Performance of a Multianalyte 'Rule-Out' Assay in Pregnant Individuals With Suspected Preeclampsia.

BACKGROUND: The ability to diagnose preeclampsia clinically is suboptimal. Our objective was to validate a novel multianalyte assay and characterize its performance, when intended for use as an aid to rule-out preeclampsia. METHODS: Prospective, multicenter cohort study of pregnant individuals presenting between 280/7 and 366/7 weeks' with preeclampsia-associated signs and symptoms. Individuals not diagnosed with preeclampsia after baseline evaluation were enrolled in the study cohort, with those who later developed preeclampsia, classified as cases and compared with a negative control group who did not develop preeclampsia. Individuals with assay values at time of enrollment ≥0.0325, determined using a previously developed algorithm, considered at risk. The primary analysis was the time to develop preeclampsia assessed using a multivariate Cox regression model. RESULTS: One thousand thirty-six pregnant individuals were enrolled in the study cohort with an incidence of preeclampsia of 30.3% (27.6%-33.2%). The time to develop preeclampsia was shorter for those with an at-risk compared with negative assay result (log-rank P<0.0001; adjusted hazard ratio of 4.81 [3.69-6.27, P<0.0001]). The performance metrics for the assay to rule-out preeclampsia within 7 days of enrollment showed a sensitivity 76.4% (67.5%-83.5%), negative predictive value 95.0% (92.8%-96.6%), and negative likelihood ratio 0.46 (0.32-0.65). Assay performance improved if delivery occurred <37 weeks and for individuals enrolled between 28 and 35 weeks. CONCLUSIONS: We confirmed that a novel multianalyte assay was associated with the time to develop preeclampsia and has a moderate sensitivity and negative likelihood ratio but high negative predictive value when assessed as an aid to rule out preeclampsia within 7 days of enrollment. REGISTRATION: The study was registered on Clinicaltrials.gov (Identifier NCT02780414).

Prediction of maternal and fetal pharmacokinetics of indomethacin in pregnancy.

AIMS: Indomethacin is used for the treatment of preterm labour, short cervices and idiopathic polyhydramnios during pregnancy. Few studies have described the pharmacokinetics (PK) of indomethacin during pregnancy. This study aimed to determine maternal and fetal PK of indomethacin during different trimesters of pregnancy using physiologically based PK (PBPK) modelling and simulations. METHODS: Full PBPK simulations were performed in nonpregnant subjects and pregnant subjects from each trimester of pregnancy at steady state using Simcyp's healthy volunteers and pregnancy PBPK model, respectively. The fetal exposures were predicted using a fetoplacental pregnancy PBPK model. The models were verified by comparing PBPK-based predictions with observed PK profiles. RESULTS: Predicted exposure (AUC0-6h ) and clearance of indomethacin in nonpregnant women and pregnant women are similar to the clinical observations. AUC0-6h of indomethacin is approximately 14, 24 and 32% lower, consistent with 18, 34 and 52% higher clearance in the first, second and third trimesters of pregnancy, respectively, compared to nonpregnant women. Predicted fetal plasma exposures increased by approximately 30% from the second trimester to the third trimester of pregnancy. CONCLUSION: A mechanistic PBPK model adequately described the maternal and the fetal PK of indomethacin during pregnancy. As the pregnancy progresses, a modest decrease (≤32%) in systemic exposures in pregnant women and a 33% increase in fetal exposures to indomethacin were predicted. Higher fetal exposures in the third trimester of pregnancy may pose safety risks to the fetus. Additional studies are warranted to understand the exposure-response relationship and provide appropriate dosing recommendations during pregnancy that consider both safety and efficacy.

Predictors of vaginal delivery after cervical ripening using a synthetic osmotic dilator.

OBJECTIVE: To evaluate the determinants of vaginal delivery and safety in women undergoing cervical ripening with a synthetic osmotic dilator (Dilapan-S) prior to induction of labor. METHODS: We conducted a secondary analysis of an international multicenter prospective observational study of Dilapan-S for cervical ripening in pregnancies greater than 32 weeks. Data were obtained in a standardized fashion and entered into a centralized electronic data capture system. The association between Bishop score and vaginal delivery was further evaluated with a multivariate receiver-operating characteristic (ROC) curve analysis. A Wilcoxon rank test and multivariable logistic regression were used for statistical analysis (significance: P < .05). RESULTS: Between May 2015 and July 2016, 444 pregnant women were included. Three hundred ten (70 %) delivered vaginally. Compared to patients who underwent cesarean delivery, those who delivered vaginally were more likely to have a history of prior vaginal delivery. Vaginal delivery rates were significantly correlated with Bishop scores of pre and post Dilapan-S and difference. After adjusting for age, BMI, number of dilators, cervical ripening time, and gestational age, both prior vaginal delivery and post-Dilapan-S Bishop scores were strong predictors of vaginal delivery (estimate coefficient: 0.1275 ± 0.03 P = .0002; 0.049 ± 0.01 P = .0001; respectively). Aggregate ROC accounting for these variables further supported these findings (AUC = 0.734). The lower confidence interval limit of vaginal delivery rates was above 50 % when post-Dilapan-S Bishop scores were ≥ 5. Cox regression analyses demonstrated that the duration of labor was significant shorter in women that had vaginal delivery. CONCLUSION: Bishop scores after cervical ripening with Dilapan-S are good predictors of vaginal delivery. Bishop scores < 5 post Dilapan-S may warrant further cervical ripening. Further level 1 trials are needed to compare osmotic dilators to other ripening methods.

