Efficacy of phloroglucinol for acceleration of labour: a systematic review and meta­analysis.

PURPOSE: To assess the efficacy of phloroglucinol for acceleration of labour. METHODS: Randomized controlled trials (RCTs) comparing phloroglucinol with placebo were searched in PubMed, Embase and the Cochrane Library. Literatures were collected up to April 2020. Primary outcomes were the duration of labour and average blood loss. Finally, a total of 4 RCTs, 377 patients were included in this meta-analysis. The included RCTs were analyzed by the software Rev Man 5. 3. RESULTS: In the phloroglucinol group, the duration of the first stage was reduced by 116.04 min (95% CI 107.71 to 124.68), and the duration of the second stage was reduced by 10.75 min (95% CI 8.79 to 12.70). The average blood loss was reduced by 16.07 ml, which was statistically different from the control group. CONCLUSION: The application of phloroglucinol is proved to be effective for accelerating the labour process, reducing the risk of maternal and neonatal complications.

Effect of hyoscine-N-butylbromide on labor duration among nullipara in a southwestern Nigerian teaching hospital: A randomized controlled trial.

OBJECTIVE: To assess the effectiveness of hyoscine-N-butylbromide on the duration of the first stage of labor among nulliparous women. METHODS: A randomized double-blind placebo-controlled study among 126 nulliparous women admitted in the active phase of labor to a teaching hospital in Sagamu, Nigeria, from January to August 2018. Based on the inclusion criteria, women were recruited and randomized to the study or control group, and given intravenous hyoscine-N-butylbromide 20 mg (1 mL) or sterile water (1 mL), respectively, during the active phase. Labor progress and outcomes were compared between the groups. RESULTS: The mean ± SD duration of active phase of first stage of labor was significantly shorter in the hyoscine-N-butylbromide group (324.9 ± 134.6 min) than in the control group (392.7 ± 119.6 min) (P = 0.004). The rate of cervical dilatation was 1.4 ± 0.8 cm/h in the hyoscine-N-butylbromide group and 1.0 ± 0.5 cm/h in the control group (P = 0.004). There were no significant differences in fetal heart rate, maternal vital signs, or Apgar scores between the two groups. CONCLUSION: Hyoscine-N-butylbromide was found to be effective in shortening the duration of the first stage of labor without adverse outcomes for mother or neonate. The trial was registered with the Pan African Clinical trials Registry (PACTR), protocol number: PACTR201808146688942 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3532).

Tecnologias não invasivas para o alívio da dor na parturição / Non-invasive technologies for pain relief in parturition / Tecnologías no invasivas para el alivio del dolor durante en el parto

Objetivo: Analisar as tecnologias não invasivas de alívio da dor no parto e nascimento. Método: Revisão integrativa de literatura, com 13 artigos obtidos nas bases de dados Web of Science, Cumulative Index to Nursing and Allied Health Literature, Literatura Latino-Americana e do Caribe em Ciências da Saúde, SciVerse Scopus TopCited, Medical Literature Analysis and Retrieval System Online e a biblioteca virtual Scientific Electronic Library Online entre o período de 2010 a 2016. Resultados: Observou o uso de mais de duas tecnologias não farmacológicas no processo de parto e nascimento, como aromaterapia isolada ou somada a mais uma tecnologia; aplicação isolada de frio e/ou calor; uso da bola suíça/bola de parto. Conclusão: A utilização de novas tecnologias no processo parturitivo resgata a autonomia da mulher frente ao seu corpo

Objective: To analyze the non-invasive technologies of pain relief in labor and birth. Method: Integrative literature review, with 13 articles from the Web of Science database, Cumulative Index to Nursing and Allied Health Literature databases, Latin American and Caribbean Literature in Health Sciences, SciVerse Scopus TopCited, Medical Literature Analysis and Retrieval System Online, and the library Scientific Electronic Library Online between 2010 and 2016. Results: Observed the use of more than two non-pharmacological technologies in the delivery and birth process, such as aromatherapy alone or added to another technology; isolated application of cold and / or heat; use of the Swiss ball / birth ball. Conclusion: The use of new technologies in the parturition process rescues the autonomy of women in front of their bodies

