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Active management of risk in nulliparous pregnancy at term: association between a higher preventive labor induction rate and improved birth outcomes

Published:January 27, 2009DOI:https://doi.org/10.1016/j.ajog.2008.08.052

      Objective

      The objective of the study was to determine whether exposure of nulliparous women to a high rate of preventive labor induction was associated with improvement in birth health.

      Study Design

      A risk-scoring system was used to guide the frequent use of preventive labor induction in 100 nulliparous women. The birth outcomes of this group were compared with those of 352 nulliparous women who received usual care. Cesarean delivery was the primary study outcome. The Adverse Outcome Index and the rate of uncomplicated vaginal delivery were used to measure overall birth health.

      Results

      The exposed group experienced a higher labor induction rate (48% vs 23.6%; P < .001), a lower cesarean rate (9% vs 25.8%; adjusted odds ratio, 0.36; P = .02), and better composite birth outcomes.

      Conclusion

      Exposure of nulliparous women to a high preventive induction rate was significantly associated with improvement in birth health. Prospective randomized trials are needed to further explore the utility of risk-guided preventive labor induction.

      Key words

      Between 1997 and 2006, the overall rate of cesarean delivery in the United States steadily increased from 22.0% to 31.1%.
      • Hamilton B.E.
      • Martin J.A.
      • Ventura S.J.
      Births: preliminary data for 2006.
      • Martin J.A.
      • Brady E.H.
      • Paul P.D.
      • Ventura S.J.
      • Menacker F.
      • Munson M.L.
      Births: final data for 2002.
      Increases in cesarean delivery rates have occurred in all 3 major obstetric groups: nulliparous women, multiparous women without previous cesarean delivery, and women with history of cesarean delivery.
      • Martin J.A.
      • Hamilton B.E.
      • Menacker F.
      • Sutton P.D.
      • Mathews T.J.
      Preliminary births for 2004: infant and maternal health.
      Despite these increases, the rates of other adverse birth outcomes, such as maternal mortality, neonatal intensive care unit (NICU) admission, and perinatal mortality, have not improved.
      • Hamilton B.E.
      • Martin J.A.
      • Ventura S.J.
      Births: preliminary data for 2006.
      • Martin J.A.
      • Brady E.H.
      • Paul P.D.
      • Ventura S.J.
      • Menacker F.
      • Munson M.L.
      Births: final data for 2002.
      • Martin J.A.
      • Hamilton B.E.
      • Menacker F.
      • Sutton P.D.
      • Mathews T.J.
      Preliminary births for 2004: infant and maternal health.
      Of concern, cesarean delivery, when compared with vaginal delivery, is associated with higher rates of a variety of adverse birth outcomes, such as major postpartum infection, NICU admission, and maternal mortality.
      • Kennare R.
      • Tucker G.
      • Heard A.
      • Chan A.
      Risks of adverse outcomes in the next birth after a first cesarean delivery.
      • Deneux-Tharaux C.
      • Carmona E.
      • Bouvier-Colle M.H.
      • Breart G.
      Postpartum maternal mortality and cesarean delivery.
      • Hager R.M.
      • Daltveit A.K.
      • Hofoss D.
      • et al.
      Complications of cesarean deliveries: rates and risk factors.
      For Editors' Commentary, see Table of Contents
      The route of delivery for a nulliparous woman, as compared with a multiparous woman, is particularly important for 2 reasons. First, a nulliparous woman who experiences a cesarean delivery for her first delivery in 2008 is unlikely to undergo a trial of labor with subsequent pregnancy.
      • Hamilton B.E.
      • Martin J.A.
      • Ventura S.J.
      Births: preliminary data for 2006.
      Second, a nulliparous woman who experiences a cesarean delivery for her first delivery is more likely, in subsequent pregnancies, to experience obstetric complications, including abnormal placentation,
      • Silver R.M.
      • Landon M.B.
      • Rouse D.J.
      • et al.
      Maternal morbidity associated with multiple repeat cesarean deliveries.
      uterine rupture,
      • Smith G.C.
      • Pell J.P.
      • Cameron A.D.
      • Dobbie R.
      Risk of perinatal death associated with labor after previous cesarean delivery in uncomplicated term pregnancies.
      and spontaneous stillbirth.
      • Kennare R.
      • Tucker G.
      • Heard A.
      • Chan A.
      Risks of adverse outcomes in the next birth after a first cesarean delivery.
      • Smith G.C.
      • Pell J.P.
      • Dobbie R.
      Caesarean section and risk of unexplained stillbirth in subsequent pregnancy.
      Whereas several recent reports have presented elective primary cesarean delivery as a way to prevent vaginal delivery-related pelvic floor damage and resultant urogynecological morbidity,
      • Minkoff H.
      • Chervenak F.A.
      Elective primary cesarean delivery.
      • Lal M.
      Prevention of urinary and anal incontinence: role of elective cesarean delivery.
      • Lukacz E.S.
      • Lawrence J.M.
      • Contreras R.
      • Nager C.W.
      • Luber K.M.
      Parity, mode of delivery, and pelvic floor disorders.
      others have suggested that such benefits may not be long lasting.
      • Dietz H.P.
      Pelvic floor trauma following vaginal delivery.
      • Hannah M.E.
      • Whyte H.
      • Hannah W.J.
      • 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.
      There is no clear evidence that the benefits of elective primary cesarean delivery are equal to, or outweigh, the benefits of attempted vaginal delivery.
      • Liu S.
      • Liston R.M.
      • Joseph K.S.
      • Heaman M.
      • Sauve R.
      • Kramer M.S.
      Maternal Health Study Group of the Canadian Perinatal Surveillance System
      Maternal mortality and severe morbidity associated with low-risk planned cesarean delivery versus planned vaginal delivery at term.
      Within the context of increasing national cesarean delivery rates and uncertainty regarding the appropriate use of elective cesarean delivery, an alternative method of preventive obstetrics was recently introduced.
      • Nicholson J.A.
      • Kellar L.C.
      • Cronholm P.F.
      • Macones G.A.
      Active management of risk in pregnancy at term in an urban population: an association between a higher induction of labor rate and a lower cesarean delivery rate.
      This alternative method, called the Active Management of Risk in Pregnancy at Term (AMOR-IPAT), utilizes preventive labor induction to ensure that pregnant women enter labor at an optimal time for the mother-baby pair. AMOR-IPAT has been associated with low rates of cesarean delivery (4-7%) in several studies involving patient cohorts of mixed parity.
      • Nicholson J.A.
      • Kellar L.C.
      • Cronholm P.F.
      • Macones G.A.
      Active management of risk in pregnancy at term in an urban population: an association between a higher induction of labor rate and a lower cesarean delivery rate.
      • Nicholson J.M.
      • Yeager D.L.
      • Macones G.A.
      A preventive approach to obstetric care in a rural hospital: association between higher rates of preventive labor induction and lower rates of cesarean delivery.
      However, because of the particular importance of the mode of delivery for a woman's first pregnancy, we wanted to develop and perform a study to evaluate the association between AMOR-IPAT exposure and cesarean delivery in nulliparous pregnant women. In addition, we wanted to evaluate the association between AMOR-IPAT exposure and other aspects of birth health.

