Association between timing of labor induction and neonatal and maternal outcomes: an observational study from China.

Growing evidence suggests that elective induction of labor at 39 weeks' gestation may lead to more favorable perinatal outcomes than expectant management, however, how to weigh the pros and cons of elective labor induction at 39 weeks, the expectation of spontaneous delivery at 40 or 41 weeks, or delayed labor induction at 40 or 41 weeks on neonatal and maternal outcomes remains a practical challenge in clinical decision-making. We compared the neonatal and maternal outcomes between elective induction of labor at 39 weeks' gestation and expectant management in a real-world setting. We also divided the expectantly managed group and compared outcomes of the spontaneous delivery at 40 or 41 weeks' gestation group and the induced group at 40 or 41 weeks' gestation with those of the elective induction at 39 weeks' gestation group. This retrospective cohort study included 21,282 participants who delivered between January 1, 2019, and June 30, 2022. Participants were initially categorized into 3 groups at 39 weeks' gestation, namely elective induction of labor, spontaneous delivery, and expectant management, for the primary analysis in which elective induction was compared with expectant management. Subsequently, the expectant management group at 39 weeks' gestation was divided into 3 groups at 40 weeks, and participants who underwent expectant management at 40 weeks were then divided into 2 groups at 41 weeks' gestation, namely elective induction and spontaneous delivery. In total, 6 groups were compared in the secondary analysis with the elective induction at 39 weeks' gestation group serving as the reference group. At 39 weeks' gestational age, participants who underwent elective induction of labor had a significantly lower risk for the primary composite outcomes than participants who were managed expectantly (adjusted odds ratio, 0.72; 95% confidence interval, 0.55-0.95), and there was no significant difference in the risk for cesarean delivery between the 2 groups. After further dividing the expectantly managed group and comparing them with participants who underwent elective induction of labor at 39 weeks' gestation, those who underwent spontaneous delivery at 40 weeks' gestation had significantly lower risks for cesarean delivery (0.61; 0.52-0.71) and chorioamnionitis (0.78; 0.61-1.00) but a higher risk for fetal distress (1.39; 1.22-1.57); those with spontaneous delivery at 41 weeks' gestation had a significantly higher risk for fetal distress (1.44; 1.16-1.79), postpartum hemorrhage (1.83; 1.26-2.66), and prolonged or arrested labor (1.61; 1.02-2.54). Moreover, when compared with participants who underwent elective induction of labor at 39 weeks' gestation, participants who were induced later in gestation had significantly higher risks for adverse neonatal and maternal outcomes, especially at 40 weeks' gestation. Our findings indicate that elective induction of labor at 39 weeks' gestation was significantly associated with lower risks for adverse short-term neonatal and maternal outcomes when compared with expectant management. Moreover, our study highlights the nuanced trade-offs in risks and benefits between elective induction at 39 weeks' gestation and waiting for spontaneous labor or delayed induction at 40 or 41 weeks' gestation, thus providing valuable insights for clinical decision-making in practice.

Hu Y ，Chen B ，Wang X ，Zhu S ，Bao S ，Lu J ，Wang L ，Wang W ，Wu C ，Qi L ，Wang Y ，Li F ，Xie W ，Wu Y ，Hu L ，Xia Y ，Lou B ，Guo R ，Xie B ，Chen X ，Han Y ，Chen D ，Ma H ，Liang Z ... -  《-》

Induction of labor vs expectant management among low-risk patients with 1 prior cesarean delivery.

