Pharmacokinetic and Biochemical Profiling of Sodium Dichloroacetate in Pregnant Ewes and Fetuses.

Sodium dichloroacetate (DCA) is an investigational drug that shows promise in the treatment of acquired and congenital mitochondrial diseases, including myocardial ischemia and failure. DCA increases glucose utilization and decreases lactate production, so it may also have clinical utility in reducing lactic acidosis during labor. In the current study, we tested the ability of DCA to cross the placenta and be measured in fetal blood after intravenous administration to pregnant ewes during late gestation and labor. Sustained administration of DCA to the mother over 72 hours achieved pharmacologically active levels of DCA in the fetus and decreased fetal plasma lactate concentrations. Multicompartmental pharmacokinetics modeling indicated that drug metabolism in the fetal and maternal compartments is best described by the DCA inhibiting lactate production in both compartments, consistent with our finding that the hepatic expression of the DCA-metabolizing enzyme glutathione transferase zeta1 was decreased in the ewes and their fetuses exposed to the drug. We provide the first evidence that DCA can cross the placental compartment to enter the fetal circulation and inhibit its own hepatic metabolism in the fetus, leading to increased DCA concentrations and decreased fetal plasma lactate concentrations during its parenteral administration to the mother. SIGNIFICANCE STATEMENT: This study was the first to administer sodium dichloroacetate (DCA) to pregnant animals (sheep). It showed that DCA administered to the mother can cross the placental barrier and achieve concentrations in fetus sufficient to decrease fetal lactate concentrations. Consistent with findings reported in other species, DCA-mediated inhibition of glutathione transferase zeta1 was also observed in ewes, resulting in reduced metabolism of DCA after prolonged administration.

Aspirin (single dose) for perineal pain in the early postpartum period.

BACKGROUND: Perineal trauma, due to spontaneous tears, surgical incision (episiotomy), or in association with operative vaginal birth, is common after vaginal birth, and is often associated with postpartum perineal pain. Birth over an intact perineum may also lead to perineal pain. There are adverse health consequences associated with perineal pain for the women and their babies in the short- and long-term, and the pain may interfere with newborn care and the establishment of breastfeeding. Aspirin has been used in the management of postpartum perineal pain, and its effectiveness and safety should be assessed. This is an update of the review, last published in 2017. OBJECTIVES: To determine the effects of a single dose of aspirin (acetylsalicylic acid), including at different doses, in the relief of acute postpartum perineal pain. SEARCH METHODS: For this update, we searched the Cochrane Pregnancy and Childbirth's Trials Register (4 October 2019), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (4 October 2019) and screened reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs), assessing single dose aspirin compared with placebo, no treatment, a different dose of aspirin, or single dose paracetamol or acetaminophen, for women with perineal pain in the early postpartum period. We planned to include cluster-RCTs, but none were identified. We excluded quasi-RCTs and cross-over studies. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of the included RCTs. Data were checked for accuracy. The certainty of the evidence for the main comparison (aspirin versus placebo) was assessed using the GRADE approach. MAIN RESULTS: We included 17 RCTs, 16 of which randomised 1132 women to aspirin or placebo; one RCT did not report numbers of women. Two RCTs (of 16) did not contribute data to meta-analyses. All women had perineal pain post-episiotomy, and were not breastfeeding. Studies were published between 1967 and 1997, and the risk of bias was often unclear, due to poor reporting. We included four comparisons: aspirin versus placebo (15 RCTs); 300 mg versus 600 mg aspirin (1 RCT); 600 mg versus 1200 mg aspirin (2 RCTs); and 300 mg versus 1200 mg aspirin (1 RCT). Aspirin versus placebo Aspirin may result in more women reporting adequate pain relief four to eight hours after administration compared with placebo (risk ratio (RR) 2.03, 95% confidence interval (CI) 1.69 to 2.42; 13 RCTs, 1001 women; low-certainty evidence). It is uncertain whether aspirin compared with placebo has an effect on the need for additional pain relief (RR 0.25, 95% CI 0.17 to 0.37; 10 RCTs, 744 women; very low-certainty evidence), or maternal adverse effects (RR 1.08, 95% CI 0.57 to 2.06; 14 RCTs, 1067 women; very low-certainty evidence), four to eight hours after administration. Analyses based on dose did not reveal any clear subgroup differences. 300 mg versus 600 mg aspirin It is uncertain whether over four hours after administration, 300 mg compared with 600 mg aspirin has an effect on adequate pain relief (RR 0.82, 95% CI 0.36 to 1.86; 1 RCT, 81 women) or the need for additional pain relief (RR 0.68, 95% CI 0.12 to 3.88; 1 RCT, 81 women). There were no maternal adverse effects in either aspirin group. 600 mg versus 1200 mg aspirin It is uncertain whether over four to eight hours after administration, 600 mg compared with 1200 mg aspirin has an effect on adequate pain relief (RR 0.85, 95% CI 0.52 to 1.39; 2 RCTs, 121 women), the need for additional pain relief (RR 1.32, 95% CI 0.30 to 5.68; 2 RCTs, 121 women), or maternal adverse effects (RR 3.00, 95% CI 0.13 to 69.52; 2 RCTs, 121 women). 300 mg versus 1200 mg aspirin It is uncertain whether over four hours after administration, 300 mg compared with 1200 mg aspirin has an effect on adequate pain relief (RR 0.62, 95% CI 0.29 to 1.32; 1 RCT, 80 women) or need for additional pain relief (RR 2.00, 95% CI 0.19 to 21.18; 1 RCT, 80 women). There were no maternal adverse effects in either aspirin group. None of the included RCTs reported on neonatal adverse effects. No RCTs reported on secondary review outcomes of: prolonged hospitalisation due to perineal pain; re-hospitalisation due to perineal pain; fully breastfeeding at discharge; mixed feeding at discharge; fully breastfeeding at six weeks; mixed feeding at six weeks; perineal pain at six weeks; maternal views; or maternal postpartum depression. AUTHORS' CONCLUSIONS: Single dose aspirin may increase adequate pain relief in women with perineal pain post-episiotomy compared with placebo. It is uncertain whether aspirin has an effect on the need for additional analgesia, or on maternal adverse effects, compared with placebo. We downgraded the certainty of the evidence because of study limitations (risk of bias), imprecision, and publication bias. Aspirin may be considered for use in non-breastfeeding women with post-episiotomy perineal pain. Included RCTs excluded breastfeeding women, so there was no evidence to assess the effects of aspirin on neonatal adverse effects or breastfeeding. Future RCTs should be designed to ensure low risk of bias, and address gaps in the evidence, such as the secondary outcomes established for this review. Current research has focused on women with post-episiotomy pain; future RCTs could be extended to include women with perineal pain associated with spontaneous tears or operative birth.

