Uso de misoprostol em obstetrícia / Misoprostol use in obstetrics

PONTOS-CHAVE O misoprostol é um análogo da prostaglandina E1 (PGE1) que consta na Lista de Medicamentos Essenciais da Organização Mundial da Saúde (OMS) desde 2005 O Brasil possui uma das regulações mais restritivas do mundo relacionadas ao uso do misoprostol, estabelecendo que o misoprostol tem uso hospitalar exclusivo, com controle especial, e venda, compra e propaganda proibidas por lei Atualmente, o misoprostol é a droga de referência para tratamento medicamentoso nos casos de aborto induzido, tanto no primeiro trimestre gestacional quanto em idades gestacionais mais avançadas O misoprostol é uma medicação efetiva para o preparo cervical e indução do parto O misoprostol é um medicamento essencial para o manejo da hemorragia pós-parto

Effect of ofatumumab on pregnancy, parturition, and lactation in cynomolgus monkeys.

Knowledge of the impacts of the anti-CD20 monoclonal antibody ofatumumab on the developing immune system is limited. This study examined the effects of intravenous ofatumumab on pregnancy, parturition, and lactation, and on pre- and postnatal survival and development in cynomolgus monkeys, an established model for developmental toxicity assessment. Pregnant cynomolgus monkeys (n = 42) were randomized to receive vehicle only (control group; n = 14), low-dose ofatumumab (n = 14), or high-dose ofatumumab (n = 14). Survival, clinical outcomes, and clinical pathology investigations were evaluated regularly until lactation day (maternal animals) and postnatal day 180±1 (infants). Anatomic pathology was investigated in euthanized infants and unscheduled terminations of maternal animals and infants. Ofatumumab treatment was not associated with maternal toxicity or embryotoxicity and had no effect on the growth and development of offspring. As expected, B-cell depletion occurred in maternal animals and their offspring, with a reduced humoral immune response in infants of mothers on high-dose ofatumumab. Both effects were reversible. In the high-dose group, perinatal deaths of 3 infants were attributed to infections, potentially secondary to pharmacologically induced immunosuppression. The no-observed adverse-effect level for initial/maintenance ofatumumab doses was 100/20 mg, and 10/3 mg/kg for pharmacological effects in infant animals, which are associated with exposures significantly higher than those following therapeutic doses in humans. In this study with cynomolgus monkeys, ofatumumab treatment was not associated with maternal toxicity or embryotoxicity and had no effect on the growth and development of offspring.

Early-Pregnancy Dydrogesterone Supplementation Mimicking Luteal-Phase Support in ART Patients Did Not Provoke Major Reproductive Disorders in Pregnant Mice and Their Progeny.

Progestogens are frequently administered during early pregnancy to patients undergoing assisted reproductive techniques (ART) to overcome progesterone deficits following ART procedures. Orally administered dydrogesterone (DG) shows equal efficacy to other progestogens with a higher level of patient compliance. However, potential harmful effects of DG on critical pregnancy processes and on the health of the progeny are not yet completely ruled out. We treated pregnant mice with DG in the mode, duration, and doses comparable to ART patients. Subsequently, we studied DG effects on embryo implantation, placental and fetal growth, fetal-maternal circulation, fetal survival, and the uterine immune status. After birth of in utero DG-exposed progeny, we assessed their sex ratios, weight gain, and reproductive performance. Early-pregnancy DG administration did not interfere with placental and fetal development, fetal-maternal circulation, or fetal survival, and provoked only minor changes in the uterine immune compartment. DG-exposed offspring grew normally, were fertile, and showed no reproductive abnormalities with the exception of an altered spermiogram in male progeny. Notably, DG shifted the sex ratio in favor of female progeny. Even though our data may be reassuring for the use of DG in ART patients, the detrimental effects on spermatogenesis in mice warrants further investigations and may be a reason for caution for routine DG supplementation in early pregnancy.

The Role of TNF-α and Anti-TNF-α Agents during Preconception, Pregnancy, and Breastfeeding.

Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.

Modulation of IL10 and Its Receptor Subunits in Normal and Progesterone-Prolonged Gestation in the Mouse.

