Original Research
Maternal and Neonatal Outcomes in Indicated Preterm Births Based on the Intended Mode of Delivery Spencer G. Kuper, MD, Rachel A. Sievert, MD, Robin Steele, Alan T. Tita, MD, PhD, and Lorie M. Harper, MD, MSCI OBJECTIVE: To compare maternal and neonatal outcomes in women who underwent induction of labor or planned cesarean delivery in indicated preterm births before 34 weeks of gestation. METHODS: We conducted a retrospective cohort study of all indicated singleton preterm births (23–34 weeks of gestation) in a tertiary center from 2011 to 2014. The primary maternal outcome was a composite of early postpartum hemorrhage, blood transfusion, operative complications, postpartum complications, and clinical chorioamnionitis. The primary neonatal outcome was a composite of neonatal death, cardiopulmonary resuscitation in the delivery room, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, culture-proven sepsis, birth trauma, arterial cord gas pH less than 7 or base excess less than 212, and 5-minute Apgar score 3 or less. Outcomes were compared by intended mode of delivery (induction of labor compared with cesarean) and adjusted for confounders. In secondary analyses, maternal and neonatal outcomes based on the intended mode of delivery were stratified by gestational age (23– 27 6/7, 28–31 6/7, and 32–33 6/7 weeks of gestation). From the University of Alabama at Birmingham, Center for Women’s Reproductive Health, Birmingham, Alabama. Presented as a poster at the Society for Maternal-Fetal Medicine’s 37th Annual Pregnancy Meeting, January 23–28, 2017, Las Vegas, Nevada. The authors thank Dr. Sima Baalbaki and Ms. Michelle Wang for assisting in data collection. Each author has indicated that he or she has met the journal’s requirements for authorship. Corresponding author: Spencer G. Kuper, MD, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Alabama at Birmingham 176F 10270, 619 19th Street, South Birmingham, AL 35249; email: [email protected]. Financial Disclosure The authors did not report any potential conflicts of interest. © 2017 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0029-7844/17
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MPH,
Joseph R. Biggio,
MD, MSHQS,
RESULTS: Of 629 patients with indicated early preterm births during the study period, 331 (53%) underwent induction of labor, of whom 208 (63%) delivered vaginally. Induction of labor was not associated with an increased risk of the primary maternal (16.3% compared with 19.5%, adjusted odds ratio [OR] 0.8, 95% CI 0.5–1.3) or neonatal composite outcome (14.5% compared with 35.9%, adjusted OR 0.7, 95% CI 0.4–1.1). Analyses stratified by gestational age were consistent with the overall analysis. CONCLUSION: Maternal and neonatal outcomes do not differ based on the intended mode of delivery. Induction of labor should be considered when early preterm birth is indicated. (Obstet Gynecol 2017;0:1–9) DOI: 10.1097/AOG.0000000000002320
P
reterm birth is the leading cause of neonatal morbidity and mortality. Over the past 8 years, spontaneous preterm birth has declined by 25%1–3; however, indicated preterm births have increased and represent 35% of all preterm births.4,5 Unfortunately, when preterm birth is indicated, many physicians forego induction of labor and opt for a planned cesarean delivery because of fear of a prolonged induction, an unfavorable cervix, or concern for fetal intolerance of labor.6–8 Consequently, the preterm cesarean delivery rate was 46.6% in 2013, and it continues to rise.9 Maternal and neonatal outcomes relating to the mode of delivery have been primarily studied in term deliveries, and it is established that vaginal delivery at term provides maternal and neonatal benefits.10 The benefits of a vaginal delivery in term neonates include decreased rates of transient tachypnea of the newborn, respiratory distress syndrome, and neonatal intensive care unit admission.10 We conducted a retrospective cohort study to compare maternal and neonatal
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outcomes in women who underwent induction of labor compared with planned cesarean delivery in indicated early preterm births (23–34 weeks of gestation). We hypothesized that maternal and neonatal outcomes do not differ based on the intended mode of delivery.
MATERIALS AND METHODS This was a retrospective cohort study of all indicated preterm births between 23 0/7 and 34 0/7 weeks of gestation who delivered between January 1, 2011, and December 31, 2014, at the University of Alabama at Birmingham Hospital. Institutional review board approval was obtained. Indications for early preterm delivery included preeclampsia, fetal growth restriction, nonreassuring antenatal testing, vaginal bleeding, abruption, oligohydramnios (not resulting from prelabor premature rupture of membranes), clinical chorioamnionitis, and nonlaboring premature rupture of membranes with laboratory confirmation of fetal lung maturity. Patients who delivered between 23 0/7 and 34 0/7 weeks of gestation during the cohort time period were identified through review of the electronic medical record system and delivery logs. Patients were included in the study if they met the following criteria: singleton gestation, maternal or fetal indication for preterm birth, no evidence of spontaneous labor, continuous electronic fetal monitoring during labor, and an intention to resuscitate the neonate if necessary. Exclusion criteria included fetal anomalies, abnormal placentation (ie, morbidly adherent placenta and placenta previa), intrauterine fetal demise, maternal cardiac disease, and human immunodeficiency virus. We decided to include malpositioned fetuses because this is a common occurrence, represented by a large group who underwent a planned cesarean delivery, and is consistent with what has been done in previously performed studies.8,11,12 The standard cervical ripening method used in our institution is a transcervical Foley catheter with concurrent oxytocin infusion. Our oxytocin infusion protocol for induction of labor is to start oxytocin at 4 milliunits per minute and increase 2–4 milliunits per minute every 30 minutes until an adequate contraction pattern is obtained. The maximum allowable oxytocin rate is 46 milliunits per minute. Our practice is to allow patients with reassuring fetal heart rate tracings to labor for at least 18 hours after rupture of membranes before diagnosing a failed induction of labor. Similarly, an arrest of dilation is not diagnosed until 4 hours of adequate contractions or 6 hours of inadequate contractions. If the fetal heart tracing is reassur-
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ing, the second stage of labor is permitted to last 3 hours. Only the first qualifying pregnancy in the time period was included, and estimated due dates for all patients were based on the earliest ultrasonogram during the pregnancy. During the study period, the labor and delivery unit was staffed 24 hours a day by two faculty members: one maternal–fetal medicine specialist and one general obstetrician–gynecologist. With individual exceptions, induction of labor is the default in our institution, regardless of gestational age or cervical examination, if no contraindication to labor exists (ie, prior classic cesarean delivery or placenta previa). Persons trained in chart abstraction used standardized chart abstraction forms in a Research Electronic Data Capture 6.10.11 system. The primary author performed 64% of the chart abstraction, and the senior author reviewed 10% of the charts. The integrity of the data was confirmed by the primary (SGK) and senior (LMH) authors. Maternal data collected included detailed information regarding demographics, medical and obstetric histories, and pregnancy events during the antepartum, intrapartum, and postpartum time periods. Detailed neonatal information collected included delivery room events, respiratory support requirements, laboratory information, and other events during the neonatal intensive care unit admission. Neonatal admission history and physicals, daily progress notes, and discharge summaries were used to accurately record diagnoses. The primary maternal outcome was a composite of early postpartum hemorrhage, blood transfusion, operative and postpartum complications, and the development of intrapartum clinical chorioamnionitis. Early postpartum hemorrhage was defined as either a clinical diagnosis recorded in the patient’s medical record by a physician or 10% or greater difference in the predelivery and lowest postdelivery hematocrits.13 Operative complications included uterine artery laceration requiring an O’Leary stitch, hysterotomy extension into the contractile portion of the uterus, surrounding organ damage (bowel, bladder, or ureter), or an unanticipated cesarean hysterectomy. Postpartum complications were defined as occurring within 6 weeks of delivery and included endometritis, wound complications (cellulitis, infection, hematoma, seroma, intraabdominal abscess, or wound dehiscence), other infections (urinary tract infection, pyelonephritis, or pneumonia [diagnosed by chest x-ray and treated with antibiotics]), intensive care unit admission, or maternal death. The primary neonatal outcome was a composite of neonatal death, cardiopulmonary resuscitation in the delivery room, grade 3 or 4 intraventricular hemorrhage, necrotizing
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Fig. 1. Flow diagram of patients who underwent medically indicated preterm deliveries within our health system between 2011 and 2014. Kuper. Intended Mode of Delivery in Preterm Births. Obstet Gynecol 2017.
enterocolitis, culture-proven sepsis, birth trauma, arterial cord blood gas pH less than 7 or base excess of less than 212, and a 5-minute Apgar score of 3 or less. Neonatal death was defined as death within 28 days of life. Birth trauma included cephalohematoma, subgaleal hematoma, subdural hematoma, fractured clavicle, brachial plexus injury, or a scalp laceration. Components of the composite outcomes were chosen based on factors that could be influenced by the mode of delivery.14–23 The maternal and neonatal outcomes were analyzed separately, and we assumed the maternal and neonatal outcomes were independent of each other. Because gestational age may influence health care provider decision-making regarding mode of delivery and neonatal outcomes, we performed a stratified analysis by gestational age at delivery (23–27 6/7, 28– 31 6/7, and 32–33 6/7 weeks of gestation). Furthermore, we performed another secondary analysis including only women whose primary delivery indication was preeclampsia. Finally, because obstetric care providers are less likely to induce nulliparous women, we stratified the analysis by this factor as well. Because these secondary analyses contain significantly smaller sample sizes, only the results for the maternal and neonatal composite outcomes are presented.