      Materials and Methods

      A retrospective cohort design was used to study the use of AMOR-IPAT in nulliparous women who delivered at the Hospital of the University of Pennsylvania. The first 100 nulliparous women who delivered at term following exposure to AMOR-IPAT (“exposed” women) did so between April 1998 and February 2004. The outcomes of these exposed women were compared with the outcomes of 352 randomly selected nulliparous women who received usual care (“nonexposed” women) and who delivered during the same time period.
      Physicians from the Department of Family Medicine and Community Health provided the prenatal care and labor management for all exposed study subjects, and physicians and nurse-midwives from the Department of Obstetrics and Gynecology provided the prenatal care and labor management for all nonexposed study subjects.
      Study inclusion criteria included: (1) singleton pregnancy, (2) delivery on or after 37 weeks 3 days' gestation, and (3) no pre-38 week maternal or fetal contraindication for trial of labor (eg, placenta praevia, previous transmural uterine surgery, reactive human immunodeficiency virus serology, fetal hydrocephalus, or major fetal anomaly). In both study groups, delivery could occur following spontaneous labor, labor induction, or elective cesarean delivery. Data were collected from the medical records of each mother-baby pair and entered into an Access database.
      The AMOR-IPAT method of care has been previously described.
      • Nicholson J.A.
      • Kellar L.C.
      • Cronholm P.F.
      • Macones G.A.
      Active management of risk in pregnancy at term in an urban population: an association between a higher induction of labor rate and a lower cesarean delivery rate.
      • Nicholson J.M.
      • Yeager D.L.
      • Macones G.A.
      A preventive approach to obstetric care in a rural hospital: association between higher rates of preventive labor induction and lower rates of cesarean delivery.
      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 uteroplacental insufficiency (UPI) category (ie, factors that lead to UPI by interfering with placental growth or accelerating placental aging) and/or (2) a cephalopelvic disproportion (CPD) category (ie, factors that lead to CPD by either accelerating fetal growth or reflect a limited pelvic size). (We prefer to use the term “cephalopelvic disproportion” rather than “failure to progress,” because CPD implies a multifactorial problem that can potentially 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
      • Nicholson J.A.
      • Kellar L.C.
      • Cronholm P.F.
      • Macones G.A.
      Active management of risk in pregnancy at term in an urban population: an association between a higher induction of labor rate and a lower cesarean delivery rate.
      (Appendix 1), and we subtracted the total number of risk days that any given patient had in each of the 2 risk categories from 41 weeks 0 days' gestation to estimate an upper limit of the optimal time of delivery (UL-OTD) for each risk category.
      The lower of the 2 category-specific UL-OTDs became each woman's final UL-OTD, but the final UL-OTD was never lower than 38 weeks 0 days' 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 patient did not develop spontaneous labor as she approached her UL-OTD, then she was offered preventive labor induction on or just before her UL-OTD. If a patient was scheduled for labor induction and had an unfavorable uterine cervix (modified Bishop's score less than 6),
      • Bujold E.
      • Blackwell S.C.
      • Hendler I.
      • Berman S.
      • Sorokin K.
      • Gauthier R.J.
      Modified Bishop's score and induction of labor in patients with a previous cesarean delivery.
      then she was offered cervical ripening with dinoprostone (prostaglandin [PG] E2 pledget), misoprostol (PGE1), or foley bulb. Occasionally, the ripening methods were combined.
      Ultrasound confirmation of pregnancy dating and adequate cervical ripening prior to the start of oxytocin were important components of the AMOR-IPAT method of care. Although preventive labor induction was the key intervention utilized in this study, it is important to point out that not all women in the AMOR-IPAT group underwent induction prior to delivery. In fact, 53% of the exposed group delivered following the spontaneous or noninduced augmented labor. However, induction of labor, with cervical ripening if needed, was regularly used in the exposed group if a woman did not developed labor by, or just before, her estimated UL-OTD.
      We compared rates and proportions of prenatal and intrapartum covariates present in the exposed and nonexposed groups. We calculated means and medians of continuous variables. Normal distributions were compared using the Student t test and nonnormal distributions were compared using 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 of age or older at the time of delivery). Dichotomous and categorical variables were compared using χ2 techniques (Fisher's exact test). We used relative risk as the measure of association. We defined statistical significance for all tests as P ≤ .05, and a statistical trend as a P value between .05 and .30.
      We compared the pre-38 week of gestation risk of cesarean delivery in the 2 study groups using an indirect standardization procedure.
      • Turnnock B.J.
      • Masterson J.W.
      Incorporating outcomes standards into perinatal regulations.
      • Haro J.M.
      • Kontodimas S.
      • Negrin M.A.
      • Ratcliff M.
      • Suarez D.
      • Windmeiger F.
      Methodological aspects in the assessment of treatment effects in observational health outcomes studies.
      Risk factors that could be identified before 38 weeks of gestation, which at least trended toward statistically different levels in the 2 groups (P ≤ .30) and which also exhibited at least a trend toward an impact on cesarean delivery rates in the nonexposed group alone (P ≤ .30), were used as variables in the indirect standardization. The expected cesarean delivery rate in the exposed group was divided by the actual cesarean delivery rate in the nonexposed group to give a standardized cesarean ratio.
      We calculated and compared rates of various birth outcomes in the 2 groups. An intention-to-treat approach was taken based on exposure to AMOR-IPAT. If a woman in the AMOR-IPAT–exposed group developed either spontaneous labor or a standard indication of labor induction prior to meeting criteria for a preventive labor induction, then for data analysis purposes, she remained in the AMOR-IPAT–exposed group. Likewise, if a woman in the nonexposed group underwent induction of labor for any reason, then for data analysis purposes, she remained in the nonexposed group. The primary outcome of the study was mode of delivery, and 4 secondary outcomes were identified a priori: (1) major perineal injury (third- or fourth-degree tear), (2) NICU admission, (3) 1-minute Apgar score less than 4, and (4) 5-minute Apgar scores less than 7. We also assessed the association between AMOR-IPAT exposure and a variety of other birth outcomes using χ2 methods (Fisher's exact test).
      We used multivariable logistic regression to adjust for potential confounding in the association between AMOR-IPAT exposure and the primary and secondary outcomes. Most covariates that could be defined only after 38 weeks 0 days' gestation were not used in the final logistic model because of the possibility that these variables could be in the causal chain between expectant management and the development of adverse outcomes. Specific covariates that were not included in our final regression model included several preadmission issues (eg, development of preeclampsia, oligohydramnios, or failed antenatal testing prior to labor onset); several admission-related issues (eg, gestational age, cervical Bishop's score, amniotic membrane status, and blood pressure); and several intrapartum issues (eg, temperature elevation, need for augmentation of labor, and birthweight). However, we developed exploratory models that contained these variables to investigate the data more completely.
      To evaluate overall birth health, we used 2 composite outcomes to compare the 2 study groups. The Adverse Outcome Index (AOI) is a previously published score
      • Kennare R.
      • Tucker G.
      • Heard A.
      • Chan A.
      Risks of adverse outcomes in the next birth after a first cesarean delivery.
      that uses 10 specific weighted outcomes to “assess not only the occurrence of deliveries with poor outcomes but also the number and relative severity of the outcomes” in any given group (Appendix 2). The AOI was calculated for each individual in each group, and the outcomes of the 2 groups were then compared using Wilcoxon rank-sum analysis. In addition, we created a composite outcome called “uncomplicated vaginal delivery” that identified a vaginal delivery not associated with mechanical assistance (vacuum or forceps), severe shoulder dystocia, major perineal injury (third- or fourth-degree tear), postpartum hemorrhage (> 500 mL), or NICU admission. The rate of this outcome was determined for each group, and the rates were then compared using χ2 techniques (Fisher's exact test) (Appendix 3).
      Finally, we determined various labor-related time intervals for each group and made comparisons using Wilcoxon rank-sum methods. We collapsed data related to gestational age at delivery, timing of induction, and mode of delivery into half-week substrata and then encoded the data to enable graphic representation. We also 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. Data were analyzed using the STATA statistical program (version 8; STATA Corp, College Station, TX). The institutional review board of the University of Pennsylvania approved the study protocol.

