American Journal of Obstetrics & Gynecology
Volume 198, Issue 5 , Pages 511.e1-511.e15, May 2008

The impact of the active management of risk in pregnancy at term on birth outcomes: a randomized clinical trial

Presented at the 28th Annual Meeting of the Society for Maternal-Fetal Medicine, Dallas, TX, Jan. 28-Feb. 2, 2008.

  • James M. Nicholson, MD, MSCE

      Affiliations

    • Department of Family Medicine and Community Health, University of Pennsylvania, Philadelphia, PA
    • ,
  • Samuel Parry, MD

      Affiliations

    • Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA
    • ,
  • Aaron B. Caughey, MD PhD

      Affiliations

    • Department of Obstetrics and Gynecology, University of California, San Francisco, CA
    • ,
  • Sarah Rosen, MD

      Affiliations

    • Pennsylvania Hospital, Philadelphia, PA
    • ,
  • Allison Keen, MD

      Affiliations

    • Pennsylvania Hospital, Philadelphia, PA
    • ,
  • George A. Macones, MD, MSCE

      Affiliations

    • Department of Obstetrics and Gynecology, Washington University, St. Louis, MO.

Article Outline

Objective

The purpose of this study was to compare birth outcomes that result from the active management of risk in pregnancy at term (AMOR-IPAT) to those outcomes that result from standard management.

Study Design

This was a randomized clinical trial with 270 women of mixed parity. AMOR-IPAT used preventive labor induction to ensure delivery before the end of an estimated optimal time of delivery. Rates of 4 adverse obstetric events and 2 composite measures were used to evaluate birth outcomes.

Results

The AMOR-IPAT–exposed group had a similar cesarean delivery rate (10.3% vs 14.9%; P = .25), but a lower neonatal intensive care unit admission rate (1.5% vs 6.7%; P = .03), a higher uncomplicated vaginal birth rate (73.5% vs 62.8%; P = .046), and a lower mean Adverse Outcome Index score (1.4 vs 8.6; P = .03).

Conclusion

AMOR-IPAT exposure improved the pattern of birth outcomes. Larger randomized clinical trials are needed to explore further the impact of AMOR-IPAT on birth outcomes and to determine the best methods of preventive labor induction.

Key words: adverse outcome index, cesarean delivery, neonatal intensive care unit admission, preventive labor induction, uncomplicated vaginal delivery

 

Over the past decade, the overall rate of cesarean delivery in the United States has increased steadily from 22%-31.1%.1, 2, 3 Increases in cesarean delivery rates have occurred in all areas of the country and in most hospitals. The reasons for these increases are multifactorial and include changing patient risk profiles,4, 5, 6 medicolegal pressures,7, 8 and a growing interest in elective primary cesarean delivery.9, 10 However, despite increases in cesarean utilization, few improvements have been made in the overall quality of birth outcomes. US rates of term neonatal intensive care unit (NICU) admission have not decreased significantly,11 and rates of maternal and neonatal mortality have increased slightly.12 Currently, there is little research targeting either ways to reverse the current rising trend in cesarean delivery or ways to improve the overall pattern of birth outcomes.

For Editors' Commentary, see Table of Contents

Several recent retrospective studies have described an alternative method of obstetric care that has been associated with low cesarean delivery rates and improvement in the pattern of birth outcomes.13, 14 This alternative method uses risk-based preventive labor induction to ensure that each pregnant woman enters labor at a gestational age that maximizes her chance for vaginal delivery. The alternative method is termed active management of risk in pregnancy at term (AMOR-IPAT). In addition to its association with lower cesarean delivery rates, AMOR-IPAT exposure has also been associated with lower NICU admission rates, decreased perineal trauma, and lower rates of low Apgar scores.13, 14, 15, 16, 17 However, the finding of previous AMOR-IPAT studies have been challenged on the basis of retrospective study design,18 potential confounding by provider type, and inability to control for individual physician differences in labor-management style apart from the variable use of labor induction.19 In response to these concerns, a randomized clinical trial was undertaken to evaluate more definitively the impact of AMOR-IPAT exposure on rates of cesarean delivery and other important birth outcomes.

The safe prevention of cesarean delivery is important because cesarean delivery, when compared with vaginal delivery, is associated with higher rates of postpartum hemorrhage, major postpartum infection, and hospital readmission.20, 21, 22, 23 In addition, cesarean delivery carries a greater likelihood for not only serious pulmonary morbidity for the neonate in the index pregnancy24 but also other major fetal complications, which include fetal loss, in subsequent pregnancies.25, 26, 27 Although several recent reports have described elective primary cesarean delivery as a way to prevent vaginal delivery–related pelvic floor damage and resultant genitourinary morbidity,28, 29, 30 other reports have suggested that such benefits are neither clear-cut nor long-lasting.31, 32 There is currently no clear evidence that the risk/benefit ratio of elective primary cesarean delivery is equal or superior to the risk/benefit ratio of the current standard of care that couples expectant management within the term period with attempted vaginal delivery. AMOR-IPAT was developed as a third option. It uses preventive labor induction relatively early in the term period of pregnancy to promote uncomplicated vaginal delivery and to prevent a variety of adverse birth outcomes.

Back to Article Outline

Materials and Methods 

Study design 

A randomized clinical trial design was used to evaluate the impact of AMOR-IPAT exposure on mode of delivery and other major birth outcomes. Pregnant women were invited to participate in the study between 32 and 37½ weeks of gestation. There were 3 study inclusion factors: (1) accurate pregnancy dating (averaging of last menstrual period and ultrasound data for 8-22 weeks of gestation if the discrepancy was ≤ 6 days, or averaging of two ultrasound evaluations at 8-22 weeks of gestation if the discrepancy was ≤ 5 days); (2) fluency with the English language; and (3) at least 1 of 6 preidentified risk factors for cesarean delivery: (a) projected maternal age ≥ 35 years at the time of delivery, (b) maternal height ≤ 62 inches, (c) body mass index ≥ 30 kg/m2 at conception, (d) blood pressure elevation (any blood pressure of > 80 mm Hg diastolic or > 120 mm Hg systolic in the first trimester), (d) first trimester hemoglobin level of < 11.0 gms/dL, and (f) history of large fetus (> 8 lb 8 oz). Although our method of pregnancy dating was unconventional, we believe that the merging of 2 good measurements improves the accuracy of the estimated date of confinement. In turn, the safety of early term labor induction is improved if pregnancy dating is accurate. Additional risk factors beyond the 6 preidentified risk factors were included in the AMOR-IPAT risk-scoring model (Appendix 1). Exclusion factors included multiple gestation, previous cesarean delivery, placenta previa, positive HIV antibody titers, previous cervical cone biopsy, or any other fetal or maternal issue that would preclude a trial of labor. Women who provided informed consent and who remained undelivered at 37 weeks 4 days of gestation were randomized to either AMOR-IPAT or usual care. For logistic and clinical reasons, cervical Bishop score was not determined before randomization, nor was it part of the randomization scheme.

