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Gestational age–specific severe maternal morbidity associated with labor induction

  • Shiliang Liu
    Correspondence
    Reprints: Shiliang Liu, MD, PhD, Health Surveillance and Epidemiology Division, Centre for Chronic Disease Prevention, Public Health Agency of Canada, Building #19, AL 1910D, Tunney's Pasture, Ottawa, Ontario, Canada, K1A 0K9.
    Affiliations
    Health Surveillance and Epidemiology Division, Center for Chronic Disease Prevention, Public Health Agency of Canada, Ottawa, Ontario, Canada

    Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada
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  • K.S. Joseph
    Affiliations
    Department of Obstetrics and Gynecology, University of British Columbia, and the Children's and Women's Hospital of British Columbia, Vancouver, British Colombia, Canada

    School of Population and Public Health, University of British Columbia, Vancouver, British Colombia, Canada
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  • Jennifer A. Hutcheon
    Affiliations
    Department of Obstetrics and Gynecology, University of British Columbia, and the Children's and Women's Hospital of British Columbia, Vancouver, British Colombia, Canada
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  • Sharon Bartholomew
    Affiliations
    Health Surveillance and Epidemiology Division, Center for Chronic Disease Prevention, Public Health Agency of Canada, Ottawa, Ontario, Canada
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  • Juan Andrés León
    Affiliations
    Health Surveillance and Epidemiology Division, Center for Chronic Disease Prevention, Public Health Agency of Canada, Ottawa, Ontario, Canada
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  • Mark Walker
    Affiliations
    Department of Obstetrics and Gynecology, University of Ottawa and Ottawa Health Research Institute, Ottawa, Ontario, Canada
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  • Michael S. Kramer
    Affiliations
    Canadian Institutes of Health Research, Ottawa, Ontario, Canada

    Departments of Pediatrics and of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
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  • Robert M. Liston
    Affiliations
    Department of Obstetrics and Gynecology, University of British Columbia, and the Children's and Women's Hospital of British Columbia, Vancouver, British Colombia, Canada
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  • Maternal Health Study Group of the Canadian Perinatal Surveillance System

      Objective

      The purpose of this study was to examine the association between labor induction and gestational age–specific severe maternal morbidity.

      Study Design

      Our study was restricted to women who delivered singletons at 37-42 weeks' gestation who had no pregnancy complications from 2003-2010 (n = 1,601,253) in Canada (excluding Quebec). Using a pregnancies-at-risk approach, the week-specific rates of specific morbidity after induction were contrasted with rates among ongoing pregnancies. Logistic regression was used to adjust for confounders.

      Results

      Induction increased the rate of postpartum hemorrhage that required blood transfusion at 38 weeks' gestation (adjusted rate ratio, 1.28; 95% confidence interval, 1.11–1.49) and 39 weeks' gestation (adjusted rate ratio, 1.21; 95% confidence interval, 1.06–1.38). Induction was also associated with higher rates of pueperal sepsis at 38 and 39 weeks' gestation and venous thromboembolism at 38 weeks' gestation. The absolute increase in morbidity rates was small; the number needed to harm was large (eg, 1270 for postpartum hemorrhage with blood transfusion at 38 weeks' gestation).

      Conclusion

      Among women without pregnancy complications, induction at earlier term is associated with higher rates of specific severe maternal morbidity, although absolute risks are low.

      Key words

      For Editors' Commentary, see Contents
      See related editorial, page 168
      Induction of labor is used widely to prevent adverse maternal, fetal, and infant outcomes.
      • American College of Obstetricians and Gynecologists
      Induction of Labor: ACOG practice bulletin no. 107.
      Currently, 22.5% of deliveries in the United States and 22.3% of deliveries in Canada occur after labor induction, with substantial variation across hospitals and regions.
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      Public Health Agency of Canada. Canadian Perinatal Health Report, 2008 ed. Ottawa, 2008. Available at: http://www.phac-aspc.gc.ca/publicat/2008/cphr-rspc/pdf/cphr-rspc08-eng.pdf. Accessed March 5, 2013.

