Sodium dichloroacetate stimulates cardiac mitochondrial metabolism and improves cardiac conduction in the ovine fetus during labor.

Previous studies in our laboratory have suggested that the increase in stillbirth in pregnancies complicated by chronic maternal stress or hypercortisolemia is associated with cardiac dysfunction in late stages of labor and delivery. Transcriptomics analysis of the overly represented differentially expressed genes in the fetal heart of hypercortisolemic ewes indicated involvement of mitochondrial function. Sodium dichloroacetate (DCA) has been used to improve mitochondrial function in several disease states. We hypothesized that administration of DCA to laboring ewes would improve both cardiac mitochondrial activity and cardiac function in their fetuses. Four groups of ewes and their fetuses were studied: control, cortisol-infused (1 g/kg/day from 115 to term; CORT), DCA-treated (over 24 h), and DCA + CORT-treated; oxytocin was delivered starting 48 h before the DCA treatment. DCA significantly decreased cardiac lactate, alanine, and glucose/glucose-6-phosphate and increased acetylcarnitine/isobutyryl-carnitine. DCA increased mitochondrial activity, increasing oxidative phosphorylation (PCI, PCI + II) per tissue weight or per unit of citrate synthase. DCA also decreased the duration of the QRS, attenuating the prolongation of the QRS observed in CORT fetuses. The effect to reduce QRS duration with DCA treatment correlated with increased glycerophosphocholine and serine and decreased phosphorylcholine after DCA treatment. There were negative correlations of acetylcarnitine/isobutyryl-carnitine to both heart rate (HR) and mean arterial pressure (MAP). These results suggest that improvements in mitochondrial respiration with DCA produced changes in the cardiac lipid metabolism that favor improved conduction in the heart. DCA may therefore be an effective treatment of fetal cardiac metabolic disturbances in labor that can contribute to impairments of fetal cardiac conduction.

Duration of Exposure to General Endotracheal Anesthesia during Cesarean Deliveries at Term and Perinatal Complications.

OBJECTIVE: To examine whether the duration of time from initiation of general endotracheal anesthesia (GETA) to delivery for cesarean deliveries (CDs) performed is related to perinatal outcomes. STUDY DESIGN: This is a retrospective study of patients with singleton nonanomalous gestations undergoing CD ≥37 weeks of gestation under GETA with reassuring fetal status at a single tertiary care center from 2000 to 2016. Duration from GETA initiation until delivery was calculated as the time interval from GETA induction to delivery (I-D), categorized into tertiles. Outcomes for those in the tertile with the shortest I-D were compared with those in the other two tertiles. The primary perinatal outcome was a composite of complications (continuous positive airway pressure or high-flow nasal cannula for ≥2 consecutive hours, inspired oxygen ≥30% for ≥4 consecutive hours, mechanical ventilation, stillbirth, or neonatal death ≤72 hours after birth). Secondary outcomes were 5-minute Apgar score <7 and a composite of maternal morbidity (bladder injury, bowel injury, and extension of hysterotomy). Bivariable and multivariable analyses were used to compare outcomes. RESULTS: Two hundred eighteen maternal-perinatal dyads were analyzed. They were dichotomized based on I-D ≤4 minutes (those in the tertile with the shortest duration) or >4 minutes. Women with I-D >4 minutes were more likely to have prior abdominal surgery and less likely to have labored prior to CD. I-D >4 minutes was associated with significantly increased frequency of the primary perinatal outcome. This persisted after multivariable adjustment. In bivariable analysis, 5-minute Apgar <7 was more common in the group with I-D >4 minutes, but this did not persist in multivariable analysis. Frequency of maternal morbidity did not differ. CONCLUSION: When CD is performed at term using GETA without evidence of nonreassuring fetal status prior to delivery, I-D interval >4 minutes is associated with increased frequency of perinatal complications. KEY POINTS: · Cesarean delivery under general anesthesia is associated with increased perinatal complications.. · Perinatal complications are increased with increasing duration of exposure to general anesthetics.. · Maternal complications were not increased with shorter duration of exposure to general anesthesia..

Epidural analgesia during labour and stress markers in the newborn.

