Which method is best for the induction of labour?: A systematic review, network meta-analysis and cost-effectiveness analysis

Background: More than 150,000 pregnant women in England and Wales have their labour induced each year. Multiple pharmacological, mechanical and complementary methods are available to induce labour. Objective: To assess the relative effectiveness, safety and cost-effectiveness of labour induction methods and, data permitting, effects in different clinical subgroups. Methods: We carried out a systematic review using Cochrane methods. The Cochrane Pregnancy and Childbirth Group’s Trials Register was searched (March 2014). This contains over 22,000 reports of controlled trials (published from 1923 onwards) retrieved from weekly searches of OVID MEDLINE (1966 to current); Cochrane Central Register of Controlled Trials (The Cochrane Library); EMBASE (1982 to current); Cumulative Index to Nursing and Allied Health Literature (1984 to current); ClinicalTrials.gov; the World Health Organization International Clinical Trials Registry Portal; and hand-searching of relevant conference proceedings and journals. We included randomised controlled trials examining interventions to induce labour compared with placebo, no treatment or other interventions in women eligible for third-trimester induction. We included outcomes relating to efficacy, safety and acceptability to women. In addition, for the economic analysis we searched the Database of Abstracts of Reviews of Effects, and Economic Evaluations Databases, NHS Economic Evaluation Database and the Health Technology Assessment database. We carried out a network meta-analysis (NMA) using all of the available evidence, both direct and indirect, to produce estimates of the relative effects of each treatment compared with others in a network. We developed a de novo decision tree model to estimate the cost-effectiveness of various methods. The costs included were the intervention and other hospital costs incurred (price year 2012–13). We reviewed the literature to identify preference-based utilities for the health-related outcomes in the model. We calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit. We represent uncertainty in the optimal intervention using cost-effectiveness acceptability curves. Results: We identified 1190 studies; 611 were eligible for inclusion. The interventions most likely to achieve vaginal delivery (VD) within 24 hours were intravenous oxytocin with amniotomy [posterior rank 2; 95% credible intervals (CrIs) 1 to 9] and higher-dose (≥ 50 μg) vaginal misoprostol (rank 3; 95% CrI 1 to 6). Compared with placebo, several treatments reduced the odds of caesarean section, but we observed considerable uncertainty in treatment rankings. For uterine hyperstimulation, double-balloon catheter had the highest probability of being among the best three treatments, whereas vaginal misoprostol (≥ 50 μg) was most likely to increase the odds of excessive uterine activity. For other safety outcomes there were insufficient data or there was too much uncertainty to identify which treatments performed ‘best’. Few studies collected information on women’s views. Owing to incomplete reporting of the VD within 24 hours outcome, the cost-effectiveness analysis could compare only 20 interventions. The analysis suggested that most interventions have similar utility and differ mainly in cost. With a caveat of considerable uncertainty, titrated (low-dose) misoprostol solution and buccal/sublingual misoprostol had the highest likelihood of being cost-effective. Limitations: There was considerable uncertainty in findings and there were insufficient data for some planned subgroup analyses. Conclusions: Overall, misoprostol and oxytocin with amniotomy (for women with favourable cervix) is more successful than other agents in achieving VD within 24 hours. The ranking according to safety of different methods was less clear. The cost-effectiveness analysis suggested that titrated (low-dose) oral misoprostol solution resulted in the highest utility, whereas buccal/sublingual misoprostol had the lowest cost. There was a high degree of uncertainty as to the most cost-effective intervention

Antiphospholipid antibodies and pregnancy outcomes in women heterozygous for Factor V Leiden

