Management of late term pregnancy

Background: The optimal time point to intervene and induce labour in women with a low-risk pregnancy, in order to decrease perinatal adverse outcome, is up for debate. Some advocate for induction of labour (IOL) at 41 gestational weeks (GW) and others for expectant management (EM) until 42 GW. Aim: To clarify, in women with a low-risk singleton pregnancy, if a policy of IOL at 41 GW (late term) compared with EM until 42 GW (postterm) was superior, in terms of neonatal and maternal outcomes, as well as health economic aspects. Furthermore, different methods of IOL in late term/postterm pregnancies were assessed. Material and methods: Paper I was a Swedish multicentre register-based randomised controlled trial in women with a low-risk late term/postterm singleton pregnancy (n=2 760) comparing IOL at 41 GW with EM until 42 GW. The trial was conducted between May 2016 and October 2018. Primary outcome was a composite of perinatal mortality and morbidity. Paper II was a one-step individual participant data (IPD) meta-analysis (n=5 161 for aggregate data and 4 561 for IPD) and included trials comparing IOL in women with a low-risk singleton pregnancy at 41 GW with EM until 42 GW. Primary outcome was a composite of perinatal morbidity and mortality. Subgroup analysis was performed on maternal age, body mass index and parity. Paper III was a cost-effectiveness analysis alongside Paper I (n=2 746). Primary outcomes were costs per gained life year (LY) and quality adjusted life year (QALY). Paper IV was a prospective cohort study on efficacy, safety and women’s childbirth experience of IOL with oral misoprostol (OM) (n=744) compared with transvaginal balloon catheter (TVBC) (n=469). Women included in Paper I, who needed cervical ripening for IOL, were assessed. Primary efficacy outcome was vaginal delivery within 24 hours, primary safety outcomes were a composite of neonatal mortality and morbidity and a composite of maternal mortality and morbidity. Women’s childbirth experience was measured with the Childbirth Experience Questionnaire (CEQ 2.0). Results: Paper I: The primary outcome did not differ between the groups. However, the trial was truncated early due to safety reasons because a significant decreased perinatal mortality was seen in the IOL group (p=0.03). Similar results in both groups were reported regarding mode of delivery and maternal adverse outcomes, except endometritis. Paper II: Three trials were eligible and two contributed with IPD. The primary outcome was significantly lower in the IOL group, relative risk (RR) 0.43 (95 % confidence interval [CI] 0.21 to 0.91), as were perinatal mortality, Peto odds ratio 0.21 (95 % CI 0.06 to 0.78) and admission to neonatal care ≥4 days, RR 0.52 (95 % CI 0.32 to 0.85). Similar results in both groups were reported regarding mode of delivery and maternal adverse outcomes. The primary outcome was significantly lower in the IOL group in nulliparous, but not in parous women. Paper III: The incremental cost-effectiveness ratio for IOL compared with EM was €545 per LY (95 % CI ranging from lower costs and better health outcomes [dominant] to €4 002) and €623 per QALY (95 % CI dominant to €4 586). Paper IV: Vaginal delivery within 24 hours was significantly lower in the OM group compared with the TVBC group, adjusted RR 0.76 (95 % CI 0.64; 0.89). Primary neonatal and maternal safety outcomes did not differ between groups. Women’s childbirth experience was overall positive and similar in the groups. Conclusion: There are medical benefits of IOL at 41 GW compared with EM until 42 GW and it is cost-effective. TVBC was slightly more effective regarding efficacy. Women approaching 41+0 GW should receive unbiased information regarding benefits and risks with IOL at 41+0 GW compared with EM in order to make an informed decision for herself and her unborn infant

Efficacy and safety of oral misoprostol versus transvaginal balloon catheter for labor induction : An observational study within the SWEdish Postterm Induction Study (SWEPIS)

