Cost-effectiveness analysis of induction of labour at 41 weeks and expectant management until 42 weeks in low risk women (INDEX trial).

Objective: To assess the cost-effectiveness of elective induction of labour (IOL) at 41 weeks and expectant management (EM) until 42 weeks. Design: Cost-effectiveness analysis from a healthcare perspective alongside a randomised controlled trial (INDEX). Setting: 123 primary care midwifery practices and 45 obstetric departments of hospitals in the Netherlands. Population: We studied 1801 low-risk women with late-term pregnancy, randomised to IOL at 41 weeks (N = 900) or EM until 42 weeks (N = 901). Methods: The incremental cost-effectiveness ratio (ICER) was expressed as the ratio of the difference in costs and the difference in main perinatal outcomes. A Cost-Effectiveness Acceptability Curve (CEAC) was constructed to assess whether induction is cost-effective for a range of monetary values as thresholds. We performed subgroup analysis for parity. Main outcome measures: Direct medical costs, composite adverse perinatal outcome (CAPO) (perinatal mortality, NICU admission, Apgar 5 min < 7, plexus brachialis injury and/or meconium aspiration syndrome) and composite severe adverse perinatal outcome (SAPO) (including Apgar 5 min < 4 instead of < 7). Results: The average costs were €3858 in the induction group and €3723 in the expectant group (mean difference €135; 95 % CI -235 to 493). The ICERs of IOL compared to EM to prevent one additional CAPO and SAPO was €9436 and €14,994, respectively. The CEAC showed a 80 % chance of IOL being cost-effective with a willingness-to-pay of €22,000 for prevention of one CAPO and €50,000 for one SAPO. Subgroup analysis showed a willingness-to-pay to prevent one CAPO for nulliparous of €47,000 and for multiparous €190,000. To prevent one SAPO the willingness-to-pay is €62,000 for nulliparous and €970,000 for multiparous women. Conclusions: Induction at 41 weeks has an 80 % chance of being cost-effective at a willingness-to-pay of €22,000 for prevention of one CAPO and €50,000 for prevention of one SAPO. Subgroup analysis suggests that induction could be cost-effective for nulliparous women while it is unlikely cost-effective for multiparous women.Cost-effectiveness in other settings will depend on baseline characteristics of the population and health system organisation and funding.

Elective induction of labour and expectant management in late-term pregnancy: A prospective cohort study alongside the INDEX randomised controlled trial.

Objective: To assess adverse perinatal outcomes and caesarean section of low-risk women receiving elective induction of labour at 41 weeks or expectant management until 42 weeks according to their preferred and actual management strategy. Design: Multicentre prospective cohort study alongside RCT. Setting: 90 midwifery practices and 12 hospitals in the Netherlands. Population: 3642 low-risk women with uncomplicated singleton late-term pregnancy. Main outcome measures: Composite adverse outcome (perinatal death, Apgar score 5' < 7, NICU admission, meconium aspiration syndrome), composite severe adverse perinatal outcome (all above with Apgar score 5' < 4 instead of < 7) and caesarean section. Results: From 2012-2016, 3642 women out of 6088 eligible women for the INDEX RCT, participated in the cohort study for observational data collection (induction of labour n = 372; expectant management n = 2174; unknown preference/management strategy n = 1096).Adverse perinatal outcome occurred in 1.1 % (4/372) in the induction group versus 1.9 % (42/2174) in the expectant group (adjRR 0.56; 95 %CI: 0.17-1.79), with severe adverse perinatal outcome occurring in 0.3 % (1/372) versus 1.0 % (22/2174), respectively (adjRR 0.39; 95 % CI: 0.05-2.88). There were no stillbirths among all 3642 women; one neonatal death occurred in the unknown preference/management group. Caesarean section rates were 10.5 % (39/372) after induction and 8.9 % (193/2174) after expectant management (adjRR 1.32; 95 % CI: 0.95-1.84).A higher incidence of adverse perinatal outcome was observed in nulliparous compared to multiparous women. Nulliparous 1.8 % (3/170) in the induction group versus 2.6 % (30/1134) in the expectant management group (adjRR 0.58; 95 % CI 0.14-2.41), multiparous 0.5 % (1/201) versus 1.1 % (11/1039) (adjRR 0.54; 95 % CI 0.07-24.19). One maternal death due to amniotic fluid embolism occurred after elective induction at 41 weeks + 6 days. Conclusion: In this cohort study among low-risk women receiving the policy of their preference in late-term pregnancy, a non-significant difference was found between induction of labour at 41 weeks and expectant management until 42 weeks in absolute risks of composite adverse (1.1 % versus 1.9 %) and severe adverse (0.3 % versus 1.0 %) perinatal outcome. The risks in this cohort study were lower than in the trial setting. There were no stillbirths among all 3642 women. Caesarean section rates were comparable.