Effects of Pregnancy on the Pharmacokinetics of Metformin.

This study's primary objective was to fully characterize the pharmacokinetics of metformin in pregnant women with gestational diabetes mellitus (GDM) versus nonpregnant controls. Steady-state oral metformin pharmacokinetics in pregnant women with GDM receiving either metformin monotherapy (n = 24) or a combination with glyburide (n = 30) as well as in nonpregnant women with type 2 diabetes mellitus (T2DM) (n = 24) were determined utilizing noncompartmental techniques. Maternal and umbilical cord blood samples were collected at delivery from 38 women. With both 500- and 1000-mg doses, metformin bioavailability, volume of distribution beta (V ß ), clearance, and renal clearance were significantly increased during pregnancy. In addition, in the women receiving metformin 500 mg, significantly higher metformin apparent oral clearance (CL/F) (27%), weight-adjusted renal secretion clearance (64%), and apparent oral volume of distribution beta (V ß /F) (33%) were seen during pregnancy. Creatinine clearance was significantly higher during pregnancy. Increasing metformin dose from 500 to 1000 mg orally twice daily significantly increased V ß /F by 28%, weight-adjusted V ß /F by 32% and CL/F by 25%, and weight-adjusted CL/F by 28% during pregnancy. Mean metformin umbilical cord arterial-to-venous plasma concentration ratio was 1.0 ± 0.1, venous umbilical cord-to-maternal concentration ratio was 1.4 ± 0.5, and arterial umbilical cord-to-maternal concentration ratio was 1.5 ± 0.5. Systemic exposure after a 500-mg dose of metformin was lower during pregnancy compared with the nonpregnant women with T2DM. However, in patients receiving metformin 1000 mg, changes in estimated bioavailability during pregnancy offset the changes in clearance leading to no significant change in CL/F with the higher dose. SIGNIFICANCE STATEMENT: Gestational diabetes mellitus complicates 5%-13% of pregnancies and is often treated with metformin. Pregnant women undergo physiological changes that alter drug disposition. Preliminary data suggest that pregnancy lowers metformin concentrations, potentially affecting efficacy and safety. This study definitively describes pregnancy's effects on metformin pharmacokinetics and expands the mechanistic understanding of pharmacokinetic changes across the dosage range. Here we report the nonlinearity of metformin pharmacokinetics and the increase in bioavailability, clearance, renal clearance, and volume of distribution during pregnancy.

Amniotic fluid embolism: principles of early clinical management.

Amniotic fluid embolism is an uncommon, but potentially lethal, complication of pregnancy. Because amniotic fluid embolism usually is seen with cardiac arrest, the initial immediate response should be to provide high-quality cardiopulmonary resuscitation. We describe key features of initial treatment of patients with amniotic fluid embolism. Where available, we recommend performing transthoracic or transesophageal echocardiography as soon as possible because this is an easy and reliable method of identifying a failing right ventricle. If such failure is identified, treatment that is tailored at improving right ventricular performance should be initiated with the use of inotropic agents and pulmonary vasodilators. Blood pressure support with vasopressors is preferred over fluid infusion in the setting of severe right ventricular compromise. Amniotic fluid embolism-related coagulopathy should be managed with hemostatic resuscitation with the use of a 1:1:1 ratio of packed red cells, fresh frozen plasma, and platelets (with cryoprecipitate as needed to maintain a serum fibrinogen of >150-200 mg/dL). In cases that require prolonged cardiopulmonary resuscitation or, after arrest, severe ventricular dysfunction refractory to medical management, consideration for venoarterial extracorporeal membrane oxygenation should be given.

Validation of a new method to assess estimated blood loss in the obstetric population undergoing cesarean delivery.