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Baseline demographics among the intended modes of delivery were compared using the Student t test, x2 test, or Fisher exact test as appropriate. Univariate analyses were then used to compare the outcomes of interest in the primary and secondary analyses. Multivariate logistic regression models were then used to adjust for confounders on the outcomes of interest in the primary and secondary analyses. Clinically relevant covariates for initial inclusion were selected using results of the univariate analyses and were removed in a backward stepwise fashion based on significant changes in the exposure-adjusted odds ratio or significant differences between hierarchical models using the likelihood ratio test. Variables considered for inclusion included nulliparous status, hypertensive disorders of pregnancy, baseline renal disease (serum creatinine greater than 1.0 g/dL, baseline 24-hour urine protein 300 mg or greater or urine protein-to-creatinine ratio 0.3 or greater), diagnosis of fetal growth restriction, results of umbilical artery Doppler assessment, most recent estimated fetal weight, primary indication for delivery, primary indication for cesarean delivery (if performed), prior vaginal delivery, prior cesarean delivery, prior preterm birth, gestational age at delivery, and administration of magnesium sulfate during the intrapartum period.
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Statistical analyses were performed using STATA 13. A P value of ,.05 and a 95% CI not crossing or including 1 was chosen as statistically significant.
RESULTS Of the 1,352 patients who delivered before 34 weeks of gestation during the study period, 723 women were excluded (Fig. 1). The remaining 629 patients who underwent an indicated early preterm birth (range 23–34 weeks of gestation, mean 30.4 weeks of gestation) were analyzed. Of those, the intended mode of delivery in 331 (53%) patients was vaginal delivery (range 23.4–34 weeks of gestation, mean 31.2 weeks of gestation) and 208 (63%) were successful. The intended mode of delivery was planned cesarean delivery in 298 (47%) patients (range 23–34 weeks of gestation, mean 29.4 weeks of gestation). Cervical ripening was performed in 215 (65.0%) of patients undergoing induction; only one patient with prelabor premature rupture of membranes underwent cervical ripening. Of the 159 nulliparous patients, 117 (73.6%) underwent cervical ripening. The median starting dilation in those undergoing induction was 0.5 cm (interquartile range 0–1 cm). The mean length of induction, defined as the start of
cervical ripening or oxytocin (whichever came first) to delivery, was 44.0 hours (interquartile range 28.6–70 hours). Baseline maternal and pregnancy characteristics for patients who underwent induction of labor were compared with those who delivered through a planned cesarean delivery (Tables 1 and 2). A larger proportion of patients in the induction of labor group were nulliparous, diagnosed with preeclampsia, had a prior vaginal delivery, and delivered at a more advanced gestational age. A lower proportion of patients in the induction of labor group had chronic hypertension, pre-existing renal disease (serum creatinine greater than 1.0 g/dL, a baseline 24-hour urine protein 300 mg or greater, or a urine protein-to-creatinine ratio 0.3 or greater), a prior preterm birth, a prior low transverse cesarean delivery, and a fetus with growth restriction compared with patients in the planned cesarean delivery group. Patients with critically abnormal umbilical artery Doppler measurements were more likely to deliver by planned cesarean. The primary indication for cesarean delivery, if performed, was different between the two groups. Fetuses in the induction of labor group were estimated to be larger than those in the planned cesarean delivery group.
Table 1. Maternal Characteristics in Indicated Preterm Births Between 23 0/7 and 34 0/7 Weeks of Gestation Based on the Intended Mode of Delivery Characteristic Age (y) Race Black White Hispanic Other Public insurance Nulliparity Married BMI (kg/m2) at delivery Obese (BMI 30 or greater) Tobacco use Diabetes mellitus Gestational Pregestational Chronic hypertension Preeclampsia Pre-existing renal disease* Prior preterm birth Prior vaginal delivery Prior low transverse cesarean delivery
Induction of Labor (n5331)
Planned Cesarean Delivery (n5298)
26.765.7
27.466.1
175 (52.9) 128 (38.7) 13 (3.9) 15 (4.5) 245 (74.0) 159 (48.0) 99 (29.9) 33.868.0 211 (63.7) 49 (14.8)
153 (51.3) 124 (41.6) 9 (3.0) 12 (4.0) 220 (73.8) 100 (33.6) 90 (30.2) 34.468.9 186 (62.4) 63 (21.1)
17 (5.1) 24 (7.3) 75 (22.7) 248 (74.9) 4 (1.2) 78 (23.6) 157 (47.4) 29 (8.8)
14 (4.7) 34 (11.4) 92 (30.9) 200 (67.1) 14 (4.7) 103 (34.6) 107 (35.9) 121 (40.6)
P .10 .83
.96 ,.001 .94 .38 .97 .12 .20
.02 .03 .015 .004 .003 ,.001
BMI, body mass index. Data are mean6SD or n (%) unless otherwise specified. * Serum creatinine greater than 1.0 g/dL, baseline 24-hour urine protein 300 mg or greater, or a urine protein-to-creatinine ratio 0.3 or greater.
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Table 2. Pregnancy Characteristics in Indicated Preterm Births Between 23 0/7 and 34 0/7 Weeks of Gestation Based on the Intended Mode of Delivery Characteristic Gestational age at delivery (wk) Estimated fetal weight before delivery (g) Male neonate Antenatal corticosteroids None Partial 1 course More than 1 course Fetal growth restriction Umbilical artery Doppler assessment for fetuses with FGR Not performed Normal Elevated* Absent end-diastolic flow Reversed end-diastolic flow Primary indication for delivery Preeclampsia Preterm PROM with PG present in vaginal fluid Nonreassuring antenatal testing Clinical chorioamnionitis FGR, normal umbilical artery Doppler FGR, absent end-diastolic flow FGR, reversed end-diastolic flow Oligohydramnios (not preterm PROM) Abruption Other maternal indications Other fetal indications Indications for cesarean delivery† Nonreassuring fetal heart tracing Malpresentation Prior cesarean delivery Failed induction of labor Other‡
Induction of Labor (n5331)
Planned Cesarean Delivery (n5298)
31.262.4 1,526.06496.3 168 (50.8)
29.463.0 1,126.06538.8 150 (50.3)
14 (4.2) 44 (13.3) 259 (78.2) 14 (4.2) 26 (7.9)
17 (5.7) 53 (17.8) 216 (72.5) 12 (4.0) 75 (25.2)
6 (1.8) 9 (2.7) 1 (0.3) 10 (3.0) 0
12 (4.0) 11 (3.7) 6 (2.0) 26 (8.7) 20 (6.7)
237 (71.6) 52 (15.7) 12 (3.6) 21 (6.3) 0 1 (0.3) 0 1 (0.3) 3 (0.9) 3 (0.9) 1 (0.3)
158 (53.0) 11 (3.7) 87 (29.2) 18 (6.0) 1 (0.3) 4 (1.3) 6 (2.0) 1 (0.3) 7 (2.3) 5 (1.7) 0
83 13 4 19 4
99 (33.2) 102 (34.2) 59 (19.8) 1 (0.3) 37 (12.4)
(67.5) (10.6) (3.3) (15.4) (3.3)
P ,.001 ,.001 .92 .33
,.001 .02
,.001
,.001
FGR, fetal growth restriction; S/D, systolic-to-diastolic ratio; PROM, prelabor rupture of membranes; PG, phosphatidylglycerol. Data are mean6SD or n (%) unless otherwise specified. * Systolic-to-diastolic ratio greater than the 97th percentile. † Denominator for indications for cesarean delivery in the induction of labor group is 123. ‡ Induction of labor group: abruption (1) and cord prolapse (3); planned cesarean delivery group: abnormal umbilical artery Doppler (8), abruption (7), prior classic cesarean delivery or myomectomy (10), cord prolapse (3), active herpes simplex virus infection (2), and serious maternal condition (7).
