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

The selective progesterone receptor modulator-promegestone-delays term parturition and prevents systemic inflammation-mediated preterm birth in mice.

BACKGROUND: Progesterone, acting via its nuclear receptors called progesterone receptors, promotes myometrial relaxation during pregnancy, and suspension of this activity triggers labor. We previously found that 20α-hydroxysteroid dehydrogenase causes a local withdrawal of progesterone in the term and preterm myometrium by converting the progesterone into an inactive form before it accesses the progesterone receptors. OBJECTIVE: We hypothesized that a selective progesterone receptor modulator called promegestone, which is not metabolized by 20α-hydroxysteroid dehydrogenase, would sustain progesterone receptor signaling and prevent/delay term labor and preterm labor in mice. STUDY DESIGN: In the term labor mouse model, promegestone (0.2 mg/dam) or a vehicle were administered subcutaneously in timed-pregnant CD-1 mice at gestational days 15, 16, and 17 (term gestational days, 19.5). In the inflammation preterm labor model, pregnant mice received promegestone or a vehicle on gestational days 15, 16, and 17, which was 24 hours before, immediately before, and 24 hours after systemic bacterial endotoxin (50 µg intraperitoneal; lipopolysaccharide group) or vehicle (saline) administration. The maternal and fetal tissues were collected on gestational day 16 6 hours after lipopolysaccharide±promegestone injection and at term gestational day 18.75. The protein levels of 10 cytokines were measured by multiplex immunoassay in maternal plasma and amniotic fluid. Myometrial, decidual, and placental messenger RNA levels of multiple cytokines and procontractile proteins were evaluated by real-time polymerase chain reaction and confirmed by immunoblotting. RESULTS: Promegestone prevented term labor and maintained mice pregnancy postterm >24 hours. The litter size and fetal weights were not different from the controls. Promegestone prevented systemic bacterial-endotoxin-induced preterm labor in 100% of the mice, blocked uterine contractions, significantly inhibited all systemic inflammation-induced myometrial cytokines, and partially inhibited decidual and placental inflammation. Promegestone did not prevent bacterial-endotoxin-induced fetal toxicity. CONCLUSION: Promegestone a selective progesterone receptor modulator that binds progesterone receptors with high affinity and is not metabolized by 20α-hydroxysteroid dehydrogenase could completely suppress term parturition and systemic bacterial-endotoxin-induced preterm birth in mice. We suggest that such selective progesterone receptor modulators may represent a potential therapeutic approach to the prevention of preterm labor in women at high risk of preterm birth.

Influence of ω3 fatty acids on maternal behavior and brain oxytocin in the murine perinatal period.

INTRODUCTION: Perinatal women often experience mood disorders and postpartum depression due to the physical load and the rapid changes in hormone levels caused by pregnancy, childbirth, and nursing. When the mother's emotions become unstable, their parental behavior (maternal behavior) may decline, the child's attachment may weaken, and the formation of mother-child bonding can become hindered. As a result, the growth of the child may be adversely affected. The objective of this study was to investigate the effect of ω3 fatty acid deficiency in the perinatal period on maternal behavior and the oxytocin concentration and fatty acid composition in brain tissue. MATERIALS AND METHODS: Virgin female C57BL/6 J mice fed a ω3 fatty acid-deficient (ω3-Def) or adequate (ω3-Adq) diet were mated for use in this study. To assess maternal behavior, nest shape was evaluated at a fixed time from gestational day (GD) 15 to postpartum day (PD) 13, and a retrieval test was conducted on PD 3. For neurochemical measurement, brains were removed from PD 1-6 dams and hippocampal fatty acids and hypothalamic oxytocin concentrations were assessed. RESULTS: Peripartum nest shape scores were similar to those reported previously (Harauma et al., 2016); nests in the ω3-Def group were small and of poor quality whereas those in the ω3-Adq group were large and elaborate. The inferiority of nest shape in the ω3-Def group continued from PD 0-7. In the retrieval test performed on PD 3, dams in the ω3-Def group took longer on several parameters compared with those in the ω3-Adq group, including time to make contact with pups (sniffing time), time to start retrieving the next pup (interval time), and time to retrieve the last pup to the nest (grouping time). Hypothalamic oxytocin concentrations on PD 1-6 were lower in the ω3-Def group than in the ω3-Adq group. DISCUSSION: Our data show that ω3 fatty acid deficiency reduces maternal behavior, a state that continued during pup rearing. This was supported by the observed decrease in hypothalamic oxytocin concentration in the ω3-Def group. These results suggest that ω3 fatty acid supplementation during the perinatal period is not only effective in delivering ω3 fatty acids to infants but is also necessary to activate high-quality parental behavior in mothers.