Risk of adverse pregnancy outcomes of late- and postterm pregnancies in advanced maternal age: A national cohort study.

INTRODUCTION: There is an increase in women delivering ≥35 years of age. We analyzed the association between advanced maternal age and pregnancy outcomes in late- and postterm pregnancies. MATERIAL AND METHODS: A national cohort study was performed on obstetrical low-risk women using data from the Netherlands Perinatal Registry from 1999 to 2010. We included women ≥18 years of age with a singleton pregnancy at term. Women with a pregnancy complicated by congenital anomalies, hypertensive disorders or diabetes mellitus were excluded. Composite adverse perinatal outcome was defined as stillbirth, neonatal death, meconium aspiration syndrome, 5-minute Apgar score <7, neonatal intensive care unit admittance and sepsis. Composite adverse maternal outcome was defined as maternal death, placental abruption and postpartum hemorrhage of >1000 mL. RESULTS: We stratified the women into three age groups: 18-34 (n = 1 321 366 [reference]); 35-39 (n = 286 717) and ≥40 (n = 40 909). Composite adverse perinatal outcome occurred in 1.6% in women aged 18-34, 1.7% in women aged 35-39 (relative risk [RR] 1.06, 95% confidence interval [95% CI] 1.03-1.08) and 2.2% in women aged ≥40 (RR 1.38, 95% CI 1.29-1.47), with 5-minute Apgar score <7 as the factor contributing most to the outcome. Composite adverse maternal outcome occurred in 4.6% in women aged 18-34, 5.0% in women aged 35-39 (RR 1.08, 95% CI 1.06-1.10) and 5.2% in women aged ≥40 (RR 1.14, 95% CI 1.09-1.19), with postpartum hemorrhage >1000 mL as the factor contributing most to the outcome. In all age categories, the risk of adverse pregnancy outcomes was higher for nulliparous than for multiparous women. The risk of adverse outcomes increased in both nulliparous and parous women with advancing gestational age. When adjusted for parity, onset of labor and gestational age, advanced maternal age is associated with an increase in both composite adverse perinatal and maternal outcomes. CONCLUSIONS: The risk of adverse pregnancy outcome increases with advancing maternal age. Women aged ≥40 have an increased risk of adverse perinatal and maternal outcome when pregnancy goes beyond 41 weeks.

Management of late-term pregnancy in midwifery- and obstetrician-led care.

Management of late-term pregnancy in midwifery- and obstetrician-led care. BACKGROUND: Since there is no consensus regarding the optimal management in late-term pregnancies (≥41.0 weeks), we explored the variety of management strategies in late-term pregnancy in the Netherlands to identify the magnitude of this variety and the attitude towards late-term pregnancy. METHODS: Two nationwide surveys amongst all midwifery practices (midwifery-led care) and all hospitals with an obstetric unit (obstetrician-led care) were performed with questions on timing, frequency and content of consultations/surveillance in late-term pregnancy and on timing of induction. Propositions about late-term pregnancy were assessed using Likert scale questions. RESULTS: The response rate was 40% (203/511) in midwifery-led care and 92% (80/87) in obstetrician-led care. All obstetric units made regional protocols with their collaborating midwifery practices about management in late-term pregnancy. Most midwifery-led care practices (93%) refer low-risk women at least once for consultation in obstetrician-led care in late-term pregnancy. The content of consultations varies among hospitals. Membrane sweeping is performed more in midwifery-led care compared to obstetrician-led care (90% vs 31%, p < 0.001). Consultation at 41 weeks should be standard care according to 47% of midwifery-led care practices and 83% of obstetrician-led care units (p < 0.001). Induction of labour at 41.0 weeks is offered less often to women in midwifery-led care in comparison to obstetrician-led care (3% vs 21%, p < 0.001). CONCLUSIONS: Substantial practice variation exists within and between midwifery-and obstetrician-led care in the Netherlands regarding timing, frequency and content of antenatal monitoring in late-term pregnancy and timing of labour induction. An evidence based interdisciplinary guideline will contribute to a higher level of uniformity in the management in late- term pregnancies.

Induction of labour at 41 weeks versus expectant management until 42 weeks (INDEX): multicentre, randomised non-inferiority trial.