The primary composite maternal and neonatal outcomes occurred in 112 (17.8%) patients and 155 (24.6%) neonates. Induction of labor was not associated with an increased risk of the primary maternal composite outcome (16.3% compared with 19.5%, adjusted odds ratio [OR] 0.8, 95% CI 0.5–1.3) or the primary neonatal composite outcome (14.5% compared with 35.9%, adjusted OR 0.7, 95% CI 0.4–1.1) (Table 3). The primary maternal outcome was adjusted for nulliparity, fetal growth restriction, renal disease (serum creatinine greater than 1.0 g/dL, baseline 24-hour urine protein 300 mg or greater, or a urine protein-to-creatinine ratio 0.3 or greater), pre-
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eclampsia, and prelabor premature rupture of membranes. The primary neonatal outcome was adjusted for fetal growth restriction, gestational age at delivery, and antenatal corticosteroids initiated. One maternal death occurred in the planned cesarean delivery group and was a result of advanced metastatic cancer and thus not related to the mode of delivery. Five neonates in the induction of labor group had a birth injury: two with cephalohematomas, two with scalp lacerations, and one with a fractured clavicle. One neonate in the planned cesarean delivery group had a brachial plexus injury. There were no vaginal deliveries with vacuum assistance. Fetal scalp electrodes
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Table 3. Adjusted Odds Ratios for Primary Maternal and Neonatal Outcomes Based on the Intended Mode of Delivery Induction of Labor (n5331)
Outcome Primary maternal composite outcome* Early postpartum hemorrhage Blood transfusion Operative complications Postpartum complications Clinical chorioamnionitis Primary neonatal composite outcome† Neonatal death CPR in the delivery room IVH, grade 3 or 4 Necrotizing enterocolitis Culture-proven sepsis Birth trauma Arterial cord gas pH less than 7 or BE less than 212 5-min Apgar score 3 or less
54 39 14 4 10 8 48 8 1 10 10 15 5 8
(16.3) (11.8) (4.2) (1.2) (3.0) (2.4) (14.5) (2.4) (0.3) (3.0) (3.0) (4.5) (1.5) (2.4)
Planned Cesarean Delivery (n5298)
RR (95% CI)
Adjusted OR (95% CI)
0.8 (0.6–1.2) —
0.8 (0.5–1.3) —
0.4 (0.3–0.5) —
0.7 (0.4–1.1) —
58 (19.5) 38 (12.8) 17 (5.7) 4 (1.3) 26 (8.7) 0 107 (35.9) 26 (8.7) 2 (0.7) 11 (3.7) 39 (13.1) 40 (13.4) 1 (0.3) 20 (6.7)
17 (5.1)
31 (10.4)
RR, relative risk; OR, odds ratio; CPR, cardiopulmonary resuscitation; IVH, intraventricular hemorrhage; BE, base excess. Data are n (%) unless otherwise specified. RR and adjusted OR for individual components of the primary maternal and neonatal outcomes not calculated as a result of a limited number of events. Early postpartum hemorrhage: clinical diagnosis recorded in a patient’s chart or predelivery compared with lowest postdelivery hematocrit 10% or greater. Operative complications: uterine artery laceration requiring an O’Leary stitch, hysterotomy extension into the contractile portion of the uterus, surrounding organ damage (bowel, bladder, or ureter), or an unanticipated cesarean hysterectomy. Postpartum complications: endometritis, wound complications (cellulitis, infection, hematoma, seroma, intraabdominal abscess, or wound dehiscence), other infections (urinary tract infection, pyelonephritis, and pneumonia [diagnosed by chest x-ray and treated with antibiotics]), intensive care unit admission, or maternal death. Birth trauma: cephalohematoma, subgaleal hematoma, subdural hematoma, fractured clavicle, brachial plexus injury, or scalp laceration. * Adjusted for nulliparity, fetal growth restriction, renal disease (serum creatinine greater than 1.0 g/dL, baseline 24-hour urine protein 300 mg or greater, or a urine protein-to-creatinine ratio 0.3 or greater), preeclampsia, and prelabor premature rupture of membranes. † Adjusted for fetal growth restriction, gestational age at delivery, and antenatal corticosteroids initiated.
Table 4. Adjusted Odds Ratios of Primary Maternal and Neonatal Outcomes Based on the Intended Mode of Delivery and Stratified by Gestational Age at Delivery 23 0/7–27 6/7 Wk of Gestation
Outcome Primary maternal composite outcome* Primary neonatal composite outcome†
28 0/7–31 6/7 Wk of Gestation
Adjusted OR IOL (95% CI) (n5121)
Planned Cesarean Delivery (n5115)
RR (95% CI)
Adjusted OR (95% CI)
0.8 (0.4–1.9)
1.0 (0.3–3.4) 25 (20.7)
24 (20.9)
1.1 (0.5–2.2)
0.9 (0.5–1.9)
0.8 (0.6–1.1)
0.7 (0.3–1.5) 14 (11.6)
22 (19.1)
0.6 (0.3–1.1)
0.9 (0.4–2.0)
IOL (n540)
Planned Cesarean Delivery (n5100)
RR (95% CI)
6 (15.0)
18 (18.0)
24 (60.0)
73 (73.0)
IOL, induction of labor; RR, relative risk; OR, odds ratio. Data are n (%) unless otherwise specified. Primary maternal composite outcome: early postpartum hemorrhage, blood transfusion, operative complications, postoperative complications, and clinical chorioamnionitis. Primary neonatal composite outcome: neonatal death, cardiopulmonary resuscitation in the delivery room, intraventricular hemorrhage grade 3 or 4, necrotizing enterocolitis, culture-proven sepsis, birth trauma, arterial cord gas pH less than 7 or base excess less than 212, and 5-minute Apgar score 3 or less. See Table 3 for definitions of early postpartum hemorrhage, operative and postpartum complications, and birth trauma. * Adjusted for nulliparity, fetal growth restriction, renal disease (serum creatinine greater than 1.0 g/dL, baseline 24-hour urine protein 300 mg or greater, or urine protein-to-creatinine ratio 0.3 or greater), preeclampsia, and prelabor premature of membranes. † Adjusted for fetal growth restriction, gestational age at delivery, and antenatal corticosteroids.
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were suspected to have caused the two scalp lacerations. A total of 12 neonates (1.9%) experienced a neonatal seizure (0.9% and 3.0% in the induction of labor and planned cesarean delivery, respectively). Although seizures were not specifically included in the primary outcome, all 12 neonates who experienced neonatal seizures had another component of the neonatal outcome. Analyses stratified by gestational age at delivery were consistent with the overall analysis (Table 4) as were the analyses confined to women with preeclampsia (Appendix 1, available online at http://links.lww. com/AOG/B19) and nulliparity (Appendix 2, available online at http://links.lww.com/AOG/B19).
