Safety of misoprostol vaginal insert for labor induction using standard vs. adjusted retrieval criteria: a comparative cohort study.

Objective To compare the safety of misoprostol vaginal insert (MVI) for labor induction using standard and adjusted criteria. Methods This was a single-center, comparative cohort study of 138 pregnant women ≥37/0 weeks undergoing labor induction with MVI using standard (69 women; administration for up to 24 h; MVI-24) or adjusted (69 women; administration for up to 10 h; MVI-10) criteria in a tertiary academic center in Germany. The main maternal safety outcomes were the rate of tachysystole and rate of tachysystole requiring tocolysis. Neonatal safety assessments included Apgar score at 5 min and postpartum arterial fetal pH. Results Uterine tachysystole occurred in more women in the MVI-24 group compared with the MVI-10 group [47.8% vs. 25.5%; P = 0.001; relative risk (RR) 2.36 (95% confidence interval [CI]: 1.39-4.00)] and as did uterine tachysystole requiring tocolysis [MVI-24: 26.1% vs. MVI-10: 11.6%; P = 0.049; RR 2.25 (95% CI: 1.05-4.83)]. The mean 5-min Apgar scores were 9.64 for the MVI-24 group and 9.87 for the MVI-10 (P = 0.016). Low postpartum umbilical arterial pH values occurred more often in the MVI-24 compared with the MVI-10 group (pH 7.10-7.19: 26.1% vs. 20.3% and pH <7.10: 4.4% vs. 0.0%, respectively). Conclusion Adjusted retrieval criteria for MVI of up to 10 h exposure instead of the standard 24 h reduced uterine tachysystole and improved the neonatal outcome.

Study of effects of mifepristone on full-term pregnancies.

The induction of labour is required for various indications in obstetrics. Various regimens and drugs are advocated for use in labour induction. Mifepristone is one such drug which has a definite role in first and second-trimester pregnancy terminations. However, its role in the third-trimester is still being reviewed. In the present study, the effect of mifepristone on cervical ripening was assessed and results interpreted.Impact statementWhat is already known on the subject? The role of mifepristone in termination of pregnancies at term is controversial. Some studies report onset of labour after giving mifepristone whereas others do not report any significant role.What do the results of the study add? Mifepristone has a role in improving Bishop score and can be used as a pre-induction cervical ripening agent before using other methods for labour induction. It does not report any adverse effects on the mother or foetus.What are the implications of these findings for clinical practice and/or further research? Mifepristone needs to be studied more in term pregnancies as induction of labour is increasingly required in today's scenario for various reasons. However, its role in improving the Bishop score as found in this study helps in decreasing dose of other labour inducing agents.

Slow-release vaginal insert of misoprostol versus orally administrated solution of misoprostol for the induction of labour in primiparous term pregnant women: a randomised controlled trial.

OBJECTIVE: To compare the World Health Organization (WHO) recommended orally administrated dosage of misoprostol (25 µg) with a vaginal slow-release (7 µg/hour) insert of misoprostol regarding time from induction to delivery and safety of the method. DESIGN: Open label, Randomised controlled trial (RCT). SETTING: Delivery ward at a secondary referral hospital in Stockholm, Sweden, from 1 October 2016 to 21 February 2018. POPULATION: One hundred and ninety-six primiparous women with singletons in cephalic presentation at ≥37 weeks of gestation and with a Bishop score of ≤4. METHODS: Women were randomised to an oral solution of misoprostol (Cytotec® n = 99) or vaginal slow-release misoprostol (Misodel® [MVI] n = 97). MAIN OUTCOME MEASURES: Primary outcome: time from induction to vaginal delivery. SECONDARY OUTCOMES: mode of delivery; proportion of vaginal deliveries within 24 hours (VD24); neonates with an Apgar score of <7 at 5 minutes; pH < 7.10; postpartum haemorrhage (PPH) of >1000 ml; hyperstimulation; and women's delivery experience (VAS). RESULTS: There was no difference in the time to delivery [corrected] (median 21.1 hours in the MVI group and 23.2 hours in the oral group; Kaplan-Mayer log rank P = 0.31). There was no difference regarding the proportion of VD24 (50.5 versus 55.7%, P = 0.16). Hyperstimulation with non-reassuring cardiotocography (CTG) was more common in the MVI group (14.4 versus 3.0%, P < 0.01). Terbutaline (Bricanyl® ) was used more often for hyperstimulation in the MVI group (22.7 versus 4.0%, P < 0.01). There was no difference in the numbers of children admitted to the neonatal intensive care unit (NICU). CONCLUSIONS: Vaginal delivery after induction of labour (IOL) with slow-release misoprostol did not result in a shorter time from induction to vaginal delivery, compared with oral misoprostol solution, but was associated with a higher risk for hyperstimulation and fetal distress. There were no differences in mode of delivery or neonatal outcome. TWEETABLE ABSTRACT: IOL with MVI was similar to oral solution of misoprostol but hyperstimulation and fetal distress were more common.