Effects of an ω3 fatty acid-biased diet on luteolysis, parturition, and uterine prostanoid synthesis in pregnant mice.

The ω3 polyunsaturated fatty acids (PUFAs) are known to have beneficial effects on health and diseases, and hence their intake is encouraged. However, it remains unknown as to how ω3 PUFAs affect female reproduction processes, in which ω6 PUFA-derived prostaglandin (PG) E2 and PGF2α play crucial roles. We therefore compared female reproductive performance between ω3 PUFA-biased linseed oil diet-fed (Lin) mice and ω6 PUFA-biased soybean oil diet-fed (Soy) mice. In Lin mice, the uterine levels of arachidonic acid (AA) and eicosapentaenoic acid (EPA) were 0.42 fold and 16 fold of those in Soy mice, respectively, with the EPA/AA ratio being 0.7 (vs 0.02 in Soy mice). Lin mice showed no alterations in any of the fertility indexes, including luteolysis and parturition. The uterine PG synthesis profiles of Lin mice were similar to those of Soy mice, but the levels of PGF2α and PGE2 were 50% of those in Soy mice, as a result of the increased EPA/AA ratio. PGF3α and PGE3 were undetectable in the uterine tissues of Soy and Lin mice. Interestingly, in Lin mice, 'luteolytic' PGF2α synthesis was considerably maintained even in the ω6 PUFA-reduced condition. These results suggest the existence of an elaborate mechanism securing PGF2α synthesis to a level that is sufficient for triggering luteolysis and parturition, even under ω6 PUFA-reduced conditions.

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.

Modification of oxytocin use through a coaching-based intervention based on the WHO Safe Childbirth Checklist in Uttar Pradesh, India: a secondary analysis of a cluster randomised controlled trial.

OBJECTIVE: To understand the prevalence of intrapartum oxytocin use, assess associated perinatal and maternal outcomes, and evaluate the impact of a WHO Safe Childbirth Checklist intervention on oxytocin use at primary-level facilities in Uttar Pradesh, India. DESIGN: Secondary analysis of a cluster-randomised controlled trial. SETTING: Thirty Primary and Community public health facilities in Uttar Pradesh, India from 2014 to 2017. POPULATION: Women admitted to a study facility for childbirth at baseline, 2, 6 or 12 months after intervention initiation. METHODS: The BetterBirth intervention aimed to increase adherence to the WHO Safe Childbirth Checklist. We used Rao-Scott Chi-square tests to compare (1) timing of oxytocin use between study arms and (2) perinatal mortality and resuscitation of infants whose mothers received intrapartum oxytocin versus who did not. MAIN OUTCOME MEASURES: Intrapartum and postpartum oxytocin administration, perinatal mortality, use of neonatal bag and mask. RESULTS: We observed 5484 deliveries. At baseline, intrapartum oxytocin was administered to 78.2% of women. Two months after intervention initiation, intrapartum oxytocin (I) was administered to 32.1% of women compared with 70.6% in the control (C) (P < 0.01); this difference diminished after the end of the intervention (I = 48.2%, C = 74.7%, P = 0.03). Partograph use remained at <1% at all facilities. Resuscitation was performed on 7.5% of infants whose mother received intrapartum oxytocin versus 2.0% who did not (P < 0.0001). CONCLUSIONS: In this setting, intrapartum oxytocin use was high despite limited maternal/fetal monitoring or caesarean capability, and was associated with increased neonatal resuscitation. The BetterBirth intervention was successful at decreasing intrapartum oxytocin use. Ongoing support is needed to sustain these practices. TWEETABLE ABSTRACT: Coaching + WHO Safe Childbirth Checklist reduces intrapartum oxytocin use and need for newborn resuscitation.