Introduction Induction of labor is increasing. A common indication for induction of labor is late term and postterm pregnancy at 41 weeks or more. We aimed to evaluate if there are any differences regarding efficacy, safety, and women's childbirth experience between oral misoprostol and transvaginal balloon catheter for cervical ripening in women with a low-risk singleton pregnancy and induction of labor at 41+0 to 42+0 to 1 weeks of gestation. Material and methods In this observational study, based on data from the Swedish Postterm Induction Study (SWEPIS), a multicenter randomized controlled trial, a total of 1213 women with a low-risk singleton pregnancy at 41 to 42 weeks of gestation were induced with oral misoprostol (n = 744) or transvaginal balloon catheter (n = 469) at 15 Swedish delivery hospitals. The primary efficacy outcome was vaginal delivery within 24 h and primary safety outcomes were neonatal and maternal composite adverse outcomes. Secondary outcomes included time to vaginal delivery and mode of delivery. Women's childbirth experience was assessed with the Childbirth Experience Questionnaire (CEQ 2.0) and visual analog scale. We present crude and adjusted mean differences and relative risks (RR) with 95% CI. Adjustment was performed for a propensity score based on delivery hospital and baseline characteristics including Bishop score. Results Vaginal delivery within 24 h was significantly lower in the misoprostol group compared with the balloon catheter group (46.5% [346/744] vs 62.7% [294/469]; adjusted RR 0.76 95% CI 0.640.89]). Primary neonatal and maternal safety outcomes did not differ between groups (neonatal composite 3.5% [36/744] vs 3.2% [15/469]; adjusted RR 0.77 [95% CI 0.31–1.89]; maternal composite 2.3% [17/744] vs 1.9% [9/469]; adjusted RR 1.70 [95% CI 0.58–4.97]). Adjusted mean time to vaginal delivery was increased by 3.8 h (95% CI 1.3–6.2 h) in the misoprostol group. Non-operative vaginal delivery and cesarean delivery rates did not differ. Women's childbirth experience was positive overall and similar in both groups. Conclusions Induction of labor with oral misoprostol compared with a transvaginal balloon catheter was associated with a lower probability of vaginal delivery within 24 h and a longer time to vaginal delivery. However, primary safety outcomes, non-operative vaginal delivery, and women's childbirth experience were similar in both groups. Therefore, both methods can be recommended in women with low-risk postdate pregnancies

Induction of labour at 41 weeks versus expectant management and induction of labour at 42 weeks (SWEdish Post-term Induction Study, SWEPIS) : multicentre, open label, randomised, superiority trial

OBJECTIVE To evaluate if induction of labour at 41 weeks improves perinatal and maternal outcomes in women with a low risk pregnancy compared with expectant management and induction of labour at 42 weeks. DESIGN Multicentre, open label, randomised controlled superiority trial. SETTING 14 hospitals in Sweden, 2016-18. PARTICIPANTS 2760 women with a low risk uncomplicated singleton pregnancy randomised (1:1) by the Swedish Pregnancy Register. 1381 women were assigned to the induction group and 1379 were assigned to the expectant management group. INTERVENTIONS Induction of labour at 41 weeks and expectant management and induction of labour at 42 weeks. MAIN OUTCOME MEASURES The primary outcome was a composite perinatal outcome including one or more of stillbirth, neonatal mortality, Apgar score less than 7 at five minutes, pH less than 7.00 or metabolic acidosis (pH <7.05 and base deficit >12 mmol/L) in the umbilical artery, hypoxic ischaemic encephalopathy, intracranial haemorrhage, convulsions, meconium aspiration syndrome, mechanical ventilation within 72 hours, or obstetric brachial plexus injury. Primary analysis was by intention to treat. RESULTS The study was stopped early owing to a significantly higher rate of perinatal mortality in the expectant management group. The composite primary perinatal outcome did not differ between the groups: 2.4% (33/1381) in the induction group and 2.2% (31/1379) in the expectant management group (relative risk 1.06, 95% confidence interval 0.65 to 1.73; P=0.90). No perinatal deaths occurred in the induction group but six (five stillbirths and one early neonatal death) occurred in the expectant management group (P=0.03). The proportion of caesarean delivery, instrumental vaginal delivery, or any major maternal morbidity did not differ between the groups. CONCLUSIONS This study comparing induction of labour at 41 weeks with expectant management and induction at 42 weeks does not show any significant difference in the primary composite adverse perinatal outcome. However, a reduction of the secondary outcome perinatal mortality is observed without increasing adverse maternal outcomes. Although these results should be interpreted cautiously, induction of labour ought to be offered to women no later than at 41 weeks and could be one (of few) interventions that reduces the rate of stillbirths