Enhanced Human Decidual Cell-Expressed FKBP51 May Promote Labor-Related Functional Progesterone Withdrawal.

Sustained plasma progesterone (P4) levels suggest initiation of human term labor by functional P4 withdrawal, reflecting reduced progesterone receptor (PR) and/or glucocorticoid receptor (GR) expression or activity. The steroid-induced immunophilin cochaperone FKBP51 inhibits PR- and GR-mediated transcription, suggesting a labor-initiating role. Gestational age-matched decidual sections were immunostained for FKBP51 and decidual cell (DC) and interstitial trophoblast (IT) markers, vimentin and cytokeratin, respectively. Term DC cultures were incubated with vehicle (control), estradiol (E2) with or without medroxyprogesterone acetate, dexamethasone (Dex), or Organon 2058. FKBP51 histologic scoring was significantly higher in DC nuclei during labor versus prelabor decidua, whereas FKBP51 immunostaining was undetected in interstitial trophoblasts (P < 0.05). In term DC cultures, E2 + medroxyprogesterone acetate or E2 + Dex enhanced FKBP51 expression (P < 0.01), whereas E2 + Organon 2058 inhibited PR expression (P < 0.05), and E2 + Dex inhibited GR expression (P < 0.05). Unlike term DCs, FKBP51 was undetected in control or Dex-treated cultured third-trimester trophoblasts. Electrophoretic mobility shift assays revealed that FKPB51 overexpression or silencing in cultured DCs altered PR-DNA binding. Increased FKBP51 levels in term DCs during labor complement our prior in situ observations of significantly lower PR in labor versus prelabor DCs. In a milieu of sustained plasma P4 levels, these reciprocal changes will amplify functional P4 withdrawal in DCs via FKBP51-mediated PR resistance coupled with declining PR levels, whereas the lack of FKBP51 expression in interstitial trophoblasts suggests unopposed constitutive GR action.

Foley Catheter or Oral Misoprostol for Induction of Labor in Women with Term Premature Rupture of Membranes: A Randomized Multicenter Trial.

Objectives To compare the Foley catheter and misoprostol for induction of labor in term women with premature rupture of membranes. Study Design A randomized controlled trial was performed in three university hospitals in Finland between March 2012 and September 2014. A total of 202 term women with ruptured membranes >18 hours, singleton pregnancies in cephalic presentation, unfavorable cervix, and no prior cesarean section were enrolled. Participants were randomly allocated to induction of labor by Foley catheter or oral misoprostol in a 1:1 ratio. All women received prophylactic antibiotics. The main outcomes were cesarean section and maternal and neonatal infections. Results Labor induction by Foley catheter or misoprostol showed no difference in cesarean delivery rates (23.6 vs. 18.2%; odds ratio [OR], 1.39; 95% confidence interval [CI], 0.69-2.82; p = 0.36), maternal intrapartum infections (2.2 vs. 2%; OR, 1.12; 95% CI, 0.15-8.9; p = 1.00), postpartum infections (1.1 vs. 2.0%; OR, 0.55; 95% CI, 0.05-6.18; p = 1.00), or neonatal infections (1.1 vs. 5.1%; OR, 0.21; 95% CI, 0.24-1.87; p = 0.22). The total time from induction to delivery was similar (1,311 vs. 1,435 minutes; p = 0.31) in the two groups. Conclusions Foley catheter or misoprostol can both be used for induction of labor in women with term premature rupture of membranes.