Melatonin and Myo-Inositol: Supporting Reproduction from the Oocyte to Birth.

Human pregnancy is a sequence of events finely tuned by several molecular interactions that come with a new birth. The precise interlocking of these events affecting the reproductive system guarantees safe embryo formation and fetal development. In this scenario, melatonin and myo-inositol seem to be pivotal not only in the physiology of the reproduction process, but also in the promotion of positive gestational outcomes. Evidence demonstrates that melatonin, beyond the role of circadian rhythm management, is a key controller of human reproductive functions. Similarly, as the most representative member of the inositol's family, myo-inositol is essential in ensuring correct advancing of reproductive cellular events. The molecular crosstalk mediated by these two species is directly regulated by their availability in the human body. To date, biological implications of unbalanced amounts of melatonin and myo-inositol in each pregnancy step are growing the idea that these molecules actively contribute to reduce negative outcomes and improve the fertilization rate. Clinical data suggest that melatonin and myo-inositol may constitute an optimal dietary supplementation to sustain safe human gestation and a new potential way to prevent pregnancy-associated pathologies.

l-Citrulline supplementation during pregnancy improves perinatal and postpartum maternal vascular function in a mouse model of preeclampsia.

Preeclampsia is a spontaneously occurring pregnancy complication diagnosed by new-onset hypertension and end-organ dysfunction with or without proteinuria. This pregnancy-specific syndrome contributes to maternal morbidity and mortality and can have detrimental effects on fetal outcomes. Preeclampsia is also linked to increased risk of maternal cardiovascular disease throughout life. Despite intense investigation of this disorder, few treatment options are available. The aim of this study was to investigate the potential therapeutic effects of maternal l-citrulline supplementation on pregnancy-specific vascular dysfunction in the male C57BL/6J × female C57BL/6J C1q-/- preeclampsia-like mouse model. l-Citrulline is a nonessential amino acid that is converted to l-arginine to promote smooth muscle and blood vessel relaxation and improve nitric oxide (NO)-mediated vascular function. To model a preeclampsia-like pregnancy, female C57BL/6J mice were mated to C1q-/- male mice, and a subset of dams was supplemented with l-citrulline throughout pregnancy. Blood pressure, systemic vascular glycocalyx, and ex vivo vascular function were investigated in late pregnancy, and postpartum at 6 and 10 mo of age. Main findings show that l-citrulline reduced blood pressure, increased vascular glycocalyx volume, and rescued ex-vivo vascular function at gestation day 17.5 in this preeclampsia-like model. The vascular benefit of l-citrulline also extended postpartum, with improved vascular function and glycocalyx measures at 6 and 10 mo of age. l-Citrulline-mediated vascular improvements appear, in part, attributable to NO pathway signaling. Taken together, l-citrulline supplementation during pregnancy appears to have beneficial effects on maternal vascular health, which may have translational implications for improved maternal cardiovascular health.

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.

Arg-Vasotocin Directly Activates Isotocin Receptors and Induces COX2 Expression in Ovoviviparous Guppies.

Oxytocin (OT) is a crucial regulator of reproductive behaviors, including parturition in mammals. Arg-vasopressin (AVP) is a nonapeptide homologous to Arg-vasotocin (AVT) in teleosts that has comparable affinity for the OT receptor. In the present study, ovoviviparous guppies (Poecilia reticulata) were used to study the effect of AVT on delivery mediated by the activation of prostaglandin (PG) biosynthesis via isotocin (IT) receptors (ITRs). One copy each of it and avt and two copies of itrs were identified in guppies. The results of the affinity assay showed that various concentrations of AVT and IT (10-6, 10-7, and 10-8 mol/L) significantly activated itr1 (P < 0.05). In vitro experiments revealed significant upregulation (P < 0.05) of cyclooxygenase 2 (cox2), which is the rate-limiting enzyme involved in PG biosynthesis, and itr1 by AVT and IT. Furthermore, dual in situ hybridization detected positive signals for itr1 and cox2 at the same site, implying that ITR1 may regulate cox2 gene expression. Measurement of prostaglandin F2a (PGF2a) concentrations showed that AVT induced PGF2a synthesis (P < 0.05) and that the effect of IT was not significant. Finally, intraperitoneal administration of PGF2a significantly induced premature parturition of guppies. This study is the first to identify and characterize AVT and ITRs in guppies. The findings suggest that AVT promotes PG biosynthesis via ITR and that PGF2a induces delivery behavior in ovoviviparous guppies.