      Although induction of labor generally is considered to be safe, associated problems include prolonged labor, chorioamnionitis, fetal death, and uterine rupture.
      • American College of Obstetricians and Gynecologists
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      Induction of labour for improving birth outcomes for women at or beyond term.
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      Perhaps the most common concern that has been related to labor induction in the past was its reported association with cesarean delivery.
      • Sanchez-Ramos L.
      • Olivier F.
      • Delke I.
      • Kaunitz A.M.
      Labor induction versus expectant management for postterm pregnancies: a systematic review with meta-analysis.

      Society of Obstetricians and Gynecologists of Canada. Induction of labour at term. No. 107, August 2001. Available at: http://www.sogc.org/guidelines/public/107E-CPG-August2001.pdf. Accessed March 5, 2013.

      • Delaney M.
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      Risk of caesarean delivery with elective induction of labor at term in nulliparous women.
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      • Lyell D.J.
      • Washington A.E.
      Induction of labor and cesarean delivery by gestational age.
      In fact, randomized controlled trials and metaanalyses of randomized trials of selected subgroups (including women with hypertension and women at or beyond term) have concluded that cesarean delivery rates are not increased after labor induction.
      • Gülmezoglu A.M.
      • Crowther C.A.
      • Middleton P.
      Induction of labour for improving birth outcomes for women at or beyond term.
      • Koopmans C.M.
      • Bijlenga D.
      • Groen H.
      • et al.
      Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomized controlled trial.
      • Caughey A.B.
      • Sundaram V.
      • Kaimal A.J.
      • et al.
      Systematic review: elective induction of labor versus expectant management of pregnancy.
      Reported associations between labor induction and adverse pregnancy outcomes are based largely on observational studies that compare induction with the spontaneous onset of labor.
      • Prysak M.
      • Castronova F.C.
      Elective induction versus spontaneous labor: a case-control analysis of safety and efficacy.
      • Seyb S.T.
      • Berka R.J.
      • Socol M.L.
      • Dooley S.L.
      Risk of caesarean delivery with elective induction of labor at term in nulliparous women.
      • Caughey A.B.
      • Nicholson J.M.
      • Cheng Y.W.
      • Lyell D.J.
      • Washington A.E.
      Induction of labor and cesarean delivery by gestational age.
      However, several researchers have highlighted the methodologic flaws that are inherent in a comparison of labor induction with spontaneous onset of labor at the same gestational age.
      • Caughey A.B.
      • Sundaram V.
      • Kaimal A.J.
      • et al.
      Systematic review: elective induction of labor versus expectant management of pregnancy.
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      • 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.
      • Gonen O.
      • Rosen D.J.D.
      • Dolfin Z.
      • Tepper R.
      • Markov S.
      • Fejgin M.D.
      Induction of labor versus expectant management in macrosomia: a randomized study.
      A more appropriate comparison group for the assessment of the effects of labor induction is constituted by ongoing pregnancies (at each gestational age and risk status) who are not induced (ie, those who are treated with expectant management instead, including those who are induced at later gestational ages).
      • Koopmans C.M.
      • Bijlenga D.
      • Groen H.
      • et al.
      Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomized controlled trial.
      • Caughey A.B.
      • Sundaram V.
      • Kaimal A.J.
      • et al.
      Systematic review: elective induction of labor versus expectant management of pregnancy.
      • 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.
      • Gonen O.
      • Rosen D.J.D.
      • Dolfin Z.
      • Tepper R.
      • Markov S.
      • Fejgin M.D.
      Induction of labor versus expectant management in macrosomia: a randomized study.
      • Snyder C.C.
      • Wolfe K.B.
      • Loftin R.W.
      • Tabbah S.
      • Lewis D.F.
      • Defranco E.A.
      The influence of hospital type on induction of labor and mode of delivery.
      • Glantz J.C.
      Term labor induction compared with expectant management.
      We therefore carried out a study to examine the gestational age–specific effects of labor induction on specific subtypes of associated severe obstetric morbidity among women without pregnancy complications by comparing women who were induced with similar women who were treated expectantly.

      Materials and Methods

      The study was based on hospital records that were collated in the Discharge Abstract Database of the Canadian Institute for Health Information for fiscal years 2003-2004 to 2010-2011. Data on hospitalizations that occurred in Quebec were not included, because comparable information for this province is not contained in the Discharge Abstract Database. The Discharge Abstract Database includes all maternal hospital admissions for delivery and their linked newborn infant admissions; hospital deliveries accounted for >98% of all births in the study jurisdictions.