The effect of labour on the coagulation system in the term neonate.

The coagulation system of the foetus is markedly different from that of adults. To assess the influence of maternal age, mode of delivery and intrapartum events, and foetal gender and weight on the foetal coagulation system. Cord blood was collected from 154 healthy pregnant women, with gestational age 37 - 42 weeks at birth. Mann-Whitney test was used for analysis of binary data and continuous variables were analysed using Pearson's correlation coefficient. Mean cord blood levels of FVIII:C, VWF:Ag, VWF:CB, FIX, FXI, FXII and plasminogen were significantly higher in babies delivered after labour, compared to those delivered after an elective caesarean. Mean cord blood levels of FII (P = 0.003), FV (P = 0.009), FVII (P = 0.0004) and FX (P = 0.0009) were significantly lower in the babies with meconium stained liquor in labour, compared with those with clear liquor. Augmentation with oxytocin, instrumental delivery, did not affect any of the factor levels and duration of labour did not have an effect on the level of coagulation proteins in cord blood. This study provides valuable information about effect of labour on the coagulation system of the foetus. It is concluded that, in cord blood, the results of coagulation parameters in the newborn baby should be considered in light of mode of delivery and events of labour.

Trends and morbidity associated with oxytocin use in labour in nulliparas at term.

AIM: To determine the trends in oxytocin use at a population level within New South Wales and to assess the maternal and neonatal morbidities associated with the use of oxytocin. METHODS: Trends in oxytocin use were assessed for women in NSW who were nulliparas at term with a singleton, cephalic fetus between 1998 and 2008. Maternal and neonatal morbidities were assessed in 2007-2008 using linked hospital and birth data with regression analysis. Oxytocin was also assessed by indication for use being either induction or augmentation of labour. RESULTS: The overall use of oxytocin increased from 10,291 (36.5%) of births in 1998 to 14,440 (45.4%) of births in 2008 (P < 0.0001) with the increase entirely because of the increased use for induction of labour. The use of oxytocin was associated with an increase in regional analgesia (65 to 22%), instrumental delivery (21 to 18%) and caesarean section (29 to 14%) as compared to women who did not receive oxytocin in labour. Oxytocin was also associated with an increase in severe maternal adjusted odds ratios ((aOR) 1.48, 95% CI 1.30-1.68) and neonatal morbidity (aOR 1.29, 95% CI 1.17-1.41). This increase in morbidity was maintained when both augmentation and induction were assessed separately. CONCLUSION: Oxytocin has an important role in the management of labour. However, its use should be carefully monitored with standardised treatment regimes to minimise maternal and neonatal morbidity.

[Cervical ripening at term. A randomized and prospective study: Misoprotol versus dinoprostone]. / Maturation cervicale à terme. Étude prospective randomisée: misoprostol versus dinoprostone.