      Results

      When comparing the demographic, past medical, past obstetric, and prenatal variables present in the exposed and nonexposed study groups, 10 of 23 variables were present at statistically different levels (Table 1). For example, exposed subjects were more likely to have Medicaid insurance, asthma, cigarette use, and a low hemoglobin level, whereas nonexposed women were more likely to be older, have chronic hypertension, and have an elevated 1 hour 50 g glucose tolerance test. Using indirect standardization, we estimated that the AMOR-IPAT–exposed group should have had a 25.3% cesarean delivery rate as compared with the 25.8% rate that actually occurred in the nonexposed group (data not shown). The standardized cesarean delivery ratio was therefore 0.98, suggesting that the 2 study groups had very similar pre-38 week risk of cesarean delivery.
      TABLE 1Levels of risk factors by study group
      VariablesExposed (n = 100)Nonexposed (n = 352)Risk ratio95% CIP value
      DEMOGRAPHICS
      Age, median20 y23 y< .001
      Calculated with the Mann-Whitney rank-sum test.
      Advanced age (≥ 35 y at delivery)3%8.2%0.360.11-1.17.07
      African American76%60.8%1.251.09-1.44.005
      Medicaid insurance62%44.6%1.391.15-1.69.002
      Single marital status81%64.2%1.261.12-1.43.002
      PAST MEDICAL
      Previous TAB63%59.4%1.060.89-1.26.51
      Previous SAB8%17.6%0.450.23-0.97.02
      Chronic hypertension2%3.4%0.590.13-2.58.47
      Asthma17%13.9%1.220.74-2.02.44
      Previous UTI9%7.1%1.270.61-2.63.53
      Previous atypical PAPS10%19.9%0.500.27-0.94.02
      Cigarette use18%9.9%1.811.07-3.06.03
      Alcohol use4%2.0%2.010.60-6.73.25
      Cocaine abuse4%1.7%2.350.68-8.15.17
      LABORATORY
      1 h glucola ≥ 1353%10.2%0.290.09-0.93.02
      Hemoglobin (first- or second-trimester ≤ 11)16%11.9%1.340.79-2.28.28
      Group B strep culture positive40%26.4%1.511.13-2.04.008
      MATERNAL HABITUS
      Preconception weight, median138 lb138.5 lb.60
      Calculated with the Mann-Whitney rank-sum test.
      Preconception weight > 160 lb32%28.4%1.130.81-1.57.49
      Height, mean64 in64 in1.00
      Calculated with the Mann-Whitney rank-sum test.
      Height < 62 in16%9.9%1.610.93-2.78.09
      Preconception BMI, kg/m223.823.4.60
      Calculated with the Mann-Whitney rank-sum test.
      Preconception BMI > kg/m216%16.8%0.970.58-1.61.91
      INDEX PREGNANCY
      Weight gain during pregnancy, median30.5 lb33 lb.07
      Calculated with the Mann-Whitney rank-sum test.
      Excess weight gain (≥ 30 lb)57%62.8%0.910.75-1.10.29
      Gestational diabetes3%2.6%1.170.32-4.25.81
      Size > dates (by at least 3 cm)24%5.4%4.452.54-7.78< .001
      Size < dates (by at least 3 cm)6%4.6%1.320.53-3.28.55
      BMI, body mass index; PAPS, papaniculaou smear; SAB, spontaneous abortion; TAB, therapeutic abortion; UTI, urinary tract infection.
      Nicholson. Management of risk in nulliparous pregnancy at term. Am J Obstet Gynecol 2009.
      a Calculated with the Mann-Whitney rank-sum test.
      When examining intrapartum characteristics, women in the exposed group were characterized by 4 important qualities: (1) they were more likely to deliver earlier in the term period of pregnancy (median gestational age of delivery, 39.1 weeks vs 40.0 weeks; P < .001), (2) they were more likely to have their labor induced (47% vs 24.2%; risk ratio [RR], 1.95; 95% confidence interval [CI], 1.47-2.57), (3) they had a lower median modified cervical Bishop's score on admission (3.8 vs 4.6; P = .01), and (4) they were more likely to receive prostaglandin medication (PGE2 or PGE1) for cervical ripening (45% vs 23.9%; RR, 1.89; 95% CI, 1.42-2.51; Table 2).
      TABLE 2Levels of intrapartum variables/factors by study group
      VariablesExposed (n = 100)Nonexposed (n = 352)Risk ratio95% CIP value
      SUBJECT STATUS ON ADMISSION
      Gestational age on admission (median)39.1 wk40.0 wk< .001
      Ruptured membranes on admission22%29.8%0.740.49-1.10.12
      Initial Bishop's score, median3.84.6.01
      Initial Bishop's score ≤ 573%56.2%1.301.12-1.51.002
      MAP on admission (mm Hg)9091.30
      Arterial pressure (MAP) on admission ≥ 1059%9.7%0.690.3170-1.30.42
      Arterial pressure (MAP) at 1 h ≥ 1057%9.4%0.750.34-1.64.46
      Vertex presentation100%97.7%.13
      INTRAPARTUM EVENTS
      Spontaneous labor22%23.1%0.960.63-1.45.83
      Induction of labor47%24.2%1.951.47-2.57< .001
      Augmentation (following premature rupture of membranes or ineffective spontaneous labor)31%51.7%0.600.44-0.82< .001
      Elective cesarean0%1.4%.23
      Prostaglandin (any use)45%23.9%1.891.42-2.51< .001
      Prostaglandin E1 (any antepartum use)6%21.6%0.280.12-0.62< .001
      Prostaglandin E2 (any antepartum use)41%3.7%11.16.20-19.89< .001
      Use of Pitocin (any)71%70.5%1.010.87-1.16.92
      Artificial rupture of membranes6%54.3%0.850.67-1.07.14
      Epidural analgesia66%89.8%0.740.64-0.85< .001
      Placement of fetal scalp electrode39%45.7%0.850.65-1.12.23
      Placement of IUPC19%38.9%0.490.32-0.75< .001
      Assisted vaginal delivery (all types)22%16.2%1.360.88-2.11.18
      Use of vacuum21%7.7%2.741.62-4.63< .001
      Use of forceps1%8.5%0.120.02-0.87.01
      INTRAPARTUM FINDINGS
      Thick meconium at ROM3%15.6%0.190.06-0.60< .001
      Fetal intolerance to labor (repetitive late decelerations)8.0%21.3%0.380.25-0.81.002
      Maternal fever prior to delivery (temperature > 100.4°F)9.0%6.0%1.500.71-3.19.28
      LABOR AND DELIVERY TIMING
      Admission, delivery (median)16 h12 h.04
      Mann-Whitney rank-sum test.
      Admission, delivery > 24 h19%15.9%1.190.75-1.91.46
      Admission, delivery > 48 h3%2.6%1.170.32-4.25.82
      Admission, labor onset (median)6.0 h2.4 h< .001
      Mann-Whitney rank-sum test.
      Admission, labor onset > 6 h50%26.4%1.891.46-2.46< .001
      First stage (median)8 h7.1 h.19
      Mann-Whitney rank-sum test.
      First stage > 12 h18.0%13.6%1.320.81-2.16.28
      Second stage (median)42 min53 min.05
      Mann-Whitney rank-sum test.
      Second stage ≥ 1 h28%36.4%0.770.28-1.00.04
      Second stage ≥ 2 h10%18.8%0.530.24-0.91.02
      Second stage ≥ 3 h5%9.4%0.470.21-1.33.16
      Second stage ≥ 4 h2%4.6%0.440.10-1.88.25
      IUPC, intrauterine pressure catheter; MAP, mean arterial pressure; ROM, rupture of membrane.
      Nicholson. Management of risk in nulliparous pregnancy at term. Am J Obstet Gynecol 2009.
      a Mann-Whitney rank-sum test.
      Graphic displays of gestational age at delivery (Figure 1, A) and the timing and frequency of labor induction (Figure 1, B) demonstrate very different distributions of these activities in the 2 study groups. Survival analysis of time to delivery during the term period demonstrates the continuous nature of earlier delivery in the exposed group as compared with the nonexposed group (Figure 2). The Cox proportional hazard ratio was 1.74 (95% CI, 1.39-21.8; P < .001).