      Public Health Agency of Canada. Canadian Perinatal Health Report, 2008 ed. Ottawa, 2008. Available at: http://www.phac-aspc.gc.ca/publicat/2008/cphr-rspc/pdf/cphr-rspc08-eng.pdf. Accessed March 5, 2013.

      Obstetric deliveries were identified with the use of a prespecified algorithm of diagnostic codes that had been validated previously by the Canadian Perinatal Surveillance System.

      Public Health Agency of Canada. Canadian Perinatal Health Report, 2008 ed. Ottawa, 2008. Available at: http://www.phac-aspc.gc.ca/publicat/2008/cphr-rspc/pdf/cphr-rspc08-eng.pdf. Accessed March 5, 2013.

      • Joseph K.S.
      • Fahey J.
      Canadian Perinatal Surveillance System
      Validation of perinatal data in the Discharge Abstract Database of the Canadian Institute for Health Information.
      Hospital medical archivists extracted the hospital discharge data, including age, parity, date of admission, home postal code (first 3 digits), clinical estimate of gestational age at delivery, province of hospital delivery, province that issued the health care insurance, date and status at discharge, principal diagnosis, up to 24 secondary diagnoses (coded according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Canada [ICD-10 CA]) and up to 25 diagnostic, therapeutic, and surgical procedures (coded according to the Canadian Classification of Health Interventions).

      Public Health Agency of Canada. Canadian Perinatal Health Report, 2008 ed. Ottawa, 2008. Available at: http://www.phac-aspc.gc.ca/publicat/2008/cphr-rspc/pdf/cphr-rspc08-eng.pdf. Accessed March 5, 2013.

      Information in the database had been validated previously and extensively used in perinatal health surveillance and research.

      Public Health Agency of Canada. Canadian Perinatal Health Report, 2008 ed. Ottawa, 2008. Available at: http://www.phac-aspc.gc.ca/publicat/2008/cphr-rspc/pdf/cphr-rspc08-eng.pdf. Accessed March 5, 2013.

      • Joseph K.S.
      • Fahey J.
      Canadian Perinatal Surveillance System
      Validation of perinatal data in the Discharge Abstract Database of the Canadian Institute for Health Information.
      • Liu S.
      • Rouleau J.
      • Joseph K.S.
      • et al.
      Epidemiology of pregnancy-associated venous thromboembolism: a population-based study in Canada.
      • Kramer M.S.
      • Rouleau J.
      • Basket T.F.
      • Joseph K.S.
      Maternal Health Study Group of the Canadian Perinatal Surveillance System
      Amniotic-fluid embolism and medical induction of labour: a retrospective population-based cohort study.
      • van Walraven C.
      • Mamdani M.
      • Cohn A.
      • Katib Y.
      • Walker M.
      • Rodger M.A.
      Risk of subsequent thromboembolism for patients with pre-eclampsia.
      Induction was defined as the use of oxytocin or prostaglandin to initiate labor and identified in the database by specific Canadian Classification of Health Interventions procedure codes. To reduce the potential for confounding of associations between induction and maternal morbidity by the clinical indication for the induction, we restricted our analysis to women without pregnancy complications. The study was restricted to women who had a singleton, vertex delivery at 37-42 completed weeks' gestation (ie, 37 weeks to 42 weeks 6 days gestation) with no previous cesarean delivery and no medical/obstetric diagnoses such as grand multiparity (≥5 previous viable pregnancies), preeclampsia, preexisting/gestational hypertensive disease, preexisting/gestational diabetes mellitus, antepartum hemorrhage, chorioamnionitis, oligohydramnios, or polyhydramnios, abruption or premature separation of the placenta, anemia, heart disease, herpes, HIV disease, pulmonary disease, systemic lupus erythematosus, chronic renal abnormalities, infant macrosomia (>4000 g) or intrauterine fetal death, fetal growth restriction, or antepartum intensive care unit (ICU) admission.
      • American College of Obstetricians and Gynecologists
      Induction of Labor: ACOG practice bulletin no. 107.

      Public Health Agency of Canada. Canadian Perinatal Health Report, 2008 ed. Ottawa, 2008. Available at: http://www.phac-aspc.gc.ca/publicat/2008/cphr-rspc/pdf/cphr-rspc08-eng.pdf. Accessed March 5, 2013.