These experiments aimed to understand the relationship between interleukin 10 (IL10), the IL10 receptor subunits, and progesterone (P4) at the time of parturition. We hypothesized that there is a biologic connection between IL10 and P4, supporting an immunomodulatory mechanism for the onset of labor. Using samples from control and P4-treated pregnant mice, we assessed the production of IL10 and its receptor subunits (IL10Rα and IL10Rß) in gestational tissues. After preliminary studies, P4-treated pregnant mice were compared with controls to assess for differences in IL10 and IL10 receptor subunit expression throughout gestation. To investigate the contribution of the P4 receptor at the onset of labor, we performed timed studies on pregnant mice after treatment with RU486. Samples collected included placentas, placentation sites, and maternal livers. IL10, IL10Rα, and IL10Rß levels were measured in homogenized tissue using ELISA assays; the cytokine results were normalized for homogenate protein concentration. Control mice delivered on gd 18-19, and P4 treatment prevented parturition to beyond gd 20, as expected. In treated mice, P4 not only prevented the anticipated nadir of IL10 at term, but maintained elevated levels of IL10 through gd 20 (p < 0.05). P4 also reversed the anticipated decrease of the IL10Rα, which was increased in P4-treated mice (p < 0.05). Treatment with RU486 did not modulate the expression of IL10 or IL10Rα, but showed a significant decrease in the level of IL10Rß (p < 0.05). Progesterone functions at least in part through the IL10 signaling pathway to prolong gestation.

CCR2 mediates the adverse effects of LPS in the pregnant mouse.

In our earlier work, we found that intrauterine (i.u.) and intraperitoneal (i.p.) injection of LPS (10-µg serotype 0111:B4) induced preterm labor (PTL) with high pup mortality, marked systemic inflammatory response and hypotension. Here, we used both i.u. and i.p. LPS models in pregnant wild-type (wt) and CCR2 knockout (CCR2-/-) mice on E16 to investigate the role played by the CCL2/CCR2 system in the response to LPS. Basally, lower numbers of monocytes and macrophages and higher numbers of neutrophils were found in the myometrium, placenta, and blood of CCR2-/- vs. wt mice. After i.u. LPS, parturition occurred at 14 h in both groups of mice. At 7 h post-injection, 70% of wt pups were dead vs. 10% of CCR2-/- pups, but at delivery 100% of wt and 90% of CCR2-/- pups were dead. Myometrial and placental monocytes and macrophages were generally lower in CCR2-/- mice, but this was less consistent in the circulation, lung, and liver. At 7 h post-LPS, myometrial ERK activation was greater and JNK and p65 lower and the mRNA levels of chemokines were higher and of inflammatory cytokines lower in CCR2-/- vs. wt mice. Pup brain and placental inflammation were similar. Using the IP LPS model, we found that all measures of arterial pressure increased in CCR2-/- but declined in wt mice. These data suggest that the CCL2/CCR2 system plays a critical role in the cardiovascular response to LPS and contributes to pup death but does not influence the onset of inflammation-induced PTL.

The impact of perinatal nicotine exposure on fetal lung development and subsequent respiratory morbidity.

Maternal smoking during pregnancy remains as a significant public health crisis as it did decades ago. Although its prevalence is decreasing in high-income countries, it has worsened globally, along with a concerning emergence of electronic-cigarette usage within the last two decades. Extensive epidemiologic and experimental evidence exists from both human and animal studies, demonstrating the detrimental long-term pulmonary outcomes in the offspring of mothers who smoke during pregnancy. Even secondhand and thirdhand smoke exposure to the developing lung might be as or even more harmful than firsthand smoke exposure. Furthermore, these effects are not limited only to the exposed progeny, but can also be transmitted transgenerationally. There is compelling evidence to support that the majority of the effects of perinatal smoke exposure on the developing lung, including the transgenerational transmission of asthma, is mediated by nicotine. Nicotine exposure induces cell-specific molecular changes in lungs, which offers a unique opportunity to prevent, halt, and/or reverse the resultant damage through targeted molecular interventions. Experimentally, the proposed interventions, such as administration of peroxisome proliferator-activated receptor gamma (PPARγ) agonists can not only block but also potentially reverse the perinatal nicotine exposure-induced respiratory morbidity in the exposed offspring. However, the development of a safe and effective intervention is still many years away. In the meantime, electropuncture at specific acupoints appears to be emerging as a more practical and safe physiologic approach to block the harmful pulmonary consequences of perinatal nicotine exposure.