Outpatient post-partum antibiotic prescription: method of identification of infection control areas demanding improvements and verification of sensitivity of infection registration.

OBJECTIVES: To evaluate data on outpatient antibiotic use in women post-labour as a potential method of monitoring infections in this group of patients. METHODS: Demographic and antibiotic prescription data originated from the registries of the National Health Fund (pol. Narodowy Fundusz Zdrowia). The measure of antibiotic use in this study was the percentage of women who purchased the drugs from prescriptions and DDDs. RESULTS: Among 67917 females who gave birth in the years 2013-14, 5050 (7.4%) purchased antibiotics prescribed by the obstetrician only. The average number of antibiotics bought per person was equivalent to ∼14 DDDs; in most cases (95.7%) these were ß-lactams. Antibiotic use occurred significantly more frequently among younger patients (11.5% patients <18 years of age), those living in rural areas (8.2%) and those who underwent Caesarean section (8.1%). No significant differences were found between the reported day of labour and the post-partum use of antibiotics. CONCLUSIONS: Antibiotic prescribing data can be used to verify/complement the information originating from hospital infection registries to monitor rates of infection in obstetric patients.

Intrapartum synthetic oxytocin and breastfeeding: a retrospective cohort study.

Non-pulsatile oxytocin given during labour can negatively affect breastfeeding. The aim of this study was to assess whether intrapartum oxytocin administration has any effect on breastfeeding. Secondly, to assess whether some maternal or neonatal variables influence breastfeeding. A retrospective cohort study was done, comparing two groups: women exposed (n = 101) and not exposed to oxytocin (n = 100) during labour. Women with caesarean section, vacuum extraction/forceps, twin pregnancy, breech presentation, premature neonates and with an Apgar score <7 at 5 minutes were excluded. Duration of breastfeeding was evaluated by a phone call interview. A regression analysis was done, evaluating possible confounding factors. The use of oxytocin during labour was demonstrated to be a predictor of impaired first hour breastfeeding (OR =2.493, CI: 1.05-5.92; p = .038). At three months' postpartum, 26.7% women in the exposed group versus 14% in the non-exposed group were not breastfeeding (p = .035). This result was not statistically significant when adjusting for possible confounders. High pregestational body mass index was the best predictor of an impaired third month's postpartum breastfeeding (OR =0.901, CI: 0.835-0.972; p = .007). Intrapartum oxytocin administration could inhibit first hour breastfeeding. A novel association was detected, pregestational body mass index was a predictor of impaired breastfeeding at three months, possibly confounding the oxytocin effect. Additional prospective studies are needed to investigate potential associations between intrapartum oxytocin and breastfeeding. Impact statement What is already known on this subject? Oxytocin is a common medical intervention during labour. Some studies suggest a negative association between intrapartum oxytocin dose, newborn sucking and an increased risk of early breastfeeding discontinuation. However, some maternal variables were not considered in these studies and the impact synthetic oxytocin may have on breastfeeding has not been thoroughly researched. What do the results of this study add? In this study, intrapartum oxytocin administration seems to inhibit the first hour breastfeeding. However, a novel association was detected, high pregestational body mass index was a predictor of impaired breastfeeding at three months, possibly confounding oxytocin effects. What are the implications of these findings for clinical practice and/or further research? Additional prospective studies are needed to investigate potential associations between intrapartum oxytocin and breastfeeding. Therefore, health care professionals should help obese women, starting from conception, to maximise breastfeeding outcomes as much as possible.

Aspirin (single dose) for perineal pain in the early postpartum period.