      • Gülmezoglu A.M.
      • Crowther C.A.
      • Middleton P.
      Induction of labour for improving birth outcomes for women at or beyond term.
      • Sanchez-Ramos L.
      • Olivier F.
      • Delke I.
      • Kaunitz A.M.
      Labor induction versus expectant management for postterm pregnancies: a systematic review with meta-analysis.
      • Liu S.
      • Liston R.M.
      • Joseph K.S.
      • et al.
      Maternal mortality and severe morbidity associated with low-risk planned cesarean delivery versus planned vaginal delivery at term.
      ICU admission was defined with the specific codes that were available in the database.
      The primary outcomes of interest were selected: specific subtypes of severe maternal morbidity that included postpartum hemorrhage that required blood transfusion, puerperal sepsis, uterine rupture during labor, postpartum ICU admission, venous thromboembolism, and obstetric shock. These outcomes were chosen to further reduce the potential for confounding by the indication for induction; such maternal morbidity is an unintended consequence of labor induction and hence is likely to be unrelated to the reason for induction.
      • Miettinen O.S.
      The need for randomization in the study of intended effects.
      • Breslow N.E.
      • Day N.E.
      Statistical methods in cancer research: vol I, the analysis of case-control studies.
      For the same reason, cases with these outcomes were identified only if they arose in the postpartum period (eg, venous thromboembolism in the postpartum period); cases with the same severe maternal morbidity with an antepartum onset (and thus a potential indication for labor induction) were not included in the study. This restriction to postpartum cases of severe maternal morbidity was carried out with the sixth digit of the International Statistical Classification of Diseases code.
      We first examined the differences in rates of maternal characteristics (eg, maternal age, parity, epidural use, gestational age at delivery) and specific severe maternal morbidity rates among women without pregnancy complications who had induction of labor and those who did not. This was followed by analyses of the more appropriate contrast between women who were induced and those women who were treated expectantly. Induction of labor at 37, 38, 39, 40, 41, and 42 weeks' gestation was compared with expectant management of pregnancy beyond each of these gestational ages. For instance, the effect of induction of labor at 37 weeks' gestation (ie, 37 weeks to 37 weeks 6 days gestation) was studied by contrasting women who delivered after induced labor at 37 weeks' gestation (induction of labor group) with all women who carried their pregnancy >37 weeks' gestation (ie, to ≥38 weeks' gestation; expectant management group). Similar comparison groups were created for women with labor induction at 38, 39, 40, 41, and 42 weeks' gestation (Figure).
      Figure thumbnail gr1
      FigureLabor induction and expectant management at 37-42 weeks' gestation
      Flow chart: women without pregnancy complications were assigned to different groups for assessment of the effects of labor induction among ongoing pregnancies.
      Liu. Effects of labor induction. Am J Obstet Gynecol 2013.
      Multivariate logistic regression was used to adjust for maternal age (<20, 20-34, and ≥35 years), parity (0, 1, ≥2, and missing), province and year of childbirth in contrasts between women who were induced at a particular week of gestation and those who were treated expectantly at that gestational week. We did not adjust for determinants, such as length of labor and mode of delivery, which are in the causal pathway between labor induction and adverse maternal outcomes. Adjusted odds ratios for severe maternal morbidity were assumed to approximate adjusted rate ratios because all severe morbidities were rare. Adjusted rate ratios for the effect of labor induction on specific outcomes and outcome rates in the expectant management group were used to obtain adjusted risk differences and the number needed to harm. Potential modification of the effect of labor induction by gestational age was assessed with the use of the odds ratio test for heterogeneity. Sensitivity analyses were carried out to determine whether parity modified the effect of labor induction on adverse maternal outcomes. All analyses were performed with SAS Unix software (version 9.2; SAS Institute, Cary, NC).
      This study was carried out by the Public Health Agency of Canada, which has a federal mandate to monitor the health of the Canadian population. The data source involved denominalized information from all hospitals in Canada (excluding Quebec); ethics review board approval was therefore not required.