Perinatal iron deficiency combined with a high salt diet in adulthood causes sex-dependent vascular dysfunction in rats.

KEY POINTS: Perinatal iron deficiency causes changes in offspring mesenteric artery function in adulthood, particularly in males, which can be exacerbated by chronic intake of a high salt diet. Perinatal iron deficient male offspring exhibit enhanced conversion of big endothelin-1 to active endothelin-1, coinciding with decreased nitric oxide levels. Perinatal iron deficient male offspring have reduced nitric oxide-mediated endothelial-dependent vasodilatation coincident with increased vascular superoxide levels following consumption of a high salt diet. Perinatal iron deficiency has no apparent effects on vascular function in female offspring, even when fed a high salt diet. These results help us better understand underlying vascular mechanisms contributing to increased cardiovascular risk from perinatal stressors such as iron deficiency. ABSTRACT: Pre- and immediate postnatal stressors, such as iron deficiency, can alter developmental trajectories and predispose offspring to long-term cardiovascular dysfunction. Here, we investigated the impact of perinatal iron deficiency on vascular function in the adult offspring, and whether these long-term effects were exacerbated by prolonged consumption of a high salt diet in adulthood. Female Sprague Dawley rats were fed either an iron-restricted or -replete diet prior to and throughout pregnancy. Six weeks prior to experimentation at 6 months of age, adult offspring were fed either a normal or high salt diet. Mesenteric artery responses to vasodilators and vasoconstrictors were assessed ex vivo by wire myography. Male perinatal iron deficient offspring exhibited decreased reliance on nitric oxide with methacholine-induced vasodilatation (interaction P = 0.03), coincident with increased superoxide levels when fed the high salt diet (P = 0.01). Male perinatal iron deficient offspring exhibit enhanced big endothelin-1 conversion to active endothelin-1 (P = 0.02) concomitant with decreased nitric oxide levels (P = 0.005). Female offspring vascular function was unaffected by perinatal iron deficiency, albeit the high salt diet was associated with impaired vasodilation and decreased nitric oxide production (P = 0.02), particularly in the perinatal iron deficient offspring. These findings implicate vascular dysfunction in the sex-specific programming of cardiovascular dysfunction in the offspring by perinatal iron deficiency.

The impact of ecbolic therapy in the early postpartum period on uterine involution and reproductive health in dairy cows.

Postpartum uterine disease due to poor uterine involution continues to be a significant factor that contributes to poor reproductive efficiency in dairy cattle. Therapy that increases the frequency, duration and strength of uterine contractions in the postpartum period might enhance uterine involution, resulting in improved reproductive performance. The objective of this clinical trial was to study the effect of two uterine ecbolic therapies, oxytocin and prostaglandinF2α on uterine involution, postpartum endometritis, and reproductive performance. A randomized double-blinded clinical trial was conducted in 118 dairy cows from two research herds that had normal parturition and expulsion of the fetal membranes. Within 24 hr after calving, cows were randomly assigned to receive intramuscular injections twice a day of 50 IU of oxytocin, or 25 mg of dinoprost (PGF2α) or saline (control) for 7 days. Cows were monitored from day 3 to day 63 ± 3 days postpartum by transrectal palpation of the uterus, vaginoscopy, Metricheck® examination and by endometrial cytology. Blood samples were collected for measurement of progesterone in weeks 3 (21 ± 3 days), 5 (35 ± 3 days), 7 (49 ± 3 days), and 9 (63 ± 3 days) postpartum. Herd breeding records were obtained to determine reproductive performance in all cows. Neither oxytocin nor prostaglandin F2α therapy during the first week postpartum had any significant effect on the rate of uterine involution, prevalence of endometritis or reproductive performance, compared to untreated controls. Ecbolic drugs, as used here, are not recommended for use in clinical practice to improve involution or reproductive tract health in normal cows.

Serum and tissue pregnanes and pregnenes after dexamethasone treatment of cows in late gestation.