Unique sets of opaque envelopes were created for each parity group and each risk type at each of 3 recruitment sites (4 sets of envelopes for each site). The 3 recruitment sites were the Hospital of the University of Pennsylvania Obstetrics Clinic (an obstetric residency training site), the Pennsylvania Hospital Obstetrics Clinic (an obstetric residency training site), and Penn Family Care (a family medicine residency training site). A block-size of 4 was used in the randomization scheme because subjects at each site were assigned randomly on the basis of both parity group (nulliparous vs multiparous) and major risk type (uteroplacental insufficiency [UPI] vs cephalopelvic disproportion [CPD]). A larger block design would have been more likely to lead to an imbalance of these factors and assignment between study groups. Because subjects provided informed consent weeks before their random assignment and because the exact ordering of consented women who were waiting to be assigned randomly could change at any time if a consented subject delivered before random assignment, it was not possible to predict which envelope would be opened for any given subject at the time informed consent was obtained. All deliveries were intended to occur at either the Hospital of the University of Pennsylvania (recruitment site 1 and recruitment site 2) or Pennsylvania Hospital (recruitment site 3). The study was constructed initially to be a double-blinded trial; however, because the active management of risk clearly involved the use of labor induction without an accepted indication and because the scheduling of preventive labor induction required hospital admission earlier than most women anticipated, the study could not be blinded completely to either subjects or providers. Accordingly, approximately one-quarter of the way through the investigation, all study subjects were informed of group assignment within 1 or 2 days of random assignment. Other than the identification of active group assignment of women who received preventive labor induction, providers were not informed routinely of study group assignment, and the neonatal staff members who made the determination of NICU admission remained functionally blinded.

The AMOR-IPAT method has been described previously.13, 14, 33 For each subject in the exposed group, specific risk factors for cesarean delivery were identified and placed in 1 of 2 risk categories: (1) a UPI category (ie, factors that interfere with placental growth or accelerate placental aging) and/or (2) a CPD category (ie, factors that accelerate fetal growth or limit maternal pelvic size). We prefer to use the term “CPD” rather than “failure to progress” because CPD implies a multifactorial problem that potentially can be both predicted and prevented. We converted the published odds ratio for cesarean delivery for each specific risk factor into a specific number of days using a previously published formula (Appendix 1).13, 14, 33 We then subtracted the total number of days that any given subject had in each of the 2 risk categories from 41 weeks 0 days of gestation to estimate an upper limit of the optimal time of delivery (UL-OTD) for each risk category.34 The lower of the 2 category-specific UL-OTDs for each woman became her final UL-OTD, but a final UL-OTD could not be < 38 weeks 0 days of gestation. Although the process of UL-OTD determination may appear complicated, its determination requires only a 1-page scoring sheet and simple addition and subtraction.

If a woman in the exposed group did not experience spontaneous labor as she approached her UL-OTD, then she was scheduled for preventive labor induction so that she would begin labor on or 1-4 days before her UL-OTD. Within this 4-day range, the exact timing of induction was often impacted by subject preference or labor floor space availability. If a woman was scheduled for labor induction but had an unfavorable uterine cervix (modified Bishop's score, < 6),35 then she was provided with cervical ripening with dinoprostone or misoprostol before the start of oxytocin. For this study, labor was defined as the presence of regular contractions that were associated with cervical change, and labor induction was defined as the use of artificial agents to promote labor in a woman with intact membranes.

Consented study subjects who experienced an accepted indication for labor induction were induced by standard protocols irrespective of gestational age, randomization status, or study group assignment. Apart from the timing of preventive labor induction, no other study protocol changes were made in the labor treatment of women in the study. Data related to prenatal, intrapartum, and postpartum events were collected from each mother and each baby.

Data analysis 

We compared rates and proportions of prenatal and intrapartum covariates that were present in the exposed and nonexposed groups. We calculated means and medians of continuous variables. Normal distributions were compared with the use of the Student t test, and nonnormal distributions were compared with the use of the Wilcoxon rank-sum test. Thereafter, we converted some continuous variables into clinically meaningful dichotomous variables (eg, an “advanced maternal age” variable was created by determining whether a woman was ≥ 35 years old at the time of delivery). Dichotomous and categoric variables were compared using chi-squared techniques. We used relative risk as the main measure of comparison and defined statistical significance for all tests as a probability value of .05.

We calculated and compared rates of various birth outcomes in the 2 groups. An intention-to-treat approach was taken on the basis of exposure to AMOR-IPAT. Some secondary analyses were based on mode-of-labor onset and parity groupings. The primary outcome of the study was mode of delivery. The trial was powered to show statistical significance if the exposed group had a cesarean delivery rate of 6% and the nonexposed group had a cesarean delivery rate of 18%. These rates were based on several previous retrospective investigations that studied women who were similar to those recruited into this study.13, 14, 15 In addition to the primary outcome “cesarean delivery,” 3 secondary outcomes were identified a priori: (1) major perineal injury (3rd- or 4th-degree tear), (2) NICU admission, and (3) 5-minute Apgar score < 7. All decisions to admit neonates to the NICU were made by members of the NICU staff. We used stepwise multivariate logistic regression to adjust for potential confounding in the association between AMOR-IPAT exposure and the primary and secondary outcomes. All potential prenatal variables, which included all risk factors that were used for UL-OTD estimation, were added to the initial model. Variables that did not impact the model significantly were then deleted in stepwise fashion with the use of likelihood ratio methods and a probability value of < .05.

We also assessed the impact of AMOR-IPAT exposure on a variety of other birth outcomes with the use of chi-squared methods (Fisher's exact test) for dichotomous outcomes and Wilcoxon rank-sum analysis for continuous outcomes. Flux in hemoglobin level was determined by subtracting the lowest postdelivery hemoglobin level from the predelivery hemoglobin level. A composite outcome entitled “Fetal intolerance of labor, all types” was created that captured the presence of any of the 4 fetal heart tone abnormalities that can lead to cesarean delivery: repetitive late decelerations, severe variable decelerations, persistent bradycardia (fetal heart tone, <90 beats per minute) or persistent tachycardia (fetal heart tone, >170 beats per minute). We determined various labor-related time intervals for each group and made comparisons using Wilcoxon rank-sum methods. In addition, we performed a survival analysis to compare the patterns of delivery as a function of gestational age in the study groups and calculated an adjusted Cox proportional hazard ratio. An analysis of the number needed to treat or the number needed to harm was done for all major outcomes that were present at statistically different levels in the 2 groups. We used bar graphs to present data that were related to the impact of gestational age on the frequency of 3 specific clinical events in the 2 study groups: (1) timing of delivery, (2) mode of onset of labor (spontaneous vs induction), and (3) type of nursery admission (regular nursery vs NICU admission).

Because of the importance of the estimation of the UL-OTD for each subject in the timing of preventive labor induction, we compared final UL-OTD estimations for women in each study group. Furthermore, we compared mean gestational age at delivery as a function of UL-OTD in the 2 study group. The study was not powered to differentiate rates of various study outcomes as a function of UL-OTD.