Labour and modes of delivery can influence the plasma levels of stress hormones and cytokines involved in pathophysiologic cascade, potentially damaging brain development of the newborn. This prospective observational, single-centre, case-control, non-profit study aimed to detect potential differences in foetal well-being such as stress neuroendocrine responses. Quantitative determinations of the stress markers interleukin (IL)-1ß, IL-8, and ß-endorphin were compared between the control group and the epidural analgesia group. We found higher IL1-ß levels but lower IL-8 and ß-endorphin levels in the epidural analgesia group than in the control group. No significant inter-group differences were observed for any parameters. Our findings demonstrate that epidural analgesia for pain relief during labour does not result in significant differences in blood stress response markers.IMPACT STATEMENTWhat is already known on this subject? We already know that plasma levels of stress hormones and cytokines are influenced by labour and delivery modes. This has a deep impact on the newborn in terms of brain damage, immune system deficits, and altered hypothalamic-pituitary axis responses. We also know that epidural analgesia is a widespread practice that offers pain relief to the woman in labour, but there are few studies on the potentially negative effects of epidural labour analgesia on the unborn child.What do the results of this study add? This study found no significative differences in blood stress response markers between the epidural analgesia group and the control group. Under this study circumstances we found out that epidural analgesia does not significantly influence the newborn's well-being during labour and delivery.What are the implications of these findings for clinical practice and/or further research? These findings must be confirmed by further studies to verify whether epidural analgesia is safe for the newborn's development.

Maternal exposure to fine particulate matter and the risk of fetal distress.

Prenatal life exposure to fine particulate matter (aerodynamic diameter less than or equal to 2.5 µm, PM2.5) has been linked with increased risk of adverse fetal development and birth outcomes in previous studies. However, to our knowledge, no study has investigated the association of maternal PM2.5 with the risk of fetal distress, which is a harmful fetal status and may lead to fetal brain damage, even fetal death. Therefore, we conducted a study to determine the association between maternal PM2.5 and fetal distress among 7835 mother-infant pairs from a birth cohort, in Wuhan, China, 2013-2015. The individual daily PM2.5 level was assessed using land use regression model. We evaluated the association of maternal PM2.5 level over the whole pregnancy with fetal distress by logistic regression model, and estimated the risk between PM2.5 exposure in specific trimester and fetal distress using generalized estimating equations. We observed that per 10 µg/m3 change of maternal PM2.5 level over the whole pregnancy was associated with 25% increased risk of fetal distress (95% confidence interval: 1.09-1.44). Further, we found PM2.5 level in the 2nd trimester, but not in the 1st and 3rd trimesters, was associated with fetal distress. Stratified analyses indicated that the association was only significant among infants who were born in cold seasons. Our study suggested that PM2.5 exposure during the whole pregnancy exhibited significant associations with the risk of fetal distress, and exposure in the 2nd trimester maybe the susceptible window. Further stratified analyses indicated that birth season is a possible modifier in the association.

Does Induction with Misoprostol Impact the Small for Gestational Age Neonate?

OBJECTIVE: To compare outcomes in small for gestational age neonates induced with misoprostol to other cervical ripening agents. We hypothesized that misoprostol use will demonstrate no significant difference in outcomes compared with alternative agents. STUDY DESIGN: Small for gestational age neonates (<10th percentile for gestational age) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) sponsored Consortium on Safe Labor database were analyzed. Neonates induced with misoprostol ± oxytocin (n = 451) were compared with neonates induced with prostaglandin E2 ± oxytocin and/or mechanical dilation ± oxytocin (n = 663). Primary outcomes included intrapartum fetal distress, cesarean section for fetal distress, cesarean section for any reason, neonatal intensive care unit admission, low 5-minute Apgar, and composite neonatal morbidity. Multiple logistic regression was used to calculate adjusted odds ratios (aORs). Data were analyzed using SAS. RESULTS: Small for gestational age neonates induced with misoprostol ± oxytocin compared with alternative agents had decreased low 5-minute Apgar scores (aOR 0.27 [0.10-0.71]). No significant differences were demonstrated among very small for gestational age neonates (<5th percentile for gestational age). CONCLUSION: Our results suggest that misoprostol does not increase risk of adverse outcomes in small for gestational age neonates; however, prospective studies are warranted to further assess optimal cervical ripening agents in this population.

Association between maternal short-term exposure to ambient air pollution and the risk of fetal distress: A matched case-control study.