Studies that have compared induction of labor in individuals with 1 prior cesarean delivery to expectant management have shown conflicting results. To determine the association between clinical outcomes and induction of labor at 39 weeks in a national sample of otherwise low-risk patients with 1 prior cesarean delivery. This cross-sectional study analyzed 2016 to 2021 US Vital Statistics birth certificate data. Individuals with vertex, singleton pregnancies, and 1 prior cesarean delivery were included. Patients with prior vaginal deliveries, delivery before 39 weeks 0 days or after 42 weeks 6 days of gestation, and medical comorbidities were excluded. The primary exposure of interest was induction of labor at 39 weeks 0 days to 39 weeks 6 days compared to expectant management with delivery from 40 weeks 0 days to 42 weeks 6 days. The primary outcome was vaginal delivery. The main secondary outcomes were separate maternal and neonatal morbidity composites. The maternal morbidity composite included uterine rupture, operative vaginal delivery, peripartum hysterectomy, intensive care unit admission, and transfusion. The neonatal morbidity composite included neonatal intensive care unit admission, Apgar score less than 5 at 5 minutes, immediate ventilation, prolonged ventilation, and seizure or serious neurological dysfunction. Unadjusted and adjusted log binomial regression models accounting for demographic variables and the exposure of interest (induction vs expectant management) were performed. Results are presented as unadjusted and adjusted risk ratios with 95% confidence intervals. From 2016 to 2021, a total of 198,797 individuals with vertex, singleton pregnancies, and 1 prior cesarean were included in the primary analysis. Of these individuals, 25,915 (13.0%) underwent induction of labor from 39 weeks 0 days to 39 weeks 6 days and 172,882 (87.0%) were expectantly managed with deliveries between 40 weeks 0 days and 42 weeks 6 days. In adjusted analyses, patients induced at 39 weeks were more likely to have a vaginal delivery when compared to those expectantly managed (38.0% vs 31.8%; adjusted risk ratio 1.32, 95% confidence interval 1.28, 1.36). Among those who had vaginal deliveries, induction of labor was associated with increased likelihood of operative vaginal delivery (11.1% vs 10.0; adjusted risk ratio 1.15, 95% confidence interval 1.07, 1.24). The maternal morbidity composite occurred in 0.9% of individuals in both the induction and expectant management groups (adjusted risk ratio 0.92, 95% confidence interval 0.79, 1.06). The rates of uterine rupture (0.3%), peripartum hysterectomy (0.04% vs 0.05%), and intensive care unit admission (0.1% vs 0.2%) were all relatively low and did not differ significantly between groups. There was also no significant difference in the neonatal morbidity composite between the induction and expectant management groups (7.3% vs 6.7%; adjusted risk ratio 1.04, 95% confidence interval 0.98, 1.09). When compared to expectant management, elective induction of labor at 39 weeks in low-risk patients with 1 prior cesarean delivery was associated with a significantly higher likelihood of vaginal delivery with no difference in composite maternal and neonatal morbidity outcomes. Prospective studies are needed to better elucidate the risks and benefits of induction of labor in this patient population.

Ukoha EP ，Wen T ，Reddy UM 《-》

Oxytocin regimen used for induction of labor and pregnancy outcomes.

Following the results of the A Randomized Trial of Induction Versus Expectant Management trial, which demonstrated a reduction in cesarean delivery with no increase in adverse perinatal outcomes after elective induction of labor in low-risk nulliparous patients at 39 weeks of gestation compared with expectant management, the use of induction of labor has increased. Current evidence is insufficient to recommend mid- to high-dose regimens over low-dose regimens for routine induction of labor. This study aimed to evaluate the association between oxytocin regimen and cesarean delivery and an adverse perinatal composite outcome in low-risk nulliparous patients undergoing induction of labor at ≥39 weeks of gestation. This was a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network's A Randomized Trial of Induction Versus Expectant Management randomized trial. Patients who received a mid- to high-dose oxytocin regimen (starting or incremental increase >2 mU/min) were compared with those who received a low-dose oxytocin regimen (starting and incremental increase ≤2 mU/min). The co-primary outcomes for this secondary analysis were (1) cesarean delivery and (2) composite of perinatal death or severe neonatal complications. Multivariate Poisson regression was used to estimate adjusted relative risks and 97.5% confidence intervals for the co-primary endpoints and 95% confidence intervals for binomial outcomes, and multinomial logistic regression was used to estimate adjusted odds ratios and 95% adjusted relative risks for multinomial outcomes. Of 6106 participants enrolled in the primary trial, 2933 underwent induction of labor with oxytocin: 861 in the mid- to high-dose group and 2072 in the low-dose group. The lower frequency of cesarean delivery in the mid- to high-dose group than in the low-dose group (20.3% vs 25.2%, respectively; relative risk, 0.81; 95% confidence interval, 0.69-0.94) was not significant after adjustment (adjusted relative risk, 0.90; 97.5% confidence interval, 0.76-1.07). The composite of perinatal death or severe neonatal complications was more frequent in the mid- to high-dose group than in the low-dose group (6.7% vs 4.3%, respectively; relative risk, 1.55; 95% confidence interval, 1.13-2.14) and remained significant after adjustment (adjusted relative risk, 1.61; 97.5% confidence interval, 1.11-2.35). Most cases in the composite were from the respiratory support (5.2% in the mid- to high-dose group vs 3.1% in the low-dose group) component, with an increase in transient tachypnea in newborns (3.8% in the mid- to high-dose group vs 2.5% in the low-dose group; adjusted relative risk, 1.63; 95% confidence interval, 1.04-2.54). The duration of neonatal respiratory support for 1 day was significantly longer in the mid- to high-dose group than in the low-dose group (3.5% vs 1.4%, respectively; adjusted relative risk, 2.59; 95% confidence interval, 1.52-4.39). However, support beyond 1 day was not different between the 2 groups. Compared with the low-dose group, the mid- to high-dose group had a higher operative vaginal delivery rate (10.0% vs 7.0%, respectively; adjusted relative risk, 1.54; 95% confidence interval, 1.18-2.00) and shorter duration of time from start of oxytocin to delivery (crude median: 12 hours [interquartile range, 8-17] vs 13 hours [interquartile range 9-19], respectively; adjusted median difference: -2 [95% CI, -2 to -1]; P<.001). The use of mid-to high-dose oxytocin regimens for induction of labor in nulliparas at ≥39 weeks of gestation was not associated with a lower cesarean delivery rate or improved neonatal outcomes compared with the use of low-dose oxytocin regimens. Although the use of mid- to high-dose oxytocin regimens was associated with a shorter duration of labor, there was an increase in self-limited neonatal respiratory support and no difference in cesarean delivery rates. More evidences are needed to define the magnitude of potential maternal and neonatal benefits and risks associated with oxytocin regimens.