      Results

      Among the 2,191,391 hospital deliveries between 2003 and 2010, 1,601,253 deliveries (73.1%) were included in the study. The overall rate of labor induction in the study population was 22.8%. Differences in maternal age between the induction and no induction groups were small although statistically significant (P < .0001). Much larger differences were evident in gestational age and parity (P < .0001). Receipt of epidural anesthesia was also associated with higher rates of labor induction (Table 1).
      Table 1Characteristics of women whose labor was induced
      CharacteristicLabor induction, n (%)No labor induction, n (%)P value
      Women, n367,227 (100.0)1,234,026 (100.0)
      Age, y
       <2019,760 (5.4)66,668 (5.4)
       20-34288,548 (78.6)973,998 (78.9)< .0001
       ≥3558,919 (16.0)193,360 (15.7)
      Gestational age, wk
       3725,374 (6.9)76,818 (6.2)
       3850,221 (13.7)204,565 (16.6)
       3965,681 (17.8)379,237 (30.7)< .0001
       4094,118 (25.6)427,275 (34.7)
       41126,863 (34.5)142,122 (11.5)
       424,970 (13.5)4,009 (0.3)
      Parity
       0154,851 (42.2)475,445 (38.5)
       177,573 (21.1)311,528 (25.3)
       234,290 (9.3)116,650 (9.5)< .0001
       3+19,900 (5.4)64,619 (5.2)
       Not available80,613 (21.2)265,784 (21.5)
      Epidural use224,138 (61.0)542,131 (43.9)< .0001
      Liu. Effects of labor induction. Am J Obstet Gynecol 2013.
      Rates of severe maternal morbidity differed among women who had labor induction vs women who had spontaneous labor. Postpartum hemorrhage with blood transfusion was 1.33 (95% confidence interval, 1.25–1.42) times more frequent among women who had labor induction compared with women who did not have labor induction. Similarly, rates of postpartum sepsis and venous thromboembolism were higher among those who had labor induction; no differences were observed in rates of uterine rupture during labor, ICU admission, or obstetric shock (Table 2).
      Table 2Labor induction and rates of severe maternal morbidity
      OutcomeLabor inductionExpectant treatmentRate ratio (95% CI)
      nRate per 1000nRate per 1000
      Postpartum hemorrhage with blood transfusion13553.6933732.731.33 (1.25–1.42)
      Postpartum sepsis3370.928010.651.41 (1.24–1.60)
      Uterine rupture during labor1910.486010.491.05 (0.90–1.25)
      Intensive care unit admission1040.283360.271.11 (0.89–1.37)
      Venous thromboembolism420.11910.071.55 (1.08–2.24)
      Obstetric shock250.07920.070.93 (0.60–1.45)
      Total number of women367,2271,234,026
      Specific severe maternal morbidity among women without pregnancy complications who had labor induction and women who were treated expectantly, Canada (excluding Quebec), 2003-2010.
      CI, confidence interval.
      Liu. Effects of labor induction. Am J Obstet Gynecol 2013.
      Comparisons of severe maternal morbidity rates among women who had labor induction vs those who were treated expectantly showed different results by gestational age week. Labor induction was associated with significantly higher rates of postpartum hemorrhage that required blood transfusion at gestational ages of 38, 39, and 40 weeks but not at 37, 41, and 42 weeks (Table 3). The rate ratios for the effect of labor induction on postpartum hemorrhage with blood transfusion decreased with increasing gestational age; the test for heterogeneity of the odds ratios showed a significant difference (P < .01). Rates of postpartum sepsis were also significantly higher at 38 and 39 weeks' gestation, but not at other gestational ages. The rate ratios decreased as gestational age increased; the test for heterogeneity of the odds ratios was significant (P < .01). Labor induction was not associated with uterine rupture during labor at any gestation (Table 3).
      Table 3Effects of labor induction on specific maternal morbidity (per 1000)
      Gestational age, wkLabor inductionExpectant treatmentAdjusted rate ratio (95% CI)
      Adjusted for maternal age, parity, year of birth, and province of hospital delivery
      Adjusted rate difference per 1000Needed to harm, n
      Calculated only if the adjusted rate difference was statistically significant.
      nOutcome frequencyRate per 1000nOutcome frequencyRate per 1000
      nn
      Postpartum hemorrhage with blood transfusion
       3725,374843.311,575,87946442.951.11 (0.89–1.37)0.31 (–0.32 to 1.05)
       3850,2211883.741,448,84242312.921.28 (1.11–1.49)0.79 (0.31–1.57)1270 (730–3217)
       3965,6812373.611,178,59535182.981.21 (1.06–1.38)0.60 (0.17–1.09)1657 (921–5775)
       4094,1183373.58705,23922713.221.12 (1.00–1.26)0.37 (0.0–0.80)2684 (1245–320,902)
       41126,8634903.86151,1015613.711.04 (0.93–1.15)0.14 (–0.25 to 4.24)
       424970193.824,009225.490.68 (0.37–1.28)−1.80 (−3.39 to 6.92)
      Postpartum sepsis
       3725,374261.021,575,87911120.711.45 (0.98–2.14)0.32 (−0.01 to 0.41)