DISCUSSION In our cohort, the maternal and neonatal outcomes between patients who underwent an induction of labor compared with a planned cesarean delivery between 23 and 34 weeks of gestation did not differ. Importantly, 63% of patients undergoing induction of labor delivered vaginally and avoided exposure to operative complications and the possibility of repeat cesarean delivery in future pregnancies. The Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists issued a joint statement in 2012 to decrease the primary cesarean delivery rate24; however, the statement focused on term deliveries. Many obstetric care providers treat labor management in preterm pregnancies differently
from term pregnancies because of a feared failed induction relating to an unfavorable cervix, fetal intolerance to labor, or a prolonged induction of labor.6–8 Furthermore, the fear of litigation likely guides some obstetric care providers’ decisions to deliver by planned cesarean.25 Thus, it is not surprising that the cesarean delivery rate for preterm deliveries is nearly 50%.9 Our findings should reassure obstetric care providers that an induction of labor does not increase the risk of adverse neonatal outcomes. Our study is unique compared with other preterm delivery outcome studies because it allows obstetric care providers to answer the pragmatic question of whether the intended mode of delivery is associated with maternal or neonatal outcomes. This is in contrast to other studies that have focused on outcomes based on the actual mode of delivery.11,26–28 Similar to our study, Alexander et al8 investigated neonatal outcomes based on the intended mode of delivery and reported similar findings as ours; yet, our study is different than theirs by including more than two times as many patients (629 compared with 278 patients), by evaluating maternal outcomes, and by having a higher successful induction rate (63% compared with 34%). Our higher successful induction rate is likely related to the contemporaneous change in the definition of the active phase from 4 to 6 cm and our use of cervical ripening. In an effort to help obstetric care providers select candidates who are likely to have a successful induction, we recently published a prediction tool using all 331 patients in the induction of labor cohort of this study.29 This tool
32 0/7–33 6/7 Wk of Gestation IOL (n5170)
Planned Cesarean Delivery (n583)
RR (95% CI)
Adjusted OR (95% CI)
23 (13.5)
16 (19.3)
0.7 (0.4–1.3)
0.6 (0.3–1.3)
10 (5.9)
12 (14.6)
0.4 (0.2–0.9)
0.4 (0.2–1.1)
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accounts for the gestational age at delivery, modified Bishop score, maternal body mass index, presence of fetal growth restriction, and the presence of chronic hypertension. It rarely misclassified candidates who would have a successful induction of labor. We recognize our study is not without limitations. First, it represents a largely black, lower socioeconomic population. Second, we attempted to control for all identified confounding variables, but it is possible residual confounding persisted. Although our study included a large number of indicated early preterm births, we had an 80% power with an a of 0.05 to detect a 50% decrease in immediate maternal and neonatal outcomes, and thus we were underpowered to detect smaller but potentially meaningful differences between groups. Finally, there was a nominal decrease in the unadjusted primary neonatal outcome for patients between 32 and 34 weeks of gestation; however, this decrease disappears after adjusting for confounders and may be the result of multiple comparisons or confounding by indication. Given the success rate and maternal and neonatal outcomes not differing based on the intended mode of delivery, induction of labor should be considered in appropriate patients when early preterm birth is indicated. Larger studies, particularly investigating special patient populations such as fetal growth restriction, should be performed to confirm our findings and add further evidence to help reduce the high cesarean delivery rate among preterm births. REFERENCES 1. Hamilton BE, Martin JA, Osterman MJ, Curtain SC. Births: preliminary data for 2014. Natl Vital Stat Rep 2015;64:1–19. 2. Lewit EM, Baker LS, Corman H, Shiono PH. The direct cost of low birth weight. Future Child 1995;5:35–56. 3. Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Mathews TJ, Kirmeyer S, et al. Births: final data for 2007. Natl Vital Stat Rep 2010;58:1–85. 4. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008;371:75–84. 5. Ananth CV, Vintzileos AM. Medically indicated preterm birth: recognizing the importance of the problem. Clin Perinatol 2008;35:53–67, viii. 6. Blackwell SC, Redman ME, Tomlinson M, Landwehr JB Jr, Tuynman M, Gonik B, et al. Labor induction for the preterm severe pre-eclamptic patient: is it worth the effort? J Matern Fetal Med 2001;10:305–11.
9. Martin JA, Hamilton BE, Osterman MJ, Curtin SC, Matthews TJ. Births: final data for 2013. Natl Vital Stat Rep 2015;64:1– 65. 10. Gregory KD, Jackson S, Korst L, Fridman M. Cesarean versus vaginal delivery: whose risks? Whose benefits? Am J Perinatol 2012;29:7–18. 11. Deulofeut R, Sola A, Lee B, Buchter S, Rahman M, Rogido M. The impact of vaginal delivery in premature infants weighing less than 1,251 grams. Obstet Gynecol 2005;105:525–31. 12. Bodner K, Wierrani F, Grünberger W, Bodner-Adler B. Influence of the mode of delivery on maternal and neonatal outcomes: a comparison between elective cesarean section and planned vaginal delivery in a low-risk obstetric population. Arch Gynecol Obstet 2011;283:1193–8. 13. Combs CA, Murphy EL, Laros RK Jr. Factors associated with postpartum hemorrhage with vaginal birth. Obstet Gynecol 1991;77:69–76. 14. Hällström M, Eerola E, Vuento R, Janas M, Tammela O. Effects of mode of delivery and necrotising enterocolitis on the intestinal microflora in preterm infants. Eur J Clin Microbiol Infect Dis 2004;23:463–70. 15. Gawade PL, Whitcomb BW, Chasan-Taber L, Pekow PS, Ronnenberg AG, Shah B, et al. Second stage of labor and intraventricular hemorrhage in early preterm infants in the vertex presentation. J Matern Fetal Neonatal Med 2013;26:1292–8. 16. Wankaew N, Jirapradittha J, Kiatchoosakun P. Neonatal morbidity and mortality for repeated cesarean section vs. normal vaginal delivery to uncomplicated term pregnancies at Srinagarind Hospital. J Med Assoc Thai 2013;96:654–60. 17. Puza S, Roth N, Macones GA, Mennuti MT, Morgan MA. Does cesarean section decrease the incidence of major birth trauma? J Perinatol 1998;18:9–12. 18. Westgren M, Dolfin T, Halperin M, Milligan J, Shennan A, Svenningsen NW, et al. Mode of delivery in the low birth weight fetus. Delivery by cesarean section independent of fetal lie versus vaginal delivery in vertex presentation. A study with long-term follow-up. Acta Obstet Gynecol Scand 1985; 64:51–7. 19. Holzer I, Lehner R, Ristl R, Husslein PW, Berger A, Farr A. Effect of delivery mode on neonatal outcome among preterm infants: an observational study. Wien Klin Wochenschr 2016 Dec 21 [Epub ahead of print]. 20. Holm C, Langhoff-Roos J, Petersen KB, Norgaard A, Diness BR. Severe postpartum haemorrhage and mode of delivery: a retrospective cohort study. BJOG 2012;119:596–604. 21. Pallasmaa N, Ekblad U, Gissler M. Severe maternal morbidity and the mode of delivery. Acta Obstet Gynecol Scand 2008;87: 662–8. 22. Bailit JL, Grobman WA, Rice MM, Wapner RJ, Reddy UM, Varner MW, et al. Evaluation of delivery options for secondstage events. Am J Obstet Gynecol 2016;214:638.e1–10. 23. Geller EJ, Wu JM, Jannelli ML, Nguyen TV, Visco AG. Maternal outcomes associated with planned vaginal versus planned primary cesarean delivery. Am J Perinatol 2010;27:675–83.
7. Nassar AH, Adra AM, Chakhtoura N, Gómez-Marín O, Beydoun S. Severe preeclampsia remote from term: labor induction or elective cesarean delivery? Am J Obstet Gynecol 1998;179: 1210–3.
24. Spong CY, Berghella V, Wenstrom KD, Mercer BM, Saade GR. Preventing the first cesarean delivery: summary of a joint Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, and American College of Obstetricians and Gynecologists Workshop. Obstet Gynecol 2012;120:1181–93.
8. Alexander JM, Bloom SL, McIntire DD, Leveno KJ. Severe preeclampsia and the very low birth weight infant: is induction of labor harmful? Obstet Gynecol 1999;93:485–8.
25. Zwecker P, Azoulay L, Abenhaim HA. Effect of fear of litigation on obstetric care: a nationwide analysis on obstetric practice. Am J Perinatol 2011;28:277–84.
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26. Lee HC, Gould JB. Survival rates and mode of delivery for vertex preterm neonates according to small- or appropriatefor-gestational-age status. Pediatrics 2006;118:e1836–44.
28. Wylie BJ, Davidson LL, Batra M, Reed SD. Method of delivery and neonatal outcome in very low-birthweight vertex-presenting fetuses. Am J Obstet Gynecol 2008;198:640.e1–7.
27. Werner EF, Han CS, Savitz DA, Goldshore M, Lipkind HS. Health outcomes for vaginal compared with cesarean delivery of appropriately grown preterm neonates. Obstet Gynecol 2013;121:1195–200.
29. Sievert RA, Kuper SG, Jauk VC, Parrish M, Biggio JR, Harper LM. Predictors of vaginal delivery in medically indicated early preterm induction of labor. Am J Obstet Gynecol 2017 May 17 [Epub ahead of print].