      Figure thumbnail gr1
      FIGURE 1Characteristics of study groups
      A, Delivery of study groups as a function of gestational age. This figure shows in bar-graph form the distribution of timing of delivery by gestational age in the 2 study groups. B, Mode of onset of labor of study groups as a function of gestational age. This figure shows in bar-graph form the distribution of induction of labor by gestational age in the 2 study groups. C, Route of delivery of study groups as a function of gestational age. This figure shows in bar-graph form the distribution of cesarean delivery by gestational age in the 2 study groups.
      Nicholson. Management of risk in nulliparous pregnancy at term. Am J Obstet Gynecol 2009.
      Figure thumbnail gr2
      FIGURE 2Survival analysis of timing of delivery by study group
      In weeks past 37 weeks 0 days' gestation, exposure to AMOR-IPAT results in a continuous impact on the timing of delivery.
      Nicholson. Management of risk in nulliparous pregnancy at term. Am J Obstet Gynecol 2009.
      The cesarean delivery rate of the exposed group was 9%, which was significantly lower than the 25.8% cesarean delivery rate found in the nonexposed group (RR, 0.35; 95% CI, 0.18-0.67; P < .001). Importantly, AMOR-IPAT exposure was associated with a significantly lower rate of cesarean delivery rate for both UPI and CPD (Table 3). When controlling for potential confounders using logistic regression, the association between AMOR-IPAT exposure and a lower cesarean delivery rate remained highly significant. The final logistic model included 5 variables: AMOR-IPAT exposure (adjusted odds ratio [aOR], 0.36; 95% CI, 0.15-0.87; P = .02), male sex of fetus (aOR, 1.93; 95% CI, 1.06-3.52), advanced maternal age (aOR, 3.20; 95% CI, 1.16-8.84), weight gain 30 lb or more (aOR, 2.77; 95% CI, 1.33-5.79), and epidural analgesia (aOR, 11.88; 95% CI, 1.58-89.59). The cesarean delivery rates were lower in the exposed group, as compared with the nonexposed group, for deliveries that occurred following both spontaneous labor (0% vs 18.5%) and deliveries that occurred following induction of labor (12.8% vs 43.5%). Finally, the frequency of cesarean delivery as a function of gestational age in the 2 study groups had different distributions (Figure 1, C).
      TABLE 3Induction of labor and major birth outcome information: overall rates and indications
      Failed testing (n = 1), polyhydramnios (n = 1), gestational diabetes (n = 2), chronic hypertension (n = 3), and unstable lie (n = 2). When not specified, rates are based on entire study group;
      VariablesExposed (n = 100)Nonexposed (n = 352)Risk ratio95% CIP value
      INDUCTION OF LABOR INFORMATION
      Induction of labor rate, overall47%24.2%1.951.47-2.57< .001
      Indicated induction(11%)(23.1%)(0.52)(0.14-7.3) (.008)
      Preventive induction(36%)(1.1%)(31.7)(11.6-86.9)(< .001)
      Use of PGE1 with labor induction4%16.2%0.250.09-0.66.002
      Use of PGE2 with labor induction40%3.4%11.76.4-21.5< .001
      REASONS FOR INDICATED LABOR INDUCTION
      > 41 wk3%10.2%0.290.09-0.93.02
      > 42 wk0%2.0%.13
      Oligohydramnios/IUGR7%4.3%1.640.69-3.92.26
      Severe preeclampsia1%3.4%0.290.04-2.23.20
      Other
      Failed testing (n = 1), polyhydramnios (n = 1), gestational diabetes (n = 2), chronic hypertension (n = 3), and unstable lie (n = 2). When not specified, rates are based on entire study group;
      0%3.1%.16
      REASONS FOR PREVENTIVE LABOR INDUCTION
      Impending cephalopelvic disproportion14%0%< .001
      Impending preeclampsia2%0.3%14.14.05-48.9< .001
      Impending IUGR or oligohydramnios6%0%17.62.08-14.9< .001
      Impending uteroplacenta insufficiency2%0%.008
      Social/miscellaneous2%0.8%2.350.40-13.9.33
      CESAREAN DELIVERY INFORMATION
      Cesarean delivery rate
      Confidence interval and P value listed here are based on univariate analysis. Confidence interval and P value determined by logistic regression modeling may be found in the text and the abstract;
      9%25.8%0.350.18-0.67
      Confidence interval and P value listed here are based on univariate analysis. Confidence interval and P value determined by logistic regression modeling may be found in the text and the abstract;
      < .001
      Confidence interval and P value listed here are based on univariate analysis. Confidence interval and P value determined by logistic regression modeling may be found in the text and the abstract;
      INDICATIONS FOR CESAREAN DELIVERY
      Failure to progress5%11.9%0.420.17-1.03.045
      Fetal intolerance4%10.8%0.370.14-1.01.039
       Nonreassuring fetal heart tracing2.0%3.1%0.640.14-2.84.55
       Acute fetal intolerance2.0%7.7%0.260.06-1.08.04
      Malpresentation (breech)0%2.3%.13
      Active herpes0%0.3%.59
      Acute vaginal bleeding0%0.3%.59
      Umbilical cord prolapsed0%0.3%.59
      OCCURRENCE OF CESAREAN DELIVERY BY MODE OF LABOR ONSET
      Spontaneous labor0%18.5%< .001
      Induction of labor (all)12.8%43.5%0.290.13-0.64< .001
      Indicated induction of labor7.7%43.2%0.180.03-1.19.01
      Preventive induction of labor14.7%50.0%0.290.08-1.05.08
      Augmentation of labor9.7%18.8%0.520.17-1.57.22
      Elective cesarean(0/0)100%
      NEONATAL INTENSIVE CAREB
      NICU admission (overall)
      Confidence interval and P value listed here are based on univariate analysis. Confidence interval and P value determined by logistic regression modeling may be found in the text and the abstract;
      5%11.9%0.420.17-1.03.045
      Sepsis, suspect or actual5%9.7%0.520.21-1.29.14
      Respiratory disorders requiring NICU admission
      Pneumonia, meconium aspiration, or hypoxia requiring mechanical ventilation;
      2%6.0%0.340.08-1.41.11
      Blood sugar, minimal ≤ 504%4.3%0.940.32-2.77.91
      COMPOSITE OUTCOMES
      AOI (mean)3.16.3 .026
      Rank-sum analysis;
      Uncomplicated vaginal birth rate
      Vaginal delivery not associated with mechanical assistance, major perineal injury, severe shoulder dystocia, post partum hemorrage, or NICU admission.
      59%47.4%1.241.02-1.51 .041
      AOI, adverse outcome index; IUGR, intrauterine growth retardation; NICU, neonatal intensive care unit.
      Nicholson. Management of risk in nulliparous pregnancy at term. Am J Obstet Gynecol 2009.
      a Failed testing (n = 1), polyhydramnios (n = 1), gestational diabetes (n = 2), chronic hypertension (n = 3), and unstable lie (n = 2). When not specified, rates are based on entire study group;
      b Confidence interval and P value listed here are based on univariate analysis. Confidence interval and P value determined by logistic regression modeling may be found in the text and the abstract;