Objetivo: Analizar tecnologías no invasivas de alivio del dolor en el parto y el nacimiento. Método: Revisión integrativa de literatura, con 13 artículos de las bases de datos de Web of Science, de Contenido etiquetado de la literatura y la literatura en América Latina y el Caribe, en Ciencias de la Salud, SciVse Scopus TopCited, Medical Literature Analysis and Retrieval System Online y la biblioteca Scientific Electronic Library virtual en línea entre el periodo de 2010 a 2016. Resultados: Observó el uso de más de dos tecnologías no farmacológicas en el parto y el proceso de parto, como la aromaterapia sola o agregada a otra tecnología; aplicación aislada de frío y / o calor; uso de la bola suiza / bola de nacimiento. Conclusión: El uso de nuevas tecnologías en el proceso de parto rescata la autonomía de las mujeres frente a sus cuerpos

Obstetric analgesia in labor and its association with neonatal outcomes / Analgesia obstétrica en el trabajo de parto y su asociación con resultados neonatales / Analgesia obstétrica no trabalho de parto e sua associação com desfechos neonatais

ABSTRACT Objetives: To investigate the association between analgesia during labor and occurrence of neonatal outcomes. Methods: Retrospective cohort study with medical records of 850 parturient. The exposure variable of interest was receiving pharmacological analgesia during labor and neonatal outcomes were: one- and five-minute Apgar, resuscitation maneuvers and referral of the newborn to Neonatal ICU. A logistic regression was carried out to obtain Odds Ratios and 95% confidence interval, with adjustment for confounding factors. Results: Among the women studied, 35% received analgesia and this use was associated with a greater chance of neonatal outcomes such as one-minute Apgar < 7 (p <0.0001), resuscitation maneuvers (p <0.001) and referral to the Neonatal ICU (p = 0.004), mostly were among low-risk pregnant women, even after adjustments. Conclusions: The use of pharmacological analgesia during labor is associated with one-minute Apgar < 7, resuscitation maneuvers and referral to the Neonatal ICU.

RESUMEN Objetivos: Investigar la asociación entre la analgesia en el trabajo de parto y la aparición de resultados neonatales. Métodos: Estudio de cohorte retrospectivo con datos de 850 parturientas. La exposición fue recibir analgesia farmacológica en el trabajo de parto, resultados: Apgar del primer y quinto minuto < 7, maniobras de reanimación y derivación a la UCIN. La regresión logística se utilizó para obtener el Odds Ratio (OR) y el intervalo de confianza del 95% (IC95%), ajustado por variables de confusión. Resultados: De las mujeres estudiadas, el 35% recibió analgesia y su uso se asoció con una mayor probabilidad de resultados como: Apgar en el primer minuto < 7 (p<0,0001), maniobras de reanimación (p<0,001) y derivación a la UCIN (p=0,004). Conclusiones: el uso de analgesia farmacológica durante el trabajo de parto se asoció con Apgar < 7 en el primer minuto, maniobras de reanimación y derivación a la UCIN.

RESUMO Objetivos: Investigar a associação entre analgesia no trabalho de parto e ocorrência de desfechos neonatais. Métodos: Estudo de coorte retrospectiva com dados de prontuários de 850 parturientes. A exposição foi receber analgesia farmacológica no trabalho de parto e os desfechos: Apgar do primeiro e quinto minuto < 7, manobras de reanimação e encaminhamento para Unidade de Terapia Intensiva Neonatal (UTI). Utilizou-se regressão logística para obter Odds Ratio (OR) e intervalo de 95% de confiança (IC95%), sendo ajustados por confundidores. Resultados: Das mulheres estudadas, 35% receberam analgesia e seu uso esteve associado a maior chance de desfechos, como: Apgar do primeiro minuto < 7 (p<0,0001), manobras de reanimação (p<0,001) e encaminhamento para UTI Neonatal (p=0,004), principalmente entre gestantes de risco habitual, mesmo após ajustes. Conclusões: O uso de analgesia farmacológica durante o trabalho de parto foi associado a Apgar do primeiro minuto < 7, manobras de reanimação e encaminhamento para UTI neonatal.