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.

Antibiotic exposure during pregnancy and childhood asthma: a national birth cohort study investigating timing of exposure and mode of delivery.

OBJECTIVE: To investigate whether antibiotic exposure during pregnancy was associated with childhood asthma and if this relationship was conditional on timing of exposure and mode of delivery. DESIGN: A cohort study using multivariable logistic regression models adjusting for a priori defined confounders. Pregnant women were recruited from 1996 to 2002. SETTING: The Danish National Birth Cohort. PATIENTS: Of the 96 832 children in the cohort, 32 651 children were included in the study population. MAIN OUTCOME MEASURE: Parent-reported childhood asthma at 11 years. RESULTS: A total of 5522 (17%) children were born to mothers exposed to antibiotics during pregnancy. In adjusted analyses, children born to exposed mothers had higher odds of asthma (OR 1.14, 95% CI 1.05 to 1.24). There was no association with antibiotic exposure in the first trimester (OR 1.02, 95% CI 0.83 to 1.26), but higher odds were observed for antibiotic exposure in the second to third trimester (OR 1.17, 95% CI 1.06 to 1.28), compared with unexposed children. The overall association between antibiotics during pregnancy and childhood asthma was only observed in vaginally born children (OR 1.17, 95% CI 1.07 to 1.28) but not in caesarean section born children (planned caesarean section: OR 0.95, 95% CI 0.66 to 1.37; caesarean emergency: OR 0.96, 95% CI 0.73 to 1.28). In exposed vaginally born children, the odds for childhood asthma requiring treatment during the preceding year were 34% higher (OR 1.34, 95% CI 1.21 to 1.49), compared with unexposed vaginally born children. CONCLUSIONS: Antibiotic exposure in mid-to-late pregnancy is associated with higher odds of childhood asthma in vaginally born children. Mode of delivery may modify the association.

Aging-induced changes in sperm DNA methylation are modified by low dose of perinatal flame retardants.

Aims: Paternal age is increasing in developed countries. Understanding of aging-related epigenetic changes in sperm is needed as well as factors that modify such changes. Materials & methods: Young pubertal and mature rats were exposed perinatally to vehicle or environmental xenobiotic 2,2',4,4'-tetrabromodiphenyl ether. Epididymal sperm was reduced representation bisulfite sequenced. Differentially methylated regions (DMRs) were identified via MethPipe. Results: In control animals, 5319 age-dependent DMRs were identified. Age-related DMRs were enriched for embryonic development. In exposed rats, DNA methylation was higher in young and lower in mature animals then in controls. Conclusions: Sperm methylome undergoes significant age-dependent changes, which may represent a causal link between paternal age and offspring phenotype. Environmental xenobiotics can interfere with the natural process of epigenetic aging.

Perinatal cortisol and blood glucose concentrations in bitches and neonatal puppies: effects of mode of whelping.

The decision on how and when to assist whelping is crucial for the survival rate of puppies and health status of the dam. However, medical or surgical therapy in dystocia can impact both maternal and neonatal stress and glucose response differently. This study aims to compare perinatal cortisol and glucose among different modes of delivery in bitches and neonates. We analyzed 50 puppies derived from 27 healthy bitches. According to the condition at birth, bitches and their puppies were allocated into either a Eutocia Group (vaginal birth with no whelping assistance), Fetal Dystocia Group (whelping assistance with fetal manipulation), Maternal Dystocia Group (whelping assistance because of partial uterine inertia corrected by oxytocin administration), or Cesarean Section Group (fetal or maternal dystocia bitches subjected to C-section). Maternal blood cortisol and glucose concentrations were analyzed during the perinatal period (prepartum, intrapartum, postpartum, and 1 h after postpartum). Neonatal blood samples were collected within 5 min and 1 h after birth for assessment of cortisol and glucose. Maternal dystocia bitches had higher cortisol concentrations at postpartum than the Fetal Dystocia Group. At 1 h postpartum, the Cesarean Section Group had higher cortisol concentrations compared with fetal dystocia bitches. The Eutocia Group presented increased cortisol concentrations at intrapartum and postpartum, whereas fetal dystocia bitches had higher intrapartum cortisol concentrations than at 1 h postpartum. The Maternal Dystocia Group presented higher postpartum cortisol concentrations than at prepartum and 1 h postpartum. Maternal glucose had a progressive increase throughout peripartum and was higher during postpartum and at 1 h postpartum. C-section bitches had the highest blood glucose concentration. Neonatal cortisol concentrations at birth were higher than 1 h after birth. Fetal dystocia puppies had higher cortisol concentrations, whereas caesarian section puppies had lower cortisol levels. Fetal dystocia and C-section puppies had higher glucose concentrations than the Eutocia Group. In conclusion, maternal dystocia leads to high cortisol concentrations in bitches immediately postpartum, whereas only fetal dystocia causes increased neonatal cortisol concentrations. Moreover, fetal dystocia and C-section are hyperglycemic obstetrical conditions for neonatal puppies; on the other hand, only C-section causes hyperglycemia in bitches.