      c Pneumonia, meconium aspiration, or hypoxia requiring mechanical ventilation;
      d Rank-sum analysis;
      e Vaginal delivery not associated with mechanical assistance, major perineal injury, severe shoulder dystocia, post partum hemorrage, or NICU admission.
      In addition to an association with a lower cesarean delivery rate, exposure to AMOR-IPAT was associated with a significantly lower overall NICU admission rate (5% vs 11.9%; OR, 0.42; 95% CI, 0.17-1.03; P = .045) and a lower major perineal trauma rate in women experiencing vaginal delivery (7.7% vs 16.9%; aOR, 0.41; P = .037). Adjustment for confounding variables lowered the strength of association between AMOR-IPAT exposure and a lower NICU admission rate to that of a statistical trend (aOR, 0.58; 95% CI, 0.25-1.36). Multivariate logistic modeling did not change the weak associations noted between exposure and improved Apgar scores (data not shown). Exposure to AMOR-IPAT was not associated with higher rates of any major adverse maternal or neonatal outcome.
      Importantly, AMOR-IPAT exposure was associated with improved rates of the 2 composite outcomes. The mean AOI score in the exposed group was 3.1, as compared with 6.3 in the nonexposed group (P = .026). As noted in Appendix 1, the difference in mean score was primarily driven by 2 maternal intensive care unit admissions in the nonexposed group, but most of the 10 adverse outcomes occurred more frequently in the nonexposed group. In addition, the exposed group had a higher uncomplicated vaginal delivery rate (59% vs 47.4%; RR, 1.24; 95% CI, 1.02-1.51; P = .041).
      Rates of several lesser outcomes differed between the 2 groups (Table 4). AMOR-IPAT exposure promoted labor when fetuses tended to be smaller (median birthweight 3134 vs 3380 g (P < .001). Exposure was linked to a lower rate of macrosomia (infants with birthweight 4000 g or greater [4% vs 9.7%; RR, 0.41; 95% CI, 0.13-1.14]) and a higher rate of low-birthweight infants (≤ 2500 g [8% vs 1.1%; RR, 7.04; 95% CI, 2.16-22.9]). Importantly, none of the AMOR-IPAT–exposed neonates who were delivered following induction of labor and who weighted less than 2500 g at birth required NICU admission. In addition, no infant born to an exposed induced woman required NICU admission for respiratory insufficiency.
      TABLE 4Outcomes based on AMOR-IPAT exposure status
      VariablesExposed (n = 100)Nonexposed (n = 352)Risk ratio95% CIP value
      MATERNAL, DELIVERY
      Assisted vaginal delivery, all22%16.5%1.330.86-2.07.20
      Third- or fourth-degree perineal injury, all7%12.5%0.560.26-1.20.12
      Third- or fourth-degree perineal injury, vaginal only7.7%16.9%0.410.18-0.95.04
      Estimated blood loss, all (mL)411 ± 258514 ± 277< .001
      Calculated with the Mann-Whitney rank-sum test.
      Excess blood loss (> 500 mL), all19.0%29.0%0.660.42-1.01.05
      Estimated blood loss, vaginal only (mL)370 ± 157399 ± 223.007
      Excess blood loss (> 500 mL), vaginal only13.2%8.8%0.04-0.03 to 0.12.23
      MATERNAL, POSTPARTUM
      Maternal fever (> 100.4°F)9.0%8.5%1.060.52-2.15.88
      Postpartum hemoglobin, median9.6 ± 1.410.0 ± 1.4.04
      Postpartum anemia (hemoglobin < 8)13%7.7%1.690.91-3.16.10
      Flux in hemoglobin with delivery (g)1.6 ± 1.71.8 ± 1.5.80
      Calculated with the Mann-Whitney rank-sum test.
      NEONATAL
      Male Infant45%47%0.960.72-1.28.77
      Minor congenital problem
      Polydactyly, umbilical hernia, undescended testes, pyelectasis.
      4%1.7%2.350.68-8.15.17
      Significant congenital problem
      Major cardiac anomalies.
      0%0.6%.46
      Minor respiratory disorders
      Assisted ventilation at birth, or transient tachypnea, without need for NICU admission.
      7%3.1%2.240.89-5.63.08
      Bilirubin, median (if checked) (mg/dL)910.79
      Calculated with the Mann-Whitney rank-sum test.
      Cephalohematoma3%8.8%0.340.11-1.09.05
      Birthweight (g)3134 ± 4573380 ± 453< .001
      Calculated with the Mann-Whitney rank-sum test.
      Large (> 4000 g)4.0%9.7%0.410.13-1.14.07
      Small (< 2500 g)8.0%
      None of these neonates required admission to the NICU.
      1.1%7.042.16-22.9< .001
      Head circumference (cm)33.4 ± 1.734.1 ± 1.9.001
      Calculated with the Mann-Whitney rank-sum test.
      Venous cord blood pH ≤ 7.25.0%8.0%2.20.74-6.58.15
      Apgar at 5 min, < 71.0%1.7%0.590.07-4.82.61
      Nicholson. Management of risk in nulliparous pregnancy at term. Am J Obstet Gynecol 2009.
      a Calculated with the Mann-Whitney rank-sum test.
      b Polydactyly, umbilical hernia, undescended testes, pyelectasis.
      c Major cardiac anomalies.
      d Assisted ventilation at birth, or transient tachypnea, without need for NICU admission.
      e None of these neonates required admission to the NICU.
      Women in the exposed group who delivered vaginally were significantly less likely to have a third- or fourth-degree perineal injury (aOR, 0.41; 95% CI, 0.18-0.95; P =.04). Median estimated blood loss was significantly lower in the exposed group (300 mL vs 500 mL; P < .001). Although the difference in blood loss was influenced by differences in cesarean delivery rates, the difference persisted when the analysis was limited only to vaginal deliveries (median 300 mL vs 400 mL; P < .001). The exposed group experienced repetitive late decelerations in only 8% of cases as compared with 21.3% in the nonexposed group (RR, 0.38; 95% CI, 0.25-0.81; P = .002) and the exposed group had thick meconium at rupture of membranes only 3% of the time, as compared with 15.6% in the nonexposed group (OR, 0.19; 95% CI, 0.06-0.60; P < .001). Rates of assisted vaginal delivery, maternal fever, neonatal hyperbilirubinemia, and low umbilical cord pH were similar in the 2 study groups.
      Regarding time intervals throughout maternal and neonatal admissions, the exposed group had a longer median time between admission and onset of labor (360 vs 144 min; P < .001), but the length of the first stage of labor was not statistically different (8.0 vs 7.1 hours; P = .19). Furthermore, the exposed group had a significantly shorter median second stage of labor (42 vs 53 min; P = .05), and significantly fewer exposed women had a second stage longer than 2 hours (10% vs 18.8%; P = .02).
      The findings related to the duration of first and second stages were present despite considerable right censoring in the nonexposed group related to its higher cesarean delivery rate. In keeping with differences in group cesarean delivery rates, the median time from delivery to maternal discharge was significantly shorter in the exposed group (48 vs 53 hours; P < .001). The overall median hospital admission time was shorter for both exposed mothers (64 vs 67 hours; P = .02) and exposed neonates (48 vs 53.5 hours; P < .001).