Obstetric analgesia in labor and its association with neonatal outcomes / Analgesia obstétrica en el trabajo de parto y su asociación con resultados neonatales / Analgesia obstétrica no trabalho de parto e sua associação com desfechos neonatais

ABSTRACT Objetives: To investigate the association between analgesia during labor and occurrence of neonatal outcomes. Methods: Retrospective cohort study with medical records of 850 parturient. The exposure variable of interest was receiving pharmacological analgesia during labor and neonatal outcomes were: one- and five-minute Apgar, resuscitation maneuvers and referral of the newborn to Neonatal ICU. A logistic regression was carried out to obtain Odds Ratios and 95% confidence interval, with adjustment for confounding factors. Results: Among the women studied, 35% received analgesia and this use was associated with a greater chance of neonatal outcomes such as one-minute Apgar < 7 (p <0.0001), resuscitation maneuvers (p <0.001) and referral to the Neonatal ICU (p = 0.004), mostly were among low-risk pregnant women, even after adjustments. Conclusions: The use of pharmacological analgesia during labor is associated with one-minute Apgar < 7, resuscitation maneuvers and referral to the Neonatal ICU.

RESUMEN Objetivos: Investigar la asociación entre la analgesia en el trabajo de parto y la aparición de resultados neonatales. Métodos: Estudio de cohorte retrospectivo con datos de 850 parturientas. La exposición fue recibir analgesia farmacológica en el trabajo de parto, resultados: Apgar del primer y quinto minuto < 7, maniobras de reanimación y derivación a la UCIN. La regresión logística se utilizó para obtener el Odds Ratio (OR) y el intervalo de confianza del 95% (IC95%), ajustado por variables de confusión. Resultados: De las mujeres estudiadas, el 35% recibió analgesia y su uso se asoció con una mayor probabilidad de resultados como: Apgar en el primer minuto < 7 (p<0,0001), maniobras de reanimación (p<0,001) y derivación a la UCIN (p=0,004). Conclusiones: el uso de analgesia farmacológica durante el trabajo de parto se asoció con Apgar < 7 en el primer minuto, maniobras de reanimación y derivación a la UCIN.

RESUMO Objetivos: Investigar a associação entre analgesia no trabalho de parto e ocorrência de desfechos neonatais. Métodos: Estudo de coorte retrospectiva com dados de prontuários de 850 parturientes. A exposição foi receber analgesia farmacológica no trabalho de parto e os desfechos: Apgar do primeiro e quinto minuto < 7, manobras de reanimação e encaminhamento para Unidade de Terapia Intensiva Neonatal (UTI). Utilizou-se regressão logística para obter Odds Ratio (OR) e intervalo de 95% de confiança (IC95%), sendo ajustados por confundidores. Resultados: Das mulheres estudadas, 35% receberam analgesia e seu uso esteve associado a maior chance de desfechos, como: Apgar do primeiro minuto < 7 (p<0,0001), manobras de reanimação (p<0,001) e encaminhamento para UTI Neonatal (p=0,004), principalmente entre gestantes de risco habitual, mesmo após ajustes. Conclusões: O uso de analgesia farmacológica durante o trabalho de parto foi associado a Apgar do primeiro minuto < 7, manobras de reanimação e encaminhamento para UTI neonatal.

Epidural Analgesia and Back Pain after Labor.

Background and Objectives: The aim of this survey was to assess the impact of epidural analgesia on post-partum back pain in post-partum women. Materials and Methods: The questionnaire was completed by post-partum women during the first days after delivery. Six months later, the women were surveyed again. The response rate was 70.66%, a total of 212 cases were included in the statistical analysis. The statistical analysis of the data was conducted using SPSS® Results. Seventy-nine (37.26%) women received epidural analgesia, 87 (41.04%) intravenous drugs, and 46 (21.7%) women gave birth without anesthesia. The prevalence of post-partum back pain was observed in 24 (30.38%) women of the epidural analgesia group, in 24 (27.58%) subjects of the intravenous anesthesia group, and in 14 (30.43%) women attributed to the group of subjects without anesthesia. The correlation between post-partum back pain and the type of anesthesia was not statistically significant (p = 0.907). Six months later, the prevalence of back pain was found in 31.65% of women belonging to the epidural analgesia group, in 28.74% of women with intravenous anesthesia, and in 23.91% of women without anesthesia. The correlation between complaints of back pain six months after delivery and the type of anesthesia applied was not statistically significant (p = 0.654). Conclusions. The labor pain relief technique did not trigger the increased risk of back pain in the early post-partum period and six months after delivery.