BACKGROUND: Postpartum hemorrhage is the leading cause of maternal mortality in developing countries and the primary cause of one-quarter of all maternal deaths globally. Inaccuracy in estimating blood loss obscures the diagnosis of postpartum hemorrhage and its management. OBJECTIVE: Our objective was to compare assessment of blood loss using the quantitative Triton system (Gauss Surgical, Inc, Los Altos, CA) with other measures of blood loss in women undergoing cesarean delivery. STUDY DESIGN: Women scheduled for cesarean deliveries at our facility were included. Intraoperative blood loss was measured using the Triton, which was masked to the clinical team, as well as estimated by the surgeon (subjective estimated blood loss). The relation between the 2 methods (Triton and subjective estimated blood loss) and postoperative hemoglobin as well as delta hemoglobin (postoperative minus preoperative hemoglobin) was determined using the Spearman correlation. Triton measurement and subjective estimated blood loss were compared between women with delta hemoglobin in the upper quartile (cases) vs all other quartiles (control). Prediction of delta hemoglobin in the upper quartile also was evaluated for each method, and the area under the receiver operating characteristic curves was compared. RESULTS: The trial enrolled 242 patients. The mean blood loss estimated by the Triton device was significantly lower than that estimated by clinical judgment (415.3±260.6 vs 799.6±215.6 mL, P<.01). The Triton estimate correlated best with delta hemoglobin. Seventy patients had delta hemoglobin in the upper quartile (delta hemoglobin ≥2). There was a significant difference in the Triton blood loss measurement between cases and controls but no difference with subjective estimated blood loss. Triton, but not subjective estimated blood loss, was predictive of delta hemoglobin ≥2 g/dL (Triton: area under the receiver operating characteristic curve, 0.66; 95% confidence interval, 0.58-0.74; P<.01 vs subjective estimated blood loss: area under the receiver operating characteristic curve, 0.53; 95% confidence interval, 0.45-0.61; P=.45). CONCLUSIONS: The Triton system provides a better estimate of blood loss than the visual estimate. Clinical trials to evaluate its benefit are warranted.

Acute Management of Ischemic Stroke During Pregnancy.

Acute stroke in pregnancy can be devastating. Although neurologists will at some point be involved in the management, most of these patients are likely to first be evaluated by an obstetric care provider. It is, therefore, important for obstetric care providers to have an understanding of the presentation and management of stroke, particularly in the initial period when the window of opportunity for therapy is critical. Once suspected, a head computed tomography (CT) without contrast media should be performed without delay to rule out a hemorrhagic component. Patients presenting within 4.5 hours of symptom onset and with an initial normal head CT scan are candidates for alteplase (tissue plasminogen activator [tPA]). Blood pressure (BP) control is paramount when administering tPA. During pregnancy, we recommend maintaining a BP between 140-160/90-110 mm Hg during tPA treatment. Pregnancy should not be a contraindication for mechanical thrombectomy in carefully selected patients. The use of therapeutic anticoagulation during the acute management of ischemic stroke is not indicated owing to an increased risk of hemorrhagic transformation. Supportive therapy should include aggressive treatment of fever, avoidance of hypotonic maintenance fluids, and maintenance of normal serum sodium levels. Serum glucose levels should be kept between 140 and 180 mg/dL. Antiplatelet agents are indicated for secondary prevention. The management of cerebral venous sinus thrombosis, carotid and vertebral dissections, and reversible cerebral vasoconstrictive disease should overall follow same guidelines as for nonpregnant individuals.

A randomized controlled trial of Dilapan-S vs Foley balloon for preinduction cervical ripening (DILAFOL trial).

OBJECTIVE: The objective of the study was to test the hypothesis that Dilapan-S is not inferior to the Foley balloon for preinduction cervical ripening at term. STUDY DESIGN: Pregnant women ≥37 weeks scheduled for induction with unfavorable cervix (≤3 cm dilated and ≤60% effaced) were randomly assigned to 12 hours of either Foley balloon inflated with 60 mL saline or Dilapan-S for cervical ripening. If the cervix remained unfavorable, then 1 more round of the assigned dilator was used. Management following ripening was left up to the clinical providers. The primary outcome was vaginal delivery. A satisfaction survey was also obtained after the preinduction period. Sample size was based on a noninferiority margin of 10%, 90% power, and an estimated frequency of vaginal delivery of 71% in Foley balloon and 76% in Dilapan-S. RESULTS: From November 2016 through February 2018, 419 women were randomized (209 to Foley balloon; 210 to Dilapan-S). In the intent-to-treat analysis, vaginal delivery was more common in Dilapan-S vs Foley balloon (81.3% vs 76.1%), with an absolute difference with respect to the Foley balloon of 5.2% (95% confidence interval, -2.7% to 13.0%) indicating noninferiority for the prespecified margin. The difference was not large enough to show superiority. Noninferiority was confirmed in the per-protocol population (n = 204 in the Foley balloon, n = 188 in Dilapan-S), supporting the robustness of the results. Secondary outcomes were not different between groups, except for a longer time the device remained in place in Dilapan-S compared with the Foley balloon. Maternal and neonatal adverse events were not significantly different between groups. A priori interaction analyses showed no difference in the effect on vaginal delivery by cervical dilation at randomization, parity, or body mass index >30 kg/m2. Patients with Dilapan-S were more satisfied than patients with the Foley balloon as far as sleep (P = .01), relaxing time (P = .001), and performance of desired daily activities (P = .001). CONCLUSION: Dilapan-S is not inferior to the Foley balloon for preinduction cervical ripening at term. Advantages of Dilapan-S over Foley include Food and Drug Administration approval, safe profile, no protrusion from the introitus, no need to keep under tension, and better patient satisfaction.