       3850,221511.021,448,84210150.701.27 (1.13–1.99)0.19 (0.09–0.68)5338 (1463–11,077)
       3965,681620.941,178,5958210.701.24 (1.09–1.82)0.17 (0.06–0.57)6004 (1765–15,995)
       4094,118790.84705,2395430.771.12 (0.88–1.14)0.09 (−0.09 to 0.11)
       41126,8631100.87151,1011430.951.04 (0.72–1.18)0.04 (−0.26 to 1.12)
       42497091.81400992.240.66 (0.31–2.00)−0.75 (−1.53 to 2.14)
      Uterine rupture during labor
       3725,374150.591,575,8797770.491.19 (0.71–1.98)0.09 (−0.41 to 0.48)
       3850,221230.461,448,8427210.500.90 (0.59–1.36)−0.05 (−0.21 to 0.48)
       3965,681400.611,178,5956140.521.14 (0.83–1.57)0.07 (−0.09 to 0.30)
       4094,118390.41705,2393920.560.74 (0.54–1.04)−0.15 (−0.26 to 0.02)
       41126,8631691.33151,1011020.680.81 (0.60–1.10)−0.13 (−0.27 to 0.07)
       42497051.01400941.000.13 (0.30–4.24)−0.87 (−0.70 to 3.24)
      Rates (per 1000) of specific severe maternal morbidity after labor induction vs expectant treatment by gestational age among women without pregnancy complications, Canada (excluding Quebec), 2003-2010.
      CI, confidence interval.
      Liu. Effects of labor induction. Am J Obstet Gynecol 2013.
      a Adjusted for maternal age, parity, year of birth, and province of hospital delivery
      b Calculated only if the adjusted rate difference was statistically significant.
      Rates of postpartum ICU admission were not higher among women with labor induction at all gestational ages between 37 and 42 weeks (Table 4); rates of venous thromboembolism were higher among women who were induced at 37 (P = .05) and 38 (P = .0006) weeks' gestation compared with those who were treated expectantly. Labor induction at 39-42 weeks' gestation was not associated with venous thromboembolism or with obstetric shock.
      Table 4Effects of labor induction on specific maternal morbidity (per 10,000)
      Gestational age, wkLabor inductionExpectant treatmentAdjusted rate ratio (95% CI)
      Adjusted for maternal age, parity, year of birth, and province of hospital delivery
      Adjusted rate difference per 10,000Needed to harm, n
      Calculated only if the adjusted rate difference was statistically significant.
      Total, nOutcome frequencyRate per 10,000Total, nOutcome frequencyRate per 10,000
      nn
      Intensive care unit admission
       3725,374111.331,575,8793902.471.78 (0.98–3.30)1.84 (−0.05 to 5.24)
       3850,221173.391,448,8423782.611.30 (0.80–2.11)0.75 (−0.55 to 2.79)
       3965,681182.741,178,5953103.631.07 (0.67–1.73)−0.89 (−1.17 to 2.49)
       4094,118222.34705,2391883.670.87 (0.56–1.36)−1.33 (−1.58 to 1.26)
       41126,863362.84151,101271.791.63 (0.99–2.70)1.05 (−0.78 to 2.90)
       42497000.00400912.49
      Venous thromboembolism
       3725,37451.971,575,8791280.812.43 (0.997–5.93)1.16 (−0.01 to 3.99)
       3850,221112.191,448,8421090.802.94 (1.59–5.46)1.56 (0.47–3.56)6410 (2809–21,186)
       3965,68181.221,178,595820.731.75 (0.85–3.62)0.55 (0.11–1.91)
       4094,11880.96705,239530.771.18 (0.56–2.48)0.14 (−0.34 to 1.14)
       41126,863100.79151,10180.531.58 (0.62–4.02)0.31 (−0.20 to 1.60)
       42497000.00400900.00
      Obstetric shock
       3725,37420.791,575,8791150.731.07 (0.26–4.32)0.05 (−0.54 to 2.42)
       3850,22130.601,448,8421070.740.81 (0.26–2.54)−0.16 (−0.55 to 1.14)
       3965,68130.461,178,595930.790.59 (0.19–1.87)−0.20 (−0.64 to 0.73)
       4094,11880.85705,239901.281.04 (0.50–2.13)0.04 (−0.64 to 1.45)
       41126,86390.71151,101120.790.89 (0.38–2.12)−0.10 (−0.49 to 0.88)
       42497000.00400900.00
      Rates (per 10,000) of specific severe maternal morbidity after induction and expectant treatment by gestational age among women without pregnancy complications, Canada (excluding Quebec), 2003-2010.
      CI, confidence interval.
      Liu. Effects of labor induction. Am J Obstet Gynecol 2013.
      a Adjusted for maternal age, parity, year of birth, and province of hospital delivery
      b Calculated only if the adjusted rate difference was statistically significant.
      Tables 3 and 4 also provide adjusted rate differences and the number needed to harm that were associated with labor induction and each specific maternal morbidity. Because rates of the specific maternal morbidity in question were low, adjusted rate differences were small. Induction of labor for 1270 women (95% confidence interval, 730–3217) led to 1 additional case of postpartum hemorrhage that required blood transfusion (compared with expectant management); the number needed to harm for postpartum sepsis at 38 or 39 weeks' gestation and venous thromboembolism at 38 weeks' gestation was >5000, with the lower bound of the confidence interval exceeding 1400.
      Sensitivity analyses with parity-specific models showed no evidence that parity modified the effects of labor induction on adverse maternal outcomes.