Effect of intramuscular and intravaginal PGE-2 treatment compared to intramuscular oxytocin treatment in eutocic sows on the farrowing performance in a free farrowing system.

A duration of parturition beyond 300 min negatively impacts the health of the sow and the survival of piglets during parturition. Hence, oxytocin is widely used to speed up the parturition. However, oxytocin's negative side effects raise the need of finding alternative treatments such as those already implemented in human medicine. The aim of this study was to evaluate the efficacy of Prostaglandin E2 (PGE2) applied intravaginally (PGE2-V) (1.0 mg) or intramuscularly (PGE2-M) (2.5 mg) to improve the parturition process after expulsion of the fourth piglet compared to a placebo (P-V), which was sterile intravaginal gel or intramuscular oxytocin application (OXY-M) (20 iu) in free farrowing systems.In total, 201 eutocic sows were examined after stratification by parity and random allocation into groups: 54 (P-V), 48 (OXY-M), 50 (PGE2-V), 49 (PGE2-M). Farrowing duration (time between first piglet and last piglet), piglet interval and placenta expulsion duration (time between first and last placenta) were recorded, and each piglet was scored for meconium staining and vitality. Furthermore, stillborn piglets were categorized into ante-partum and intra-partum deaths.Under the present conditions, neither administration of PGE2 nor oxytocin revealed a significant effect on the farrowing process or the vitality of the piglets when compared to untreated sows. Nonetheless, significant differences could be detected between PGE-2 and oxytocin treatments. The duration of farrowing was significantly shorter in oxytocin-treated sows (156 min) compared to sows treated intramuscularly with PGE2 (238 min). Furthermore, the placenta expulsion duration in the OXY-M group (130 min) significantly differed from PGE2-V (198 min) and PGE2-M group (218 min). Although these accelerations of parturition might be considered as a beneficial effect, routine treatment with uterotonic agents after birth of the fourth piglet in free farrowing eutocic sows cannot be recommended, because an overall benefit when compared to untreated sows was not approved.

Aging Induces Profound Changes in sncRNA in Rat Sperm and These Changes Are Modified by Perinatal Exposure to Environmental Flame Retardant.

Advanced paternal age at fertilization is a risk factor for multiple disorders in offspring and may be linked to age-related epigenetic changes in the father's sperm. An understanding of aging-related epigenetic changes in sperm and environmental factors that modify such changes is needed. Here, we characterize changes in sperm small non-coding RNA (sncRNA) between young pubertal and mature rats. We also analyze the modification of these changes by exposure to environmental xenobiotic 2,2',4,4'-tetrabromodiphenyl ether (BDE-47). sncRNA libraries prepared from epididymal spermatozoa were sequenced and analyzed using DESeq 2. The distribution of small RNA fractions changed with age, with fractions mapping to rRNA and lncRNA decreasing and fractions mapping to tRNA and miRNA increasing. In total, 249 miRNA, 908 piRNA and 227 tRNA-derived RNA were differentially expressed (twofold change, false discovery rate (FDR) p ≤ 0.05) between age groups in control animals. Differentially expressed miRNA and piRNA were enriched for protein-coding targets involved in development and metabolism, while piRNA were enriched for long terminal repeat (LTR) targets. BDE-47 accelerated age-dependent changes in sncRNA in younger animals, decelerated these changes in older animals and increased the variance in expression of all sncRNA. Our results indicate that the natural aging process has profound effects on sperm sncRNA profiles and this effect may be modified by environmental exposure.