Finally, after all other data analyses, we assessed our study's findings using 2 composite outcomes. The first was the adverse birth outcome index (AOI). This previously published index evaluates the outcomes of any given group based on a weighted scoring system of 10 specific adverse outcomes (Appendix 2).36 As in the study that introduced the AOI, we calculated and compared mean AOI scores. In addition, we compared the distributions of this outcome in the 2 study groups using Wilcoxon rank-sum testing. The second composite outcome was a construct entitled “uncomplicated vaginal birth” (UVB; Appendix 3). A UVB identifies a vaginal delivery that is not impacted by any of 5 adverse events: (1) mechanical assistance (vacuum or forceps), (2) severe shoulder dystocia (ie, shoulder dystocia that, according to the delivery note, appeared prolonged, required multiple maneuvers [McRobert's, suprapubic pressure, Woods screw, second level provider, knee chest positioning], and required considerable traction), (3) major perineal trauma (3rd- or 4th-degree tear), (4) postpartum hemorrhage (estimated blood loss, > 500 mL), or (5) NICU admission. We compared UVB rates using chi-squared methods, and the number needed to treat analysis was done for the UVB composite outcome. All data were analyzed with the STATA Statistical Program (version 8; Stata Corporation, College Station, TX). The National Institutes of Child Health and Human Development of the National Institutes of Health and the Institutional Review Board of the University of Pennsylvania approved the study protocol. The study was performed under 2 investigational new drug numbers from the Food and Drug Administration because of the experimental use of both misoprostol and dinoprostone for cervical ripening before preventive labor induction.

Back to Article Outline

Results 

The development of the 2 study groups is outlined in Figure 1. One hundred thirty-six women made up the exposed group, and 134 women made up the nonexposed group. Two hundred one women came from the obstetric clinic of the Hospital of the University of Pennsylvania (74.4%); 61 women came from the obstetric clinic at Pennsylvania Hospital (22.6%), and 8 women came from the family medicine offices of Hospital of the University of Pennsylvania (3%).

  • View full-size image.
  • FIGURE 1. 

    Study group development

  • The flow of subjects throughout the study is shown.

  • Nicholson. The impact of the active management of risk in pregnancy at term on birth outcomes: a randomized clinical trial. Am J Obstet Gynecol 2008.

The 2 final study groups were similar, with reference to rates of common demographic, prenatal variables, and study risk factors (Table 1). Statistically significant differences in rates of previous abortion and anemia probably were due to chance. As expected, based on study design (Table 2), the exposed group exhibited 4 clinical features: (1) earlier delivery within the term period of pregnancy (median gestational age of delivery, 39.1 vs 40.0 weeks; P < .001), (2) higher labor induction rate (58% vs 21.6%; P < .001), (3) lower median modified cervical Bishop's score on admission (3 vs 5; P = .001), and (4) higher rate of cervical ripening using prostaglandins (prostaglandin E2 or E1; 40.4% vs 17.2%; relative risk, 2.36; P < .001; Table 2). Survival analysis of time-to-delivery during the term period demonstrates the continuous nature of the earlier delivery in the exposed group, compared with the nonexposed group (Figure 2). The Cox proportional hazard ratio for the survival analysis was 2.30 (95% CI, 1.78-2.98; P < .001). Graphic displays of gestational age at delivery (Figure 3A) and the timing and frequency of labor induction (Figure 3B) demonstrate very different distributions of these events in the 2 study groups.

TABLE 1. Levels of predelivery risk factors by study group: prenatal variables in the 2 study groups
VariableGroupRisk ratio95% CIP value
Exposed (n = 136)Nonexposed (n = 134)
Demographic
Median age (y)23.423.3——.91a
Advanced age: ≥ 35 y at delivery (%)4.43.71.180.37-3.78.78b
African American (%)89.786.61.040.95-1.13.42
Medicaid insurance (%)92.691.81.010.94-1.08.79
Married (%)14.715.70.950.54-1.67.87
Medical history
Previous SAB (%)21.326.90.790.52-1.22.29
Previous TAB (%)23.542.50.550.39-0.79<.001
Any blood pressure elevation during first trimester: diastolic > 80 mm Hg or systolic > 120 mm Hg (%)3934.31.140.83-1.56.43b
Chronic hypertension (%)10.37.50.670.64-3.00.41c
Asthma (%)19.417.60.910.55-1.50.71
Cigarette use (%)18.117.71.020.59-1.75.94c
Marijuana abuse (%)9.76.71.440.60-3.47.40
Obstetric history
Baby > 8 lbs 8 oz (%)11.819.40.610.34-1.08.08b
Vacuum or forceps (%)3.75.20.700.23-2.16.54c
Laboratory data
1-hr glucola level ≥ 135 mg/dL (%)8.110.40.770.36-1.64.50
Mean hemoglobin level
First trimester (gms/dL)11.812.1——.03
Second trimester (gms/dL)10.711.2——.02
Anemia: first trimester hemoglobin level < 11 gms/dL or second trimester hemoglobin level < 10 gms/dL (%)34.623.11.491.02-2.20.04b
Sickle cell trait (%)3.78.20.450.16-1.25.11c
Positive group B strep culture (%)35.342.50.830.61-1.12.22
Maternal habitus
Mean height (in)64.163.6——.22a
Short stature: height ≤ 5 ft 2 in (%)33.140.30.820.60-1.13.22
Mean preconception weight (lb)172.3167.8——.68a
Body mass index at conception (kg/m2)29.328.9——.92a
Body mass index > 30 kg/m2 at conception (%)42.741.81.020.77-1.35.89b
Index pregnancy
Mean weight gain during pregnancy (lb)31.830.5——.61a,c
Fetal sex: female (%)52.950.80.960.75-1.22.72

SAB, spontaneous abortion; TAB, therapeutic abortion.

Nicholson. The impact of the active management of risk in pregnancy at term on birth outcomes: a randomized clinical trial. Am J Obstet Gynecol 2008.

aCalculated with the Mann Whitney rank-sum test.

bStudy risk factors used in subject selection.

cOther risk factors used for risk scoring

TABLE 2. Levels of intrapartum factors by study group: intrapartum factors (status on admission, labor induction activity, anesthesia) and duration of various events in the 2 study groups
VariableGroupRisk ratio95% CIP value
Exposed (n = 136)Nonexposed (n = 134)
Subject status on admission
Nulliparous (%)47.847.01.020.79-1.31.80
Median gestational age at delivery (wk)39.140.0——<.001
Ruptured membranes on admission (%)1425.40.550.33-0.92.02
Initial Bishop's score
Median35——.001
≤ 5 (%)79.469.41.140.99-1.14.06
Intrapartum events
Spontaneous labor (%)22.145.50.480.34-0.70<.001
Induction of labor (%)58.121.62.681.89-3.82<.001
Augmentation after premature rupture of membranes or ineffective spontaneous labor (%)19.832.80.620.40-0.92.02
Prostaglandin: any use (%)40.417.22.361.54-3.60<.001
Prostaglandin E1: any antepartum use (%)32.411.92.710.61-4.56<.001
Prostaglandin E2: any antepartum use (%)11.05.22.116.20-19.89<.001
Use of pitocin: any (%)76.564.21.191.02-1.39.03
Artificial rupture of membranes (%)72.164.91.110.94-1.31.21
Epidural analgesia (%)81.684.30.970.87-1.08.55
Intrapartum findings
Thick meconium at rupture of membranes (%)3.78.20.450.16-1.25.11
Fetal intolerance to labor: all types (%)a22.833.60.680.46-1.00.049
Severe variable decelerations (%)13.216.40.810.45-1.43.46
Repetitive late decelerations (%)15.420.90.730.44-1.23.24
Persistent nonterminal bradycardia: <100 beats/min (%)1.52.20.660.11-3.87.64
Persistent tachycardia: >170 beats/min (%)0.80.70.990.06-15.6.99
Median maternal temperature (°F)98.698.6——.86
Maternal fever before delivery: >100.4°F (%)4.43.01.480.43-5.12.53
Labor and delivery timing
Admission (mean)
Mean labor onset: all (hr)6.23.6——<.001b
First stage: all (hr)7.36.4——.11b
First stage: nulliparous (hr)8.68.3——.69b
First stage: multiparous (hr)6.35.0——.13b
Second stage: all (min)4148——.43b
First stage: nulliparous (min)5877——.20b
First stage: multiparous (min)2827——.73b
Second stage > 2 hr: nulliparous (%)8.16.71.200.50-2.81.67b
Second stage > 1 hr: multiparous (%)11.45.81.970.62-6.25.24
Mean delivery discharge, mother: all (hr)51.959.3——.02b
Overall admission: mean
Mother, all (hr)66.370.5——.70b
Baby, all (hr)54.066.1——.01b

Nicholson. The impact of the active management of risk in pregnancy at term on birth outcomes: a randomized clinical trial. Am J Obstet Gynecol 2008.

aAt least 1 of the 4 types of fetal heart tone abnormalities.

bMann-Whitney rank-sum test.