Progesterone and cAMP synergize to inhibit responsiveness of myometrial cells to pro-inflammatory/pro-labor stimuli.

Progesterone (P4) acting through the P4 receptor (PR) isoforms, PR-A and PR-B, promotes uterine quiescence for most of pregnancy, in part, by inhibiting the response of myometrial cells to pro-labor inflammatory stimuli. This anti-inflammatory effect is inhibited by phosphorylation of PR-A at serine-344 and -345 (pSer344/345-PRA). Activation of the cyclic adenosine monophosphate (cAMP) signaling pathway also promotes uterine quiescence and myometrial relaxation. This study examined the cross-talk between P4/PR and cAMP signaling to exert anti-inflammatory actions and control pSer344/345-PRA generation in myometrial cells. In the hTERT-HMA/B immortalized human myometrial cell line P4 inhibited responsiveness to interleukin (IL)-1ß and forskolin (increases cAMP) and 8-Br-cAMP increased this effect in a concentration-dependent and synergistic manner that was mediated by activation of protein kinase A (PKA). Forskolin also inhibited the generation of pSer344/345-PRA and expression of key contraction-associated genes. Generation of pSer344/345-PRA was catalyzed by stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Forskolin inhibited pSer344/345-PRA generation, in part, by increasing the expression of dual specificity protein phosphatase 1 (DUSP1), a phosphatase that inactivates mitogen-activated protein kinases (MAPKs) including SAPK/JNK. P4/PR and forskolin increased DUSP1 expression. The data suggest that P4/PR promotes uterine quiescence via cross-talk and synergy with cAMP/PKA signaling in myometrial cells that involves DUSP1-mediated inhibition of SAPK/JNK activation.

Evening primrose oil and labour, is it effective? A randomised clinical trial.

The purpose of the present study was to evaluate the effects of evening primrose oil (EvPO) on the duration of pregnancy and labour. The study was performed as a triple blind placebo controlled randomised clinical trial on nulliparous low-risk women with a certain gestational age of 40 weeks of pregnancy and a Bishop score of less than 4. In the case group (EvPO group), EvPO capsules were administered, 1000 mg, twice daily, for 7 days, and in the control group, placebo was administered similarly. The women of the two groups were followed up to delivery. In total, 80 women finished the study (40 in each group). The women of the two groups did not have significant differences according to age, BMI, Bishop Score at the beginning of the study, gestational age at entering the study, employment status and education level, the number of capsules used and duration of using medications. There was no significant difference between the two groups according to gestational age at delivery, need for induction or augmentation of labour, duration of different stages of labour, neonatal weight and Apgar scores, and the indications for hospital admission. Impact statement What is already known on this subject? Evening primrose oil has been used for the treatment of systemic disorders, which are accompanied with chronic inflammation such as atopic dermatitis, rheumatoid arthritis and psoriasis. Also, it has been proposed for some women's health conditions including breast pain (mastalgia), symptoms of premenstrual syndrome and menopausal symptoms, cervical ripening and induction or augmentation of labour. What do the results of this study add? Evening primrose oil does not have any impact on Bishop Score and the duration of different stages of labour. What are the implications of these findings for clinical practice and/or further research? According to the present study and the other performed studies, there is not enough evidence confirming effectiveness of Evening primrose oil for cervical ripening and duration of labour. It is suggested that pending further data its usage should be limited to experimental RCTs and its use in clinical practice should be prevented. Also, different routes of administration and different dosages should be investigated.

Castor oil as a natural alternative to labor induction: A retrospective descriptive study.

