI, 1.15–1.46), respectively, but was not associated with an increased frequency of cesarean delivery at 39 weeks of gestation. Admission-to-delivery time was longer for women who underwent nonmedically indicated induction by approximately 3-4 hours, but delivery-to-discharge time was no different between the groups.

 

Table 5 shows the reasons for delivery in the expectantly treated group. Spontaneous labor occurred in most cases; postdates (≥41 0/7 weeks of gestation), preeclampsia, oligohydramnios, nonreassuring fetal status, or intrauterine growth restriction were the most common reasons for delivery.

 

 

Comment

Among our cohort of low-risk nulliparous women, those who had nonmedically indicated induction were less likely to have several maternal and neonatal complications compared with those who were expectantly treated. In addition, there appeared to be no difference in the chance of cesarean delivery when nonmedically indicated induction was performed at 39 weeks of gestation, although the chance of cesarean delivery was statistically higher when the nonmedically indicated induction was performed at either 38 or 40 weeks of gestation. The differences in maternal outcomes are clinically significantly different as well as statistically significant (for example, a difference of 2.4-10.6% for maternal infection at 38 weeks of gestation and 5.8-11.1% for maternal infection at 39 weeks of gestation).

 

Our data help contribute to the understanding of the consequences that are related to nonmedically indicated induction in nulliparous women. Previous studies that have documented an increase in cesarean delivery with labor induction largely have compared women who underwent labor induction with those in spontaneous labor. Yet, when women who underwent labor induction have been compared with women who underwent the actual clinical alternative (that is, expectant treatment) that increase has not been documented, even for women with an unfavorable cervix.11, 12 and 13 Our results support this finding for women at 39 weeks of gestation but not at 38 and 40 weeks of gestation. Studies have also suggested perinatal benefit from labor induction with regard to meconium aspiration syndrome and perinatal death and improvement in outcomes when induction was done for hypertension/preeclampsia.14, 15 and 16 Our work supports and extends the evidence for perinatal benefit with regard to respiratory morbidity and NICU admission.

 

This study did not examine outcomes at <38 weeks of gestation because there were so few examples of nonmedically indicated induction before this time. Furthermore, previous studies have examined neonatal outcomes17 and 18 and demonstrated that perinatal outcomes are worse at <39 weeks of gestation. Nothing in this study would call into question the current recommendations to avoid nonmedically indicated induction deliveries at <39 weeks of gestation. We did not examine stillbirths because a live fetus on arrival was part of the entry criteria for the study; therefore, we did not have adequate data to study stillbirths. The lack of information about stillbirths would make expectant management seem to have fewer risks than it does in reality. We did not account for Bishop score because it was not collected in the parent study for women who underwent expectant treatment. The lack of Bishop score data could bias the study towards making non-medically indicated inductions seem more advantageous because this group may have had more women with favorable cervixes than the expectant treatment group.

 

Although administrative data have the advantage of capturing a large number of hospitals and subjects for analysis, it has the disadvantage of lacking sensitivity and specificity when it comes to determining nonmedically indicated induction accurately.8 and 9 The quality of the data that were used in our study is high because the data were abstracted by trained personnel and because the data entry was checked by edits and audits. In the context of observational studies, cohort analyses that use high-quality data will provide the best possible answer regarding the consequences of nonmedically indicated induction. Nevertheless, this study and other observational studies before it cannot eliminate the possibility of bias and unmeasured confounding. The suggestion, however, that nonmedically indicated induction may not be associated with worse perinatal outcomes and may improve maternal outcomes underscores the need for a randomized trial.19

 

Acknowledgments

The authors thank the following subcommittee members who participated in protocol development and coordination between clinical research centers (Cynthia Milluzzi, RN; Joan Moss, RNC, MSN), protocol/data management and statistical analysis (Elizabeth Thom, PhD; Madeline M. Rice, PhD), and protocol development and oversight (Catherine Y. Spong, MD; Brian M. Mercer, MD).