  • View full-size image.
  • FIGURE 2. 

    Kaplan-Meier survival estimates, by exposed

  • Survival analysis of timing of delivery by study group: the number of weeks beyond 37 weeks 0 days of gestation at the time of delivery

  • Nicholson. The impact of the active management of risk in pregnancy at term on birth outcomes: a randomized clinical trial. Am J Obstet Gynecol 2008.

  • View full-size image.
  • FIGURE 3. 

    Timing of delivery, mode of labor onset, and type of nursery admission as a function of gestational age

  • The continuous nature of earlier gestational age at delivery in the exposed group, as compared with the nonexposed group, is shown. A, Distribution of gestational age at delivery by study group: the timing of delivery by half weeks of gestation in the 2 study groups is shown. B, Distribution of mode of labor onset by gestational age and study group: the timing of labor induction and spontaneous labor by half weeks of gestation in the 2 study groups is shown. C, Distribution of type of nursery admission by gestational age and study group: the timing of NICU admission by half weeks of gestation in the 2 study groups is shown.

  • Nicholson. The impact of the active management of risk in pregnancy at term on birth outcomes: a randomized clinical trial. Am J Obstet Gynecol 2008.

The cesarean delivery rate of the exposed group was 10.3%, compared with 14.9% in the usual care group (relative risk, 0.69; 95% CI, 0.36-1.31; P = .25; Table 3). Adjustment for parity and short stature changed these estimates only slightly (adjusted odds ratio, 0.66; P = .28; Table 4). Cesarean delivery rates in the nulliparous subgroup and the multiparous subgroup were 18.5% vs 25.8% (P = .32) and 2.8% vs 5.6% (P = .41), respectively. When the secondary outcomes were examined, the infants of women in the exposed group were admitted to the NICU less frequently than the infants of women in the nonexposed group (1.5% vs 6.7%; relative risk, 0.22; 95% CI, 0.05-0.99; P = .03; Table 3). The statistical significance of this difference remained after adjustment for sex of infant and site of prenatal care (adjusted odds ratio, 0.18; P = .037; Table 4). Figure 3C shows the timing of NICU admissions as a function of gestational age at delivery in the 2 study groups. Rates of low Apgar score at 5 minutes (< 7) and major perineal injury were not statistically different in the 2 study groups. All 7 major perineal injuries were 3rd-degree spontaneous tears, and only 1 of these followed a 2nd-degree episiotomy.

TABLE 3. Major study outcomes: rates of adverse outcomes and composite outcome data in the 2 study groups
VariableGroupRisk ratio95% CIP value
Exposed (n = 136)Nonexposed (n = 134)
Cesarean delivery information (%)
Cesarean delivery rate (all)10.314.90.690.36-1.31.25
Primigravid18.525.80.720.37-1.39.32
Multiparous2.85.60.510.10-2.68.41
Indications for cesarean delivery (%)
Failure to progress3.78.20.450.16-1.25.11
Fetal intolerance6.66.01.110.4-2.79.83
Elective (history of shoulder dystocia)00.8——.31
Occurrence of cesarean delivery by mode of labor onset (%)
Spontaneous labor6.78.20.810.17-3.95.80
Induction of labor (all)11.424.10.470.19-1.15.10
Augmentation of labor11.118.20.610.18-2.1.42
NICU admission information (n)
Admission: overall2(1.5%)9(6.7%)0.220.05-0.99.03
Sepsis: suspect or actual1(0.75%)6(4.5%)0.160.02-1.34.053
Respiratory disorders that required NICU admission1(0.75%)2(1.5%)0.490.04-5.37.55
High serum bilirubin level (n)01(0.8%) .31
Other secondary outcomes
Perineal injury
Any (%)41.938.81.080.81-1.44.60
First degree (%)17.615.71.130.66-1.92.66
Second degree (%)20.621.60.830.60-1.51.83
Third degree (%)3.71.50.260.49-12.5.26
Apgar score at 5 min
Mean8.928.90——.91a
< 7 (n)01(0.8%)0 .31
Composite outcomes
AOI (mean)1.48.6——.03a
Nulliparous1.88.1——.03
Multiparous1.18.6——.28a
UVB (%)b73.562.71.781.01-3.13.046c
Nulliparous (%)63.149.21.280.94-1.75.11
Multiparous (%)83.174.61.110.94-1.32.22

Nicholson. The impact of the active management of risk in pregnancy at term on birth outcomes: a randomized clinical trial. Am J Obstet Gynecol 2008.

aCalculated with the Mann-Whitney rank-sum test.

bVaginal delivery without mechanical assistance, major perineal tear, severe shoulder dystocia, estimated blood loss of > 500 mL, or NICU admission.

cAdjusted for parity group.

TABLE 4. Logistic regression models for cesarean delivery and NICU admission: the logistic regression models used to evaluate the outcomes
VariableUnadjusted odds ratioP valueAdjusted odds ratioAdjusted P value
Cesarean delivery
Exposure to AMOR-IPAT0.65.250.66.28
Multiparous (previous vaginal birth)0.16<.0010.16<.001
Short stature (≤ 62 in)2.47.0152.25.04
NICU admission
Exposure to AMOR-IPAT0.21.0470.18.037
Fetus sex: male2.99.113.20.10
Location of prenatal care
Hospital of the University of Pennsylvania Obstetrics Clinic1.00—1.00—
Penn Family Care7.07.09810.51.06
Pennsylvania Hospital Obstetrics Clinic5.50.015.91.01
UVB
Exposure to AMOR-IPAT0.60.0570.58.046
Multiparous (previous vaginal birth)0.16<.0010.34<.001

Nicholson. The impact of the active management of risk in pregnancy at term on birth outcomes: a randomized clinical trial. Am J Obstet Gynecol 2008.

Table 5 shows that the rate of high estimated blood loss was lower in the exposed group, compared with the usual care group (5.9% vs 14.2%; P = .02). In addition, infants in the exposed group had significantly lower birthweights (3197 vs 3372 g; P = .005) and were less likely to experience the outcome: “fetal intolerance of labor, all types” (P = .049; Table 2). Although the exposed group had more infants with a birthweight of < 2500 g, none of these relatively small infants required NICU admission. Two infants in the exposed group required NICU admission after labor induction (1 for respiratory depression possibly because of intravenous narcotic dosage just before delivery and 1 for possible sepsis), and 2 infants in the usual care group required NICU admission after labor induction (both infants required 7 days of antibiotic therapy for possible sepsis). There was 1 perinatal death in the control group; however, the mother of this infant delivered at 37 weeks 4 days of gestation, and the death probably was not related to study group assignment.