AIM: To compare the efficacy and safety of cervical ripening at term by vaginal Misoprostol and Dinoprostone. METHODS: We performed a prospective randomized study on cervical ripening with misoprostol and dinoprostone in the third trimester of pregnancy. 300 patients have been divided into two groups: one consisted by 150 patients who received Misoprostol (Cytotec ®) and the second consisted by 150 patients who received Dinoprostone (Prépidil ®). RESULTS: Analysis of our results allowed to reveal: a significant decrease in the time of entry into work for the Misoprostol group (9.08 hours versus 12.51 hours, p = 0.007), a significant reduction delivery time (14.48 hours versus 19.30 hours, p = 0.001). Moreover, the birth rate in the first 24 hours after the first dose was significantly higher in the Misoprostol group (86.7% versus 72.7%, p = 0.003). The use of oxytocin was significantly reduced with Misoprostol (44% versus 58.7%, p = 0.01). The mode of delivery was not influenced by membership in one or other of the two groups. CONCLUSION: Misoprostol seems an interesting molecule for cervical ripening and labor induction.

Foley Bulb Added to an Oral Misoprostol Induction Protocol: A Cluster Randomized Trial.

OBJECTIVE: To evaluate whether the induction of labor in term gravid women with cervical dilation 2 cm or less and intact membranes by using oral misoprostol preceded by transcervical Foley bulb placement results in a significantly increased vaginal delivery rate compared with the use of oral misoprostol alone. METHODS: We randomized the induction method by week of admission to labor and delivery, with each week group described as a cluster in a block randomized design. Women with gestational age of 37 weeks or greater, cervical dilation 2 cm or less, intact membranes, and indication for labor induction were included. Study arms were either 100 micrograms of oral misoprostol after transcervical Foley bulb placement or 100 micrograms of oral misoprostol alone. The primary outcome was vaginal delivery with the first induction attempt. Secondary outcomes included time to delivery, clinical chorioamnionitis (maternal temperature of 38°C or greater during labor with or without fundal tenderness, without other identified cause), cesarean delivery indication, and adverse outcomes. We estimated that a sample size of 1,077 per arm was needed to detect a 5% increase in vaginal delivery rate with a type I error of 5% and power of 80%, accounting for interim analysis and cluster size of 30 inductions per week. This was a pragmatic trial, and analysis was by intention-to-treat. RESULTS: From January 1, 2018, to May 13, 2019, 1,117 women (34 clusters) were assigned to oral misoprostol plus Foley and 1,110 women (34 clusters) to oral misoprostol alone. Demographic characteristics were similar. Vaginal delivery at the first induction occurred in 78% of the misoprostol plus Foley arm and in 77% of the misoprostol arm (relative risk [RR] 1.00; 95% CI 0.96-1.05; adjusted relative risk [aRR], 1.00; 95% CI 0.95-1.05). Clinical chorioamnionitis occurred in 18% of the misoprostol plus Foley arm and in 14% of the misoprostol arm (RR 1.30; 95% CI 1.07-1.58; aRR 1.30; 95% CI 1.08-1.56). There were no differences in neonatal outcomes. CONCLUSION: Induction of labor in gravid women at term with intact membranes by using oral misoprostol plus Foley bulb did not result in a higher vaginal delivery rate, but it did result in more clinical chorioamnionitis compared with the use of oral misoprostol alone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03407625.

The effect of initiating intravenous oxytocin infusion before uterine incision on the blood loss during elective cesarean section: a randomized clinical trial.

Objective: This study compares the effect of starting intravenous oxytocin infusion early before uterine incision versus late after umbilical cord clamping on the blood loss during elective cesarean section (CS). Methods: A single-blinded randomized clinical trial conducted on 200 pregnant women at term (>37 weeks) gestation scheduled for elective CS were assigned to either IV infusion of 30 IU of oxytocin started before uterine incision (Group I) or started immediately after clamping the umbilical cord (Group II). The primary outcome was the mean volume of blood loss during CS. The secondary outcomes included the mean volume of postoperative blood loss, the mean reduction in the hemoglobin and hematocrit levels, the need for additional uterotonics, blood transfusion and additional surgical procedures. Results: The baseline characteristics of both groups are quiet similar. No statistical significant difference between both groups as regard to pre- and postpartum hemoglobin levels (p = .06 and 0.24 respectively) and hematocrit values (p = .12 and .51 respectively). There was a significant reduction in the intraoperative blood loss in group I compared with group II (432.7 ± 90.6 versus 588.9 ± 96.3 mL respectively, p = .001). The need for additional uterotonics was more frequent in the group II (19 women) than in group I (seven women) with statistical significance (p = .002). No differences between both groups regarding the need for blood transfusion or additional surgical procedures. Conclusions: Initiating intravenous oxytocin infusion before uterine incision during elective CS could be associated with reduction in the intraoperative blood loss and the need for additional uterotonics.