BACKGROUND: Ambient air pollution has been linked to gestational complications. However, the evidence on the relationship between air pollution and fetal distress is limited. OBJECTIVES: To investigate the relationship between maternal short-term air pollution exposure and fetal distress, and to identify a potential susceptible population. METHODS: This matched case-control study, involving 313 pregnancy women with fetal distress was conducted in Xi'an, the largest city in Northwest China from 2013 to 2016. Each woman with fetal distress was randomly matched with four women without fetal distress of the same age, same gestational week, and registration in the same period (n = 1252). Inverse distance-weighted (IDW) interpolation was applied to estimate maternal air pollution exposure based on the residential addresses. We employed conditional logistic regression model to evaluate the relationship between air pollutants and fetal distress. Distributed lag nonlinear model (DLNM) was performed to examine the exposure-response relationship between air pollutants and fetal distress. RESULTS: Maternal short-term exposure to PM10, PM2.5-10 (PMc), SO2, NO2, and CO was associated with increased risk of fetal distress. Each 10 µg/m3 increment in PM10, PMc, SO2 at lag 014, and NO2 at lag 010, the odds ratio (ORs) of fetal distress were 1.027 (95 % confidence interval (CI): 1.004, 1.050), 1.058 (95 % CI: 1.014, 1.105), 1.140 (95 % CI: 1.029, 1.264), and 1.158 (95 % CI: 1.046, 1.283), respectively. Similarly, with a 0.1 mg/m3 increment in CO at lag 014, the OR of fetal distress was 1.029 (95 % CI: 1.002, 1.058). Stratified analyses showed that the estimate associations of PM10, PM2.5 and CO appeared to be stronger, although not statistically significantly, among women with gestational complications. CONCLUSION: Maternal short-term exposure to ambient air pollution may increase the risk of fetal distress. Understanding the detrimental role of air pollution in fetal distress can help us better develop preventative methods in reducing its' impact on maternal and fetal health.

Maternal ethanol exposure induces transient impairment of umbilical circulation and fetal hypoxia in monkeys.

When ethanol was administered intravenously to pregnant monkeys, a transient but marked collapse of umbilical vasculature was observed uniformly within about 15 minutes. The ethanol-induced impairment of umbilical circulation produced severe hypoxia and acidosis in the fetus; recovery occurred during the succeeding hour. This striking interruption of feto-placental circulation may explain one of the mechanisms of mental retardation, a frequent manifestation in children afflicted with fetal alcohol syndrome.

High-dose versus low-dose of oxytocin for labour augmentation: a randomised controlled trial.

PROBLEM: Delayed labour progress is common in nulliparous women, often leading to caesarean section despite augmentation of labour with synthetic oxytocin. BACKGROUND: High- or low-dose oxytocin can be used for augmentation of delayed labour, but evidence for promoting high-dose is weak. Aim To ascertain the effect on caesarean section rate of high-dose versus low-dose oxytocin for augmentation of delayed labour in nulliparous women. Methods Multicentre parallel double-blind randomised controlled trial (ClinicalTrials.gov: NCT01587625) in six labour wards in Sweden. Healthy nulliparous women at term with singleton cephalic fetal presentation, spontaneous labour onset, confirmed delay in labour and ruptured membranes (n=1351) were randomised to labour augmentation with either high-dose (6.6 mU/minute) or low-dose (3.3 mU/minute) oxytocin infusion. FINDINGS: 1295 women were included in intention-to-treat analysis (high-dose n=647; low-dose n=648). Caesarean section rates did not differ between groups (12.4% and 12.3%, 95% Confidence Interval -3.7 to 3.8). Women with high-dose oxytocin had: shorter labours (-23.4min); more uterine tachysystole (43.2% versus 33.5%); similar rates of instrumental vaginal births, with more due to fetal distress (43.8% versus 22.7%) and fewer due to failure to progress (39.6% versus 58.8%). There were no differences in neonatal outcomes. DISCUSSION: Our study could not confirm results of two systematic reviews indicating, with weak evidence, that use of high-dose oxytocin was associated with lower frequency of caesarean section. CONCLUSION: We found no advantages for routine use of high-dose oxytocin in the management of delay in labour. Low-dose oxytocin regimen is recommended to avoid unnecessary events of tachysystole and fetal distress.

Uterine rupture during induction of labor at term with intravaginal misoprostol.