TABLE 5. Maternal and neonatal outcomes based on AMOR- IPAT exposure status: univariate maternal and neonatal outcomes in the 2 study groups
VariableGroupRisk ratio95% CIP value
Exposed (n = 136)Nonexposed (n = 134)
Maternal
Delivery
Assisted vaginal delivery: all types (%)5.99.70.610.26-1.42.24
Use of vacuum (%)1.56.00.250.05-1.14.05
Use of forceps (%)4.43.71.180.37-3.78.78
Shoulder dystocia, severe (%)01.5%——.15
Episiotomy: first or second degree (%)1.51.50.980.14-6.89.99
Mean estimated blood loss (mL)403±236485±416——<.001a
High estimated blood loss
Vaginal > 500 mL (n/N)8/122(6.6)12/114(10.5%)0.620.26-1.47.27
Cesarean > 1000 mL (n/N)0/147/20(35%)——.01
Postpartum period
Mean maternal temperature (°F)98.898.9 .048
Maternal fever: > 100.4°F (%)5.25.20.980.36-2.7.98
Mean hemoglobin level (gm/dL)10.0±1.5110.0±1.58——.90
Anemia: hemoglobin level < 8 (gm/dL) (n/N)8/86(9.3%)10/97(10.3%)0.900.37-2.18.82
Flux in hemoglobin level with delivery (g)1.19±0.871.68±1.19——.007
(n = 80)(n = 92)
Maternal transfusion (n)2(1.5%)4(3.0%)0.490.09-2.64.40
Postpartum septic pelvic thrombophlebitis (n)02(1.5%)——.15
Neonatal
Male infant (%)47.4500.950.74-1.21.67
Abnormal nursery course (%)1.58.20.180.04-0.79.01
NICU admission: overall (n)2(1.5%)9(6.7%)0.220.05-0.99.03
Special care nursery (n)01(0.75%)———
Neonatal death (n)01(0.75%)———
Mean birthweight (g)3197±4973372±425——.005a
Large: > 4000 g (%)2.97.50.390.13-1.23.09
Small: < 2500 g (%)b5.2%1.5%3.40.73-16.3.09
Head circumference (cm)33.6±1.533.9±1.6——.25
Discordant discharge: ≥ 1 d (%)2.97.50.390.13-1.23.09

Nicholson. The impact of the active management of risk in pregnancy at term on birth outcomes: a randomized clinical trial. Am J Obstet Gynecol 2008.

aCalculated with the Mann-Whitney rank-sum test.

bNo neonate who weighed <2500 g required admission to the NICU.

The time intervals for various components of maternity admissions were somewhat different in the 2 study groups. The exposed group had a longer mean time between admission and onset of labor (6.2 vs 3.6 hours; P < .001), but the length of the first stage of labor was not statistically different (7.3 vs 6.4 hours; P = .11). The exposed group had a similar mean second stage of labor (41 vs 48 min; P = .43); the similarity extended to both the nulliparous and multiparous subgroups (data not shown). However, the median time from delivery to maternal discharge was significantly shorter in the exposed group (51.9 vs 59.3 hours; P = .02), and the overall median hospital admission time was similar for exposed and nonexposed mothers (66.3 vs 70.5 hours; P = .07). The neonates of exposed mothers experienced significantly shorter hospital stays (54.0 vs 66.1 hours; P = .01).

The first composite outcome to be evaluated was the AOI. The raw AOI scoring data are given in Appendix 2. The exposed group experienced a significantly lower median AOI score (1.4 vs 8.6; P = .03). Lower scores were also noted for nulliparous exposed women (1.8 vs 8.1; P = .03) but were statistically similar for exposed multiparous women (1.1 vs 8.6; P = .28; Table 3). The second composite outcome was the UVB rate. Women in the exposed group achieved an UVB 77.2% of the time, compared with 62.7% in the usual care group. After adjustment for parity, this difference remained statistically significant (adjusted odds ratio, 1.7; 95% CI, 1.01-2.94; P = .046; Table 4). However, the higher rate of UVB was not statistically significant when analysis was limited to the nulliparous subgroup (63.1% vs 49.2%; P = .11) or the multiparous subgroup (83.1% vs 74.6%; P = .22; Table 3).

Significant reductions in rates of both single and composite adverse outcomes and trends toward reduction of rates of both cesarean delivery and fetal macrosomia were found in the exposed group, despite a difference in median gestational age at delivery of only 6 days between the 2 study groups. For example, the impact of AMOR-IPAT on the rate of macrosomia may be puzzling superficially, because a typical fetus gains only approximately 200 g of weight per week during the term period. However, the key feature of AMOR-IPAT is that it differentially responds to each woman's overall constellation of risk. With the macrosomia example, the more risk of CPD, the earlier preventive labor is recommended. Hence, exposed women who were at especially high risk for CPD (which usually included risk factors for macrosomia) were delivered >6 days before nonexposed women with similar risk profiles. Appendix 4 shows that the greater the quantity of risk, the greater the discrepancy in gestational age at delivery in the 2 study groups. Within Appendix 4, 1 Yeager unit equals 1 day. Finally, the number needed to treat to prevent 1 NICU admission was estimated to be 19.2 (1/[0.067 – 0.015]), and the number needed to treat to obtain 1 uncomplicated vaginal delivery was 9.3 (1/[0.735 – 0.627]).

Back to Article Outline

Comment 

In this randomized clinical trial, a high rate of preventive labor induction during the term period of pregnancy led to 3 important findings: (1) a significantly lower NICU admission rate, (2) a significantly higher UVB rate, and (3) a significantly lower AOI. Although the rate of cesarean delivery was not significantly lower in the exposed group, the greater use of preventive labor induction in the exposed group clearly did not increase its rate of cesarean delivery. Taken together, the findings of the study indicate that the active approach to obstetric risk during the term period of pregnancy, with the use of preventive labor induction as needed, improved birth outcomes.

Our results are consistent with 2 previously completed retrospective investigations that involved preventive labor induction. The first study involved 400 urban primarily African American women and reported similar rates of NICU admission (9% vs 14.3%; P = .23) but lower rates of cesarean delivery (4% vs 16.7%; P < .001) in women who were exposed to AMOR-IPAT.13 The second study involved 1869 rural primarily Caucasian women and reported lower rates of both NICU admission (2.3% vs 4.2%; P = .03) and cesarean delivery (5.3% vs 11.7%; P < .001) in women who were exposed to AMOR-IPAT.14 Both retrospective studies also found that the rates of other adverse outcomes were either unchanged or lower in the AMOR-IPAT–exposed groups.

Further support for the validity of the AMOR-IPAT approach may be found in a recent retrospective study of labor induction that defined the control group as those women who were treated expectantly beyond the gestational age of induction. In this study, induction of labor at 38 and 39 weeks of gestation was associated with lower cesarean delivery rates.37 In addition, multiple recent publications have demonstrated that deliveries that occur relatively early within the term period of pregnancy are associated with the lowest rates of a variety of adverse birth outcomes.34, 38, 39, 40, 41 Finally, multiple randomized clinical studies have demonstrated improved birth outcomes for low-risk women after routine labor induction at 41 weeks of gestation, compared with expectant management beyond 41 weeks of gestation.42, 43 AMOR-IPAT incorporates these 2 ideas by using preventive labor induction before 41 weeks of gestation in a manner that is proportional to the amount of cumulative risk for cesarean delivery that is present in any given pregnancy. In keeping with the concept that AMOR-IPAT may promote labor when the cephalopelvic ratio is more favorable and the placenta is healthier, the AMOR-IPAT group in this randomized clinical trial had a lower average birthweight and a lower rate of major fetal heart tone abnormalities during labor.