BACKGROUND: Perineal trauma (due to spontaneous tears, surgical incision (episiotomy) or in association with operative vaginal birth) is common after vaginal birth, and is often associated with postpartum perineal pain. Birth over an intact perineum may also lead to perineal pain. There are adverse health consequences associated with perineal pain for the women and their babies in the short- and long-term, and the pain may interfere with newborn care and the establishment of breastfeeding. Aspirin has been used in the management of postpartum perineal pain and its effectiveness and safety should be assessed. OBJECTIVES: To determine the efficacy of a single dose of aspirin (acetylsalicylic acid), including at different doses, in the relief of acute postpartum perineal pain. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (30 August 2016), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (31 May 2016) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing single dose aspirin compared with placebo, no treatment, a different dose of aspirin, or single dose paracetamol/acetaminophen for women with perineal pain in the early postpartum period. We planned to include cluster-RCTs but none were identified. Quasi-RCTs and cross-over studies were not eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of the included RCTs. Data were checked for accuracy. The quality of the evidence for the main comparison (aspirin versus placebo) was assessed using the GRADE approach. MAIN RESULTS: We included 17 RCTs, with 16 involving 1132 women randomised to aspirin or placebo (one RCT did not report numbers of women). Two RCTs (of 16) did not contribute data to review meta-analyses. All women had perineal pain post-episiotomy, and were not breastfeeding. Studies were published between 1967 and 1997, and the risk of bias was often unclear due to poor reporting.We included four comparisons: aspirin versus placebo (data from 15 RCTs); 300 mg versus 600 mg aspirin (1 RCT); 600 mg versus 1200 mg aspirin (2 RCTs); and 300 mg versus 1200 mg aspirin (1 RCT). Primary outcomes Aspirin versus placeboMore women who received aspirin experienced adequate pain relief compared with women who received placebo over four to eight hours after administration (risk ratio (RR) 2.03, 95% confidence intervals (CI) 1.69 to 2.42; 13 RCTs, 1001 women; low-quality evidence). Women who received aspirin were less likely to need additional pain relief over four to eight hours after administration (RR 0.25, 95% CI 0.17 to 0.37; 10 RCTs, 744 women; very low-quality evidence). There was no difference in maternal adverse effects over four to eight hours post-administration (RR 1.08, 95% CI 0.57 to 2.06; 14 RCTs, 1067 women; very low-quality evidence). Subgroup analyses based on dose did not reveal any clear subgroup differences.There was no clear difference over four hours after administration between 300 mg and 600 mg aspirin for adequate pain relief (RR 0.82, 95% CI 0.36 to 1.86; 1 RCT, 81 women) or need for additional pain relief (RR 0.68, 95% CI 0.12 to 3.88; 1 RCT, 81 women). There were no maternal adverse effects in either aspirin group.There was no clear difference over four to eight hours after administration between 600 mg and 1200 mg aspirin for adequate pain relief (RR 0.85, 95% CI 0.52 to 1.39; 2 RCTs, 121 women), need for additional pain relief (RR 1.32, 95% CI 0.30 to 5.68; 2 RCTs, 121 women), or maternal adverse effects (RR 3.00, 95% CI 0.13 to 69.52; 2 RCTs, 121 women).There was no clear difference over four hours after administration between 300 mg and 1200 mg aspirin for adequate pain relief (RR 0.62, 95% CI 0.29 to 1.32; 1 RCT, 80 women) or need for additional pain relief (RR 2.00, 95% CI 0.19 to 21.18; 1 RCT, 80 women). There were no maternal adverse effects in either aspirin group.None of the included RCTs reported on neonatal adverse effects. Secondary outcomesNo studies reported on secondary review outcomes: prolonged hospitalisation due to perineal pain; re-hospitalisation due to perineal pain; fully breastfeeding at discharge; mixed feeding at discharge; fully breastfeeding at six weeks; mixed feeding at six weeks; perineal pain at six weeks; maternal views; maternal postpartum depression. AUTHORS' CONCLUSIONS: We found low-quality evidence to suggest that single dose aspirin compared with placebo can increase pain relief in women with perineal pain post-episiotomy. Very low-quality evidence also suggested that aspirin can reduce the need for additional analgesia, without increasing maternal adverse effects. Evidence was downgraded based on study limitations (risk of bias), imprecision, and publication bias or both. RCTs excluded breastfeeding women so there is no evidence to assess the effects of aspirin on neonatal adverse effects or breastfeeding.With international guidance recommending mothers initiate breastfeeding within one hour of birth, and exclusively breastfeed for the first six months, the evidence from this review is not applicable to current recommended best practice. Aspirin may be considered for use in non-breastfeeding women with post-episiotomy perineal pain. Although formal assessment was beyond the remit of this review, current guidance suggests that other analgesic drugs (including paracetamol) should be considered first for postpartum perineal pain. Such agents are the focus of other reviews in this series on drugs for perineal pain in the early postpartum period. It is considered most likely that if RCTs are conducted in the future they could compare aspirin with other pain relievers. Future RCTs should be designed to ensure high methodological quality, and address gaps in the evidence, such as the secondary outcomes established for this review. Current research has focused on women with post-episiotomy pain, future RCTs could be extended to women with perineal pain associated with spontaneous tears or operative birth.

IGF-1 as an Important Endogenous Growth Factor for Recovery from Impaired Urethral Continence Function in Rats with Simulated Childbirth Injury.