Reddy UM ，Sandoval GJ ，Tita ATN ，Silver RM ，Mallett G ，Hill K ，El-Sayed YY ，Rice MM ，Wapner RJ ，Rouse DJ ，Saade GR ，Thorp JM Jr ，Chauhan SP ，Costantine MM ，Chien EK ，Casey BM ，Srinivas SK ，Swamy GK ，Simhan HN ，Macones GA ，Grobman WA ，Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network ... -  《-》

Maternal and perinatal outcomes after implementation of a more active management in late- and postterm pregnancies in Sweden: A population-based cohort study.

The risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. We evaluated maternal and perinatal outcomes after a national shift from expectancy and induction at 42+0 weeks to a more active management of late-term pregnancies in Sweden offering induction from 41+0 weeks or an individual plan aiming at birth or active labour no later than 42+0 weeks. Women with a singleton pregnancy lasting 41+0 weeks or more with a fetus in cephalic presentation (N = 150,370) were included in a nationwide, register-based cohort study. Elective cesarean sections were excluded. Outcomes during period 1, January 2017 to December 2019 (before the shift) versus outcomes during period 2, January 2020 to October 1, 2023 (after the shift) were analysed. For comparison, outcomes of pregnancies lasting 39+0 to 40+6 weeks (N = 358,548) were also studied. Primary outcomes were: First, peri/neonatal death (stillbirth or neonatal death before 28 days); second, composite adverse peri/neonatal outcome (peri/neonatal death, Apgar score <4 at 5 min, hypoxic ischemic encephalopathy grades 1-3, meconium aspiration syndrome, birth trauma, or admission to a neonatal intensive care unit (NICU) ≥4 days); third, composite adverse peri/neonatal outcome excluding admission to NICU; and fourth, emergency cesarean section. Secondary outcomes included the components of the primary composite outcomes. Relative risks (RRs) with 95% confidence intervals (CIs) for binary outcomes period 2 versus period 1 were computed using modified Poisson regression analyses with adjustments for maternal age, parity, body mass index (BMI), smoking, and educational level. Induction rates among pregnancies lasting 41+0 weeks or more increased from 33.7% in period 1 to 52.4% in period 2. Mean (standard deviation) gestational age at birth decreased from 290.7 (2.9) days to 289.6 (2.3) days. Infants born during period 2 were at lower risk of peri/neonatal death compared to infants born during period 1; 0.9/1,000 versus 1.7/1,000 born infants (adjusted RR 0.52; 95% CI [0.38, 0.69]; p < 0.001), and they had a lower risk of having the composite adverse neonatal outcome, both including (50.5/1,000 versus 53.9/1,000, adjusted RR 0.92; 95% CI [0.88, 0.96]; p < 0.001) or excluding NICU admission (18.5/1,000 versus 22.5/1,000, adjusted RR 0.79; 95% CI [0.74, 0.85]; p < 0.001). The cesarean section rate increased from 10.5% in period 1 to 11.9% in period 2 (adjusted RR 1.07; 95% CI [1.04, 1.10]; p < 0.001). For births at 39 to 40 weeks the adjusted RR for peri/neonatal death was 0.86 (95% CI [0.72, 1.02]). One limitation of the study is that we had no data on to what extent monitoring of fetal health was performed. A more active management of pregnancies lasting 41+0 weeks or more was associated with a decrease in peri/neonatal deaths, and a decrease in composite adverse peri/neonatal outcomes. Increased rate of emergency cesarean sections was observed. Women with pregnancies advancing towards 41 gestational weeks should be given balanced information on the benefits and risks of induction of labour at 41 weeks compared to expectant management until 42 weeks and be offered induction of labour at 41 weeks or active surveillance of pregnancies from 41 weeks in order to decrease peri/neonatal mortality.