In contrast to our findings, many previous retrospective studies have found an association between labor induction and higher rates of both NICU admission44 and cesarean delivery.45, 46, 47, 48, 49 However, most of these retrospective studies failed to account for at least 1 of 3 methods issues: (1) confounding by indication,50 (2) gestational age at delivery,51 and (3) the impact of a mode-of-labor-onset design vs a group-oriented design.13, 14, 33 Also in contrast to our findings, several randomized clinical trials have found a lack of benefit with labor induction, compared with expectant management. However, these studies all focused on women with already established problems such as oligohydramnios,52 macrosomia,53 and insulin-dependent diabetes mellitus.54 In addition, several often-cited randomized clinical studies that did not find benefit with labor induction either took place before the availability of prostaglandin cervical ripening protocols or were not powered sufficiently to evaluate fully the full spectrum of birth outcomes.55, 56, 57, 58 The prospective trials that have demonstrated improvement in birth outcomes due to labor induction were studies of women with mild-to-moderate risk profiles for whom labor induction was used before the development of a recognized complication.59, 60, 61

Our study has several potential limitations. First, it involved primarily African American women who delivered at 2 hospitals that were part of the same healthcare system. Hence, its generalizability to other racial/ethnic groups and other settings is unclear. However, evidence of association between AMOR-IPAT exposure and improved rates of adverse birth outcomes was found in a rural nonacademic population that was composed primarily of Caucasian women.14 Second, all study subjects were assigned randomly by and received all study communication from the study research assistants or the principal investigator. In addition, all chart abstraction and data entry were performed by the principal investigator's research team, which raises the possibility of information bias. However, the main prenatal issues involved with this study and the main study outcomes are dichotomous and relatively easy to determine. Hence, the likelihood that information bias significantly affected the main study findings is low. Third, the use of both the AOI and the UVB rate were not a part of the original study design. Therefore, the face validity of our findings that are related to these composite outcomes is lessened somewhat. However, the study that introduced the AOI was not published until after our study was initiated. In addition, based on the potential importance of the AOI, we would have included AOI data even if the results had not been significant. The decision to use the rate of UVB was based on our interest in evaluating both adverse birth outcomes and birth health.

The fourth limitation of this investigation was based on the nature of the intervention. Study group assignment could not be and was not completely blinded to either providers or study subjects. This raises the possibility of assessment bias on the part of the healthcare team who managed each woman's delivery. We are aware that medical judgments that are related to many obstetric outcomes, which includes the decision to perform a cesarean delivery or admit an infant to the NICU, contain subjective elements that could be impacted by incomplete blinding. However, it is unlikely that knowledge of study group assignment would have led to lower rates of NICU admission rates and cesarean delivery in the exposed group. Specifically, the NICU team would be unlikely to tolerate more neonatal respiratory insufficiency just because an infant was part of an investigation that is studying early term labor induction. Similarly, an obstetric team would be unlikely to tolerate more fetal intolerance or longer periods of dystocia just because a woman was undergoing preventive labor induction. In addition, any intentional delay of cesarean delivery in the active management group should have resulted in longer labor times and more neonatal complications at delivery in the exposed group. However, neither the range of nor the mean duration of the second stage of labor were longer in the exposed group, and overall neonatal outcomes were better in the AMOR-IPAT exposed group. Hence, although the lack of blinding theoretically could have affected study outcomes, the pattern of outcomes that were actually observed in this clinical trial are not consistent with assessment bias.

In summary, we found that exposure to AMOR-IPAT, through the frequent use of preventive labor induction, significantly reduced NICU admission rates in women with increased risk for cesarean delivery. Furthermore, the use of the composite outcomes AOI and UVB strongly suggests that exposure to AMOR-IPAT leads to significant improvements in overall birth health. The finding that AMOR-IPAT exposure did not increase the rate of any major adverse birth outcome requires a reconsideration of the belief that labor induction necessarily leads to adverse birth outcomes. Larger randomized clinical trials in more diverse populations are needed to further the study of the impact of this alternative method of obstetric care on both single and composite measures of birth health.

Back to Article Outline

Acknowledgments 

We thank Dr David Yeager for originally developing the concept of risk-guided prostaglandin-assisted preventive labor induction; Morgan Stenson, Linda Mules, and Shawn Puri for assistance with subject recruitment, chart abstraction, data entry, and study management; Marjorie Bowman, MD, for assistance with manuscript review; Russell Localio, JD, MS, MPH, Susan Friedman, MD, Edward Buchanan, MD, and Amy Crawford-Faucher, MD, for their involvement in this trial's Data Safety and Monitoring Committee; and Jack Ludmir, MD, for enabling patient recruitment at Pennsylvania Hospital.

Back to Article Outline

Appendix 1. AMOR-IPAT – UL-OTD calculation sheet: the scoring sheet used to estimate the upper limit of the optimal time of delivery for each study subject 

FactorOdds ratioTime unit (d)Score
Uteroplacental
History of chronic hypertension1.86
Gestational diabetes mellitus1.86
Insulin-dependent diabetes mellitus2.410
Sickle cell trait1.53
Elevated alpha fetoprotein1.43
Cigarette use1.32
Size < dates (≤ 3 cm)1.64
Advanced age (≥ 35 y at delivery)1.86
Anemia (first trimester ≤ 10.0 gm/dL)1.64
Total uteroplacental insufficiency time units
UL-OTD – UPI (41 wk – total UPI time units)
Cephalopelvic
Elevated body mass index (≥ 30 kg/m2)1.32
Short stature (≤ 62 in)1.86
Excess weight gain (≥ 30 lbs)1.86
Size > dates (≥ 3 cm)1.74
Gestational diabetes mellitus1.86
Type I diabetes mellitus2.410
History vacuum/forceps2.29
Previous macrosomia (≥ 4000 g)2.07
Total CPD time units
UL-OTD – CPD (41 wk – total CPD time units)

Final UL-OTD: lower of the 2 UL-OTDs (UL-OTD – UPI vs UL-OTD – CPD), but the final UL-OTD is always ≥38 weeks of gestation.

Back to Article Outline

Appendix 2. AOI by study group: detailed information about the generation of the AOI in the 2 study groups 

VariableGroup (n)Weight
Exposed (n = 136)Nonexposed (n = 134)
Maternal death00750
Intrapartum or neonatal death01 (0.75%)400
Uterine rupture00100
Maternal intensive care unit admission0065
Infant birth trauma (Erb's palsy, vacuum or forceps injury)04 (3.0%)60
Return to operating room of labor and delivery unit02 (1.5%)40
Admission to NICU2 (1.5%)9 (6.7%)35
Apgar score < 7 at 5-min01 (.75%)25
Maternal blood transfusion2 (1.5%)4 (3%)20
Third- or fourth-degree perineal tear5 (3.7%)2 (1.5%)5
Overall frequency of at least 1 adverse outcomea9 (4.4%)19 (14.2%)
Mean AOI scoreb1.48.6

Nicholson. The impact of the active management of risk in pregnancy at term on birth outcomes: a randomized clinical trial. Am J Obstet Gynecol 2008.

aP = .04, chi-square (Fisher's exact test) of proportions.

bP = .03, Wilcoxon rank-sum analysis.