PURPOSE: We examined the functional role of endogenous IGF-1 (insulin-like growth factor-1) in the recovery phase of stress urinary incontinence induced by simulated childbirth trauma using an IGF-1 receptor inhibitor. MATERIALS AND METHODS: Simulated birth trauma was induced by vaginal distension in female Sprague Dawley® rats. The IGF-1 receptor antagonist JB-1 (10 and 100 µg/kg per day) or vehicle was continuously delivered from 1 day before vaginal distension for 7 days using subcutaneous osmotic pumps. Seven, 14 and 21 days after vaginal distension the effect of JB-1 treatment was examined by functional analyses, including leak point and urethral baseline pressure, and urethral responses during passive increments in intravesical pressure, as well as molecular analyses in urethral tissues, including phosphorylation of Akt, apoptotic changes and peripheral nerve density using Western blot and immunohistochemistry. RESULTS: On functional analyses vehicle treated rats with vaginal distension had significantly decreased leak point and urethral baseline pressure, and urethral responses at 7 days, which recovered to the normal level 14 and 21 days after vaginal distension. In the JB-1 treated vaginal distension group leak point and urethral baseline pressure, and urethral responses were still significantly reduced 21 days after vaginal distension. On molecular analyses JB-1 treatment increased apoptotic cells, induced a significant decrease in phosphorylated Akt and prolonged the decrease of peripheral nerve density in urethral tissues. CONCLUSIONS: Suppression of endogenous IGF-1 activity delayed recovery from stress urinary incontinence induced by simulated childbirth trauma in rats. Thus, IGF-1 is likely to be an important endogenous mediator for functional recovery from childbirth related stress urinary incontinence. This suggests that IGF-1 could be an effective target for treating stress urinary incontinence in women.

Propranolol and oxytocin versus oxytocin alone for induction and augmentation of labor: a meta-analysis of randomized trials.

BACKGROUND: We sought to study the effect of propranolol co-administration with oxytocin during the latent and active phases of labor on labor outcomes. MATERIALS AND METHODS: We searched Medline, Scopus, ClinicalTrials.gov and Cochrane Central Register databases. The meta-analysis was performed with the RevMan 5.1 software. Six studies were included in the present meta-analysis which enrolled 609 parturient. RESULTS: According to the findings of our study, propranolol administration during the latent phase effectively reduces the cesarean section rates (OR 0.49, 95 % CI 0.27, 0.89). However, this beneficial effect is not observed during the active phase of labor. The 5 min neonatal Apgar scores are not influenced by its administration (MD -0.07, 95 % CI -0.017, 0.02). Respectively, the neonatal admissions to a NICU are similar to those of neonates exposed only to oxytocin (OR 0.96, 95 % CI 0.36, 2.53). CONCLUSION: Propranolol's effect on the duration of the various stages of labor was underreported, however, evidence seem to support that it shortens the latent phase and possibly the total duration of labor. Firm results are, however, precluded due to the low number enrolled parturient and due to the significant methodological heterogeneity of included studies.

Carbetocin at Cesarean delivery for labour arrest: a sequential allocation trial to determine the effective dose.

PURPOSE: The aim of this study was to estimate the effective dose 90% (ED90) of carbetocin to provide adequate uterine tone at Cesarean delivery (CD) for labour arrest. METHODS: We conducted a double-blind dose-finding study of carbetocin using a biased-coin up-and-down design in women undergoing CD for labour arrest under epidural anesthesia. Forty healthy term pregnant women who had received at least three hours of oxytocin infusion during labour were recruited for the study. Carbetocin was administered intravenously upon delivery of the anterior shoulder of the fetus. The first patient received 20 µg, and the dose for the subsequent patient was determined according to the response of the previous patient as per the biased-coin allocation scheme using increments or decrements of 20 µg (maximum 140 µg). Uterine tone was assessed by the obstetrician and rated as satisfactory or unsatisfactory throughout the intraoperative period. The primary outcome was satisfactory uterine tone with no need for additional uterotonic drugs intraoperatively. Secondary outcomes included use of additional uterotonic drugs postoperatively in the first 24 hr, estimated blood loss, and adverse effects. RESULTS: The ED90 of carbetocin to produce adequate uterine tone was estimated at 121 µg (95% confidence interval [CI]: 111 to 130; 99% CI: 108 to 133) using the truncated Dixon and Mood (DM) method. The isotonic estimator of ED90 was 140 µg; however, the observed response rate across all doses was < 90%. Also, the 95% CI of the DM estimator is likely to have lower than expected coverage, while the 99% CI may have about 90% coverage. Therefore, these results should be interpreted with caution. The overall median (range) estimated blood loss was 1,014 (104-2,436) mL. The overall incidence of hypotension and tachycardia were 45% and 57.5%, respectively. At a dose of 140 µg, the incidence of tachycardia and intraoperative arrhythmias was 76% and 14%, respectively. CONCLUSION: The ED90 of carbetocin at CD for labour arrest, as determined in our study, should be interpreted with caution since it may be underestimated. This dose is higher than the currently recommended dose of 100 µg at elective CD and should not be used routinely given the uncertainty regarding its efficacy and the high incidence of arrhythmias at higher doses. This trial was registered at ClinicalTrials.gov, number: NCT01725243.

Unintended clinical consequences of the implementation of a checklist-based, low-dose oxytocin protocol.

OBJECTIVE: Standardized oxytocin protocols have been used to improve the safety and quality of obstetric care. We examined rates of chorioamnionitis and labor dystocia requiring cesarean delivery as unintended consequences of the implementation of a low-dose, checklist-based oxytocin protocol. STUDY DESIGN: We performed a retrospective cohort study of live singleton deliveries that underwent a trial of labor in two 15-month periods, comparing outcomes in those who delivered before to after protocol implementation. Patients and outcomes were identified using a combination of electronic medical records and International Classification of Diseases, 9th Revision, Clinical Modification codes. Time trend analysis was performed to evaluate for secular trends. RESULTS: A total of 8,717 women were included; 5,077 received oxytocin. Despite an unchanged rate of cesarean deliveries from before to after initiation of the protocol (15.15 vs. 14.75%, p = 0.60), deliveries after protocol implementation were generally characterized by higher rates of chorioamnionitis (7.48 vs. 5.97%, p < 0.001), longer median time from admission to delivery (524 vs. 462 minutes, p < 0.001), more cesarean deliveries performed for labor dystocia (50.62 vs. 40.92%, p < 0.001), and fewer cesarean deliveries performed for fetal distress (32.52 vs. 38.67%, p = 0.02). CONCLUSION: Low-dose oxytocin protocols are intended to increase safety, but they may have unintended consequences related to prolonged labor, and should be studied before widespread use.