Källén K ，Norman M ，Elvander C ，Bergh C ，Sengpiel V ，Hagberg H ，Svanvik T ，Wennerholm UB ... -  《-》

Determining optimal timing of birth for women with chronic or gestational hypertension at term: The WILL (When to Induce Labour to Limit risk in pregnancy hypertension) randomised trial.

Chronic or gestational hypertension complicates approximately 7% of pregnancies, half of which reach 37 weeks' gestation. Early term birth (at 37 to 38 weeks) may reduce maternal complications, cesareans, stillbirths, and costs but may increase neonatal morbidity. In the WILL Trial (When to Induce Labour to Limit risk in pregnancy hypertension), we aimed to establish optimal timing of birth for women with chronic or gestational hypertension who reach term and remain well. This 50-centre, open-label, randomised trial in the United Kingdom included an economic analysis. WILL randomised women with chronic or gestational hypertension at 36 to 37 weeks and a singleton fetus, and who provided documented informed consent to "Planned early term birth at 38+0-3 weeks" (intervention) or "usual care at term" (control). The coprimary outcomes were "poor maternal outcome" (composite of severe hypertension, maternal death, or maternal morbidity; superiority hypothesis) and "neonatal care unit admission for ≥4 hours" (noninferiority hypothesis). The key secondary was cesarean. Follow-up was to 6 weeks postpartum. The planned sample size was 540/group. Analysis was by intention-to-treat. A total of 403 participants (37.3% of target) were randomised to the intervention (n = 201) or control group (n = 202), from 3 June 2019 to 19 December 2022, when the funder stopped the trial for delayed recruitment. In the intervention (versus control) group, losses to follow-up were 18/201 (9%) versus 15/202 (7%). In each group, maternal age was about 30 years, about one-fifth of women were from ethnic minorities, over half had obesity, approximately half had chronic hypertension, and most were on antihypertensives with normal blood pressure. In the intervention (versus control) group, birth was a median of 0.9 weeks earlier (38.4 [38.3 to 38.6] versus 39.3 [38.7 to 39.9] weeks). There was no evidence of a difference in "poor maternal outcome" (27/201 [13%] versus 24/202 [12%], respectively; adjusted risk ratio [aRR] 1.16, 95% confidence interval [CI] 0.72 to 1.87). For "neonatal care unit admission for ≥4 hours," the intervention was considered noninferior to the control as the adjusted risk difference (aRD) 95% CI upper bound did not cross the 8% prespecified noninferiority margin (14/201 [7%] versus 14/202 [7%], respectively; aRD 0.003, 95% CI -0.05 to +0.06), although event rates were lower-than-estimated. The intervention (versus control) was associated with no difference in cesarean (58/201 [29%] versus 72/202 [36%], respectively; aRR 0.81, 95% CI 0.61 to 1.08. There were no serious adverse events. Limitations include our smaller-than-planned sample size, and lower-than-anticipated event rates, so the findings may not be generalisable to where hypertension is not treated with antihypertensive therapy. In this study, we observed that most women with chronic or gestational hypertension required labour induction, and planned birth at 38+0-3 weeks (versus usual care) resulted in birth an average of 6 days earlier, and no differences in poor maternal outcome or neonatal morbidity. Our findings provide reassurance about planned birth at 38+0-3 weeks as a clinical option for these women. isrctn.com ISRCTN77258279.

Magee LA ，Kirkham K ，Tohill S ，Gkini E ，Moakes CA ，Dorling J ，Green M ，Hutcheon JA ，Javed M ，Kigozi J ，Mol BWM ，Singer J ，Hardy P ，Stubbs C ，Thornton JG ，von Dadelszen P ，WILL Trial Study Group ... -  《-》