BACKGROUND: Misoprostol (prostaglandin E1) compares favorably with dinoprostone (prostaglandin E2) and oxytocin for labor induction at term. Excessive uterine activity has been reported using high-dose regimens, but no negative effect on outcomes has been observed. CASE: Labor was induced in a 34-year-old multipara at 39 weeks' gestation using intravaginal misoprostol tablets. Five hours after administration of the second 25-microgram dose, fetal bradycardia prompted emergency cesarean delivery. Hysterectomy and left salpingo-oophorectomy were necessary to control bleeding from a 15-cm posterior uterine wall rupture. CONCLUSION: Misoprostol can cause excessive uterine activity and uterine rupture.

Oxytocin in active-phase abnormalities of labor: a randomized study.

Seven hundred fifty-nine of 926 women in abnormal labor (82%) were entered into an open randomized trial to compare the effects of oxytocin and saline. Patients were classified as having either primary dysfunctional labor or secondary arrest of cervical dilatation. The end points chosen were an increase in the rate of cervical dilatation or a change in cervical dilatation. Patients who failed to respond to the initial solution were crossed over to the other solution. Oxytocin was significantly superior to saline in treating both labor abnormalities. Administration of oxytocin did not increase the need for cesarean delivery for fetal distress.

Use of tocolytic drugs to reverse oxytocin-induced uterine hypertonus and fetal distress.

The use of oxytocin in labor has the inherent danger of producing uterine hyperstimulation with resultant fetal distress. When produced by gradual titration of intravenous oxytocin, discontinuation of the medication is usually sufficient to reverse the process. However, the rapid administration of a large intravenous dose of oxytocin, as occurred in this patient, may result in hypertonic uterine contractions and fetal distress unresponsive to traditional measures. The rationale for using a tocolytic drug to reverse the uterine hypertonus, produce intrauterine fetal resuscitation, and prevent cesarean section is discussed in this report.

Dihydralazine or ketanserin for severe hypertension in pregnancy? Preliminary results.

OBJECTIVE: To compare the efficacy and safety of intravenous dihydralazine with ketanserin in the management of severe hypertension in the third trimester. STUDY DESIGN: A double blind randomised controlled trial, comparing 5 mg dihydralazine with 10 mg ketanserin after an intravenous infusion of 500 ml of a crystalloid solution. Medication was repeated every 20 min till the therapeutic goal of 90 mm Hg was reached, to a maximum of 4 dosages. Main outcome measures were treatment failures and emergency deliveries for fetal distress. RESULTS: The therapeutic goal was met more often in patients receiving dihydralazine (36/38 compared to 27/42; P < 0.01). The need for delivery for fetal distress did not differ (3 after dihydralazine, 1 after ketanserin, P = 0.29) No therapy related perinatal loss occurred, but one mother with an undiagnosed phaechromocytoma died 24 h after receiving dihydralazine. CONCLUSION: Ketanserin in this dosage is less effective to lower diastolic blood pressure. The place of a fluid load prior to dihydralazine needs to be further investigated, as fetal heart rate decelerations were less common than previously reported.

Pharmacokinetics of meperidine in pregnancy.

The disposition of meperidine was studied in 11 term pregnant humans after the administration of a single 50 mg intravenous dose of meperidine through 48 h post-injection. Half-lives of the rapid and terminal elimination phases were calculated as 2.3 and 13.3 h, respectively. These values are much greater than previously reported half-lives which were based on data collected over less than 8 h after injection. An accurate value for t1/2 beta may be particularly important in sequential dosing of analgesic medication. These pharmacokinetic constants calculated on data collected through 48 h in this study may have important clinical correlates.

Peripartum cocaine use: estimating risk of adverse pregnancy outcome.

Pregnancy outcome of 83 patients with a positive urine toxicology screen for cocaine in the third trimester were reviewed. The outcomes of pregnancies complicated by cocaine abuse were compared to those of matched controls selected from our general obstetric population. We observed a statistically significant increase in the incidence of premature separation of the placenta, low birthweight infants, preterm deliveries, and the incidence of fetal distress requiring cesarean section. On admission, 55% of patients denied recent cocaine use. These observations have implications for planning perinatal services.

Acetaminophen poisoning in late pregnancy. A case report.