Perineal pain in focus: reviewing topical anaesthetic treatments.

Midwives have opportunities to help postnatal mothers to minimise perineal discomfort associated with perineal trauma following vaginal birth. Perineal trauma and associated pain is common and can have a negative impact on the physical, psycho-social transition to motherhood and family life. This article considers the role local anaesthetic agents have in helping women to relieve perineal pain. Key evidence is presented with associated practice considerations, and future research areas are suggested to broaden our understanding of this important aspect of postnatal care.

A randomized trial of the effects of antibiotic prophylaxis on epidural-related fever in labor.

BACKGROUND: It has been suggested that the development of maternal fever during epidural analgesia could be due to intrapartum infection. We investigated whether antibiotic prophylaxis before epidural placement decreases the rate of epidural-related fever. METHODS: In this double-blind, placebo-controlled trial, 400 healthy nulliparous women requesting epidural analgesia were randomly assigned to receive either cefoxitin 2 g or placebo immediately preceding initiation of epidural labor analgesia. Maternal tympanic temperature was measured hourly, and intrapartum fever was defined as a maternal temperature of ≥38°C. Neonates born to women with fever were evaluated for possible sepsis, and available placentas were evaluated for the presence of neutrophilic inflammation. The primary outcome was maternal fever during epidural analgesia. RESULTS: Thirty-eight percent of women in the cefoxitin group and 40% of women in the placebo group developed fever (P = 0.68). The risk difference (95% confidence interval) for fever ≥38°C during labor (antibiotic versus placebo) was -2.0% (-11.5 to 7.5), and for fever >39°C during labor was -1.5% (-4.7 to 1.7). Approximately half of each study group had placental neutrophilic inflammation, but administration of cefoxitin had no significant effect on any grade of neutrophilic inflammation. Fever developed significantly more often in the women with placental neutrophilic inflammation compared with those without such inflammation (73/158 vs 33/144, P < 0.001; risk difference 23% [95% confidence interval, 13.0-34.0]). There were no significant differences in any neonatal outcomes between the antibiotic and placebo study groups. Sepsis was not diagnosed in any of the infants. There were no neonatal deaths. CONCLUSION: Fever during labor epidural analgesia is associated with placental inflammation, but fever and placental inflammation were not reduced with antibiotic prophylaxis. This finding suggests that infection is unlikely to be the cause in its development.

Umbilical cord blood acid-base status in pregnancy with congenital heart disease.

BACKGROUND: The risk of fetal and neonatal complications is higher in pregnant women with congenital heart disease (CHD). It remains unknown whether umbilical cord blood gas values are different between pregnant women with CHD and healthy women undergoing elective cesarean section during combined spinal-epidural anesthesia. The purpose of the present study was to compare umbilical cord blood acid-base status and gas values in pregnant women with CHD vs. healthy pregnant women undergoing elective cesarean section during combined spinal-epidural (CSE) anesthesia. METHODS: Patients with singleton pregnancy undergoing elective cesarean delivery under CSE anesthesia were enrolled. Patients were divided into two groups: healthy pregnant women (group H) and pregnant with congenital heart disease (group CHD). Immediately after delivery, umbilical cord arterial blood sample and venous blood sample were collected and measured. The comparison between two groups was performed using grouped t-test. RESULTS: Forty-four women in group H and 33 women in group CHD were analyzed finally. Umbilical arterial blood pH, base excess (BE) and HCO3 (-) (pH 7.29 ± 0.05, BE -1.4 ± 1.9 mmol/L, HCO3 (-) 21.5 ± 1.4 mmol/L) were significantly lower in pregnant women with CHD than in healthy pregnant women (pH 7.33 ± 0.03, BE -0.1 ± 2.1 mmol/L, HCO3 (-) 22.5 ± 1.4 mmol/L). CONCLUSIONS: The lower values of umbilical arterial blood pH, BE and HCO3 (-) were observed in pregnant women with CHD than in healthy women undergoing elective cesarean section during CSE anesthesia.

Standard- or high-dose oxytocin for nulliparous women with confirmed delay in labour: quantitative and qualitative results from a pilot randomised controlled trial.