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Maternal and Neonatal Outcomes in Indicated Preterm Births Based on the Intended Mode of Delivery Spencer G. Kuper, MD, Rachel A. Sievert, MD, Robin Steele, Alan T. Tita, MD, PhD, and Lorie M. Harper, MD, MSCI OBJECTIVE: To compare maternal and neonatal outcomes in women who underwent induction of labor or planned cesarean delivery in indicated preterm births before 34 weeks of gestation. METHODS: We conducted a retrospective cohort study of all indicated singleton preterm births (23–34 weeks of gestation) in a tertiary center from 2011 to 2014. The primary maternal outcome was a composite of early postpartum hemorrhage, blood transfusion, operative complications, postpartum complications, and clinical chorioamnionitis. The primary neonatal outcome was a composite of neonatal death, cardiopulmonary resuscitation in the delivery room, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, culture-proven sepsis, birth trauma, arterial cord gas pH less than 7 or base excess less than 212, and 5-minute Apgar score 3 or less. Outcomes were compared by intended mode of delivery (induction of labor compared with cesarean) and adjusted for confounders. In secondary analyses, maternal and neonatal outcomes based on the intended mode of delivery were stratified by gestational age (23– 27 6/7, 28–31 6/7, and 32–33 6/7 weeks of gestation). From the University of Alabama at Birmingham, Center for Women’s Reproductive Health, Birmingham, Alabama. Presented as a poster at the Society for Maternal-Fetal Medicine’s 37th Annual Pregnancy Meeting, January 23–28, 2017, Las Vegas, Nevada. The authors thank Dr. Sima Baalbaki and Ms. Michelle Wang for assisting in data collection. Each author has indicated that he or she has met the journal’s requirements for authorship. Corresponding author: Spencer G. Kuper, MD, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Alabama at Birmingham 176F 10270, 619 19th Street, South Birmingham, AL 35249; email: [email protected]. Financial Disclosure The authors did not report any potential conflicts of interest. © 2017 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0029-7844/17
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MPH,
Joseph R. Biggio,
MD, MSHQS,
RESULTS: Of 629 patients with indicated early preterm births during the study period, 331 (53%) underwent induction of labor, of whom 208 (63%) delivered vaginally. Induction of labor was not associated with an increased risk of the primary maternal (16.3% compared with 19.5%, adjusted odds ratio [OR] 0.8, 95% CI 0.5–1.3) or neonatal composite outcome (14.5% compared with 35.9%, adjusted OR 0.7, 95% CI 0.4–1.1). Analyses stratified by gestational age were consistent with the overall analysis. CONCLUSION: Maternal and neonatal outcomes do not differ based on the intended mode of delivery. Induction of labor should be considered when early preterm birth is indicated. (Obstet Gynecol 2017;0:1–9) DOI: 10.1097/AOG.0000000000002320
P
reterm birth is the leading cause of neonatal morbidity and mortality. Over the past 8 years, spontaneous preterm birth has declined by 25%1–3; however, indicated preterm births have increased and represent 35% of all preterm births.4,5 Unfortunately, when preterm birth is indicated, many physicians forego induction of labor and opt for a planned cesarean delivery because of fear of a prolonged induction, an unfavorable cervix, or concern for fetal intolerance of labor.6–8 Consequently, the preterm cesarean delivery rate was 46.6% in 2013, and it continues to rise.9 Maternal and neonatal outcomes relating to the mode of delivery have been primarily studied in term deliveries, and it is established that vaginal delivery at term provides maternal and neonatal benefits.10 The benefits of a vaginal delivery in term neonates include decreased rates of transient tachypnea of the newborn, respiratory distress syndrome, and neonatal intensive care unit admission.10 We conducted a retrospective cohort study to compare maternal and neonatal
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outcomes in women who underwent induction of labor compared with planned cesarean delivery in indicated early preterm births (23–34 weeks of gestation). We hypothesized that maternal and neonatal outcomes do not differ based on the intended mode of delivery.
MATERIALS AND METHODS This was a retrospective cohort study of all indicated preterm births between 23 0/7 and 34 0/7 weeks of gestation who delivered between January 1, 2011, and December 31, 2014, at the University of Alabama at Birmingham Hospital. Institutional review board approval was obtained. Indications for early preterm delivery included preeclampsia, fetal growth restriction, nonreassuring antenatal testing, vaginal bleeding, abruption, oligohydramnios (not resulting from prelabor premature rupture of membranes), clinical chorioamnionitis, and nonlaboring premature rupture of membranes with laboratory confirmation of fetal lung maturity. Patients who delivered between 23 0/7 and 34 0/7 weeks of gestation during the cohort time period were identified through review of the electronic medical record system and delivery logs. Patients were included in the study if they met the following criteria: singleton gestation, maternal or fetal indication for preterm birth, no evidence of spontaneous labor, continuous electronic fetal monitoring during labor, and an intention to resuscitate the neonate if necessary. Exclusion criteria included fetal anomalies, abnormal placentation (ie, morbidly adherent placenta and placenta previa), intrauterine fetal demise, maternal cardiac disease, and human immunodeficiency virus. We decided to include malpositioned fetuses because this is a common occurrence, represented by a large group who underwent a planned cesarean delivery, and is consistent with what has been done in previously performed studies.8,11,12 The standard cervical ripening method used in our institution is a transcervical Foley catheter with concurrent oxytocin infusion. Our oxytocin infusion protocol for induction of labor is to start oxytocin at 4 milliunits per minute and increase 2–4 milliunits per minute every 30 minutes until an adequate contraction pattern is obtained. The maximum allowable oxytocin rate is 46 milliunits per minute. Our practice is to allow patients with reassuring fetal heart rate tracings to labor for at least 18 hours after rupture of membranes before diagnosing a failed induction of labor. Similarly, an arrest of dilation is not diagnosed until 4 hours of adequate contractions or 6 hours of inadequate contractions. If the fetal heart tracing is reassur-
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ing, the second stage of labor is permitted to last 3 hours. Only the first qualifying pregnancy in the time period was included, and estimated due dates for all patients were based on the earliest ultrasonogram during the pregnancy. During the study period, the labor and delivery unit was staffed 24 hours a day by two faculty members: one maternal–fetal medicine specialist and one general obstetrician–gynecologist. With individual exceptions, induction of labor is the default in our institution, regardless of gestational age or cervical examination, if no contraindication to labor exists (ie, prior classic cesarean delivery or placenta previa). Persons trained in chart abstraction used standardized chart abstraction forms in a Research Electronic Data Capture 6.10.11 system. The primary author performed 64% of the chart abstraction, and the senior author reviewed 10% of the charts. The integrity of the data was confirmed by the primary (SGK) and senior (LMH) authors. Maternal data collected included detailed information regarding demographics, medical and obstetric histories, and pregnancy events during the antepartum, intrapartum, and postpartum time periods. Detailed neonatal information collected included delivery room events, respiratory support requirements, laboratory information, and other events during the neonatal intensive care unit admission. Neonatal admission history and physicals, daily progress notes, and discharge summaries were used to accurately record diagnoses. The primary maternal outcome was a composite of early postpartum hemorrhage, blood transfusion, operative and postpartum complications, and the development of intrapartum clinical chorioamnionitis. Early postpartum hemorrhage was defined as either a clinical diagnosis recorded in the patient’s medical record by a physician or 10% or greater difference in the predelivery and lowest postdelivery hematocrits.13 Operative complications included uterine artery laceration requiring an O’Leary stitch, hysterotomy extension into the contractile portion of the uterus, surrounding organ damage (bowel, bladder, or ureter), or an unanticipated cesarean hysterectomy. Postpartum complications were defined as occurring within 6 weeks of delivery and included endometritis, wound complications (cellulitis, infection, hematoma, seroma, intraabdominal abscess, or wound dehiscence), other infections (urinary tract infection, pyelonephritis, or pneumonia [diagnosed by chest x-ray and treated with antibiotics]), intensive care unit admission, or maternal death. The primary neonatal outcome was a composite of neonatal death, cardiopulmonary resuscitation in the delivery room, grade 3 or 4 intraventricular hemorrhage, necrotizing
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Fig. 1. Flow diagram of patients who underwent medically indicated preterm deliveries within our health system between 2011 and 2014. Kuper. Intended Mode of Delivery in Preterm Births. Obstet Gynecol 2017.
enterocolitis, culture-proven sepsis, birth trauma, arterial cord blood gas pH less than 7 or base excess of less than 212, and a 5-minute Apgar score of 3 or less. Neonatal death was defined as death within 28 days of life. Birth trauma included cephalohematoma, subgaleal hematoma, subdural hematoma, fractured clavicle, brachial plexus injury, or a scalp laceration. Components of the composite outcomes were chosen based on factors that could be influenced by the mode of delivery.14–23 The maternal and neonatal outcomes were analyzed separately, and we assumed the maternal and neonatal outcomes were independent of each other. Because gestational age may influence health care provider decision-making regarding mode of delivery and neonatal outcomes, we performed a stratified analysis by gestational age at delivery (23–27 6/7, 28– 31 6/7, and 32–33 6/7 weeks of gestation). Furthermore, we performed another secondary analysis including only women whose primary delivery indication was preeclampsia. Finally, because obstetric care providers are less likely to induce nulliparous women, we stratified the analysis by this factor as well. Because these secondary analyses contain significantly smaller sample sizes, only the results for the maternal and neonatal composite outcomes are presented.