Dexamethasone (DEX) initiates parturition by inducing progesterone withdrawal and affecting placental steroidogenesis, but the effects of DEX in fetal and maternal tissue steroid synthetic capacity remains poorly investigated. Blood was collected from cows at 270 days of gestation before DEX or saline (SAL) treatment, and blood and tissues were collected at slaughter 38 h later. Steroid concentrations were determined by liquid chromatography tandem mass spectrometry to detect multiple steroids including 5α-reduced pregnane metabolites of progesterone. The activities of 3ß-hydroxysteroid dehydrogenase (3ßHSD) in cotyledonary and luteal microsomes and mitochondria and cotyledonary microsomal 5α-reductase were assessed. Quantitative PCR was used to further assess transcripts encoding enzymes and factors supporting steroidogenesis in cotyledonary and luteal tissues. Serum progesterone, pregnenolone, 5α-dihydroprogesterone (DHP) and allopregnanolone (3αDHP) concentrations (all <5 ng/mL before treatment) decreased in cows after DEX. However, the 20α-hydroxylated metabolite of DHP, 20αDHP, was higher before treatment (≈100 ng/mL) than at slaughter but not affected by DEX. Serum, cotyledonary and luteal progesterone was lower in DEX- than SAL-treated cows. Progesterone was >100-fold higher in luteal than cotyledonary tissues, and serum and luteal concentrations were highly correlated in DEX-treated cows. 3ßHSD activity was >5-fold higher in luteal than cotyledonary tissue, microsomes had more 3ßHSD than mitochondria in luteal tissue but equal in cotyledonary sub-cellular fractions. DEX did not affect either luteal or cotyledonary 3ßHSD activity but luteal steroidogenic enzyme transcripts were lower in DEX-treated cows. DEX induced functional luteal regression and progesterone withdrawal before any changes in placental pregnene/pregnane synthesis and/or metabolism were detectable.

Effects of macrophage depletion on characteristics of cervix remodeling and pregnancy in CD11b-dtr mice.

To test the hypothesis that macrophages are essential for remodeling the cervix in preparation for birth, pregnant homozygous CD11b-dtr mice were injected with diphtheria toxin (DT) on days 14 and 16 postbreeding. On day 15 postbreeding, macrophages (F4/80+) were depleted in cervix and kidney, but not in liver, ovary, or other non-reproductive tissues in DT-compared to saline-treated dtr mice or wild-type controls given DT or saline. Within 24 h of DT-treatment, the density of cell nuclei and macrophages declined in cervix stroma in dtr mice versus controls, but birefringence of collagen, as an indication of extracellular cross-linked structure, remained unchanged. Only in the cervix of DT-treated dtr mice was an apoptotic morphology evident in macrophages. DT-treatment did not alter the sparse presence or morphology of neutrophils. By day 18 postbreeding, macrophages repopulated the cervix in DT-treated dtr mice so that the numbers were comparable to that in controls. However, at term, evidence of fetal mortality without cervix ripening occurred in most dtr mice given DT-a possible consequence of treatment effects on placental function. These findings suggest that CD11b+ F4/80+ macrophages are important to sustain pregnancy and are required for processes that remodel the cervix in preparation for parturition.

Daily gentamicin using ideal body weight demonstrates lower risk of postpartum endometritis and increased chance of successful outcome compared with traditional 8-hour dosing for the treatment of intrapartum chorioamnionitis.

