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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Intra-vaginal prostaglandin E2 versus double-balloon catheter for labor induction in term oligohydramnios.

OBJECTIVE: Compare mechanical and pharmacological ripening for patients with oligohydramnios at term. STUDY DESIGN: Fifty-two patients with oligohydramnios ⩽ 5 cm and Bishop score ⩽ 6 were randomized for labor induction with a vaginal insert containing 10 mg timed-release dinoprostone (PGE2) or double-balloon catheter. The primary outcome was time from induction to active labor. Time to labor, neonatal outcomes and maternal satisfaction were also compared. RESULT: Baseline characteristics were similar. Time from induction to active labor (13 with PGE2 vs 19.5 h with double-balloon catheter; P = 0.243) was comparable, with no differences in cesarean rates (15.4 vs 7.7%; P = 0.668) or neonatal outcomes. The PGE2 group had higher incidence of early device removal (76.9 vs 26.9%; P = 0.0001), mostly because of active labor or non-reassuring fetal heart rate. Fewer PGE2 patients required oxytocin augmentation for labor induction (53.8 vs 84.6% P = 0.034). Time to delivery was significantly shorter with PGE2 (16 vs 20.5 h; P = 0. 045). CONCLUSION: Intravaginal PGE2 and double-balloon catheter are comparable methods for cervical ripening in term pregnancies with oligohydramnios.

Effects of maternal exposure to phthalates and bisphenol A during pregnancy on gestational age.

OBJECTIVE: Phthalates and bisphenol A (BPA) are ubiquitous environmental toxicants, present in high concentrations in numerous consumer products. We hypothesized that maternal exposure to phthalates and BPA in pregnancy is associated with shortened gestation. METHODS: Urinary phthalate and BPA metabolites from 72 pregnant women were measured at the last obstetric clinic visit prior to delivery. Using linear regression models, we estimated the change in gestational age associated with each interquartile range (IQR) increase in phthalate and BPA metabolite concentration. RESULTS: IQR increases in urinary mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and BPA concentrations were associated with 4.2 and 1.1 d decreases in gestation, respectively. When stratified by gender, these alterations were found only in male infants. CONCLUSIONS: We conclude that MEHHP and BPA (free + glucuronide) are associated with reductions in gestation, with effects observed only in males. Our findings are consistent with the idea that these agents induce gender-specific alterations in signaling via PPAR-γ transcription factor, androgen precursors and/or inflammatory mediators during the initiation of labor.

A comparison of obstetrical outcomes with labor induction agents used at term.

OBJECTIVE: To compare the obstetrical outcomes of term pregnancies induced with one of four commonly used labor induction agents. METHODS: This is a retrospective cohort study of induced deliveries between 1 August 1995 and 31 December 2007 occurring at the Los Angeles County + University of Southern California Medical Center. Viable, singleton, term pregnancies undergoing induction were identified. Exclusion criteria included gestational age less than 37 weeks, previous cesarean delivery, breech presentation, stillbirth, premature rupture of membranes, and fetal anomaly. Induction methods studied were oxytocin, misoprostol, dinoprostone and Foley catheter. Our primary outcome was cesarean delivery rate among the four induction agents. Secondary outcomes included rate of failed induction, obstetrical complications, and immediate neonatal complications. RESULTS: A total of 3707 women were included in the study (1486 nulliparous; 2221 multiparous). Outcomes were compared across induction methods using Chi-square Tests (Pearson or Fisher's, as appropriate). Among the nulliparous patients, there was no statistical difference among the four induction agents with regards to cesarean delivery rate (p = 0.51), frequency of failed inductions (p = 0.49), the cesarean delivery frequency for "fetal distress" (p = 0.82) and five minute Apgar score <7 (p = 0.24). Among parous patients, the cesarean delivery rate varied significantly by induction method (p < 0.001), being lowest among those receiving misoprostol (10%). Those receiving oxytocin and transcervical Foley catheter had cesarean rates of 22%, followed by dinoprostone at 18%. The rate of failed inductions was 2% among those receiving misoprostol, compared to 7-8% among those in the other groups (p < 0.01). Although cases of "fetal distress" between the four induction agents was not significantly different amongst multipara women, the cesarean delivery indication for "fetal distress" was higher among multipara receiving misoprostol (p = 0.004). There was no difference among the different induction agents with regards to five minute Apgar <7 (p = 0.34). CONCLUSION: Among nulliparous women, all induction methods have similar rate of cesarean delivery. The use of misoprostol appears to be associated with a lower risk of cesarean birth among parous women induced at our institution.

Effectiveness of zinc supplementation to full term normal infants: a community based double blind, randomized, controlled, clinical trial.

UNLABELLED: The study was aimed to test whether zinc supplementation, if initiated early, can prevent stunting and promote optimum body composition in full term infants. For this, full term pregnant women from low income urban community were enrolled and were followed-up for 24 months postpartum. Body mass index (BMI) was calculated from maternal weight and height that were collected one month after delivery. Infants' weight, and length, head, chest and mid upper arm circumferences and skin fold thicknesses at triceps, biceps and subscapular area were collected at baseline (before randomization) and once in three months up till 24 months. Three hundred and twenty four infants were randomized and allocated to zinc (163) or placebo (161) groups respectively. Supplementation of zinc was initiated from 4 months of age and continued till children attained 18 months. The control (placebo) group of children received riboflavin 0.5 mg/day, whereas the intervention (zinc) group received 5 mg zinc plus riboflavin 0.5 mg/day. When infants were 18 months old, dietary intakes (in 78 children) were calculated by 24 hour diet recall method and hemoglobin, zinc, copper and vitamin A were quantified in blood samples collected from 70 children. The results showed prevalence of undernutrition (body mass index <18.5) in 37% of the mothers. Mean±SD calorie consumption and zinc intakes from diets in infants were 590±282.8 Kcal/day and 0.97±0.608 mg/day respectively. Multiple linear regression models demonstrated maternal weight as a strong predictor of infants' weight and length at 18 months of age. As expected, diarrhea duration impacted infants' linear growth and weight gain adversely. Zinc supplementation for a mean period of 190 days, starting from 4 months up to 18 months of age, in full term normal infants, consuming an average energy of 590 Kcal/day, had significant effect on the skin fold thicknesses, but not on their linear growth. TRIAL REGISTRATION: Clinical Trail Registration India (CTRI) CTRI/2012/08/002884.

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.

Developmental neurotoxicity of ketamine in pediatric clinical use.

Ketamine is widely used as an anesthetic, analgesic, and sedative in pediatric clinical practice and it is also listed as an illicit drug by most countries. Recent in vivo and in vitro animal studies have confirmed that ketamine can induce neuronal cell death in the immature brain, resulting from widespread neuronal apoptosis. These effects can disturb normal development further altering the structure and functions of the brain. Our recent studies further indicate that ketamine can alter neurogenesis from neural stem progenitor cells in the developing brain. Taken together, these findings identify a novel complication associated with ketamine use in premature infants, term newborns, and pregnant women. Recent data on the developmental neurotoxicity of ketamine are reviewed with proposed future directions for evaluating the safety of ketamine in these patient populations.