AIM: To describe birthing outcomes among women who consumed castor oil cocktail as part of a freestanding birth center labor induction protocol. METHODS: De-identified data from birth logs and electronic medical records were entered into SPSS Statistics 22.0 for analysis for all women who received the castor oil cocktail (n=323) to induce labor between January 2008 and May 2015 at a birth center in the United States. Descriptive statistics were analyzed for trends in safety and birthing outcomes. RESULTS: Of the women who utilized the castor oil cocktail to stimulate labor, 293 (90.7%) birthed vaginally at the birth center or hospital. The incidence of maternal adverse effects (e.g., nausea, vomiting, extreme diarrhea) was less than 7%, and adverse effects of any kind were reported in less than 15% of births. An independent sample t-test revealed that parous women were more likely to birth vaginally at the birth center after using the castor oil cocktail than their nulliparous counterparts (p<.010), while gestational age (p=.26), woman's age (p=.23), and body mass index (p=.28) were not significantly associated. CONCLUSIONS: Nearly 91% of women in the study who consumed the castor oil cocktail to induce labor were able to give birth vaginally with little to no maternal or fetal complications. Findings indicate further research is needed to compare the safety and effectiveness of natural labor induction methodologies, including castor oil, to commonly used labor induction techniques in a prospective study or clinical trial.

Effect of programmed intermittent epidural boluses and continuous epidural infusion on labor analgesia and obstetric outcomes: a randomized controlled trial.

PURPOSE: Continuous epidural infusion and programmed intermittent epidural boluses are analgesic techniques routinely used for pain relief in laboring women. We aimed to assess both techniques and compare them with respect to labor analgesia and obstetric outcomes. METHODS: After Institutional Review Board approval, 132 laboring women aged between 18 and 45 years were randomized to epidural analgesia of 10 mL of a mixture of 0.1% bupivacaine plus 2 µg/mL of fentanyl either by programmed intermittent boluses or continuous infusion (66 per group). Primary outcome was quality of analgesia. Secondary outcomes were duration of labor, total drug dose used, maternal satisfaction, sensory level, motor block level, presence of unilateral motor block, hemodynamics, side effects, mode of delivery, and newborn outcome. RESULTS: Patients in the programmed intermittent epidural boluses group received statistically less drug dose than those with continuous epidural infusion (24.9 vs 34.4 mL bupivacaine; P = 0.01). There was no difference between groups regarding pain control, characteristics of block, hemodynamics, side effects, and Apgar scores. CONCLUSIONS: Our study evidenced a lower anesthetic consumption in the programmed intermittent boluses group with similar labor analgesic control, and obstetric and newborn outcomes in both groups.

Endogenous hydrogen sulfide contributes to uterine quiescence during pregnancy.

Recent evidence suggests that uterine activation for labor is associated with inflammation within uterine tissues. Hydrogen sulfide (H2S) plays a critical role in inflammatory responses in various tissues. Our previous study has shown that human myometrium produces H2S via its generating enzymes cystathionine-γ-lyase (CSE) and cystathionine-ß-synthetase (CBS) during pregnancy. We therefore explored whether H2S plays a role in the maintenance of uterine quiescence during pregnancy. Human myometrial biopsies were obtained from pregnant women at term. Uterine smooth muscle cells (UMSCs) isolated from myometrial tissues were treated with various reagents including H2S. The protein expression of CSE, CBS and contraction-associated proteins (CAPs) including connexin 43, oxytocin receptor and prostaglandin F2α receptor determined by Western blot. The levels of cytokines were measured by ELISA. The results showed that CSE and CBS expression inversely correlated to the levels of CAPs and activated NF-κB in pregnant myometrial tissues. H2S inhibited the expression of CAPs, NF-κB activation and the production of interleukin (IL)-1ß, IL-6 and tumor necrosis factor α (TNFα) in cultured USMCs. IL-1ß treatment reversed H2S inhibition of CAPs. Knockdown of CSE and CBS prevented H2S suppression of inflammation. H2S modulation of inflammation is through KATP channels and phosphoinositide 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) signaling pathways. H2S activation of PI3K and ERK signaling is dependent on KATP channels. Our data suggest that H2S suppresses the expression of CAPs via inhibition of inflammation in myometrium. Endogenous H2S is one of the key factors in maintenance of uterine quiescence during pregnancy.

Does Preprocedural Ultrasound Increase the First-Pass Success Rate of Epidural Catheterization Before Cesarean Delivery? A Randomized Controlled Trial.