      Comment

      In this study, we found a significant association between exposure of nulliparous women to a high rate of preventive labor induction and a lower rate of primary cesarean delivery. In addition, the exposed group had a significantly lower AOI and a significantly higher rate of uncomplicated vaginal delivery. Hence, the lower cesarean delivery rate that was associated with AMOR-IPAT exposure was paralleled by a better pattern of other undesirable birth outcomes and a higher rate of uncomplicated vaginal delivery.
      Multiple prospective studies found that routine induction of labor at 41 weeks' gestation, as compared with expectant management beyond 41 weeks' gestation, leads to lower cesarean delivery risk and decreased neonatal mortality.
      • Sanches-Ramos L.
      • Olivier F.
      • Delke I.
      • Kaunitz A.M.
      Labor induction versus expectant management for postterm pregnancies: a systematic review with meta-analysis.
      • Gülmezoglu A.M.
      • Crowther C.A.
      • Middleton P.
      Induction of labour for improving birth outcomes for women at or beyond term.
      • Crowley P.
      Interventions for preventing or improving the outcome of delivery at or beyond term.
      AMOR-IPAT pushes the gestational age of delivery in the exposed group to below 41 weeks (median age of delivery 39 weeks 1 day). A recently published randomized clinical trial involving women of mixed parity found that nulliparous women treated with AMOR-IPAT (n = 65), as compared with women treated with usual care (n = 63), had cesarean delivery rates of 18.5% and 25.8%, respectively (P = .23).
      • Nicholson J.M.
      • Parry S.
      • Caughey A.B.
      • Rosen S.
      • Keen A.
      • Macones G.A.
      The impact of the active management of risk in pregnancy at term on birth outcomes: a randomized clinical trial.
      There is only 1 previous randomized controlled trial that compared routine nulliparous labor induction at 39 weeks' gestation with expectant management until 42 weeks.
      • Amano K.
      • Saito T.
      • Tani A.
      • Yoshihara H.
      • Nishijima M.
      Elective induction of labor at 39 weeks of gestation: a prospective randomized trial.
      This study showed lower rates of meconium-stained amniotic fluid and lower rates of fetal resuscitation in the early induction group but no change in NICU admission or cesarean delivery rates. However, in this study, women randomized to the expectant management group who required postdates induction (a group of women who were at increased risk for adverse outcomes) were excluded from the analysis. Two prospective randomized trials from the 1970s involving groups of mixed parity
      • Cole R.A.
      • Howie P.W.
      • Macnaughton M.C.
      Elective induction of labour A randomized prospective trial.
      • Martin F.H.
      • Thompson W.
      • Pinkerton J.H.
      • Watson J.D.
      A randomized controlled trial of selective planned delivery.
      showed modest improvements in neonatal birth outcomes in the induced groups but no significant change in cesarean delivery rate. However, these studies were relatively small (n = 111,
      • Cole R.A.
      • Howie P.W.
      • Macnaughton M.C.
      Elective induction of labour A randomized prospective trial.
      n = 264
      • Martin F.H.
      • Thompson W.
      • Pinkerton J.H.
      • Watson J.D.
      A randomized controlled trial of selective planned delivery.
      ) and occurred prior to the availability of cervical ripening agents.
      In contrast, the clinical activity described in the 2 previously published retrospective studies involving AMOR-IPAT
      • Nicholson J.A.
      • Kellar L.C.
      • Cronholm P.F.
      • Macones G.A.
      Active management of risk in pregnancy at term in an urban population: an association between a higher induction of labor rate and a lower cesarean delivery rate.
      • Nicholson J.M.
      • Yeager D.L.
      • Macones G.A.
      A preventive approach to obstetric care in a rural hospital: association between higher rates of preventive labor induction and lower rates of cesarean delivery.
      included women who received cervical ripening and had greater power. These 2 studies reported numerically lower nulliparous cesarean delivery rates in the exposed group. The first
      • Nicholson J.A.
      • Kellar L.C.
      • Cronholm P.F.
      • Macones G.A.
      Active management of risk in pregnancy at term in an urban population: an association between a higher induction of labor rate and a lower cesarean delivery rate.
      showed a 6.9% nulliparous cesarean delivery rate in the exposed group as compared with a rate of 20.1% in the nonexposed group (P = .11). The second
      • Nicholson J.M.
      • Yeager D.L.
      • Macones G.A.
      A preventive approach to obstetric care in a rural hospital: association between higher rates of preventive labor induction and lower rates of cesarean delivery.
      showed an 8.1% nulliparous cesarean delivery rate in the exposed group as compared with a rate of 14.2% in the nonexposed group (P = .008).
      The goal of reduction of cesarean delivery in nulliparous women is probably not attainable simply by raising the threshold for performing this procedure (eg, tolerating longer periods of dystocia or greater amounts of fetal intolerance of labor). Raising these thresholds would probably increase the incidence of birth-related morbidity for both the mother and the neonate.
      • Sachs B.P.
      • Kobelin C.
      • Castro M.A.
      • Frigoletto F.
      The risks of lowering the cesarean-delivery rate.
      • Gould J.B.
      • Danielsen B.
      • Korst L.M.
      • et al.
      Cesarean delivery rates and neonatal morbidity in a low-risk population.
      Rather, the goal is attainable only if other changes occur within the management of term pregnancy that prevent the common causes of cesarean delivery.
      AMOR-IPAT contains several significant changes in the management of term maternity care. First, it encourages labor to occur at an earlier gestational age. Previous studies have suggested that adverse birth outcomes become more frequent with increasing gestational age during the term period.
      • Nicholson J.M.
      • Kellar L.C.
      • Kellar G.M.
      The impact of the interaction between increasing gestational age and obstetrical risk on birth outcomes: evidence of a varying optimal time of delivery.
      • Caughey A.B.
      • Musci T.J.
      Complications of term pregnancies beyond 37 weeks of gestation.
      • Caughey A.B.
      • Washington A.E.
      • Laros Jr, R.K.
      Neonatal complications of term pregnancy: rates by gestational age increase in a continuous, not threshold, fashion.
      • Caughey A.B.
      • Stotland N.E.
      • Washington A.E.
      • Escobar G.J.
      Maternal and obstetric complications of pregnancy are associated with increasing gestational age at term.