Antiphospholipid antibodies are associated with a spectrum of pregnancy complications, including preeclampsia and small for gestational age (SGA) fetuses. We sought to assess anticardiolipin and anti-β2-glycoprotein I (anti-β2-GPI) IgG and IgM antibody prevalence and the relationship of these antibodies to pregnancy complications in women with the Factor V Leiden (FVL) mutation. The study comprised a secondary analysis of a multicenter, prospective observational study of FVL prevalence among 5188 asymptomatic pregnant women. A subset of 362 women (117 FVL heterozygotes, 245 matched controls) had serum collected at the time of the original study and underwent serum analysis for anticardiolipin and anti-β2-GPI IgG and IgM as a part of this analysis. The primary outcome was preeclampsia and/or SGA (<10%). The overall prevalence of anticardiolipin and anti-β2-GPI IgG and IgM antibodies was low and did not vary with FVL status. Forty-seven women (13.0%) developed preeclampsia and/or SGA. There were no differences in primary outcome rates between women with and without aPL antibodies, regardless of FVL mutation status. Among FVL carriers, the presence of antiphospholipid antibodies does not appear to contribute to adverse pregnancy outcome

The MFMU Cesarean Registry: Impact of time of day on cesarean complications

Studies suggest that sleep deprivation adversely affects performance. We hypothesized that cesarean delivery complications would be more frequent during the night shift (11 pm-7 am), and evaluated morbidities by delivery shift. Eighteen thousand nine hundred and thirty-nine term women undergoing an unscheduled cesarean delivery in 13 centers from 1999 to 2000 within a prospective observational study were included. Maternal/neonatal morbidities and time from decision to cesarean delivery were evaluated by time of delivery (7 am-3 pm, 3 pm-11 pm, 11 pm-7 am). A composite of maternal morbidities was evaluated by logistic regression controlling for potentially confounding factors. Controlling for age, race, insurance, cardiac disease, preeclampsia, diabetes, previous incision type, and prenatal care, shift of delivery had no impact on maternal morbidity (11 pm-7 am OR 0.9 [95% CI 0.81-1.0]). NICU admissions were slightly increased at night but neonatal complications were not. Maternal and neonatal complications of cesarean delivery do not increase with delivery during the night shift

The MFMU Cesarean Registry: Uterine atony after primary cesarean delivery

The purpose of this study was to define independent risk factors for uterine atony after primary cesarean delivery, and to assess their overall association with atony in the study cohort. This was a 13–university center prospective observational study. All women who underwent primary cesarean from January 1, 1999 to December 31, 2000 were eligible. Trained and certified research nurses performed systematic data abstraction. The definition of atony required both the clinical diagnosis and the use of methergine or a prostaglandin preparation. Risk factors for uterine atony were assessed in univariable and multivariable logistic regression analyses, and these analyses then used to inform an assessment of the association of the various risk factors with the occurrence of uterine atony in the overall cohort. Twenty-three thousand, three hundred and ninety pregnancies were analyzed. Uterine atony occurred in 1416 women (6%). Several variables were independently associated with atony in a multivariable model, including multiple gestation (odds ratio [OR] 2.40, 95% CI 1.95-2.93), maternal Hispanic race (2.21, 1.90-2.57), induced or augmented labor for >18 hours (2.23, 1.92-2.60), infant birth weight >4500 g (2.05, 1.53-2.69), and clinically diagnosed chorioamnionitis (1.80, 1.55-2.09). However, because the various risk factors were not very powerful, approximately half of the cases of atony were associated with the 2/3 of women lacking a given risk factor or combination of risk factors. Although certain risk factors and uterine atony were clearly associated, the associations are of limited practical clinical use

Randomized trial of inhaled beclomethasone dipropionate versus theophylline for moderate asthma during pregnancy