      Comment

      In this large, population-based study of women without pregnancy complications, induction of labor was associated with an increased risk of a few specific subtypes of severe maternal morbidity, mostly at earlier term gestational ages. In particular, we observed a significantly increased risk of severe postpartum hemorrhage at 37, 38, 39, and 40 weeks' gestation, puerperal sepsis at 38 and 39 weeks' gestation, and venous thromboembolism at 38 weeks' gestation. These findings confirm those from previous studies that have also inferred a deleterious effect of labor induction that is related to such specific severe maternal morbidity.
      • American College of Obstetricians and Gynecologists
      Induction of Labor: ACOG practice bulletin no. 107.
      • Grobman W.A.
      • Gilbert S.
      • Landon M.B.
      • et al.
      Outcomes of induction of labor after one prior cesarean.
      • Kramer M.S.
      • Rouleau J.
      • Basket T.F.
      • Joseph K.S.
      Maternal Health Study Group of the Canadian Perinatal Surveillance System
      Amniotic-fluid embolism and medical induction of labour: a retrospective population-based cohort study.
      • Wennerholm U.B.
      • Hagberg H.
      • Brorsson B.
      • Bergh C.
      Induction of labor versus expectant management for post-date pregnancy: is there sufficient evidence for a change in clinical practice?.
      • Joseph K.S.
      • Rouleau J.
      • Kramer M.S.
      • et al.
      Investigation of an increase in postpartum haemorrhage in Canada.
      • Kramer M.S.
      • Dahhou M.
      • Vallerand D.
      • Liston R.
      • Joseph K.S.
      Risk factors for postpartum hemorrhage: can we explain the recent temporal increase?.
      The magnitude of the effect of labor induction on severe maternal morbidity was small, however, and the numbers needed to harm were substantial. The clinical significance of these findings varies depending on the context; the individual woman who undergoes labor induction is likely to view these relatively rare side-effects as a modest downside, although the frequent use of labor induction and the severity of the adverse effects implies a significant contribution to population morbidity.
      Labor induction is indicated when the benefits of delivery outweigh the fetal or maternal risks that are associated with expectant management. The use of labor induction when indicated can be life-saving for the fetus and/or the mother and can serve to reduce neonatal and maternal morbidity. On the other hand, labor induction sometimes can have serious adverse effects and thus should be reserved for situations in which it is medically indicated.
      The estimates of the effect of labor induction on severe maternal morbidity that were studied generally followed a gestational age–specific pattern. Adverse effects tended to be larger and significant at 38 and 39 weeks' gestation but small and nonsignificant at later gestation. For example, the rate ratios for postpartum hemorrhage with blood transfusion were 1.28 at 38 weeks' gestation, 1.21 at 39 weeks' gestation, 1.12 at 40 weeks' gestation, 1.04 at 41 weeks' gestation, and 0.68 at 42 weeks' gestation. The rate ratio pattern for postpartum sepsis was very similar. The tests for heterogeneity of these odds ratios were significant. These findings are plausible biologically because they are compatible with the understanding that the complications of labor induction are more likely to occur when induction is performed before the cervix, uterus, and other maternal tissues have undergone the necessary physiologic changes that are required for labor.
      • Tan P.C.
      • Suguna S.
      • Vallikkannu N.
      • Hassan J.
      Ultrasound and clinical predictors for Caesarean delivery after labour induction at term.
      • Laughon S.K.
      • Zhang J.