High-dose compared with low-dose oxytocin for induction of labour of nulliparous women at term.

BACKGROUND: The optimal oxytocin infusion regimen to induce labour with the lowest caesarean section rate, instrumental delivery rate and length of active labour is unclear. We compared the effect of a low-dose to high-dose oxytocin regimen to induce labour. MATERIALS AND METHODS: We conducted a retrospective study of nulliparous women induced at term in a single tertiary centre from 2009 to 2015. The oxytocin induction protocol changed from a high to low-dose regimen in November 2012, affording us the opportunity to compare outcomes 3 years prior to, and following the change in protocol. Main outcome measures were caesarean section rate, instrumental delivery rate and length of active labour. RESULTS: Four thousand eight hundred and eighty-five participants were included, 2211 were induced via the low-dose regimen, and 2674 using the high-dose regimen. There was no difference in caesarean section rate (adjusted OR 0.99; 95% CI 0.87-1.13) or instrumental delivery rates once adjusted for regional anaesthesia (adjusted OR 1.16; 95% CI 0.99-1.36) between the different regimens. Surprisingly, the length of labour was longer in the high-dose oxytocin group (adjusted mean difference 0.60 h; 95%CI 0.81-0.12). There were significantly more postpartum haemorrhage ≥1000 ml (10.5% versus 7.8%, p < .001) and regional anaesthesia use (55.8% versus 52.1%, p = .03) in the low-dose cohort. There were no differences in neonatal outcomes. CONCLUSION: Outcomes between high- and low-dose oxytocin induction regimens are relatively comparable with similar caesarean section and instrumental delivery rates. Therefore, either regimen is acceptable for use for induction of labour.

Interest of cervical ripening using double balloon catheters for labour induction in term nulliparous women.

OBJECTIVE: To compare the efficiency of double balloon catheters with that of intravaginal prostaglandins alone for the labor induction of unfavourable cervices in term nulliparous women. METHODS: 50 nulliparous patients induced with a double balloon device were compared to 53 patients induced using intravaginal prostaglandins alone. The main outcome measure was labour induction failure, characterized by the absence of active labour. The secondary outcome measures were the improvement of the Bishop score, the average durations of ripening and labour induction, the average time to active labour, the need for a second cervical ripening agent, the total dose of prostaglandins used in each group, the use of oxytocins, as well as the rates of vaginal delivery, abnormal foetal heart rate during labour and perinatal maternal infection. RESULTS: The rate of failed labour induction was of 28% in the double balloon group, against 13% in the prostaglandins group. The average durations of ripening and labour induction, as well as the time to active labour were higher in the double balloon group. The improvement of the Bishop score was significantly lower in the double balloon group. DISCUSSION AND CONCLUSION: In our study, the use of double balloon catheters does not seem to reduce the rate of failed labour induction in nulliparous women when compared to the use of prostaglandins alone. In addition, it could lengthen the labour induction duration, although more powerful studies would be necessary not to recommend its use for nulliparous women.

Cord serum visfatin at term birth: maternal smoking unmasks the relation to foetal growth.