BACKGROUND: Preprocedural ultrasound may improve the efficacy and safety of epidural catheterization, especially in difficult cases. Most studies of ultrasound-assisted epidural catheterization in the obstetric population are dated and nonblinded with inconsistent designs. This double-blind, randomized controlled study aimed to compare the ultrasound-assisted with the conventional palpation techniques for epidural catheterization in parturients undergoing cesarean delivery. We hypothesized that the use of preprocedural ultrasound would increase the success rate of epidural catheterization at the first needle pass. METHODS: Eligible subjects were American Society of Anesthesiologists physical status II parturients with full-term singleton pregnancy undergoing elective cesarean delivery using double-interspace combined spinal-epidural anesthesia. Exclusion criteria were age <19 or >40 years, body mass index ≥35 kg/m, women presenting in labor or having any contraindication to neuraxial anesthesia, marked spinal deformity, previous spinal surgery, or impalpable anatomical landmarks. One hundred ten patients were randomly allocated into 2 equal groups (palpation and ultrasound groups). All procedures were performed by a single experienced anesthesiologist. Patients and investigators assessing the outcome data were blinded to group allocation. A systematic spinal ultrasound assessment and a sham procedure were performed in the ultrasound and palpation groups, respectively, before attempting epidural catheterization. The primary outcome was the rate of successful epidural catheterization at the first needle pass. Secondary outcomes were the rate of successful epidural catheterization at the first skin puncture, number of performed needle passes and skin punctures, duration of the epidural procedure, patient satisfaction from the procedure, and complications of the procedure (incidence of unintentional dural and vascular punctures, failed block, unilateral or patchy block, and backache). RESULTS: Data from 108 patients (55 patients in the palpation group and 53 patients in the ultrasound group) were analyzed. The rate of successful epidural catheterization at the first needle pass was 60% in the palpation group and 58.5% in the ultrasound group (95% confidence interval of the difference in proportions between groups is -18.5% to 21.6%; P > 0.99). There were no significant differences between the 2 groups in the success rate at the first skin puncture, the number of needle passes and skin punctures, or patient satisfaction. The median (range) duration of the epidural procedure was 185 (57-680) seconds in the ultrasound group and 215 (114-720) seconds in the palpation group (P = 0.036 with the Mann-Whitney U test and P = 0.083 with the Student t test with unequal variances). The overall rate of complications of the procedure was low in both groups. CONCLUSIONS: For experienced anesthesiologists, it remains unclear whether preprocedural ultrasound improves the epidural catheterization technique in parturients with palpable anatomical landmarks undergoing cesarean delivery.

Modeling hormonal and inflammatory contributions to preterm and term labor using uterine temporal transcriptomics.

BACKGROUND: Preterm birth is now recognized as the primary cause of infant mortality worldwide. Interplay between hormonal and inflammatory signaling in the uterus modulates the onset of contractions; however, the relative contribution of each remains unclear. In this study we aimed to characterize temporal transcriptome changes in the uterus preceding term labor and preterm labor (PTL) induced by progesterone withdrawal or inflammation in the mouse and compare these findings with human data. METHODS: Myometrium was collected at multiple time points during gestation and labor from three murine models of parturition: (1) term gestation; (2) PTL induced by RU486; and (3) PTL induced by lipopolysaccharide (LPS). RNA was extracted and cDNA libraries were prepared and sequenced using the Illumina HiSeq 2000 system. Resulting RNA-Seq data were analyzed using multivariate modeling approaches as well as pathway and causal network analyses and compared against human myometrial transcriptome data. RESULTS: We identified a core set of temporal myometrial gene changes associated with term labor and PTL in the mouse induced by either inflammation or progesterone withdrawal. Progesterone withdrawal initiated labor without inflammatory gene activation, yet LPS activation of uterine inflammation was sufficient to override the repressive effects of progesterone and induce a laboring phenotype. Comparison of human and mouse uterine transcriptomic datasets revealed that human labor more closely resembles inflammation-induced PTL in the mouse. CONCLUSIONS: Labor in the mouse can be achieved through inflammatory gene activation yet these changes are not a requisite for labor itself. Human labor more closely resembles LPS-induced PTL in the mouse, supporting an essential role for inflammatory mediators in human "functional progesterone withdrawal." This improved understanding of inflammatory and progesterone influence on the uterine transcriptome has important implications for the development of PTL prevention strategies.