      The survival analysis captured in Figure 2 demonstrates that AMOR-IPAT exposure was associated with the systematic delivery of exposed women earlier within the term period of pregnancy as compared with the pattern of delivery of nonexposed women. The median gestational age at delivery in the exposed group of this study was 39.1 weeks as compared with 40.0 weeks in the nonexposed group (P < .001).
      Second, as a consequence of delivery earlier within the term period of pregnancy, AMOR-IPAT exposure promoted labor when fetuses tended to be smaller. In this study, the median birthweight was 3134 g in the exposed group as compared with 3380 g in the nonexposed group (P < .001). In addition, only 4% of exposed neonates weighed more than 4000 g as compared with 9.7% of nonexposed neonates (RR, 0.41; 95% CI, 0.13-1.14; P = .07).
      Possibly because of smaller average birthweight, women in the exposed group who delivered vaginally were significantly less likely to have a third- or fourth-degree perineal injury as compared with women who delivered vaginally in the nonexposed group (7.7% vs 16.9%; RR, 0.41; 95% CI, 0.18-0.95; P = .04).
      Third, and also as a consequence of delivery earlier in the term period of pregnancy, AMOR-IPAT exposure may have promoted labor when the uteroplacental unit was younger and healthier. In this study, the exposed group experienced repetitive late decelerations in only 8% of cases as compared with 21.3% in the nonexposed group (RR, 0.38; 95% CI, 0.25-0.81; P = .002). In addition, the exposed group had thick meconium at rupture of membranes only 3% of the time, as compared with 15.6% in the nonexposed group (odds ratio, 0.19; 95% CI, 0.06-0.60; P < .001). Both findings suggest that fetuses in the exposed group may have been better supported by their placenta during labor.
      We are very aware that many previous studies of labor induction have concluded that labor induction is associated with increased risks of cesarean delivery and other adverse birth outcomes.
      • Cammu H.
      • Martens G.
      • Ruyssinck G.
      • Amy J.J.
      Outcome after elective induction in nulliparous women: a matched cohort study.
      • Yeast J.D.
      • Jones A.
      • Poskin M.
      Induction of labor and the relationship to cesarean delivery: a review of 7001 consecutive inductions.
      • Coonrod D.V.
      • Bay R.C.
      • Kishi G.Y.
      The epidemiololgy of labor induction: Arizona 1997.
      • Seyb S.T.
      • Berka R.J.
      • Socol M.L.
      • Dooley S.L.
      Risk of cesarean delivery with elective induction of labor at term in nulliparous women.
      • 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.
      However, most previous studies of labor induction contain at least some potential flaws, the most significant of which is confounding by indication. If most indicated inductions are done in response to identified complications of pregnancy (eg, oligohydramnios, severe preeclampsia, failed antenatal testing), it is possible that the higher rates of cesarean delivery (or other untoward outcome) is due to the established complications of pregnancy rather than the induction per se. Furthermore, accurate assessment of the risks of preventive induction cannot be ascertained by comparing women with indicated inductions to women who generally have no complications and who enter labor spontaneously. Even when such studies include elective and preventive inductions in a cohort of indicated inductions, indicated inductions constitute the majority of the inductions, making it impossible to determine the relative impact of preventive inductions.
      We believe that evaluation of the impact of labor induction on birth outcomes can best be made through the use of population-based strategies that compare the outcomes of a group of women characterized by a high (and largely preventive) labor induction rate with the outcomes of a group of women characterized by a more standard (and largely indicated) labor induction rate.
      • Nicholson J.A.
      • Kellar L.C.
      • Cronholm P.F.
      • Macones G.A.
      Active management of risk in pregnancy at term in an urban population: an association between a higher induction of labor rate and a lower cesarean delivery rate.
      • Nicholson J.M.
      • Yeager D.L.
      • Macones G.A.
      A preventive approach to obstetric care in a rural hospital: association between higher rates of preventive labor induction and lower rates of cesarean delivery.
      This study has several potential limitations. First, although we identified and controlled for confounding factors in our analyses, and an indirect standardization suggested that the pre-38 week risk of cesarean delivery in the 2 study groups was similar, it is possible that unidentified factors may have accounted for some or all of the difference in outcomes between the exposed and nonexposed groups.
      Second, based on study design, we could not control for specialty of provider. It is well known that a variety of provider characteristics have a significant impact on group cesarean delivery rates. However, other than the use of preventive induction, type of prostaglandin for cervical ripening, and variable usage of epidural analgesia, there is little evidence that there were major differences in basic labor management. In addition, the obstetrics group made all decisions concerning the timing of cesarean delivery in both study groups. The possibility that AMOR-IPAT–exposed women were subjected to longer, more difficult, or more complicated vaginal delivery is refuted by both the finding of a shorter length of second stage in the exposed group and a subtle pattern of more favorable Apgar scores in the exposed group.
      Third, the study took place in an urban setting, occurred at an academic institution, and involved primarily African American women. Hence, the generalizability of this study to other settings is unclear. However, a large recently published retrospective study of white women in a rural setting also found a significantly lower cesarean delivery rate in nulliparous women exposed to AUOR-IPAT.
      • Hager R.M.
      • Daltveit A.K.
      • Hofoss D.
      • et al.
      Complications of cesarean deliveries: rates and risk factors.
      • Nicholson J.M.
      • Yeager D.L.
      • Macones G.A.
      A preventive approach to obstetric care in a rural hospital: association between higher rates of preventive labor induction and lower rates of cesarean delivery.
      Despite the limitations of this study, we believe that data presented here strongly suggest that the AMOR-IPAT method of care represents a potential strategy to safely improve birth health in nulliparous pregnant women at term. An adequately powered multisite clinical trial will be essential to determine the impact of AMOR-IPAT on the birth outcomes of nulliparous women and their infants. If AMOR-IPAT is demonstrated to have positive effects on birth health in the context of a prospective randomized study, then it may be time to critically reevaluate the balance between the expectant management of pregnancy during the term period and the use of preventive labor induction.