OBJECTIVE: Visfatin is an adipocytokine involved in insulin action and oxidative stress. The regulation of circulating concentrations in the human foetus is unknown. We studied whether, at term birth, the serum concentrations of visfatin are related to foetal size, both in the absence and in the presence of maternal smoking during pregnancy. DESIGN: A cross-sectional, hospital-based study. PATIENTS: Seventy-eight singleton, healthy neonates [39 girls and 39 boys; gestational age (GA) 39.5 +/- 0.2 weeks; birth weight (BW) 3.3 +/- 0.04 kg]. METHODS: Cord serum visfatin, insulin and IGF-I measured by specific immunoassays. RESULTS: In infants from nonsmoking mothers (N = 48), cord serum visfatin levels were unrelated to either BW or birth length (BL). In infants from smoking mothers (N = 30), however, serum visfatin was inversely associated with both BW (r = -0.57; P < 0.001) and BL (r = -0.60; P < 0.0001) and it was directly associated with the number of cigarettes smoked (P < 0.05) in heavy smokers. In a multiple regression analysis, cord serum visfatin accounted for 36% of BW and 32% of BL variance in infants from smoking mothers. Cord serum visfatin was unrelated to insulin or IGF-I in either subgroup. CONCLUSION: At term birth, there is no readily detectable relation between circulating visfatin and indices of foetal size; however, maternal smoking unmasked a strikingly inverse relationship between cord serum visfatin and the foetal growth status, indicating that smoking can elicit a rise or a fall of cord serum visfatin, depending on whether the foetus is, respectively, of smaller or larger size.

A prospective randomized trial of acute tocolysis in term labour with atosiban or ritodrine.

OBJECTIVE: To study the effects of the tocolytics atosiban and ritodrine in term labour. STUDY DESIGN: Women in term labour, requiring acute tocolysis, were prospectively randomized for treatment with either atosiban i.v. (n=70) or ritodrine i.v. (n=70). There were three indications for acute tocolysis: (1) fetal distress followed by continuation of labour, (2) fetal distress followed by emergency caesarean section (CS), and (3) arrest of contractions in women waiting for a secondary CS in the absence of fetal distress. Primary endpoints were maternal blood pressure (MBP) and maternal heart rate (MHR). Secondary endpoints were intra-uterine pressure, fetal heart rate (FHR), 5'-Apgar score and umbilical arterial pH. RESULTS: Baseline characteristics did not differ between the study groups. The ritodrine group showed a significant rise in MHR (p<0.001), MHR remained unaltered in the atosiban group (p=0.31). No significant changes occurred in systolic and diastolic BP in either group. FHR rose by a maximum of 11.6 bpm (8.5%) in the ritodrine group (p<0.001) compared to a rise of 4.9 bpm (4.8%) in the atosiban group (p=0.27). No differences were found in blood loss and fetal outcome. Compared to baseline, uterine pressure was reduced by a maximum of 55% (p<0.001) after ritodrine administration, compared to a maximal reduction of 54% (p<0.001) after atosiban administration. These effects did not differ between the two treatment groups. CONCLUSION: Considering the maternal effects, our results suggest a possible role for atosiban bolus in acute tocolysis in term labour.

Potential pathways by which maternal second-hand smoke exposure during pregnancy causes full-term low birth weight.

It is well documented that maternal exposure to second-hand smoke (SHS) during pregnancy causes low birth weight (LBW), but its mechanism remains unknown. This study explored the potential pathways. We enrolled 195 pregnant women who delivered full-term LBW newborns, and 195 who delivered full-term normal birth weight newborns as the controls. After controlling for maternal age, education level, family income, pre-pregnant body mass index, newborn gender and gestational age, logistic regression analysis revealed that LBW was significantly and positively associated with maternal exposure to SHS during pregnancy, lower placental weight, TNF-α and IL-1ß, and that SHS exposure was significantly associated with lower placental weight, TNF-α and IL-1ß. Structural equation modelling identified two plausible pathways by which maternal exposure to SHS during pregnancy might cause LBW. First, SHS exposure induced the elevation of TNF-α, which might directly increase the risk of LBW by transmission across the placenta. Second, SHS exposure first increased maternal secretion of IL-1ß and TNF-α, which then triggered the secretion of VCAM-1; both TNF-α and VCAM-1 were significantly associated with lower placental weight, thus increasing the risk of LBW. In conclusion, maternal exposure to SHS during pregnancy may lead to LBW through the potential pathways of maternal inflammation and lower placental weight.