OBJECTIVE: Evidence suggests that a high dose of oxytocin for nulliparous women at 37-42 weeks of gestation with confirmed delay in labour increases spontaneous vaginal birth. We undertook a pilot study to test the feasibility of this treatment. DESIGN: Pilot double-blind randomised controlled trial. SETTING: Three teaching hospitals in the UK. POPULATION: A total of 94 consenting nulliparous women at term with confirmed delay in labour were recruited, and 18 were interviewed. METHODS: Women were assigned to either a standard (2 mU/min, increasing every 30 minutes to 32 mU/minute) or a high-dose regimen (4 mU/minute, increasing every 30 minutes to 64 mU/minutes) oxytocin by computer-generated randomisation. Simple descriptive statistics were used, as the sample size was insufficient to evaluate clinical outcomes. The constant comparative method was used to analyse the interviews. MAIN OUTCOMES MEASURES: The main outcome measures: number of women eligible; maternal and neonatal birth; safety; maternal psychological outcomes and experiences; health-related quality of life outcomes using validated tools and data on health service resource use; incidence of suspected delay of labour (cervical dilatation of <2 cm after 4 hours, once labour is established); and incidence of confirmed delay of labour (progress of <1 cm on repeat vaginal examination after a period of 2 hours). RESULTS: We successfully developed systems to recruit eligible women in labour and to collect data. Rates of spontaneous vaginal birth (10/47 versus 12/47, RR 1.2, 95% CI 0.6-2.5) and caesarean section (15/47 versus 17/47, RR 1.1, 95% CI 0.6-2.0) were increased, and rates of instrumental birth were reduced (21/47 versus 17/47, RR 0.8, 95% CI 0.5-1.3). No evidence of increased harm for either mother or baby was found. The incidences of suspected delay (14%) and confirmed delay (11%) in labour were less than anticipated. Of those who did not go on to have delayed labour confirmed, all except one woman gave birth vaginally. CONCLUSIONS: A pilot trial assessing the efficacy of high-dose oxytocin was feasible, but uncertainty remains, highlighting the need for a large definitive trial. The implementation of national guidance of suspected and confirmed delay in labour is likely to reduce intervention.

Oxytocin versus no treatment or delayed treatment for slow progress in the first stage of spontaneous labour.

BACKGROUND: Slow progress in the first stage of spontaneous labour is associated with an increased caesarean section rate and fetal and maternal morbidity. Oxytocin has long been advocated as a treatment for slow progress in labour but it is unclear to what extent it improves the outcomes for that labour and whether it actually reduces the caesarean section rate or maternal and fetal morbidity. This review will address the use of oxytocin and whether it improves the outcomes for women who are progressing slowly in labour compared to situations where it is not used or where its administration is delayed. OBJECTIVES: To determine if the use of oxytocin for the treatment of slow progress in the first stage of spontaneous labour is associated with a reduction in the incidence of caesarean sections, or maternal and fetal morbidity compared to situations where it is not used or where its administration is delayed. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 February 2013) and bibliographies of relevant papers. SELECTION CRITERIA: Randomised controlled trials which compared oxytocin with either placebo, no treatment or delayed oxytocin in the active stage of spontaneous labour in low-risk women at term. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion, assessed risk of bias and extracted data. We sought additional information from trial authors. MAIN RESULTS: We included eight studies in the review involving a total of 1338 low-risk women in the first stage of spontaneous labour at term. Two comparisons were made; 1) the use of oxytocin versus placebo or no treatment (three trials); 2) the early use of oxytocin versus its delayed use (five trials). There were no significant differences in the rates of caesarean section or instrumental vaginal delivery in either comparison. Early use of oxytocin resulted in an increase in uterine hyperstimulation associated with fetal heart changes. However, the early use of oxytocin versus its delayed use resulted in no significant differences in a range of neonatal and maternal outcomes. Use of early oxytocin resulted in a statistically significant reduction in the mean duration in labour of approximately two hours but did not increase the normal delivery rate. There was significant heterogeneity for this analysis and we carried out a random-effects meta-analysis; however, all of the trials are strongly in the same direction so it is reasonable to conclude that this is the true effect. We also performed a random-effects meta-analysis for the four other analyses which showed substantial heterogeneity in the review. AUTHORS' CONCLUSIONS: For women making slow progress in spontaneous labour, treatment with oxytocin as compared with no treatment or delayed oxytocin treatment did not result in any discernable difference in the number of caesarean sections performed. In addition there were no detectable adverse effects for mother or baby. The use of oxytocin was associated with a reduction in the time to delivery of approximately two hours which might be important to some women. However, if the primary goal of this treatment is to reduce caesarean section rates, then doctors and midwives may have to look for alternative options.

Antispasmodics for labour.

BACKGROUND: Prolonged labour can lead to increased maternal and neonatal mortality and morbidity due to increased risks of maternal exhaustion, postpartum haemorrhage and sepsis, fetal distress and asphyxia and requires early detection and appropriate clinical response. The risks for complications of prolonged labour are much greater in poor resource settings. Active management of labour versus physiological, expectant management, has shown to decrease the occurrence of prolonged labour. Administering antispasmodics during labour could also lead to faster and more effective dilatation of the cervix. Interventions to shorten labour, such as antispasmodics, can be used as a preventative or a treatment strategy in order to decrease the incidence of prolonged labour. As the evidence to support this is still largely anecdotal around the world, there is a need to systematically review the available evidence to obtain a valid answer. OBJECTIVES: To assess the effects of antispasmodics on labour in term pregnancies. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2013), the ProQuest dissertation and thesis database, the dissertation database of the University of Stellenbosch and Google Scholar (28 February 2013) and reference lists of articles. We also contacted pharmaceutical companies and experts in the field. We did not apply language restrictions. SELECTION CRITERIA: Randomised controlled trials comparing antispasmodics with placebo or no medication in women with term pregnancies. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and selected studies for inclusion, assessed risk of bias and extracted data. Data were checked for accuracy. We contacted trial authors when data were missing. MAIN RESULTS: Twenty-one trials (n = 3286) were included in the review. Seventeen trials (n = 2617) were included in the meta-analysis. Antispasmodics used included valethamate bromide, hyoscine butyl-bromide, drotaverine hydrochloride, rociverine and camylofin dihydrochloride. Most studies included antispasmodics as part of their package of active management of labour. Overall, the quality of studies was poor, as only four trials were assessed as low risk of bias. Thirteen trials (n = 1995) reported on the duration of first stage of labour, which was significantly reduced by an average of 74.34 minutes when antispasmodics were administered (mean difference (MD) -74.34 minutes; 95% confidence Interval (CI) -98.76 to -49.93). Seven studies (n = 797) reported on the total duration of labour, which was significantly reduced by an average of 85.51 minutes (MD -85.51 minutes; 95% CI -121.81 to -49.20). Six studies (n = 820) had data for the outcome: rate of cervical dilatation. Administration of antispasmodics significantly increased the rate of cervical dilatation by an average of 0.61 cm/hour (MD 0.61 cm/hour; 95% CI 0.34 to 0.88). Antispasmodics did not affect the duration of second and third stage of labour. The rate of normal vertex deliveries was not affected either. Only one study explored pain relief following administration of antispasmodics and no conclusions can be drawn on this outcome. There was significant heterogeneity for most outcomes and therefore, we undertook random-effects meta-analysis. Subgroup analysis was undertaken to explore heterogeneity, but remained largely unexplained. Maternal and neonatal adverse events were reported inconsistently. The main maternal adverse event reported was tachycardia. No serious neonatal adverse events were reported. AUTHORS' CONCLUSIONS: There is low quality evidence that antispasmodics reduce the duration of first stage of labour and increase the cervical dilatation rate. There is very low quality evidence that antispasmodics reduce the total duration of labour. There is moderate quality evidence that antispasmodics do not affect the rate of normal vertex deliveries. There is insufficient evidence to make any conclusions regarding the safety of these drugs for both mother and baby. Large, rigorous randomised controlled trials are needed to evaluate the effect of antispasmodics on prolonged labour and to evaluate their effect on labour in a context of expectant management of labour.