 

Appendix

The other members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network are listed below:

 

Case Western Reserve University–MetroHealth Medical Center, Cleveland, OH: B. Mercer, C. Milluzzi, W. Dalton, T. Dotson, P. McDonald, C. Brezine, A. McGrail; Northwestern University, Chicago, IL: G. Mallett, M. Ramos-Brinson, A. Roy, L. Stein, P. Campbell, C. Collins, N. Jackson, M. Dinsmoor (NorthShore University HealthSystem), J. Senka (NorthShore University HealthSystem), K. Paychek (NorthShore University HealthSystem), A. Peaceman; Columbia University, New York, NY: M. Talucci, M. Zylfijaj, Z. Reid (Drexel University), R. Leed (Drexel University), J. Benson (Christiana H.), S. Forester (Christiana Hospital), C. Kitto (Christiana Hospital), S. Davis (St. Peter’s University Hospital), M. Falk (St. Peter’s University Hospital), C. Perez (St. Peter’s University Hospital); University of Utah Health Sciences Center, Salt Lake City, UT: K. Hill, A. Sowles, J. Postma (Latter Day Saints Hospital), S. Alexander (Latter Day Saints Hospital), G. Andersen (Latter Day Saints Hospital), V. Scott (McKay-Dee Hospital), V. Morby (McKay-Dee Hospital), K. Jolley (Utah Valley Regional Medical Center), J. Miller (Utah Valley Regional Medical Center), B. Berg (Utah Valley Regional Medical Center); University of North Carolina at Chapel Hill, Chapel Hill, NC: J. Thorp, K. Dorman, J. Mitchell, E. Kaluta, K. Clark (WakeMed Health and Hospitals), K. Spicer (WakeMed Health and Hospitals), S. Timlin (Rex), K. Wilson (Rex Hospital); University of Texas Southwestern Medical Center, Dallas, TX: L. Moseley, M. Santillan, J. Price, K. Buentipo, V. Bludau, T. Thomas, L. Fay, C. Melton, J. Kingsbery, R. Benezue; University of Pittsburgh, Pittsburgh, PA: H. Simhan, M. Bickus, D. Fischer, T. Kamon (deceased), D. DeAngelis; The Ohio State University, Columbus, OH: P. Shubert (St. Ann’s Hospital), C. Latimer, L. Guzzo (St. Ann’s Hospital), F. Johnson, L. Gerwig (St. Ann’s Hospital), S. Fyffe, D. Loux (St. Ann’s Hospital), S. Frantz, D. Cline, S. Wylie, J. Iams; University of Alabama at Birmingham, Birmingham, AL: M. Wallace, A. Northen, J. Grant, C. Colquitt; University of Texas Medical Branch, Galveston, TX: J. Moss, A. Salazar, A. Acosta, G. Hankins; Wayne State University, Detroit, MI: N. Hauff, L. Palmer, P. Lockhart, D. Driscoll, L. Wynn, C. Sudz, D. Dengate, C. Girard, S. Field; Brown University, Providence, RI: P. Breault, F. Smith, N. Annunziata, D. Allard, J. Silva, M. Gamage, J. Hunt, J. Tillinghast, N. Corcoran, M. Jimenez; The University of Texas Health Science Center at Houston-Children’s Memorial Hermann Hospital, Houston, TX: F. Ortiz, P. Givens, B. Rech, C. Moran, M. Hutchinson, Z. Spears, C. Carreno, B. Heaps, G. Zamora; Oregon Health & Science University, Portland, OR: J. Seguin, M. Rincon, J. Snyder, C. Farrar, E. Lairson, C. Bonino, W. Smith (Kaiser Permanente), K. Beach (Kaiser Permanente), S. Van Dyke (Kaiser Permanente), S. Butcher (Kaiser Permanente); The George Washington University Biostatistics Center, Washington, DC: E. Thom, M. Rice, P. McGee, V. Momirova, R. Palugod, B. Reamer, M. Larsen, T. Williams; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD: C. Spong, S. Tolivaisa.