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Baseline demographics among the intended modes of delivery were compared using the Student t test, x2 test, or Fisher exact test as appropriate. Univariate analyses were then used to compare the outcomes of interest in the primary and secondary analyses. Multivariate logistic regression models were then used to adjust for confounders on the outcomes of interest in the primary and secondary analyses. Clinically relevant covariates for initial inclusion were selected using results of the univariate analyses and were removed in a backward stepwise fashion based on significant changes in the exposure-adjusted odds ratio or significant differences between hierarchical models using the likelihood ratio test. Variables considered for inclusion included nulliparous status, hypertensive disorders of pregnancy, baseline renal disease (serum creatinine greater than 1.0 g/dL, baseline 24-hour urine protein 300 mg or greater or urine protein-to-creatinine ratio 0.3 or greater), diagnosis of fetal growth restriction, results of umbilical artery Doppler assessment, most recent estimated fetal weight, primary indication for delivery, primary indication for cesarean delivery (if performed), prior vaginal delivery, prior cesarean delivery, prior preterm birth, gestational age at delivery, and administration of magnesium sulfate during the intrapartum period.
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Statistical analyses were performed using STATA 13. A P value of ,.05 and a 95% CI not crossing or including 1 was chosen as statistically significant.
RESULTS Of the 1,352 patients who delivered before 34 weeks of gestation during the study period, 723 women were excluded (Fig. 1). The remaining 629 patients who underwent an indicated early preterm birth (range 23–34 weeks of gestation, mean 30.4 weeks of gestation) were analyzed. Of those, the intended mode of delivery in 331 (53%) patients was vaginal delivery (range 23.4–34 weeks of gestation, mean 31.2 weeks of gestation) and 208 (63%) were successful. The intended mode of delivery was planned cesarean delivery in 298 (47%) patients (range 23–34 weeks of gestation, mean 29.4 weeks of gestation). Cervical ripening was performed in 215 (65.0%) of patients undergoing induction; only one patient with prelabor premature rupture of membranes underwent cervical ripening. Of the 159 nulliparous patients, 117 (73.6%) underwent cervical ripening. The median starting dilation in those undergoing induction was 0.5 cm (interquartile range 0–1 cm). The mean length of induction, defined as the start of
cervical ripening or oxytocin (whichever came first) to delivery, was 44.0 hours (interquartile range 28.6–70 hours). Baseline maternal and pregnancy characteristics for patients who underwent induction of labor were compared with those who delivered through a planned cesarean delivery (Tables 1 and 2). A larger proportion of patients in the induction of labor group were nulliparous, diagnosed with preeclampsia, had a prior vaginal delivery, and delivered at a more advanced gestational age. A lower proportion of patients in the induction of labor group had chronic hypertension, pre-existing renal disease (serum creatinine greater than 1.0 g/dL, a baseline 24-hour urine protein 300 mg or greater, or a urine protein-to-creatinine ratio 0.3 or greater), a prior preterm birth, a prior low transverse cesarean delivery, and a fetus with growth restriction compared with patients in the planned cesarean delivery group. Patients with critically abnormal umbilical artery Doppler measurements were more likely to deliver by planned cesarean. The primary indication for cesarean delivery, if performed, was different between the two groups. Fetuses in the induction of labor group were estimated to be larger than those in the planned cesarean delivery group.
Table 1. Maternal Characteristics in Indicated Preterm Births Between 23 0/7 and 34 0/7 Weeks of Gestation Based on the Intended Mode of Delivery Characteristic Age (y) Race Black White Hispanic Other Public insurance Nulliparity Married BMI (kg/m2) at delivery Obese (BMI 30 or greater) Tobacco use Diabetes mellitus Gestational Pregestational Chronic hypertension Preeclampsia Pre-existing renal disease* Prior preterm birth Prior vaginal delivery Prior low transverse cesarean delivery
Induction of Labor (n5331)
Planned Cesarean Delivery (n5298)
26.765.7
27.466.1
175 (52.9) 128 (38.7) 13 (3.9) 15 (4.5) 245 (74.0) 159 (48.0) 99 (29.9) 33.868.0 211 (63.7) 49 (14.8)
153 (51.3) 124 (41.6) 9 (3.0) 12 (4.0) 220 (73.8) 100 (33.6) 90 (30.2) 34.468.9 186 (62.4) 63 (21.1)
17 (5.1) 24 (7.3) 75 (22.7) 248 (74.9) 4 (1.2) 78 (23.6) 157 (47.4) 29 (8.8)
14 (4.7) 34 (11.4) 92 (30.9) 200 (67.1) 14 (4.7) 103 (34.6) 107 (35.9) 121 (40.6)
P .10 .83
.96 ,.001 .94 .38 .97 .12 .20
.02 .03 .015 .004 .003 ,.001
BMI, body mass index. Data are mean6SD or n (%) unless otherwise specified. * Serum creatinine greater than 1.0 g/dL, baseline 24-hour urine protein 300 mg or greater, or a urine protein-to-creatinine ratio 0.3 or greater.
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Table 2. Pregnancy Characteristics in Indicated Preterm Births Between 23 0/7 and 34 0/7 Weeks of Gestation Based on the Intended Mode of Delivery Characteristic Gestational age at delivery (wk) Estimated fetal weight before delivery (g) Male neonate Antenatal corticosteroids None Partial 1 course More than 1 course Fetal growth restriction Umbilical artery Doppler assessment for fetuses with FGR Not performed Normal Elevated* Absent end-diastolic flow Reversed end-diastolic flow Primary indication for delivery Preeclampsia Preterm PROM with PG present in vaginal fluid Nonreassuring antenatal testing Clinical chorioamnionitis FGR, normal umbilical artery Doppler FGR, absent end-diastolic flow FGR, reversed end-diastolic flow Oligohydramnios (not preterm PROM) Abruption Other maternal indications Other fetal indications Indications for cesarean delivery† Nonreassuring fetal heart tracing Malpresentation Prior cesarean delivery Failed induction of labor Other‡
Induction of Labor (n5331)
Planned Cesarean Delivery (n5298)
31.262.4 1,526.06496.3 168 (50.8)
29.463.0 1,126.06538.8 150 (50.3)
14 (4.2) 44 (13.3) 259 (78.2) 14 (4.2) 26 (7.9)
17 (5.7) 53 (17.8) 216 (72.5) 12 (4.0) 75 (25.2)
6 (1.8) 9 (2.7) 1 (0.3) 10 (3.0) 0
12 (4.0) 11 (3.7) 6 (2.0) 26 (8.7) 20 (6.7)
237 (71.6) 52 (15.7) 12 (3.6) 21 (6.3) 0 1 (0.3) 0 1 (0.3) 3 (0.9) 3 (0.9) 1 (0.3)
158 (53.0) 11 (3.7) 87 (29.2) 18 (6.0) 1 (0.3) 4 (1.3) 6 (2.0) 1 (0.3) 7 (2.3) 5 (1.7) 0
83 13 4 19 4
99 (33.2) 102 (34.2) 59 (19.8) 1 (0.3) 37 (12.4)
(67.5) (10.6) (3.3) (15.4) (3.3)
P ,.001 ,.001 .92 .33
,.001 .02
,.001
,.001
FGR, fetal growth restriction; S/D, systolic-to-diastolic ratio; PROM, prelabor rupture of membranes; PG, phosphatidylglycerol. Data are mean6SD or n (%) unless otherwise specified. * Systolic-to-diastolic ratio greater than the 97th percentile. † Denominator for indications for cesarean delivery in the induction of labor group is 123. ‡ Induction of labor group: abruption (1) and cord prolapse (3); planned cesarean delivery group: abnormal umbilical artery Doppler (8), abruption (7), prior classic cesarean delivery or myomectomy (10), cord prolapse (3), active herpes simplex virus infection (2), and serious maternal condition (7).