High-dose versus low-dose oxytocin for augmentation of delayed labour.

BACKGROUND: A major cause of failure to achieve spontaneous vaginal birth is delay in labour due to presumed inefficient uterine action. Oxytocin is given to increase contractions and high-dose regimens may potentially increase the number of spontaneous vaginal births, but as oxytocin can cause hyperstimulation of the uterus, there is a possibility of increased adverse events. OBJECTIVES: To compare starting dose and increment dose of oxytocin for augmentation for women delayed in labour to determine whether augmentation by high-dose regimens of oxytocin improves labour outcomes and to examine the effect on both maternal/neonatal outcomes and women's birth experiences. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. SELECTION CRITERIA: We included all randomised and quasi-randomised controlled trials for women in delayed labour requiring augmentation by oxytocin comparing high-dose regimens (defined as starting dose and increment of equal to or more than 4 mU per minute) with low-dose regimens (defined as starting dose and an increment of less than 4 mU per minute). Increase interval: between 15 and 40 minutes. The separation of low- and high-dose regimens is based on an arbitrary decision. DATA COLLECTION AND ANALYSIS: Four review authors undertook assessment of trial eligibility, risk of bias, and data extraction independently. MAIN RESULTS: We included four studies involving 644 pregnant women. Three studies were randomised controlled trials and one trial was a quasi-randomised study. A higher dose of oxytocin was associated with a significant reduction in length of labour reported from one trial (mean difference (MD) -3.50 hours; 95% confidence interval (CI) -6.38 to -0.62; one trial, 40 women). There was a decrease in the rate of caesarean section (risk ratio (RR) 0.62; 95% CI 0.44 to 0.86 four trials, 644 women) and an increase in the rate of spontaneous vaginal birth in the high-dose group (RR 1.35; 95% CI 1.13 to 1.62, three trials, 444 women), although for both of these outcomes there were inconsistencies between studies in the size of effect. When we carried out sensitivity analysis (temporarily removing a study at high risk of bias) the differences between groups were no longer statistically significantThere were no significant differences between high- and low-dose regimens for instrumental vaginal birth, epidural analgesia, hyperstimulation, postpartum haemorrhage, chorioamnionitis or women's perceptions of experiences. For neonatal outcomes, there was no significant difference between groups for Apgar scores, umbilical cord pH, admission to special care baby unit, or neonatal mortality. The following outcomes were not evaluated in the included studies: perinatal mortality, uterine rupture, abnormal cardiotocography, women's pyrexia, dystocia and neonatal neurological morbidity. AUTHORS' CONCLUSIONS: Higher-dose regimens of oxytocin (4 mU per minute or more) were associated with a reduction in the length of labour and in caesarean section, and an increase in spontaneous vaginal birth. However, there is insufficient evidence to recommend that high-dose regimens are advised routinely for women with delay in the first stage of labour. Further research should evaluate the effect of high-dose regimens of oxytocin for women delayed in labour and should include maternal and neonatal outcomes as well as the effects on women.

Effect of maternal body mass index on oxytocin treatment for arrest of dilatation.

To determine whether the effectiveness of oxytocin treatment of arrest of dilatation differed in obese compared to lean women, we did a retrospective analysis of 118 subjects in spontaneous labor whose arrest of dilatation was treated with oxytocin. Cases were stratified by maternal body mass index (BMI): Group A, <25 kg/m2; Group B, 25.0-29.9 kg/m2; Group C, 30.0-34.9 kg/m2; and Group D, ≥ 35 kg/m². Groups were comparable in maternal age, parity, gestational age, birth weight, and the frequency of infection. Full dilatation was reached in about 90% of Group A and B, 72% of Group C, and 39% of Group D, the most obese women (P<0.001). The cesarean rate was directly related to maternal BMI, 11.4%, 22.9%, 34.3%, and 69.6% in Groups A through D, respectively (P<0.001). Significantly more oxytocin was used in group D than in the other groups during the first 3h of infusion in attempting to overcome the arrest (P=0.003). We conclude that oxytocin treatment of arrest of dilatation was less effective in obese than in lean women. This effect was most prominent in women with a BMI >35 kg/m2, who were, despite having received more oxytocin than those in the leaner groups, less than half as likely to attain full dilatation and more than twice as likely to deliver by cesarean.