Labor stimulation with oxytocin: effects on obstetrical and neonatal outcomes / Estimulação do parto com oxitocina: efeitos nos resultados obstétricos e neonatais / Estimulación del parto con oxitocina: efectos en los resultados obstétricos y neonatales

Abstract Objective: to evaluate the effects of labor stimulation with oxytocin on maternal and neonatal outcomes. Method: descriptive and analytical study with 338 women who gave birth at a tertiary hospital. Obstetric and neonatal variables were measured and compared in women submitted and non-submitted to stimulation with oxytocin. Statistics were performed using Chi-square test, Fisher exact test, Student t-test; and crude Odds Ratio with 95% confidence interval were calculated. A p < 0.05 was considered statistically significant. Results: stimulation with oxytocin increases the rates of cesarean sections, epidural anesthesia and intrapartum maternal fever in primiparous and multiparous women. It has also been associated with low pH values of umbilical cord blood and with a shorter duration of the first stage of labor in primiparous women. However, it did not affect the rates of 3rd and 4th degree perineal lacerations, episiotomies, advanced neonatal resuscitation, 5-minute Apgar scores and meconium. Conclusion: stimulation with oxytocin should not be used systematically, but only in specific cases. These findings provide further evidence to health professionals and midwives on the use of oxytocin during labor. Under normal conditions, women should be informed of the possible effects of labor stimulation with oxytocin.

Resumo Objetivo: avaliar os efeitos da estimulação do parto com oxitocina nos resultados maternos e neonatais. Método: estudo descritivo e analítico, com 338 mulheres que deram à luz em um hospital de nível terciário. Variáveis obstétricas e neonatais foram medidas e comparadas em mulheres com e sem estimulação com oxitocina. Estatísticas foram feitas utilizando-se o teste Qui-quadrado, teste exato de Fisher e o teste t-Student; e as Odds Ratio brutas com intervalo de confiança de 95% foram calculadas. Um valor de p < 0,05 foi considerado estatisticamente significativo. Resultados: a estimulação com oxitocina aumentou as taxas de cesarianas, anestesia peridural, febre materna intraparto em primíparas e multíparas. Ela também foi associada com baixos valores de pH do cordão umbilical e com uma menor duração da primeira fase do parto em primíparas. No entanto, ela não afetou as taxas de laceração perineal de terceiro e quarto graus, a episiotomia, a reanimação neonatal avançada, o teste de Apgar de 5 minutos e o mecônio. Conclusão: a estimulação com oxitocina não deveria ser utilizada de maneira sistemática, mas apenas em casos muito específicos. Estes resultados fornecem evidências adicionais aos profissionais de saúde e às parteiras sobre o uso de oxitocina durante o parto. Em condições normais, as mulheres deveriam ser informadas sobre os possíveis efeitos da estimulação com oxitocina.

Resumen Objetivo: valorar los efectos de la estimulación del parto con oxitocina en los resultados maternos y neonatales. Método: estudio descriptivo y analítico con 338 mujeres que parieron en un hospital de tercer nivel. Variables obstétricas y neonatales fueron medidas y comparadas en mujeres con y sin estimulación con oxitocina. Estadísticos Chi-cuadrado, test exacto de Fisher, test t-Student, Odd Ratio cruda y un intervalo de confianza del 95% fueron calculados. Un valor p < 0,05 se consideró estadísticamente significativo. Resultados: la estimulación con oxitocina incrementó el ratio de cesáreas, analgesia epidural, fiebre materna intraparto en primíparas y multíparas; también se relacionó con bajos valores de pH de cordón umbilical, y menor duración de la primera fase del parto en primíparas. Sin embargo no afectó la tasa de desgarros de 3-4 grado, episiotomías, reanimación neonatal avanzada, test de Apgar a los 5 minutos o meconio. Conclusión: la estimulación con oxitocina no debería emplearse de forma sistemática, sino solo en casos muy indicados. Estos hallazgos proporcionan mayor evidencia a los profesionales y matronas a cerca del uso de oxitocina durante el parto. En condiciones normales, las mujeres deberían estar informadas de los posibles efectos de la estimulación con oxitocina.

Hypoxia-induced force increase (HIFI) is a novel mechanism underlying the strengthening of labor contractions, produced by hypoxic stresses.