Back to Article Outline

Appendix 3. UVB by study group: detailed information about the generation of the UVB rate in the 2 study groups 

VariableGroup (n)
Exposed (n = 136)Nonexposed (n = 134)
Cesarean delivery14 (10.3%)20 (14.9%)
Assisted vaginal delivery (vacuum or forceps)8 (5.9%)13 (9.7%)
Shoulder dystocia (severe)02 (1.5%)
Major perineal trauma (3rd- or 4th-degree tear)5 (3.7%)2 (1.5%)
Postpartum hemorrhage (vaginal and cesarean)21 (15.4%)30 (22.4%)
NICU admission2 (1.5%)9 (6.7%)
Overall frequency of complicated trial of labor (at least 1 of the 6 complications)36 (26.5%)50 (37.3%)
Overall frequency of UVB (none of the 6 identified adverse outcomes)100 (73.5%)84 (62.8%)

Nicholson. The impact of the active management of risk in pregnancy at term on birth outcomes: a randomized clinical trial. Am J Obstet Gynecol 2008.

Back to Article Outline

Appendix 4. 

Average gestational age at delivery as a function of Yeager group: the relationship between magnitude of risk of cesarean delivery (measured in Yeager units [or days subtracted from 41 weeks 0 days of gestation]) and mean gestational age at delivery in the 2 study groups. In the exposed group, greater risk resulted in earlier mean gestational age at delivery than in the nonexposed group

Key:

Yeager group 1: 1-3 Yeager units

Yeager group 2: 4-6 Yeager units

Yeager group 3: 7-9 Yeager units

Yeager group 4: 10-12 Yeager units

Yeager group 5: 13-15 Yeager units

Yeager group 6: 16-18 Yeager units

Yeager group 7: 19-21 Yeager units

Yeager group 8: >21 Yeager units

Nicholson. The impact of the active management of risk in pregnancy at term on birth outcomes: a randomized clinical trial. Am J Obstet Gynecol 2008.