Background: Clinical chorioamnionitis complicates approximately 1-4% of pregnancies overall. Although universal agreement does not exist regarding the antibiotic regimen of choice, most studies have evaluated intravenous ampicillin dosed at 2 g every 6 hours plus gentamicin dosed every 8 hours. Only three studies have examined daily gentamicin for the treatment of intrapartum chorioamnionitis and thus is insufficiently investigated. Objective: This study seeks to determine whether daily dosing of gentamicin using ideal body weight for the treatment of intrapartum chorioamnionitis is more or equivalently efficacious when compared to traditional 8-hour dosing regimens. Materials and methods: We conducted a retrospective cohort study and reviewed charts on all women receiving treatment for intrapartum chorioamnionitis, which included intravenous gentamicin daily dosing calculated using 5 mg/kg ideal body weight or receiving traditional every 8 hours dosing of gentamicin at two large academic centers. Our primary outcomes were resolution of infection following delivery without the development of maternal endometritis and/or neonatal sepsis. Baseline characteristics were compared between dosing groups using Welch two-sample t-tests for continuous variables, uncorrected X2 test and exact binomial 95% confidence intervals. We calculated the risk ratios of each outcome in the ideal versus traditional dosing groups using modified Poisson regression, both crude and adjusted. Adjusted models were controlled for variables determined to be potential confounders, which included BMI, diabetes mellitus, gestational blood pressure >140/90, group ß-Streptococcus status, race, advanced maternal age (>34 y), and parity. Results: The study included 500 patients with 255 patients receiving daily dosing of gentamicin and 245 receiving traditional dosing of gentamicin. Of the patients receiving daily gentamicin compared to traditional dosing, 95.7% (95% CI 94.9-96.6%) achieved the primary outcome versus 92% (95% CI 90.8 - 93.2%), 2.4% (95% CI 1.8-3%) developed endometritis versus 5.6% (4.5-6.7%), 1.6% (95% CI 1.1-2.1%) delivered neonates with sepsis versus 3.3% (CI 2.5-4.1%), and 36.9% required cesarean delivery versus 41.4%. In crude analysis, compared to traditional dosing, IDW daily dosing was associated with a lower risk of postpartum endometritis (RR 0.42, 95% CI 0.16-1.10, p = .032). After adjusting for BMI, diabetes mellitus, gestational blood pressure >140/90, group ß-Streptococcus status, race, advanced maternal age (>34 y), and parity, the IDW daily dosing group had a 5% greater chance of successful outcome (RR 1.05, 95% CI 1.00-1.10, p = .046) and a 64% lower risk of endometritis (RR 0.35, 95% CI 0.15-0.83, p = .017). Conclusion: Daily dosing of gentamicin using ideal body weight is associated with a lower risk of postpartum endometritis and high chance of a successful outcome in the treatment of intrapartum chorioamnionitis compared with traditional 8-hour dosing in our ethnically diverse, urban population and thus may be considered a superior option to every 8 hours dosing regimens.

Perioperative noninvasive cardiac output monitoring in parturients with singleton and twin pregnancies undergoing cesarean section under spinal anesthesia with prophylactic phenylephrine drip: a prospective observational cohort study.

Purpose: Spinal anesthesia is considered the gold standard anesthetic technique for cesarean deliveries (CDs) but is associated with a high rate of hypotension. The recent international consensus recommends continuous prophylactic phenylephrine infusion (PPI) administered throughout CD to prevent hypotension. However, little information is available on the hemodynamic profiles of women with twin pregnancies as compared to singleton pregnancies perioperatively. Therefore, in this study, we aim to compare maternal hemodynamic changes both intraoperatively and postoperatively with the use of the NICAS bioimpendence monitor in healthy singleton versus twin parturients undergoing CD deliveries with spinal anesthesia with PPI. Materials and methods: After IRB approval and signed informed consent, healthy term women with either twin or singleton pregnancies undergoing spinal anesthesia for uncomplicated CD were enrolled. The following data were collected - cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), and total peripheral resistance (TPR). Measurements were measured at five time points: (1) before arrival in OR, (2) after spinal anesthesia with PPI, (3) after beginning of oxytocin infusion, (4) in post anesthesia care room, (5) 24 hours postoperatively, and (6) 48 hours postoperatively. All parturients received standardized spinal solution consisting of 12 mg hyperbaric bupivacaine, 20 µg fentanyl and 100-µg preservative-free morphine. PPI administered was titrated to preserve blood pressure to 20% of baseline blood pressure and stopped at the end of surgery. Oxytocin was administered as a continuous infusion (20-units/1000 cm3 Ringer's lactate) at a rate of 100 cm3/h. Results: One hundred and thirty seven parturients with singleton pregnancies and 27 parturients with twin pregnancies completed the study. There were no significant differences between groups in age or BMI. Intraoperatively, there was no difference in any hemodynamic parameter. However, postoperatively at all three times women with twin pregnancies had higher MAP, lower CO and higher TPR compared with parturients with singleton pregnancies. Conclusions: There were significant hemodynamic changes postoperatively but not intraoperatively in parturients with twin pregnancies compared to women with singleton pregnancies. These changes need to be further investigated.