The primary composite maternal and neonatal outcomes occurred in 112 (17.8%) patients and 155 (24.6%) neonates. Induction of labor was not associated with an increased risk of the primary maternal composite outcome (16.3% compared with 19.5%, adjusted odds ratio [OR] 0.8, 95% CI 0.5–1.3) or the primary neonatal composite outcome (14.5% compared with 35.9%, adjusted OR 0.7, 95% CI 0.4–1.1) (Table 3). The primary maternal outcome was adjusted for nulliparity, fetal growth restriction, renal disease (serum creatinine greater than 1.0 g/dL, baseline 24-hour urine protein 300 mg or greater, or a urine protein-to-creatinine ratio 0.3 or greater), pre-
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eclampsia, and prelabor premature rupture of membranes. The primary neonatal outcome was adjusted for fetal growth restriction, gestational age at delivery, and antenatal corticosteroids initiated. One maternal death occurred in the planned cesarean delivery group and was a result of advanced metastatic cancer and thus not related to the mode of delivery. Five neonates in the induction of labor group had a birth injury: two with cephalohematomas, two with scalp lacerations, and one with a fractured clavicle. One neonate in the planned cesarean delivery group had a brachial plexus injury. There were no vaginal deliveries with vacuum assistance. Fetal scalp electrodes
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Table 3. Adjusted Odds Ratios for Primary Maternal and Neonatal Outcomes Based on the Intended Mode of Delivery Induction of Labor (n5331)
Outcome Primary maternal composite outcome* Early postpartum hemorrhage Blood transfusion Operative complications Postpartum complications Clinical chorioamnionitis Primary neonatal composite outcome† Neonatal death CPR in the delivery room IVH, grade 3 or 4 Necrotizing enterocolitis Culture-proven sepsis Birth trauma Arterial cord gas pH less than 7 or BE less than 212 5-min Apgar score 3 or less
54 39 14 4 10 8 48 8 1 10 10 15 5 8
(16.3) (11.8) (4.2) (1.2) (3.0) (2.4) (14.5) (2.4) (0.3) (3.0) (3.0) (4.5) (1.5) (2.4)
Planned Cesarean Delivery (n5298)
RR (95% CI)
Adjusted OR (95% CI)
0.8 (0.6–1.2) —
0.8 (0.5–1.3) —
0.4 (0.3–0.5) —
0.7 (0.4–1.1) —
58 (19.5) 38 (12.8) 17 (5.7) 4 (1.3) 26 (8.7) 0 107 (35.9) 26 (8.7) 2 (0.7) 11 (3.7) 39 (13.1) 40 (13.4) 1 (0.3) 20 (6.7)
17 (5.1)
31 (10.4)
RR, relative risk; OR, odds ratio; CPR, cardiopulmonary resuscitation; IVH, intraventricular hemorrhage; BE, base excess. Data are n (%) unless otherwise specified. RR and adjusted OR for individual components of the primary maternal and neonatal outcomes not calculated as a result of a limited number of events. Early postpartum hemorrhage: clinical diagnosis recorded in a patient’s chart or predelivery compared with lowest postdelivery hematocrit 10% or greater. Operative complications: uterine artery laceration requiring an O’Leary stitch, hysterotomy extension into the contractile portion of the uterus, surrounding organ damage (bowel, bladder, or ureter), or an unanticipated cesarean hysterectomy. Postpartum complications: endometritis, wound complications (cellulitis, infection, hematoma, seroma, intraabdominal abscess, or wound dehiscence), other infections (urinary tract infection, pyelonephritis, and pneumonia [diagnosed by chest x-ray and treated with antibiotics]), intensive care unit admission, or maternal death. Birth trauma: cephalohematoma, subgaleal hematoma, subdural hematoma, fractured clavicle, brachial plexus injury, or scalp laceration. * Adjusted for nulliparity, fetal growth restriction, renal disease (serum creatinine greater than 1.0 g/dL, baseline 24-hour urine protein 300 mg or greater, or a urine protein-to-creatinine ratio 0.3 or greater), preeclampsia, and prelabor premature rupture of membranes. † Adjusted for fetal growth restriction, gestational age at delivery, and antenatal corticosteroids initiated.
Table 4. Adjusted Odds Ratios of Primary Maternal and Neonatal Outcomes Based on the Intended Mode of Delivery and Stratified by Gestational Age at Delivery 23 0/7–27 6/7 Wk of Gestation
Outcome Primary maternal composite outcome* Primary neonatal composite outcome†
28 0/7–31 6/7 Wk of Gestation
Adjusted OR IOL (95% CI) (n5121)
Planned Cesarean Delivery (n5115)
RR (95% CI)
Adjusted OR (95% CI)
0.8 (0.4–1.9)
1.0 (0.3–3.4) 25 (20.7)
24 (20.9)
1.1 (0.5–2.2)
0.9 (0.5–1.9)
0.8 (0.6–1.1)
0.7 (0.3–1.5) 14 (11.6)
22 (19.1)
0.6 (0.3–1.1)
0.9 (0.4–2.0)
IOL (n540)
Planned Cesarean Delivery (n5100)
RR (95% CI)
6 (15.0)
18 (18.0)
24 (60.0)
73 (73.0)
IOL, induction of labor; RR, relative risk; OR, odds ratio. Data are n (%) unless otherwise specified. Primary maternal composite outcome: early postpartum hemorrhage, blood transfusion, operative complications, postoperative complications, and clinical chorioamnionitis. Primary neonatal composite outcome: neonatal death, cardiopulmonary resuscitation in the delivery room, intraventricular hemorrhage grade 3 or 4, necrotizing enterocolitis, culture-proven sepsis, birth trauma, arterial cord gas pH less than 7 or base excess less than 212, and 5-minute Apgar score 3 or less. See Table 3 for definitions of early postpartum hemorrhage, operative and postpartum complications, and birth trauma. * Adjusted for nulliparity, fetal growth restriction, renal disease (serum creatinine greater than 1.0 g/dL, baseline 24-hour urine protein 300 mg or greater, or urine protein-to-creatinine ratio 0.3 or greater), preeclampsia, and prelabor premature of membranes. † Adjusted for fetal growth restriction, gestational age at delivery, and antenatal corticosteroids.
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were suspected to have caused the two scalp lacerations. A total of 12 neonates (1.9%) experienced a neonatal seizure (0.9% and 3.0% in the induction of labor and planned cesarean delivery, respectively). Although seizures were not specifically included in the primary outcome, all 12 neonates who experienced neonatal seizures had another component of the neonatal outcome. Analyses stratified by gestational age at delivery were consistent with the overall analysis (Table 4) as were the analyses confined to women with preeclampsia (Appendix 1, available online at http://links.lww. com/AOG/B19) and nulliparity (Appendix 2, available online at http://links.lww.com/AOG/B19).