This study was undertaken to compare the efficacy of inhaled beclomethasone dipropionate to oral theophylline for the prevention of asthma exacerbation(s) requiring medical intervention. A prospective, double-blind, double placebo-controlled randomized clinical trial of pregnant women with moderate asthma was performed. There was no significant difference ( P = .554) in the proportion of asthma exacerbations among the 194 women in the beclomethasone cohort (18.0%) versus the 191 in the theophylline cohort (20.4%; risk ratio [RR] = 0.9, 95% CI = 0.6-1.3). The beclomethasone cohort had significantly lower incidences of discontinuing study medications caused by side effects (RR = 0.3, 95% CI = 0.1-0.9; P = .016), and proportion of study visits with forced expiratory volume expired in 1 second (FEV1) less than 80% predicted (0.284±0.331 vs 0.284±0.221, P = .039). There were no significant differences in treatment failure, compliance, or proportion of peak expiratory flow rate less than 80% predicted. There were no significant differences in maternal or perinatal outcomes. The treatment of moderate asthma with inhaled beclomethasone versus oral theophylline resulted in similar rates of asthma exacerbations and similar obstetric and perinatal outcomes. These results favor the use of inhaled corticosteroids for moderate asthma during pregnancy because of the improved FEV1 and because theophylline had more side effects and requires serum monitoring

Is there a seasonal variation in the diagnosis of oligohydramnios?

Objective. We hypothesized that oligohydramnios would be diagnosed more frequently in the warm summer months when dehydration might be more common. Methods. The clinical diagnosis of oligohydramnios was extracted from the databases of four completed National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network protocols. These data were stratified by quarter of delivery and compared using Fisher's Exact Test. Results. The clinical diagnosis of oligohydramnios was made more frequently in deliveries occurring in the summer months of June, July and August as compared with the remainder of the calendar year (7.2% vs 5.9%, p = 0.0178). Conclusions. In these studies the diagnosis of oligohydramnios is made more frequently in those pregnancies delivered during the summer months. Although not proven by this association, maternal dehydration may contribute to this finding

Midpregnancy genitourinary tract infection with Chlamydia trachomatis: Association with subsequent preterm delivery in women with bacterial vaginosis and Trichomonas vaginalis

The objective of the study was to estimate whether midpregnancy genitourinary tract infection with Chlamydia trachomatis is associated with an increased risk of subsequent preterm delivery. Infection with C. trachomatis was determined using a ligase chain reaction assay (performed in batch after delivery) of voided urine samples collected at the randomization visit (16 0/7 to 23 6/7 weeks' gestation) and the follow-up visit (24 0/7 to 29 6/7 weeks) among 2470 gravide women with bacterial vaginosis or Trichomonas vaginalis infection enrolled in 2 multicenter randomized antibiotic treatment trials (metronidazole versus. placebo). The overall prevalence of genitourinary tract C. trachomatis infection at both visits was 10%. Preterm delivery less than 37 weeks' or less than 35 weeks' gestational age was not associated with the presence or absence of C. trachomatis infection at either the randomization (less than 37 weeks: 14% versus 13%, P=.58; less than 35 weeks: 6.4% versus 5.5%, P=.55) or the follow-up visit (less than 37 weeks: 13% versus 11%, P=.33; less than 35 weeks: 4.4% versus 3.7, P=.62). Treatment with an antibiotic effective against chlamydia infection was not associated with a statistically significant difference in preterm delivery. In this secondary analysis, midtrimester chlamydia infection was not associated with an increased risk of preterm birth. Treatment of chlamydia was not associated with a decreased frequency of preterm birth

Spirometry is related to perinatal outcomes in pregnant women with asthma

The purpose of this study was to test the hypothesis that maternal asthma symptoms and pulmonary function are related to adverse perinatal outcomes. Asthmatic patients were recruited from the 16 centers of the Maternal Fetal Medicine Units. Forced expiratory volume in 1 second was obtained at enrollment and at monthly study visits, and the frequency of asthma symptoms was assessed from enrollment to delivery. Perinatal data were obtained at postpartum chart reviews. The final cohort included 2123 participants with asthma. After adjustment for demographic characteristics, smoking, acute asthmatic episodes, and oral corticosteroid use, significant relationships were demonstrated between gestational hypertension and preterm birth and lower maternal gestational forced expiratory volume in 1 second. The data did not show any significant independent relationship between asthma symptom frequency and perinatal outcomes. Lower pulmonary function during pregnancy is associated with increased gestational hypertension and prematurity in the pregnancies of women with asthma, which may be due to inadequate asthma control or factors that are associated with increased asthma severity