Association between non-invasive nursing care technologies during childbirth and neonatal vitality: a cross-sectional study / Asociación entre tecnologías no-invasivas de cuidado en el parto y la vitalidad neonatal: estudio transversal / Associação entre tecnologias não invasivas de cuidado no parto e vitalidade do recém-nascido: estudo transversal

Abstract Objective: to compare the use of non-invasive midwifery care technologies (TNICEO) with the use of traditional care model practices, having as parameters the presence of meconium in the amniotic fluid and its repercussion on the newborn's vitality. Method: a cross-sectional study with secondary data of 10,219 parturients who delivered by midwives between September 2004 and October 2016. Logistic regression was used to assess Apgar> 8 Odds Ratio in exposure to noninvasive midwifery care technologies when compared to traditional care. Results: there were higher percentages of light amniotic fluid and neonates with good vitality in parturients who used only TNICEO compared with those exposed only to traditional care. Conclusion: nurse midwives' provision of TNICEO and its use by women are efficient strategies to reduce unfavorable neonatal outcomes. Implications of practice: investments in the performance of these experts is important, as their know-how to make them not medicalized through TNICEO confirms a process of humanized, safe and quality care that meets official recommendations and contributes to the change in the care model.

Resumen Objetivo: comparar el uso de tecnologías no invasivas de cuidado de enfermería obstétrica (TNICEO) con el uso de prácticas del modelo tradicional de cuidado, con la presencia de meconio en el líquido amniótico y su repercusión en la vitalidad del recién nacido. Método: estudio transversal, com datos secundários, de 10.219 parturientas, asistidas por enfermeras obstétricas entre septiembre de 2004 y octubre de 2016. Se utilizó la regresión logística para evaluar la probabilidad de Apgar> 8 en la exposición a TNICEO en comparación con la atención tradicional. Resultados: se observaron porcentajes más altos de líquido amniótico claro y recién nacido con buena vitalidad en las parturientas que solo usaron TNICEO en comparación con las expuestas solo a la atención tradicional. Conclusión: la oferta de TNICEO por las enfermeras obstétricas y su uso por las mujeres es una estrategia eficaz para reducir los resultados neonatales desfavorables. Implicaciones para la práctica: enfatizase la importancia de los investimentos en el desempeño de estos especialistas, ya que su experiencia, a través del TNICEO, constituye un proceso de atención humanizada, segura y de alta calidad, que cumple con las recomendaciones oficiales y contribuye para cambiar el modelo de atención.

Resumo Objetivo: comparar o uso de tecnologias não invasivas de cuidado de enfermagem obstétrica (TNICEO) com o emprego de práticas do modelo de assistência tradicional, tendo como parâmetros a presença de mecônio no líquido amniótico e sua repercussão sobre a vitalidade do recém-nascido. Método: estudo transversal, com dados secundários, de 10.219 parturientes que tiveram parto acompanhado por enfermeiras obstétricas entre setembro/2004 e outubro/2016. Utilizou-se a regressão logística para avaliar a chance de Apgar >8 na exposição às tecnologias não invasivas de cuidado de enfermagem obstétrica quando comparada à assistência tradicional. Resultados: constataram-se maiores percentuais de líquido amniótico claro e neonatos com boa vitalidade nas parturientes que utilizaram somente TNICEO, em comparação com aquelas expostas, apenas, à assistência tradicional. Conclusão: o oferecimento das TNICEO pelas enfermeiras obstétricas e o seu uso pelas mulheres se configuram como estratégias eficientes para reduzir desfechos neonatais desfavoráveis. Implicações para a prática: destaca-se a importância de investimentos na atuação dessas especialistas, pois seu saber fazer desmedicalizado, por meio das TNICEO, confirma um processo de cuidar humanizado, seguro e de qualidade, que atende às recomendações oficiais e contribui para a mudança do modelo assistencial.

ED50 and ED95 of intrathecal hyperbaric ropivacaine for parturients undergoing cesarean section with prophylactic infusion of phenylephrine: A Prospective dose-finding Study.