Effects of continuous infusion of phenylephrine vs. norepinephrine on parturients and fetuses under LiDCOrapid monitoring: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Hypotension following spinal anesthesia (SA) during cesarean delivery (CD) occurs commonly and is related with maternal and fetal complications. Norepinephrine infusion is increasingly used for prevention of post-SA hypotension; however, its effects as compared to the traditional phenylephrine infusion remain unclear. This study aimed to compare the effects of phenylephrine and norepinephrine administered as continuous infusion during elective CD on maternal hemodynamic parameters and maternal and fetal outcomes. METHODS: This prospective, single-center, randomized, controlled study included 238 consecutive term parturients who underwent CD from February 2019 to October 2019. They were randomized to receive continuous infusion of 0.25 µg/kg/min phenylephrine, 0.05 µg/kg/min norepinephrine, or placebo. Hemodynamic monitoring was performed at 10 time points using LiDCOrapid. We analyzed umbilical vein (UV), umbilical artery (UA), and peripheral vein (PV) blood gas indexes and recorded intraoperative complications. RESULTS: In phenylephrine group, the systolic blood pressure (SBP) remain during the whole operation. Compared to the control group, phenylephrine, but not norepinephrine, significantly increased the systemic vascular resistance (SVR) to counteract the SA-induced vasodilatation, 3 min following norepinephrine/phenylephrine/LR administration (T4): 957.4 ± 590.3 vs 590.1 ± 273.7 (P < 0.000001); 5 min following norepinephrine/phenylephrine/LR administration (T5): 1104 ± 468.0 vs 789.4 ± 376.2 (P = 0.000002). at the time of incision (T6): 1084 ± 524.8 vs 825.2 ± 428.6 (P = 0.000188). Parturients in the phenylephrine group had significantly lower UV (1.91 ± 0.43) (P = 0.0003) and UA (2.05 ± 0.61) (P = 0.0038) lactate level compared to controls. Moreover, the UV pH value was higher in the phenylephrine than in the control group7.37 ± 0.03(P = 0.0013). Parturients had lower incidence of nausea, tachycardia, hypotension in phenylephrine group. CONCLUSIONS: In this dataset, continuous phenylephrine infusion reduced the incidence of SA-induced hypotension, ameliorated SVR, while decreasing overall maternal complications. Phenylephrine infusions are considered the better choice during CD because of the significant benefit to the fetus. TRIAL REGISTRATION: Clinicaltrial.gov Registry, NCT03833895 , Registered on 1 February 2019.

Evaluation of the birth plan implementation: a parallel convergent mixed study.

BACKGROUND: Pregnancy, birth, and motherhood are among the most important events of every woman's life. Training and participation of mothers in the decision-making process of delivery play an essential role in physical as well as psychosocial preparation of the mother. The healthcare system can improve and enhance the level of care by involving the patient in their self-care process. The aim of the present study is to assess the implementation of the birth plan for the first time in Iran in Tabriz city. METHODS/DESIGN: The present study uses a mixed-method with a parallel convergence approach, including both quantitative and qualitative phases. The quantitative phase is a randomized controlled clinical trial performed on 106 pregnant women, 32-36 weeks of pregnancy, referring to Taleghani educational hospital in Tabriz city. The participants will be assigned into intervention and control groups using a randomized block method. A training session will be held about the items of the birth plan checklist at weeks 32-36 of gestation for the participants in the intervention group, whereby a mother-requested birth plan will be developed. It will then be implemented by the researcher after admitting them to the delivery ward. Also, those in the control group will receive routine care. During and after the delivery, the questionnaire of delivery information, neonatal information, and Delivery Fear Scale (DFS) will be completed. Also, a partogram will be completed for all participants by the researcher. The participants in both groups will be followed up until six weeks post-delivery, whereby the instruments of Childbirth Experience Questionnaire (CEQ2.0), Edinburgh's Postpartum Depression Scale and PTSD Symptom Scale 1 (PSS-I) will be completed six weeks 4-6 weeks postpartum by the researcher through an interview with participants in Taleghani educational hospital. The general linear model and multivariate logistic regression model will be used while controlling the possible confounding variables. The qualitative phase will be performed to explore the women's perception of the effect of the birth plan on childbirth experience within 4-6 weeks postpartum. The sampling will be of a purposeful type on the women who would receive the birth plan and will continue until data saturation. In-depth, semi-structured individual interviews would be used for data collection. The data analysis will be done through content analysis with a conventional approach. The results of the quantitative and qualitative phases will be analyzed separately, and then combined in the interpretation stage. DISCUSSION: By investigating the effect of implementing the birth plan on the childbirth experience of women as well as other maternal and neonatal outcomes, an evidence-based insight can be offered using a culturally sensitive approach. The presentation of the results obtained from this study using the mixed method may be effective in improving the quality of care provided for women during labor. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N58. Date of registration: July 7, 2020. URL: https://en.irct.ir/user/trial/47007/view.