OBJECTIVE: To compare induction of labour at 41 weeks with expectant management until 42 weeks in low risk women. DESIGN: Open label, randomised controlled non-inferiority trial. SETTING: 123 primary care midwifery practices and 45 hospitals (secondary care) in the Netherlands, 2012-16. PARTICIPANTS: 1801 low risk women with an uncomplicated singleton pregnancy: randomised to induction (n=900) or to expectant management until 42 weeks (n=901). INTERVENTIONS: Induction at 41 weeks or expectant management until 42 weeks with induction if necessary. PRIMARY OUTCOME MEASURES: Primary outcome was a composite of perinatal mortality and neonatal morbidity (Apgar score <7 at five minutes, arterial pH <7.05, meconium aspiration syndrome, plexus brachialis injury, intracranial haemorrhage, and admission to a neonatal intensive care unit (NICU). Secondary outcomes included maternal outcomes and mode of delivery. The null hypothesis that expectant management is inferior to induction was tested with a non-inferiority margin of 2%. RESULTS: Median gestational age at delivery was 41 weeks+0 days (interquartile range 41 weeks+0 days-41 weeks+1 day) for the induction group and 41 weeks+2 days (41 weeks+0 days-41 weeks+5 days) for the expectant management group. The primary outcome was analysed for both the intention-to-treat population and the per protocol population. In the induction group, 15/900 (1.7%) women had an adverse perinatal outcome versus 28/901 (3.1%) in the expectant management group (absolute risk difference -1.4%, 95% confidence interval -2.9% to 0.0%, P=0.22 for non-inferiority). 11 (1.2%) infants in the induction group and 23 (2.6%) in the expectant management group had an Apgar score <7 at five minutes (relative risk (RR) 0.48, 95% CI 0.23 to 0.98). No infants in the induction group and three (0.3%) in the expectant management group had an Apgar score <4 at five minutes. One fetal death (0.1%) occurred in the induction group and two (0.2%) in the expectant management group. No neonatal deaths occurred. 3 (0.3%) neonates in the induction group versus 8 (0.9%) in the expectant management group were admitted to an NICU (RR 0.38, 95% CI 0.10 to 1.41). No significant difference was found in composite adverse maternal outcomes (induction n=122 (13.6%) v expectant management n=102 (11.3%)) or in caesarean section rate (both groups n=97 (10.8%)). CONCLUSIONS: This study could not show non-inferiority of expectant management compared with induction of labour in women with uncomplicated pregnancies at 41 weeks; instead a significant difference of 1.4% was found for risk of adverse perinatal outcomes in favour of induction, although the chances of a good perinatal outcome were high with both strategies and the incidence of perinatal mortality, Apgar score <4 at five minutes, and NICU admission low. TRIAL REGISTRATION: Netherlands Trial Register NTR3431.

Perinatal death beyond 41 weeks pregnancy: an evaluation of causes and substandard care factors as identified in perinatal audit in the Netherlands.

BACKGROUND: Late- and postterm pregnancy are associated with adverse perinatal outcomes, like perinatal death. We evaluated causes of death and substandard care factors (SSFs) in term and postterm perinatal death. METHODS: We used data from the Perinatal Audit Registry of the Netherlands (PARS). Women with a term perinatal death registered in PARS were stratified by gestational age into early-/full-term (37.0-40.6) and late-/postterm (≥41.0 weeks) death. Cause of death and SSFs ≥41 weeks were scored and classified by the local perinatal audit teams. RESULTS: During 2010-2012, 947/479,097 (0.21%) term deaths occurred, from which 707 cases (75%) were registered and could be used for analyses. Five hundred ninety-eight early-/full-term and 109 late-/postterm audited deaths were registered in the PARS database. Of all audited cases of perinatal death in the PARS database, 55.2% in the early-/fullterm group occurred antepartum compared to 42.2% in the late-/postterm group, while intrapartum death occurred in 7.2% in the early-/full-term group compared to 19.3% in the late-/postterm group in the audited cases from the PARS database. According to the local perinatal audit, the most relevant causes of perinatal death ≥41 weeks were antepartum asphyxia (7.3%), intrapartum asphyxia (9.2%), neonatal asphyxia (10.1%) and placental insufficiency (10.1%). In the group with perinatal death ≥41 weeks there was ≥1SSF identified in 68.8%. The most frequent SSFs concerned inadequate cardiotocography (CTG) evaluation and/or classification (10.1%), incomplete registration or documentation in medical files (4.6%) or inadequate action on decreased foetal movements (4.6%). CONCLUSIONS: In the Netherlands Perinatal Audit Registry, stillbirth occurred relatively less often antepartum and more often intrapartum in pregnancies ≥41 weeks compared to pregnancies at 37.0-40.6 weeks in the audited cases from the PARS database. Foetal, intrapartum and neonatal asphyxia were identified more frequently as cause of death in pregnancies ≥41 weeks. The most identified SSFs related to death in pregnancies ≥41 weeks concerned inadequate CTG monitoring (evaluation, classification, registration or documentation) and inadequate action on decreased foetal movements.