Electroencephalography during general anaesthesia differs between term-born and premature-born children.

OBJECTIVES: Premature birth is associated with a wide range of complications in later life, including structural and functional neurological abnormalities and altered pain sensitivity. We investigated whether during anaesthesia premature-born children display different patterns of background EEG activity and exhibit increased responses to nociceptive stimuli. METHODS: We examined background EEG and time-locked responses to clinical cannulation in 45 children (mean age (±SD) at study: 4.9(±3.0)years) under sevoflurane monoanaesthesia maintained at a steady-state end-tidal concentration of 2.5%. 15 were born prematurely (mean gestational age at birth: 29.2 ± 3.9 weeks) and 30 were age-matched term-born children. RESULTS: Background levels of alpha and beta power were significantly lower in the premature-born children compared to term-born controls (p=0.048). Clinical cannulation evoked a significant increase in delta activity (p=0.032), which was not significantly different between the two groups (p=0.44). CONCLUSIONS: The results indicate that whilst under anaesthesia premature-born children display different patterns of background brain activity compared to term-born children. SIGNIFICANCE: As electrophysiological techniques are increasingly used by anaesthetists to gauge anaesthetic depth, differences in background levels of electrophysiological brain activity between premature and term-born children may be relevant when considering titration of anaesthetic dose.

Epidural analgesia during labour, routinely or on request: a cost-effectiveness analysis.

OBJECTIVE: To assess the cost-effectiveness of routine labour epidural analgesia (EA), from a societal perspective, as compared with labour analgesia on request. STUDY DESIGN: Women delivering of a singleton in cephalic presentation beyond 36+0 weeks' gestation were randomly allocated to routine labour EA or analgesia on request in one university and one non-university teaching hospital in the Netherlands. Costs included all medical, non-medical and indirect costs from randomisation to 6 weeks postpartum. Effectiveness was defined as a non-operative, spontaneous vaginal delivery without EA-related maternal adverse effects. Incremental cost-effectiveness ratio (ICER) was defined as the ratio of the difference in costs and the difference in effectiveness between both groups. Data were analysed according to intention to treat and divided into a base case analysis and a sensitivity analysis. RESULTS: Total delivery costs in the routine EA group (n=233) were higher than in the labour on request group (n=255) (difference -€ 322, 95% CI -€ 60 to € 355) due to more medication costs (including EA), a longer stay in the labour ward, and more operations including caesarean sections. Total postpartum hospital costs in the routine EA group were lower (difference -€ 344, 95% CI -€ 1338 to € 621) mainly due to less neonatal admissions (difference -€ 472, 95% CI -€ 1297 to € 331), whereas total postpartum home and others costs were comparable (difference -€ 20, 95% CI -€ 267 to € 248, and -€ 1, 95% CI -€ 67 to € 284, respectively). As a result, the overall mean costs per woman were comparable between the routine EA group and the analgesia on request group (€ 8.708 and € 8.710, respectively, mean difference -€ 2, 95% CI -€ 1.012 to € 916). Routine labour EA resulted in more deliveries with maternal adverse effects, nevertheless the ICER remained low (€ 8; bootstrap 95% CI -€ 6.120 to € 8.659). The cost-effectiveness acceptability curve indicated a low probability that routine EA is cost-effective. CONCLUSION: Routine labour EA generates comparable costs as analgesia on request, but results in more operative deliveries and more EA-related maternal adverse effects. Based on cost-effectiveness, no preference can be given to routine labour EA as compared with analgesia on request.

Sleep-wake cycle of the healthy term newborn infant in the immediate postnatal period.