Back to Article Outline

References 

  1. Martin JA, Brady EH, Paul PD, Ventura SJ, Menacker F, Munson ML. Births: final data for 2002. Natl Vital Stat Rep. 2003;52:1–117
  2. Martin JA, Hamilton BE, Menacker F, Sutton PD, Mathews TJ. Preliminary births for 2004: infant and maternal health: health e-stats. Hyattsville (MD): National Center for Health Statistics; 2005;
  3. Hamilton BE, Martin JA, Ventura SJ. Births: preliminary data for 2006. Natl Vital Stat Rep. 2007;56:1–18
  4. Linne Y. Effects of obesity on women's reproduction and complication during pregnancy. Obes Rev. 2004;5:137–143
  5. Ecker JL, Frigoletto FD. Cesarean delivery and the risk-benefit calculus. N Engl J Med. 2007;356:885–888
  6. Boulet SL, Alexander GR, Salihu HM. Secular trends in cesarean delivery rates among macrosomic deliveries in the United States, 1989 to 2002. J Perinatol. 2005;25:569–576
  7. Localio AR, Lawthers AG, Bengston JM, et al. Relationship between malpractice claims and cesarean delivery. N Engl J Med. 1993;269:366–373
  8. Murthy K, Grobman WA, Lee TA, Holl JL. Association between rising professional liability insurance premiums and primary cesarean delivery rates. Obstet Gynecol. 2007;110:1264–1269
  9. Lal M. Prevention of urinary and anal incontinence: role of elective cesarean delivery. Curr Opin Obstet Gynecol. 2003;15:439–448
  10. Minkoff H, Chervenak FA. Elective primary cesarean delivery. N Engl J Med. 2003;348:946s–950s
  11. Singh GK, Yu SM. Infant mortality in the United States: trends, differentials, and projections, 1950-2010. Am J Public Health. 1995;85:957–964
  12. Kung HC, Hoyert DL, Xu J, Murphy SL. Deaths: preliminary data for 2005: health e-stats. Hyattsville (MD): National Center for Health Statistics; 2007;
  13. Nicholson JA, Kellar LC, Cronholm PF, Macones GA. Active management of risk in pregnancy at term: an association between a higher induction of labor rate and a lower cesarean delivery rate. Am J Obstet Gynecol. 2004;191:1516–1528
  14. Nicholson JM, Yeager DL, Macones GA. A preventive approach to obstetric care in a rural hospital: association between higher rates of preventive labor induction and lower rates of cesarean delivery. Ann Fam Med. 2007;5:310–319
  15. Nicholson JM, Kellar LC, Cronholm PF, Macones GA. Active management of risk in pregnancy at term in an urban population: an association between higher induction of labor rates and lower cesarean delivery rates [abstract]. Am J Obstet Gynecol. 2003;189(suppl):S131
  16. Nicholson JM, Holt M, Caughey AB, Macones GA. The active management of risk in nulliparous patients at term: an association between a higher preventive labor induction rate and a lower cesarean delivery rate [abstract]. Am J Obstet Gynecol. 2005;193(suppl):S117
  17. Nicholson JM, Caughey AB, Stenson M, Kellar LC, Cronholm PF. The active management of risk in multiparous patients at term: an association between a higher preventive induction of labor rate and a lower cesarean delivery rate [abstract]. Am J Obstet Gynecol. 2006;195(suppl):S99
  18. Socol M. Elective induction of labor: should we make a fuss?. Am J Obstet Gynecol. 2004;191:1509–1510
  19. Klein MC. Association not causation: what is the intervention?. Ann Fam Med. 2007;5:294–297
  20. Deneux-Tharaux C, Carmona E, Bouvier-Colle MH, Breart G. Postpartum maternal mortality and cesarean delivery. Obstet Gynecol. 2006;108:541–548
  21. Liu S, Liston RM, Joseph KS, et al. Maternal mortality and severe morbidity associated with low-risk planned cesarean delivery versus planned vaginal delivery at term. Can Med Assoc J. 2007;176:455–460
  22. Hager RM, Daltveit AK, Hofoss D, et al. Complications of cesarean deliveries: rates and risk factors. Am J Obstet Gynecol. 2004;190:428–434
  23. Thompson JF, Roberts CL, Currie M, Ellwood DA. Prevalence and persistence of health problems after childbirth: associations with parity and method of birth. Birth. 2002;29:83–94
  24. Villar J, Carroli G, Zavaleta N, et al. Maternal and neonatal individual risks and benefits associated with caesarean delivery: multicenter prospective study. BMJ. 2007;335:1025–1029
  25. MacDorman MF, Declercq E, Menacker F, Malloy MH. Infant and neonatal mortality for primary cesarean and vaginal births to women with “no indicated risk”, United States, 1998-2001 birth cohorts. Birth. 2006;33:175–182
  26. Kennare R, Tucker G, Heard A, Chan A. Risks of adverse outcomes in the next birth after a first cesarean delivery. Obstet Gynecol. 2007;109:270–276
  27. Smith GC, Pell JP, Dobbie R. Caesarean section and risk of unexplained stillbirth in subsequent pregnancy. Lancet. 2003;362:1779–1784
  28. Minkoff H, Chervenak FA. Elective primary cesarean delivery. N Engl J Med. 2003;348:946–950
  29. Rogers R. Urinary stress incontinence in women. N Engl J Med. 2008;358:1029–1036
  30. Lukacz E, Lawrence J, Contreras R, Nager CW, Luber K. Parity, mode of delivery, and pelvic floor disorders. Obstet Gynecol. 2006;107:1253–1260
  31. Hannah ME, Whyte H, Hannah WJ, et al. Maternal outcomes at 2 years after planned cesarean delivery versus planned vaginal birth for breech presentation at term: the international randomized term breech trial. Am J Obstet Gynecol. 2004;191:917–927
  32. Dietz HP. Pelvic floor trauma following vaginal delivery. Curr Opin Obstet Gynecol. 2006;18:528–537
  33. Nicholson JM, Holt M. Will active management of obstetric risk lower C/S rates?. Contemp Obstet Gynecol. 2005;50:38–53
  34. Nicholson JM, Kellar LC, Kellar GM. The impact of the interaction between increasing gestational age and obstetrical risk on birth outcomes: evidence of a varying optimal time of delivery. J Perinatol. 2006;26:392–402
  35. Bujold E, Blackwell SC, Hendler I, Berman S, Sorokin K, Gauthier RJ. Modified Bishop's score and induction of labor in patients with a previous cesarean delivery. Am J Obstet Gynecol. 2004;191:1644–1648
  36. Nielsen PE, Goldman MB, Mann S, et al. Effects of teamwork training on adverse outcomes and process of care in labor and delivery. Obstet Gynecol. 2007;109:48–55
  37. Caughey AB, Nicholson JM, Cheng YW, Lyell DJ, Washington AE. Induction of labor and cesarean delivery by gestational age. Am J Obstet Gynecol. 2006;195:700–705
  38. Caughey AB, Musci TJ. Complications of term pregnancies beyond 37 weeks of gestation. Obstet Gynecol. 2004;103:57–62
  39. Caughey AB, Washington AE, Laros RK. Neonatal complications of term pregnancy: Rates by gestational age increase in a continuous, not threshold, fashion. Am J Obstet Gynecol. 2005;192:185–190
  40. Caughey AB, Stotland NE, Washington AE, Escobar GJ. Maternal and obstetric complications of pregnancy are associated with increasing gestational age at term. Am J Obstet Gynecol. 2007;196:155–156
  41. Heimstad R, Romundstad PR, Eik-Nes SH, Salvesen KA. Outcomes of pregnancy beyond 37 weeks of gestation. Obstet Gynecol. 2006;108:500–508
  42. Sanchez-Ramos L, Olivier F, Delke I, Kaunitz AM. Labor induction versus expectant management for postterm pregnancies: a systematic review with meta-analysis. Obstet Gynecol. 2003;101:1312–1318
  43. Crowley P. Interventions for preventing or improving the outcome of delivery at or beyond term. Cochrane Database Syst Rev. 2007;(3):CD000170
  44. Main EK, Bloomfield L, Hunt G. Development of a large-scale obstetric quality-improvement program that focused on the nulliparous patient at term. Am J Obstet Gynecol. 2004;190:1747–1758
  45. Cammu H, Martens G, Ruyssinck G, Amy JJ. Outcome after elective induction in nulliparous women: a matched cohort study. Am J Obstet Gynecol. 2002;186:240–244
  46. Yeast JD, Jones A, Poskin M. Induction of labor and the relationship to cesarean delivery: a review of 7001 consecutive inductions. Am J Obstet Gynecol. 1999;180:628–633
  47. Coonrod DV, Bay RC, Kishi GY. The epidemiology of labor induction: Arizona 1997. Am J Obstet Gynecol. 2000;182:1355–1362
  48. Seyb ST, Berka RJ, Socol ML, Dooley SL. Risk of cesarean delivery with elective induction of labor at term in nulliparous women. Obstet Gynecol. 1999;94:600–607
  49. Ben-Haroush A, Yogev Y, Bar J, Glickman H, Kaplan B, Hod M. Indicated labor induction with vaginal prostaglandin E2 increases the risk of cesarean section even in multiparous women with no previous cesarean section. J Perinatal Med. 2004;32:31–36
  50. Alexander JM, MCIntire DD, Leveno KJ. Prolonged pregnancy: induction of labor and cesarean births. Obstet Gynecol. 2001;97:911–915
  51. Caughey AB. What is the optimal gestational age for delivery?. J Perinatol. 2006;26:387–388
  52. Ek S, Andersson A, Johansson A, Kublicas M. Oligohydramnios in uncomplicated pregnancies beyond 40 completed weeks: a prospective, randomized, pilot study on maternal and neonatal outcomes. Fetal Diagn Ther. 2005;20:182–185
  53. Gonen O, Rosen DJ, Dolfin Z, Tepper R, Markov S, Fedjin MD. Induction of labor versus expectant management in macrosomia: a randomized study. Obstet Gynecol. 1997;89:913–917
  54. Kjos SL, Henry OA, Montoro M, Buchanan TA, Mestman JH. Insulin-requiring diabetes in pregnancy: a randomized trial of active induction of labor and expectant management. Am J Obstet Gynecol. 1993;169:611–615
  55. Martin DH, Thompson W, Pinkerton JHM, Watson JD. A randomized controlled trial of selective planned delivery. BJOG. 1978;85:109–113
  56. Nielsen PE, Howard BC, Hill CC, Larson PL, Holland RH, Smith PN. Comparison of elective induction of labor with favorable Bishop scores versus expectant management: a randomized clinical trial. J Matern Fetal Neonat Med. 2005;18:59–64
  57. Ohel G, Rahav D, Rothbart H, Ruach M. Randomized trial of outpatient induction of labor with vaginal PGE2 at 40-41 weeks of gestation versus expectant management. Arch Gynecol Obstet. 1996;258:109–112
  58. Amano K, Saito K, Shoda T, Tani A, Yoshihara H, Nishijima M. Elective induction of labor at 39 weeks of gestation: a prospective randomized trial. J Obstet Gynaecol Res. 1999;25:33–37
  59. Cole RA, Howie PW, Macnaughton MC. Elective induction of labour: a randomized prospective. Lancet. 1975;1:767–770
  60. Dyson DC, Miller PD, Armstrong MA. Management of prolonged pregnancy: induction of labor versus antepartum fetal testing. Am J Obstet Gynecol. 1987;156:928–934
  61. Hannah ME, Hannah WJ, Hellmann J, et al. Induction o labor as compared with serial antenatal monitoring in post-term pregnancy. N Engl J Med. 1992;326:1587–1592

 Supported by the National Institute of Child Health and Human Development of the National Institutes of Health (K23-HD-42043) and by a research grant from the First Hospital Foundation. Forest Pharmaceuticals provided dinoprostone pledgets for use at the Hospital of the University of Pennsylvania.

 Cite this article as: Nicholson JM, Parry S, Caughey AB, Rosen S, Keen A, Macones GA. The impact of the active management of risk in pregnancy at term on birth outcomes: a randomized clinical trial. Am J Obstet Gynecol 2008;198:511.e1-511.e15.

 Reprints not available from the authors.

PII: S0002-9378(08)00301-3

doi:10.1016/j.ajog.2008.03.037

American Journal of Obstetrics & Gynecology
Volume 198, Issue 5 , Pages 511.e1-511.e15, May 2008

Article Tools

* Image Usage & Resolution