BACKGROUND: Studies have reported that the ED50 of intrathecal ropivacaine was increased when using prophylactic infusion of phenylephrine to prevent spinal-induced hypotension. However, ED95 is more meaningful to clinical practice than ED50. Therefore, we conducted this study to determine the 95% effective dose (ED95) of intrathecal hyperbaric ropivacaine for cesarean section in parturients receiving prophylactic infusion of phenylephrine to prevent spinal-induced hypotension. METHODS: A hundred of healthy parturients undergoing elective cesarean section under combined spinal-epidural anesthesia (CSEA) were enrolled in this randomized, double-blinded, dose-ranging study. Patients were randomly assigned to receive 7, 9, 11, 13 or 15 mg intrathecal hyperbaric ropivacaine respectively. The prophylactic phenylephrine infusion (50 µg/min) was initiated immediately at the same time of spinal injection. Successful spinal anesthesia was defined as a T5 sensory level achieved within 10 min after intrathecal drug administration and no epidural supplement was required during the surgery. The ED95 was calculated with Probit analysis. RESULTS: The ED95 of intrathecal ropivacaine with 5 µg sufentanil for successful anesthesia was 15.2 mg (95%CI, 13.5-18.8 mg), when receiving prophylactic infusion of phenylephrine. CONCLUSION: Under the conditions of the present study, the ED95 of intrathecal hyperbaric ropivacaine for successful spinal anesthesia for cesarean section in healthy parturient receiving prophylactic infusion of phenylephrine was 15.2 mg.

Progesterone, the maternal immune system and the onset of parturition in the mouse.

The role of progesterone (P4) in the regulation of the local (uterine) and systemic innate immune system, myometrial expression of connexin 43 (Cx-43) and cyclooxygenase 2 (COX-2), and the onset of parturition was examined in (i) naïve mice delivering at term; (ii) E16 mice treated with RU486 (P4-antagonist) to induce preterm parturition; and (iii) in mice treated with P4 to prevent term parturition. In naïve mice, myometrial neutrophil and monocyte numbers peaked at E18 and declined with the onset of parturition. In contrast, circulating monocytes did not change and although neutrophils were increased with pregnancy, they did not change across gestation. The myometrial mRNA and protein levels of most chemokines/cytokines, Cx-43, and COX-2 increased with, but not before, parturition. With RU486-induced parturition, myometrial and systemic neutrophil numbers increased before and myometrial monocyte numbers increased with parturition only. Myometrial chemokine/cytokine mRNA abundance increased with parturition, but protein levels peaked earlier at between 4.5 and 9 h post-RU486. Cx-43, but not COX-2, mRNA expression and protein levels increased prior to the onset of parturition. In mice treated with P4, the gestation-linked increase in myometrial monocyte, but not neutrophil, numbers was prevented, and expression of Cx-43 and COX-2 was reduced. On E20 of P4 supplementation, myometrial chemokine/cytokine and leukocyte numbers, but not Cx-43 and COX-2 expression, increased. These data show that during pregnancy P4 controls myometrial monocyte infiltration, cytokine and prolabor factor synthesis via mRNA-dependent and independent mechanisms and, with prolonged P4 supplementation, P4 action is repressed resulting in increased myometrial inflammation.

A diet supplemented with n-3 polyunsaturated fatty acids influences the metabomscic and endocrine response of rabbit does and their offspring.

The aim of the present study was to evaluate the productive, endocrine, and metabomscic responses as well as oxidative stress of rabbit does and their offspring when fed a diet supplemented with -3 PUFA during their first productive cycle. To this aim, a total of 105 rabbit does were fed ad mscibitum from d 60 to 172 of age 2 isoenergetic and isoproteic diets differing in fatty acid composition. The control diet ( = 52 does) contained 45.9 g/kg of -3 of the total fatty acids and the enriched diet ( = 53 does) contained 149.2 g/kg of -3 of the total fatty acids. Both experimental groups had similar feed intake during rearing, pregnancy, and lactation. The enrichment of diet had no effect on ultrasonographic assessment of does on d 9 and 16 of pregnancy, with an embryonic vesicle number and fetus and placenta size similar between groups ( > 0.05). Even though there were no major effects ( > 0.05) on fertimscity, duration of gestation, and number born amscive and stillborn kits at parturition, mscive kits from enriched does were longer (71.6 ± 2.42 vs. 79.5 ± 2.13 mm; < 0.05) and tended to be heavier (42.5 ± 3.94 vs. 50.8 ± 3.47 g; = 0.07) than those from control does ( < 0.05). The 2 groups had similar milk production and mortamscity values during lactation; consequently, there were no differences between diets in ADG, mscitter weight, and number of weaned kits ( > 0.05). In enriched does, higher plasma leptin and estradiol concentrations than in control does ( < 0.05) were observed. In addition, enriched females also had lower total and high-density mscipoprotein cholesterol (HDL-c) than control females during lactation ( < 0.05). Regarding offspring, the enrichment of diet with PUFA caused a hypermscipidemic status (greater values of plasma triglycerides, total cholesterol, and HDL-c; < 0.05) at 1 d postpartum (dpp), compared with the control group, that disappeared at 32 dpp. Supplemented does before parturition and their offspring at 1 dpp had greater oxidative stress than those in the control group. In conclusion, an increase of -3 PUFA concentration in the diet of rabbit does and, consequently, of their offspring during a productive cycle alters their mscipid profile and the indicators of oxidative stress, without major endocrine modifications or improvements in the productive variables.