BACKGROUND: Acetaminophen poisoning is a major cause of hospital admission and has been extensively reviewed. Its occurrence in pregnant women has been reported seldom, and the prognosis has been good except for one case, in which the fetus died. We report on a case of acetaminophen poisoning that resulted in the death of both the mother and the infant. CASE: A 38-year-old woman whose pregnancy was at 31 weeks' gestational age was evaluated for treatment of an acetaminophen overdose. She was admitted more than 26 hours after taking 35 g of acetaminophen. An emergency cesarean section was performed one hour after admission because of acute fetal distress. A grossly normal, 1,620-g, female infant was delivered and had Apgar scores at 1, 5 and 10 minutes of 0, 0 and 1, respectively, despite the initiation of resuscitation immediately following delivery. Acidosis was noted in the mother during the operation; it was followed by acute hepatorenal failure 16 hours after admission. That resulted in the mother's death 40 hours after admission. The infant also died 34 hours after delivery. CONCLUSION: Delays in administering the antidote treatment, N-acetylcysteine, after acetaminophen intoxication significantly increase the risk of mortality in both the mother and infant. The development of acidosis carries a poor prognosis in such patients and may necessitate liver transplantation to save the life of the mother.

Intrapartum cocaine use. A case report.

The use of cocaine during pregnancy appears to be reaching epidemic proportions. In the first reported case of intrapartum cocaine use, fetal heart rate abnormalities were detected.

Methylergonovine-induced hypertonus in term pregnancy. A case report.

The administration of methylergonovine maleate to a patient at term is rare. A patient received the drug at 36 weeks' gestation, with subsequent development of fetal distress secondary to uterine tetany. Treatment with terbutaline and magnesium sulfate was unsuccessful in alleviating the uterine hypertonus, necessitating cesarean section.

[Dinoprostone: slow release vaginal insert (Propess) and intracervical gel (Prepidil) for the induction of labour with unriped cervix]. / Dinoprostone: inserto vaginale a lento rilascio (Propess) e gel intracervicale (Prepidil) nell'induzione del travaglio di parto con Bishop score sfavorevole.

AIM: The purpose of the present study is to compare the effectiveness and safety of a slow release vaginal PGE2 insert (Propess) with intracervical PGE2 gel (Prepidil gel) in the induction of cervical ripening and labour. METHODS: For the induction of labour we selected 103 single pregnancies at term presenting a Bishop score of less than 5. Fifty-one were induced with Propess, and 52 with intracervical Prepidil. RESULTS: The 2 groups were homogeneous as regards indications to induction and obstetric characteristics. The success of induction (achievement of uncomplicated vaginal delivery) was comparable in the 2 groups: Propess 67%, Prepidil 65%. The times needed to induce labour were on average longer with Propess (16 h 59 min) than with Prepidil (12 h 54 min), (p<0.05); nevertheless the time needed to achieve delivery by the vaginal route within 24 hours was comparable (49% vs 48%). The number of patients requiring more than one application of prostaglandin was less in the Propess group (5.9%) than in the Prepidil group (55.8%) (p<0.001). The times relative to dilation and expulsion did not differ significantly. Resort to cesarean section for fetal indication (cardiotocographic changes) was greater in inductions with Prepidil (8 cases) compared to Propess (2 cases), p<0.05. CONCLUSION: The systems proved equally effective, nevertheless Propess seems to be safer thanks to the lower incidence of cardiotocographic changes such as to indicate urgent cesarean section. Propess would seem to be more acceptable on the part of patients thanks to the smaller number of applications necessary.

Acute leukemia and pregnancy. Case report.

In this case report we describe a case of acute myeloid leukemia (AML; FAB M4) diagnosed in a 27-year-old female at the 20th week of gestation. After informed consent, the patient chose to undergo anti-leukemic treatment without therapeutic abortion. Complete remission was obtained following standard chemotherapy for AML (doxorubicin, cytosin-arabinoside, 6-thioguanine). The patient successively underwent an autologous bone marrow transplant (ABMT). No fetal malformation was observed. Urgent cesarean section was necessary at the 29th gestational week because of the onset of foetal sufferance. Fourteen months after diagnosis and seven months after ABMT the patient died due to relapse of AML. The child is presently 3.5 year old and well. In our opinion, the care of a pregnant woman with acute leukemia is feasible and it needs a multi-specialist effort that is easier to be achieved in a tertiary care institution.