      Appendix 1

      Tabled 1AMOR-IPAT–UL-OTD calculation sheet
      VariablesOdds ratioTime units, d
      Uteroplacental factors
      Hx chronic hypertension1.86——————
      Gestational diabetes1.86——————
      Insulin-dependent diabetes2.410——————
      Sickle cell trait1.53——————
      Elevated AFP1.43——————
      Cigarette use1.32——————
      Size less than dates (≤ 3 cm)1.64——————
      Advanced age (≥ 35 y at delivery)1.86——————
      Anemia (first trimester ≤ 10.0)1.64——————
      Total UPI time units——————
      UL-OTD-UPI = (41 wks − total UPI time units) =——————
      Cephalopelvic factors
      Elevated BMI (≥ 30 kg/m2)1.32——————
      Short stature (≤ 62 in)1.86——————
      Excess weight gain (≥ 30 lb)1.86——————
      Size greater than dates (≥ 3 cm)1.74——————
      Gestational diabetes1.86——————
      Type 1 diabetes2.410——————
      Hx vacuum/forceps2.29——————
      Previous macrosomia (> 4000 g)2.07——————
      Total CPD time units——————
      UL-OTD-CPD = (41 wks − total CPD time units) =——————
      This appendix describes how the timing of preventive labor induction was determined in the AMOR-IPAT–exposed group. Final UL-OTD is the lower of the 2 UL-OTDs (UL-OTD-UPI vs UL-OTD-CPD), but the final UL-OTD is never less than 38 weeks, 0 days.
      AFP, alpha fetoprotein; BMI, body mass index; Hx, history.
      Nicholson. Management of risk in nulliparous pregnancy at term. Am J Obstet Gynecol 2009.

      Appendix 2

      Tabled 1Development of adverse outcome index by group
      VariablesExposed, n (rate) (n = 100)Nonexposed, n (rate) (n = 352)Relative weight, g
      Maternal death0 (0%)0 (0%)750
      Intrapartum or neonatal death0 (0%)1 (0.75%)400
      Uterine rupture0 (0%)0 (0%)100
      Maternal ICU admission0 (0%)2 (0.6%)65
      Infant birth trauma (Erb's palsy, vacuum or forceps injury)0 (0%)3 (0.8%)60
      Return to operating room of labor and delivery unit0 (0%)2 (1.5%)40
      Admission to NICU5 (5%)42 (11.9%)35
      Apgar score < 7 at 5 min1 (1%)6 (1.7%)25
      Maternal blood transfusion0 (0%)4 (1.1%)20
      Third- or fourth-degree perineal tear7 (7%)44 (12.5%)5
      Mean AOI score3.16.30.026
      Overall frequency of at least 1 adverse outcome13 (13%)82 (23.3%)P = .03
      3.1, as compared with 6.3, in the nonexposed group (P = .026).
      ICU, intensive care unit.
      Nicholson. Management of risk in nulliparous pregnancy at term. Am J Obstet Gynecol 2009.

      Appendix 3

      Tabled 1Development of the uncomplicated vaginal delivery rate by group
      VariablesExposed, n (rate) (n = 100)Nonexposed, n (rate) (n = 352)
      Cesarean delivery9 (9%)91 (25.8%)
      Assisted vaginal delivery (vacuum or forceps)21 (21%)27 (7.7%)
      Shoulder dystocia (severe)3 (3%)4 (1.1%)
      Major perineal trauma (third- or fourth-degree injury)7 (7%)44 (12.5%)
      Postpartum hemorrhage (vaginal delivery, EBL > 500 mL)19 (19%)102 (29%)
      NICU admission5 (5%)42 (11.9%)
      Overall frequency of complicated vaginal delivery (at least 1 complication)41 (41%)185 (52.6 %)
      Overall frequency of uncomplicated vaginal delivery (none of the 5 identified adverse outcomes)59 (59%)167 (47.4%)
      P = .041
      EBL, estimated blood loss.
      Nicholson. Management of risk in nulliparous pregnancy at term. Am J Obstet Gynecol 2009.

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