Timing induction of labour at 41 or 42 weeks? A closer look at time frames of comparison: A review.

BACKGROUND: Postterm pregnancy is associated with increased perinatal risk. The WHO defines postterm pregnancy as a pregnancy at or beyond 42 weeks + 0 days, though currently labour is induced at 41 weeks in many settings. Guidelines on timing of labour induction are frequently based on the Cochrane systematic review 'Induction of labour for improving birth outcomes for women at or beyond term' in which is concluded that a policy of induction of labour is associated with fewer adverse perinatal outcome and fewer Caesarean sections. However, the included trials differed regarding the timing of induction, ranging from 39 to beyond 42 weeks while the upper limit of expectant management exceeded a gestational age of 42 weeks in most studies. OBJECTIVE: to evaluate perinatal mortality, meconium aspiration syndrome and Caesarean section rate of trials comparing a policy of elective induction of labour and expectant management according to timeframes of comparison with a focus on studies within the 41-42 weeks' timeframe. DESIGN: Review. METHODS: The systematic review of Cochrane was used as a starting point for assessing relevant trials and a search was performed for additional recent trials. We evaluated incidence and causes of perinatal mortality, incidence of meconium aspiration syndrome and Caesarean section according to three time frames of comparison. We pooled estimates and heterogeneity was tested. The quality of the included trials was assessed using the Quality Assessment Tool for Quantative Studies (EPHPP). FINDINGS: In total 22 trials were included which had all different timeframes of comparison. Only one trial compared induction of labour at 41 weeks + 0-2 days with induction at 42 weeks + 0 days, three other trials compared induction of labour at 41 weeks + 0-6 days with induction at 42 weeks + 0-6 days. In 18 trials the comparison was outside the 41-42 weeks' timeframe: in six trials induction was planned ≤ 40 weeks and in another 12 trials expectant management was beyond 43 weeks. The incidence of potentially gestational age associated perinatal mortality between 41 and 42 weeks was 0/2.444 [0%] (induction) versus 4/2.452 [0.16%] (expectant management), NNT 613; 95%CI 613 - infinite. Two trials in the timeframe of comparison 41-42 weeks were available for evaluation of meconium aspiration syndrome (6/554 (induction) versus 14/554 (expectant management), RR 0.44; 95%CI 0.17-1.16). Three trials in the timeframe 41-42 weeks could be evaluated for Caesarean section, with different inclusion criteria regarding Bishop score. There was no significant difference in the Caesarean section rate 93/629 (induction) versus 106/629 (expectant management), RR 0.88; 95%CI 0.68-1.13. CONCLUSION: Evidence is lacking for the recommendation to induce labour at 41 weeks instead of 42 weeks for the improvement of perinatal outcome. More studies comparing both timeframes with an adequate sample size are needed to establish the optimal timing of induction of labour in late-term pregnancies.

Effects of induction of labour versus expectant management in women with impending post-term pregnancies: the 41 week - 42 week dilemma.

BACKGROUND: Post-term pregnancy, a pregnancy exceeding 294 days or 42 completed weeks, is associated with increased perinatal morbidity and mortality and is considered a high-risk condition which requires specialist surveillance and induction of labour. However, there is uncertainty on the policy concerning the timing of induction for post-term pregnancy or impending post-term pregnancy, leading to practice variation between caregivers. Previous studies on induction at or beyond 41 weeks versus expectant management showed different results on perinatal outcome though conclusions in meta-analyses show a preference for induction at 41 weeks. However, interpretation of the results is hampered by the limited sample size of most trials and the heterogeneity in design. Most control groups had a policy of awaiting spontaneous onset of labour that went far beyond 42 weeks, which does not reflect usual care in The Netherlands where induction of labour at 42 weeks is the regular policy. Thus leaving the question unanswered if induction at 41 weeks results in better perinatal outcomes than expectant management until 42 weeks. METHODS/DESIGN: In this study we compare a policy of labour induction at 41 + 0/+1 weeks with a policy of expectant management until 42 weeks in obstetrical low risk women without contra-indications for expectant management until 42 weeks and a singleton pregnancy in cephalic position. We will perform a multicenter randomised controlled clinical trial. Our primary outcome will be a composite outcome of perinatal mortality and neonatal morbidity. Secondary outcomes will be maternal outcomes as mode of delivery (operative vaginal delivery and Caesarean section), need for analgesia and postpartum haemorrhage (≥1000 ml). Maternal preferences, satisfaction, wellbeing, pain and anxiety will be assessed alongside the trial. DISCUSSION: This study will provide evidence for the management of pregnant women reaching a gestational age of 41 weeks. TRIAL REGISTRATION: Dutch Trial Register (Nederlands Trial Register): NTR3431. Registered: 14 May 2012.