The influence of bupivacaine on the whole blood chemiluminescence in laboring women--a preliminary report.

OBJECTIVE: Local anesthetics are able to inhibit inflammatory phenomena. The influence of bupivacaine broadly applied in obstetrical anesthesia on the reactive oxygen species (ROS) production is a matter of controversy. The study was aimed at elucidation of the influence of racemic bupivacaine on the opsonized zymosan (OZ) stimulated-peripheral blood chemiluminescence (CL) in laboring women, reflecting the reactive oxygen species (ROS) production associated with phagocytosis. MATERIAL AND METHODS: Blood samples drawn from 8 healthy parturients in active spontaneous labor and from 5 healthy non-pregnant controls were incubated with the 0.3, 30, and 3000 microM bupivacaine concentrations and then luminol-dependent OZ-stimulated whole blood CL was assessed. RESULTS: Bupivacaine depressed CL; however the inhibitory effect was significant only at the highest, clinically irrelevant concentration (3000 microM), in parturients being comparable to that observed in non-pregnant women. CONCLUSIONS: Bupivacaine at clinically relevant concentrations does not influence ROS production accompanying phagocytosis in peripheral blood of laboring women. The effect is comparable in parturients and non-pregnant controls.

Prevalence and management of severe intrapartum hypertension in patients with preeclampsia at an urban tertiary care medical center.

OBJECTIVES: Data on management of severe intrapartum hypertension is lacking. The aim of this study is to explore the proportion of timely interventions in severe, persistent intrapartum hypertension treatment by exploring the prevalence and management of intrapartum hypertension trends. STUDY DESIGN: This was a retrospective case-control study of pregnant women who delivered at the University of Chicago between January 2015 and March 2017. Patients with severe preeclampsia who underwent labor (either induced or spontaneous) were stratified into two groups: severe intrapartum hypertension and no severe intrapartum hypertension. MAIN OUTCOME MEASURES: Type of treatment and timing to treatment of severe hypertensive episodes were explored as well as prevalence of maternal adverse outcomes. RESULTS: A total of 95 patients with severe preeclampsia in labor were identified. In patients with persistent severe intrapartum hypertension (n = 52), 15 (28.9%) received treatment. Patients experiencing greater than three episodes of blood pressure elevation were more likely to receive treatment as compared to those with fewer episodes. There was no significant difference in severe maternal morbidity (SMM) between those treated within 60 min compared to those untreated or treated after 60 min (16.7% vs 27.5%; p = 0.71). CONCLUSIONS: Management protocols of intrapartum hypertensive episodes are variable or not universally implemented. Inadequately treated episodes of severe intrapartum hypertension trend towards higher rates of SMM.

Oxytocin versus no treatment or delayed treatment for slow progress in the first stage of spontaneous labour.

BACKGROUND: Slow progress in the first stage of spontaneous labour is associated with an increased caesarean section rate and fetal and maternal morbidity. Oxytocin has long been advocated as a treatment for slow progress in labour but it is unclear to what extent it improves the outcomes for that labour and whether it actually reduces the caesarean section rate or maternal and fetal morbidity. This review will address the use of oxytocin and whether it improves the outcomes for women who are progressing slowly in labour compared to situations where it is not used or where its administration is delayed. OBJECTIVES: To determine if the use of oxytocin for the treatment of slow progress in the first stage of spontaneous labour is associated with a reduction in the incidence of caesarean sections, or maternal and fetal morbidity compared to situations where it is not used or where its administration is delayed. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2011) and bibliographies of relevant papers. SELECTION CRITERIA: Randomised controlled trials which compared oxytocin with either placebo, no treatment or delayed oxytocin in the active stage of spontaneous labour in low-risk women at term. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion, assessed risk of bias and extracted data. We sought additional information from trial authors. MAIN RESULTS: We included eight studies in the review involving a total of 1338 low-risk women in the first stage of spontaneous labour at term. Two comparisons were made; 1) the use of oxytocin versus placebo or no treatment (three trials); 2) the early use of oxytocin versus its delayed use (five trials). There were no significant differences in the rates of caesarean section or instrumental vaginal delivery in either comparison. Early use of oxytocin resulted in an increase in uterine hyperstimulation associated with fetal heart changes. However, the early use of oxytocin versus its delayed use resulted in no significant differences in a range of neonatal and maternal outcomes. Use of early oxytocin resulted in a statistically significant reduction in the mean duration in labour of approximately two hours but did not increase the normal delivery rate. There was significant heterogeneity for this analysis and we carried out a random-effects meta-analysis; however, all of the trials are strongly in the same direction so it is reasonable to conclude that this is the true effect. We also performed a random-effects meta-analysis for the four other analyses which showed substantial heterogeneity in the review. AUTHORS' CONCLUSIONS: For women making slow progress in spontaneous labour, treatment with oxytocin as compared with no treatment or delayed oxytocin treatment did not result in any discernable difference in the number of caesarean sections performed. In addition there were no detectable adverse effects for mother or baby. The use of oxytocin was associated with a reduction in the time to delivery of approximately two hours which might be important to some women. However, if the primary goal of this treatment is to reduce caesarean section rates, then doctors and midwives may have to look for alternative options.