Effects of SA237, a humanized anti-interleukin-6 receptor monoclonal antibody, on pre- and postnatal development in cynomolgus monkey.

BACKGROUND: SA237 is a humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody in which the constant and variable regions have been engineered for a longer plasma half-life. According to literature, blocking of IL-6 related functions could have an influence on pregnancy sustainment, development of the immune system, and brain growth. METHODS: SA237 effects on dams, embryo-fetal development, parturition and postnatal development were investigated in an enhanced pre- and postnatal development study, in which SA237 was subcutaneously administered to pregnant cynomolgus monkeys at dose levels of 2 or 50 mg/kg once weekly from gestation day 20 until parturition. Infant development, including immune function and learning ability tests, was comprehensively assessed at multiple examinations until approximately 10 months after birth. RESULTS: SA237 plasma concentrations were almost equivalent between dams and their infants and dropped throughout the postnatal period, pharmacologically relevant exposure was maintained for 147 days after birth at 50 mg/kg. Because the binding of SA237 to IL-6R inhibited IL-6R-mediated clearance of IL-6, serum IL-6 increased in dams and infants. However, there were no SA237-related adverse effects on dams, embryos, fetuses, or infants. SA237 pharmacological effects contributed to the suppression of plasma cell differentiation and antibody production by inhibiting IL-6 signaling, and T cell-dependent antibody reaction was minimally suppressed in infants, but physiological immunoglobulin class switching and general antibody production against a T cell-dependent antigen were maintained. CONCLUSION: The exposure to SA237 did not adversely affect dams, embryo-fetal development, parturition, and postnatal development, including immune function and neuronal development. Birth Defects Research 109:843-856, 2017. © 2017 Wiley Periodicals, Inc.

Interleukin (IL)-1 in rat parturition: IL-1 receptors 1 and 2 and accessory proteins abundance in pregnant rat uterus at term - regulation by progesterone.

The role of interleukin-1 (IL-1), a pro-inflammatory cytokine, in parturition is typically noted by changes in its concentrations. Studying the expression of its receptor family, IL-1 receptor (IL-1R) 1, IL-1R2, IL-1R accessory protein (IL-1RAcP), and its predominantly brain isoform, IL-1RAcPb, during late gestation in the uterus in the Long-Evans rat is another. We assessed changes in their mRNA and protein relative abundance in the uterus and compared IL-1RAcP and IL-1RAcPb mRNA abundance in uterus, cervix, ovaries, placenta, and whole blood of Long-Evans rats during late gestation or in RU486 and progesterone-treated dams using quantitative real-time PCR and western immunoblotting. IL-1R1, IL-1RAcP, and IL-1RAcPb mRNA abundance significantly increased in the uterus at delivery whereas IL-1R2 mRNA abundance significantly decreased. IL-1R1 protein increased at term and IL-1R2 protein decreased at term compared to nonpregnant uteri. IL1-RAcPb mRNA abundance was less than IL-1RAcP, but in the lower uterine segment it was the highest of all tissues examined. RU486 stimulated preterm delivery and an increase in IL-1R1 mRNA abundance whereas progesterone administration extended pregnancy and suppressed the increase in IL-1R1. These data suggest that changes in uterine sensitivity to IL-1 occur during late gestation and suggest another level of regulation for the control of delivery. The roles for IL-1RAcP and IL-1RAcPb need to be determined, but may relate to different intracellular signaling pathways.