Effects of dietary inulin during late gestation on sow physiology, farrowing duration and piglet performance.

In this study there was evaluation of effects of dietary inulin during late gestation on sow physiology, farrowing duration and piglet performance. At day 80 of gestation sows were randomly assigned to four groups：basal diet (CON); or basal diet with 0.8 %; 1.6 %; or 2.4 % inulin. The feeding of the diet with 1.6 % inulin resulted in larger weights of the litter at birth a shorter duration of the farrowing period, lesser average birth interval between piglets, lesser number of piglets dead at birth, and fewer piglets/sow dead at birth (P < 0.05). When sows were fed 0.8 % and 1.6 % IN, there was a larger litter weight at weaning, sow average daily feed intake and piglet average daily gain during lactation compared with values for these variables in the CON group (P <  0.05). Additionally, there was an increase in serum concentration of free fatty acid, total cholesterol, and high-density lipoprotein cholesterol with increasing amounts of inulin in the diet (linear, P <  0.05). Sows fed 1.6 % IN had greater serum concentrations of glucose than those in the CON group (P <  0.05). Furthermore, there was a linear increase in serum activity of total antioxidant capacity, total superoxide dismutase and glutathione peroxidase with increasing amounts of inulin in the diet (P <  0.05). In conclusion, results of the present study indicated feeding inulin during late gestation improved reproductive performance of sows, thus, may be a novel additive for the pig industry in improving efficiency of pork production.

Management of oxytocin for labour augmentation in relation to mode of birth in Robson group 1.

OBJECTIVE: To compare mode of birth in Robson group 1 according to administration of oxytocin for labour augmentation. DESIGN AND PARTICIPANTS: A retrospective review of 724 medical records from women in Robson group 1 was performed. The outcome measurements were: mode of birth in relation to presence of labour dystocia when initiating augmentation with oxytocin, duration of augmentation with oxytocin, increase of the oxytocin infusion according to recommendations and cervical dilation when initiating augmentation with oxytocin. SETTING: The review was based on medical records from a medium-sized tertiary level obstetric unit in southern Sweden, with approximately 3700 births per year. Data was collected between January 2017 and October 2017. MEASUREMENTS AND FINDINGS: Oxytocin for labour augmentation was used in 64.1% of the births. Oxytocin administered according to the national recommendations was related to a greater likelihood of vaginal birth than when these recommendations were not followed. Only 47.8% of the women who underwent a caesarean section was treated according to recommendations. Receiving augmentation with oxytocin at a later stage of labour was related to a greater likelihood of a vaginal birth. The total time treated with oxytocin was significantly longer in women who had an assisted vaginal birth or a caesarean section than those who had a vaginal birth with augmentation. KEY CONCLUSIONS: Oxytocin for labour augmentation was over-used in Robson group 1. Oxytocin early in labour, a long duration of stimulation with oxytocin and a slower increase of the infusion than recommended had a relationship with caesarean section. IMPLICATION FOR PRACTICE: Due to risks for adverse maternal and neonatal outcomes when using oxytocin for labour augmentation, caregivers should implement strict protocols for its use. According to a high use of oxytocin there is a need to describe women's experiences of labour augmentation in labour dystocia but also when received despite normal labour progress.