OBJECTIVE: To examine sleep-wake cycle (SWC) composition of healthy term infants in the immediate postnatal period using EEG, and investigate factors that might influence it. METHODS: Multichannel video-EEG was recorded for a median of 61.9 min (IQR: 60.0-69.3). The absolute and relative scores of sleep states were calculated for each infant's recording. Parametric/non-parametric statistical tests and multiple linear regression analysis were used to investigate the influence of perinatal factors on SWC composition. RESULTS: Eighty healthy term infants aged 1-36 h were studied. A well-developed SWC was evident as early as within the first 6h after birth. The mean (SD) percentage of active sleep (AS) was 52.1% (12.9) and quiet sleep (QS) was 38.6% (12.5). AS was longer and QS shorter in infants delivered by elective caesarean section (CS) compared to infants delivered by vaginal delivery or emergency CS. CONCLUSIONS: This is the first large cohort EEG study that has quantified neonatal sleep. SWC is clearly present immediately after birth, it is dominated by AS, and is influenced by mode of delivery. SIGNIFICANCE: This knowledge of the early neonatal EEG/SWC can be used as reference data for EEG studies of neurologically compromised infants.

Vaginal misoprostol for cervical ripening at term: comparison of outpatient vs. inpatient administration.

OBJECTIVE: To compare outpatient with inpatient misoprostol for preinduction cervical ripening at term. STUDY DESIGN: This concurrent cohort study was conducted between August 1999 and July 2002 at a rural community hospital. Pregnancies > or =38 weeks with an unfavorable cervix were eligible if there was a reactive nonstress test with no regular contractions or active medical/obstetric complications. Outpatients were given a single dose of misoprostol (50 microg intravaginally). A cohort group consisted of similar patients undergoing misoprostol therapy in the hospital. RESULTS: No differences were found between the outpatient (n=177) and inpatient (n=96) misoprostol groups for maternal age, parity, gestational age, and initial cervical dilation and station. No home deliveries occurred with outpatient therapy. Advanced cervical dilation at hospital admission the next morning was more common with outpatient misoprostol (10.2% vs. 2.1%; RR 5.0, 95% CI 1.2, 21.5). Differences in mean times from admission to vaginal delivery were significantly shorter with outpatient than inpatient misoprostol (nulliparas, 3.1 hours, 95% CI 1.5, 4.7; multiparas, 5.3 hours; 95% CI 3.8, 6.8). The very low proportions of fetal intolerance to labor, low Apgar scores and newborn complications were not different between the 2 groups. CONCLUSION: Outpatient vaginal misoprostol in a selected population led to more advanced cervical dilation at hospital admission the next morning and explained the shorter time until vaginal delivery.

Fetal and neonatal outcomes after term and preterm delivery following betamethasone administration.

OBJECTIVE: To determine the effects of betamethasone on fetal growth and neonatal outcomes. METHODS: A retrospective cohort study was performed of deliveries that occurred at Charité University Hospital Berlin, Germany, between January 1996 and December 2008. The betamethasone group included women with preterm labor and symptomatic contractions, cervical insufficiency, preterm premature rupture of membranes, or vaginal bleeding. Women in the control group were matched for gestational age at time of delivery and had not received betamethasone. Fetal growth changes and neonatal anthropometry were compared. RESULTS: Among 1799 newborns in the betamethasone group and 42 240 in the control group, betamethasone was associated with significantly lower birth weight (154 g lower on average) after adjusting for confounders (e.g. hypertension, smoking, and maternal weight), sex, and gestational age at delivery (P<0.05). The higher the dose, the greater the difference in mean birth weight versus controls in births before 34(+0)weeks (≤16 mg -444 g; 24 mg -523 g; >24 mg -811 g), without a detectable improvement in neonatal morbidity or mortality. There was a dose-dependent decline in expected fetal weight gain as estimated by serial ultrasonography examinations 6-8 weeks after betamethasone administration (P<0.05). CONCLUSION: Betamethasone exposure reduces fetal weight gain in a dose-dependent manner without improving neonatal morbidity or mortality.