For successful birth, contractions need to become progressively stronger. The underlying mechanisms are unknown, however. We have found that a novel mechanism, hypoxia-induced force increase (HIFI), is switched on selectively, at term, and is essential to strengthening contractions. HIFI is initiated as contractions cyclically reduce blood flow and produce repeated hypoxic stresses, with associated metabolic and transcriptomic changes. The increases in contractility are a long-lasting, oxytocin-independent, intrinsic mechanism present only in the full-term pregnant uterus. HIFI is inhibited by adenosine receptor antagonism and blockade of cyclooxygenase-2 signaling, and partially reproduced by brief episodes of acidic (but not alkalotic) pH. HIFI explains how labor can progress despite paradoxical metabolic challenge, and provides a new mechanistic target for the 1 in 10 women suffering dysfunctional labor because of poor contractions.

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.

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.

The citrus flavone nobiletin reduces pro-inflammatory and pro-labour mediators in fetal membranes and myometrium: implications for preterm birth.

Spontaneous preterm birth is the leading cause of infant death and of neurological disabilities in survivors. A significant proportion of spontaneous preterm births are associated with infection. Infection activates inflammation which induces a cascade of events that leads to myometrial contractions and rupture of fetal membranes. In non-gestational tissues, the citrus flavone nobiletin has been shown to exert potent anti-inflammatory properties. Thus, in this study, we sought to determine the effect of nobiletin on pro-inflammatory mediators in human fetal membranes and myometrium. Human fetal membranes and myometrium were treated with bacterial endotoxin lipopolysaccharide (LPS) in the absence or presence of nobiletin. In addition, the effect of nobiletin in fetal membranes taken from spontaneous preterm deliveries with and without infection (i.e. histological chorioamnionitis) was also examined. In human fetal membranes and myometrium, nobiletin significantly decreased LPS-stimulated expression of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6 and IL-8) and MMP-9 expression and pro-MMP-9 secretion. Additionally, nobiletin significantly decreased COX-2 expression and subsequent prostaglandin (PG) E2 production. Notably, nobiletin was also able to reduce the expression and production of pro-inflammatory cytokines and MMP-9 in fetal membranes taken from women after spontaneous preterm birth. In conclusion, our study demonstrates that nobiletin can reduce infection-induced pro-inflammatory mediators in human fetal membranes and myometrium. These in vitro studies further support the increasing volume and quality of evidence that high fruit and vegetable intake in pregnancy is associated with a decreased risk of adverse pregnancy outcomes.

Rapid target allopurinol concentrations in the hypoxic fetus after maternal administration during labour.

OBJECTIVE: Perinatal hypoxia-induced free radical formation is an important cause of hypoxic-ischaemic encephalopathy and subsequent neurodevelopmental disabilities. Allopurinol reduces the formation of free radicals, which potentially limits hypoxia-induced brain damage. We investigated placental transfer and safety of allopurinol after maternal allopurinol treatment during labour to evaluate its potential role as a neuroprotective agent in suspected fetal hypoxia. DESIGN: We used data from a randomised, double-blind multicentre trial comparing maternal allopurinol versus placebo in case of imminent fetal hypoxia (NCT00189007). PATIENTS: We studied 58 women in labour at term, with suspected fetal hypoxia prompting immediate delivery, in the intervention arm of the study. SETTING: Delivery rooms of 11 Dutch hospitals. INTERVENTION: 500 mg allopurinol, intravenously to the mother, immediately prior to delivery. MAIN OUTCOME MEASURES: Drug disposition (maternal plasma concentrations, cord blood concentrations) and drug safety (maternal and fetal adverse events). RESULTS: Within 5 min after the end of maternal allopurinol infusion, target plasma concentrations of allopurinol of ≥2 mg/L were present in cord blood. Of all analysed cord blood samples, 95% (52/55) had a target allopurinol plasma concentration at the moment of delivery. No adverse events were observed in the neonates. Two mothers had a red and/or painful arm during infusion. CONCLUSIONS: A dose of 500 mg intravenous allopurinol rapidly crosses the placenta and provides target concentrations in 95% of the fetuses at the moment of delivery, which makes it potentially useful as a neuroprotective agent in perinatology with very little side effects. TRIAL REGISTRATION: The study is registered in the Dutch Trial Register (NTR1383) and the Clinical Trials protocol registration system (NCT00189007).