      • Troendle J.
      • Sun L.
      • Reddy U.M.
      Using a simplified Bishop score to predict vaginal delivery.
      An important methodologic strength of our study is that it simulates the intention-to-treat analysis of a randomized trial, because women who had induction of labor were compared with those who were treated expectantly. Further, our study was restricted to the unintended effects of therapy among women without pregnancy complications and thus was less likely to be confounded by indication.
      • Glantz J.C.
      Term labor induction compared with expectant management.
      • Miettinen O.S.
      The need for randomization in the study of intended effects.
      Finally, our large study size permitted an examination of rare, but potentially serious, consequences of induction.
      • Gülmezoglu A.M.
      • Crowther C.A.
      • Middleton P.
      Induction of labour for improving birth outcomes for women at or beyond term.
      The potential bias because of confounding by indication is a major concern in observational studies of the effects of labor induction. Despite our “intention-to-treat” approach and our efforts to minimize confounding by indication, it is possible that some of the effects that we observed were caused by preexisting maternal conditions that were not documented in the database (such as maternal obesity, history of coagulation disorders, or history of postpartum hemorrhage). Although we excluded women with any documented pregnancy complication from the study, our data source did not contain information on indications for labor induction. A second limitation of our study is that we were unable to exclude elective (prelabor) cesarean deliveries directly. Our exclusion criteria (previous cesarean delivery, noncephalic presentation, and maternal risk factors) would have eliminated the vast majority of elective cesarean deliveries, but any remaining elective cesarean deliveries would have been included in the expectant management group. Finally, our contrast was between morbidity rates among women who were induced at any gestational week vs morbidity rates among women who were treated expectantly who delivered in the subsequent week or later. This represents a conservative approach and assumed that women who required induction are unlikely to deliver spontaneously in the same week (if not induced).
      • Caughey A.B.
      • Nicholson J.M.
      • Cheng Y.W.
      • Lyell D.J.
      • Washington A.E.
      Induction of labor and cesarean delivery by gestational age.
      In conclusion, our study confirmed that induction of labor is associated with higher rates of specific severe maternal morbidity among women without documented pregnancy complications, especially at 38 and 39 weeks' gestation, although all rate differences were small and the numbers needed to harm were large. Nevertheless, these serious risks must be balanced against potential benefits whenever the decision to induce labor is considered.

      Acknowledgments

      This study was carried out under the auspices of the Canadian Perinatal Surveillance System. Contributing members of the Maternal Health Study Group of the Canadian Perinatal Surveillance System include: Alexander Allen (Dalhousie University), John Fahey (Nova Scotia Reproductive Care Program), Joy Fletcher (Canadian Institute of Health Information), William Fraser (University of Montreal), Maureen Heaman (University of Manitoba), Russell S. Kirby (South Florida University), Patricia O'Campo (University of Toronto), Jocelyn Rouleau (Public Health Agency of Canada), Reg Sauve (University of Calgary), and Anne-Marie Ugnat (Public Health Agency of Canada). We thank the Canadian Institute for Health Information for providing access to the Discharge Abstract Database.

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