Induction of labour at 41 weeks or expectant management until 42 weeks: A systematic review and an individual participant data meta-analysis of randomised trials

Background The risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. Several randomised controlled trials (RCTs) have assessed if induction of labour (IOL) in uncomplicated pregnancies at 41 weeks will improve perinatal outcomes. We performed an individual participant data meta-analysis (IPD-MA) on this subject. Methods and findings We searched PubMed, Excerpta Medica dataBASE (Embase), The Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and PsycINFO on February 21, 2020 for RCTs comparing IOL at 41 weeks with expectant management until 42 weeks in women with uncomplicated pregnancies. Individual participant data (IPD) were sought from eligible RCTs. Primary outcome was a composite of severe adverse perinatal outcomes: mortality and severe neonatal morbidity. Additional outcomes included neonatal admission, mode of delivery, perineal lacerations, and postpartum haemorrhage. Prespecified subgroup analyses were conducted for parity (nulliparous/multiparous), maternal age (<35/≥35 years), and body mass index (BMI) (<30/≥30). Aggregate data meta-analysis (MA) was performed to include data from RCTs for which IPD was not available. From 89 full-text articles, we identified three eligible RCTs (n = 5,161), and two contributed with IPD (n = 4,561). Baseline characteristics were similar between the groups regarding age, parity, BMI, and higher level of education. IOL resulted overall in a decrease of severe adverse perinatal outcome (0.4% [10/2,281] versus 1.0% [23/2,280]; relative risk [RR] 0.43 [95% confidence interval [CI] 0.21 to 0.91], p-value 0.027, risk difference [RD] -57/10,000 [95% CI -106/10,000 to -8/10,000], I2 0%). The number needed to treat (NNT) was 175 (95% CI 94 to 1,267). Perinatal deaths occurred in one (<0.1%) versus eight (0.4%) pregnancies (Peto odds ratio [OR] 0.21 [95% CI 0.06 to 0.78], p-value 0.019, RD -31/10,000, [95% CI -56/10,000 to -5/10,000], I2 0%, NNT 326, [95% CI 177 to 2,014]) and admission to a neonatal care unit ?4 days occurred in 1.1% (24/2,280) versus 1.9% (46/2,273), (RR 0.52 [95% CI 0.32 to 0.85], p-value 0.009, RD -97/10,000 [95% CI -169/10,000 to -26/10,000], I2 0%, NNT 103 [95% CI 59 to 385]). There was no difference in the rate of cesarean delivery (10.5% versus 10.7%; RR 0.98, [95% CI 0.83 to 1.16], p-value 0.81) nor in other important perinatal, delivery, and maternal outcomes. MA on aggregate data showed similar results. Prespecified subgroup analyses for the primary outcome showed a significant difference in the treatment effect (p = 0.01 for interaction) for parity, but not for maternal age or BMI. The risk of severe adverse perinatal outcome was decreased for nulliparous women in the IOL group (0.3% [4/1,219] versus 1.6% [20/1,264]; RR 0.20 [95% CI 0.07 to 0.60], p-value 0.004, RD -127/10,000, [95% CI -204/10,000 to -50/10,000], I2 0%, NNT 79 [95% CI 49 to 201]) but not for multiparous women (0.6% [6/1,219] versus 0.3% [3/1,264]; RR 1.59 [95% CI 0.15 to 17.30], p-value 0.35, RD 27/10,000, [95% CI -29/10,000 to 84/10,000], I2 55%). A limitation of this IPD-MA was the risk of overestimation of the effect on perinatal mortality due to early stopping of the largest included trial for safety reasons after the advice of the Data and Safety Monitoring Board. Furthermore, only two RCTs were eligible for the IPDMA; thus, the possibility to assess severe adverse neonatal outcomes with few events was limited. Conclusions In this study, we found that, overall, IOL at 41 weeks improved perinatal outcome compared with expectant management until 42 weeks without increasing the cesarean delivery rate. This benefit is shown only in nulliparous women, whereas for multiparous women, the incidence of mortality and morbidity was too low to demonstrate any effect. The magnitude of risk reduction of perinatal mortality remains uncertain. Women with pregnancies approaching 41 weeks should be informed on the risk differences according to parity so that they are able to make an informed choice for IOL at 41 weeks or expectant management until 42 weeks. Study Registration: PROSPERO CRD42020163174