DISCUSSION In our cohort, the maternal and neonatal outcomes between patients who underwent an induction of labor compared with a planned cesarean delivery between 23 and 34 weeks of gestation did not differ. Importantly, 63% of patients undergoing induction of labor delivered vaginally and avoided exposure to operative complications and the possibility of repeat cesarean delivery in future pregnancies. The Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists issued a joint statement in 2012 to decrease the primary cesarean delivery rate24; however, the statement focused on term deliveries. Many obstetric care providers treat labor management in preterm pregnancies differently
from term pregnancies because of a feared failed induction relating to an unfavorable cervix, fetal intolerance to labor, or a prolonged induction of labor.6–8 Furthermore, the fear of litigation likely guides some obstetric care providers’ decisions to deliver by planned cesarean.25 Thus, it is not surprising that the cesarean delivery rate for preterm deliveries is nearly 50%.9 Our findings should reassure obstetric care providers that an induction of labor does not increase the risk of adverse neonatal outcomes. Our study is unique compared with other preterm delivery outcome studies because it allows obstetric care providers to answer the pragmatic question of whether the intended mode of delivery is associated with maternal or neonatal outcomes. This is in contrast to other studies that have focused on outcomes based on the actual mode of delivery.11,26–28 Similar to our study, Alexander et al8 investigated neonatal outcomes based on the intended mode of delivery and reported similar findings as ours; yet, our study is different than theirs by including more than two times as many patients (629 compared with 278 patients), by evaluating maternal outcomes, and by having a higher successful induction rate (63% compared with 34%). Our higher successful induction rate is likely related to the contemporaneous change in the definition of the active phase from 4 to 6 cm and our use of cervical ripening. In an effort to help obstetric care providers select candidates who are likely to have a successful induction, we recently published a prediction tool using all 331 patients in the induction of labor cohort of this study.29 This tool
32 0/7–33 6/7 Wk of Gestation IOL (n5170)
Planned Cesarean Delivery (n583)
RR (95% CI)
Adjusted OR (95% CI)
23 (13.5)
16 (19.3)
0.7 (0.4–1.3)
0.6 (0.3–1.3)
10 (5.9)
12 (14.6)
0.4 (0.2–0.9)
0.4 (0.2–1.1)
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accounts for the gestational age at delivery, modified Bishop score, maternal body mass index, presence of fetal growth restriction, and the presence of chronic hypertension. It rarely misclassified candidates who would have a successful induction of labor. We recognize our study is not without limitations. First, it represents a largely black, lower socioeconomic population. Second, we attempted to control for all identified confounding variables, but it is possible residual confounding persisted. Although our study included a large number of indicated early preterm births, we had an 80% power with an a of 0.05 to detect a 50% decrease in immediate maternal and neonatal outcomes, and thus we were underpowered to detect smaller but potentially meaningful differences between groups. Finally, there was a nominal decrease in the unadjusted primary neonatal outcome for patients between 32 and 34 weeks of gestation; however, this decrease disappears after adjusting for confounders and may be the result of multiple comparisons or confounding by indication. Given the success rate and maternal and neonatal outcomes not differing based on the intended mode of delivery, induction of labor should be considered in appropriate patients when early preterm birth is indicated. Larger studies, particularly investigating special patient populations such as fetal growth restriction, should be performed to confirm our findings and add further evidence to help reduce the high cesarean delivery rate among preterm births. REFERENCES 1. Hamilton BE, Martin JA, Osterman MJ, Curtain SC. Births: preliminary data for 2014. Natl Vital Stat Rep 2015;64:1–19. 2. Lewit EM, Baker LS, Corman H, Shiono PH. The direct cost of low birth weight. Future Child 1995;5:35–56. 3. Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Mathews TJ, Kirmeyer S, et al. Births: final data for 2007. Natl Vital Stat Rep 2010;58:1–85. 4. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008;371:75–84. 5. Ananth CV, Vintzileos AM. Medically indicated preterm birth: recognizing the importance of the problem. Clin Perinatol 2008;35:53–67, viii. 6. Blackwell SC, Redman ME, Tomlinson M, Landwehr JB Jr, Tuynman M, Gonik B, et al. Labor induction for the preterm severe pre-eclamptic patient: is it worth the effort? J Matern Fetal Med 2001;10:305–11.
9. Martin JA, Hamilton BE, Osterman MJ, Curtin SC, Matthews TJ. Births: final data for 2013. Natl Vital Stat Rep 2015;64:1– 65. 10. Gregory KD, Jackson S, Korst L, Fridman M. Cesarean versus vaginal delivery: whose risks? Whose benefits? Am J Perinatol 2012;29:7–18. 11. Deulofeut R, Sola A, Lee B, Buchter S, Rahman M, Rogido M. The impact of vaginal delivery in premature infants weighing less than 1,251 grams. Obstet Gynecol 2005;105:525–31. 12. Bodner K, Wierrani F, Grünberger W, Bodner-Adler B. Influence of the mode of delivery on maternal and neonatal outcomes: a comparison between elective cesarean section and planned vaginal delivery in a low-risk obstetric population. Arch Gynecol Obstet 2011;283:1193–8. 13. Combs CA, Murphy EL, Laros RK Jr. Factors associated with postpartum hemorrhage with vaginal birth. Obstet Gynecol 1991;77:69–76. 14. Hällström M, Eerola E, Vuento R, Janas M, Tammela O. Effects of mode of delivery and necrotising enterocolitis on the intestinal microflora in preterm infants. Eur J Clin Microbiol Infect Dis 2004;23:463–70. 15. Gawade PL, Whitcomb BW, Chasan-Taber L, Pekow PS, Ronnenberg AG, Shah B, et al. Second stage of labor and intraventricular hemorrhage in early preterm infants in the vertex presentation. J Matern Fetal Neonatal Med 2013;26:1292–8. 16. Wankaew N, Jirapradittha J, Kiatchoosakun P. Neonatal morbidity and mortality for repeated cesarean section vs. normal vaginal delivery to uncomplicated term pregnancies at Srinagarind Hospital. J Med Assoc Thai 2013;96:654–60. 17. Puza S, Roth N, Macones GA, Mennuti MT, Morgan MA. Does cesarean section decrease the incidence of major birth trauma? J Perinatol 1998;18:9–12. 18. Westgren M, Dolfin T, Halperin M, Milligan J, Shennan A, Svenningsen NW, et al. Mode of delivery in the low birth weight fetus. Delivery by cesarean section independent of fetal lie versus vaginal delivery in vertex presentation. A study with long-term follow-up. Acta Obstet Gynecol Scand 1985; 64:51–7. 19. Holzer I, Lehner R, Ristl R, Husslein PW, Berger A, Farr A. Effect of delivery mode on neonatal outcome among preterm infants: an observational study. Wien Klin Wochenschr 2016 Dec 21 [Epub ahead of print]. 20. Holm C, Langhoff-Roos J, Petersen KB, Norgaard A, Diness BR. Severe postpartum haemorrhage and mode of delivery: a retrospective cohort study. BJOG 2012;119:596–604. 21. Pallasmaa N, Ekblad U, Gissler M. Severe maternal morbidity and the mode of delivery. Acta Obstet Gynecol Scand 2008;87: 662–8. 22. Bailit JL, Grobman WA, Rice MM, Wapner RJ, Reddy UM, Varner MW, et al. Evaluation of delivery options for secondstage events. Am J Obstet Gynecol 2016;214:638.e1–10. 23. Geller EJ, Wu JM, Jannelli ML, Nguyen TV, Visco AG. Maternal outcomes associated with planned vaginal versus planned primary cesarean delivery. Am J Perinatol 2010;27:675–83.
7. Nassar AH, Adra AM, Chakhtoura N, Gómez-Marín O, Beydoun S. Severe preeclampsia remote from term: labor induction or elective cesarean delivery? Am J Obstet Gynecol 1998;179: 1210–3.
24. Spong CY, Berghella V, Wenstrom KD, Mercer BM, Saade GR. Preventing the first cesarean delivery: summary of a joint Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, and American College of Obstetricians and Gynecologists Workshop. Obstet Gynecol 2012;120:1181–93.
8. Alexander JM, Bloom SL, McIntire DD, Leveno KJ. Severe preeclampsia and the very low birth weight infant: is induction of labor harmful? Obstet Gynecol 1999;93:485–8.
25. Zwecker P, Azoulay L, Abenhaim HA. Effect of fear of litigation on obstetric care: a nationwide analysis on obstetric practice. Am J Perinatol 2011;28:277–84.
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26. Lee HC, Gould JB. Survival rates and mode of delivery for vertex preterm neonates according to small- or appropriatefor-gestational-age status. Pediatrics 2006;118:e1836–44.
28. Wylie BJ, Davidson LL, Batra M, Reed SD. Method of delivery and neonatal outcome in very low-birthweight vertex-presenting fetuses. Am J Obstet Gynecol 2008;198:640.e1–7.
27. Werner EF, Han CS, Savitz DA, Goldshore M, Lipkind HS. Health outcomes for vaginal compared with cesarean delivery of appropriately grown preterm neonates. Obstet Gynecol 2013;121:1195–200.
29. Sievert RA, Kuper SG, Jauk VC, Parrish M, Biggio JR, Harper LM. Predictors of vaginal delivery in medically indicated early preterm induction of labor. Am J Obstet Gynecol 2017 May 17 [Epub ahead of print].
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