Transabdominal recordings of fetal heart rate in extremely small fetuses.

INTRODUCTION: As part of the fetal assessment for the Safe Passage Study, we recorded raw data of the fetal ECG via five maternal abdominal wall electrodes from 20 weeks to 23 weeks 6 days' gestation. MATERIALS: For this study were extracted and analyzed the FHR patterns from the stored raw data in 16 stillbirths where the fetus weighed less than 1000 g and where autopsy was performed. RESULTS: Birth weights ranged from 190 to 970 g. The proportion FHR signal loss ranged from 0.3% to 21.1%. In the smallest fetus the heart weighed 1.3 g, yet the FHR signal loss was only 0.9%.

Performance of Risk Assessment Models for Peripartum Thromboprophylaxis.

OBJECTIVE: There is no consensus on which risk stratification approach to use for thromboprophylaxis in pregnancy, and most available risk assessment models (RAMs) for venous thromboembolism (VTE) events have not been validated in pregnancy. Our objective was to compare the performance of some of the most commonly used VTEs RAMs in our patient population in the peripartum period. STUDY DESIGN: This is a retrospective cohort of women who delivered at our institution in 2015 and 2016. We excluded patients with history of prior or current VTEs or those already receiving anticoagulants. Antepartum, intrapartum, and postpartum records were reviewed. Data were collected on known risk factors for VTEs in order to calculate scores for 3 RAMs on admission for delivery: Padua, Caprini, and Royal College of Obstetricians and Gynaecologists (RCOG). The primary objective was to the estimate the performance of the various RAMs in preventing postpartum VTEs. We calculated the proportion of women who would have been high risk, determined the number of VTEs cases within high- and low-risk categories, as well as calculated the number needed to treat (NNT) for each RAM. We performed analyses using different RAM scores cutoffs, VTEs outcome rates, and effectiveness of anticoagulation to prevent VTEs. The P value <.05 was considered statistically significant. RESULTS: A total of 6094 women were included. Three women had VTEs for an overall rate of 0.04% (N = 3; 95% confidence interval [CI]: 0.01-0.15). The proportion of women categorized as high risk for VTEs were 62% (95% CI: 61-64) for RCOG, 0.8% (95% CI: 0.6-1.0) for Padua, and 94% (95% CI: 94-95) for Caprini. Of the 3 VTEs, the RCOG model classified 1 woman as high risk and Padua model classified 3 women as high risk; whereas the Caprini did not identify any women as high risk. Assuming 100% effectiveness of thromboprophylaxis, the observed NNT was 3838 using RCOG, not able to calculate using Padua (no VTEs cases occurred in the high-risk group, thus none were prevented), and 1927 using Caprini. CONCLUSION: The rates of VTEs in pregnancy are very low and the available RAMs do not identify most of them. The RCOG and Caprini RAMs would categorize a large proportion of women as high risk and are associated with high NNTs. The Padua RAM appears to have the lowest NNT but missed all the VTEs in our cohort.

Effect of CYP2C9 Polymorphisms on the Pharmacokinetics of Indomethacin During Pregnancy.

BACKGROUND AND OBJECTIVE: Cytochrome P450 (CYP) 2C9 catalyzes the biotransformation of indomethacin to its inactive metabolite O-desmethylindomethacin (DMI). The aim of this work was to determine the effect of CYP2C9 polymorphisms on indomethacin metabolism in pregnant women. METHODS: Plasma concentrations of indomethacin and DMI at steady state were analyzed with a validated LC-MS/MS method. DNA was isolated from subject blood and buccal smear samples. Subjects were grouped by genotype for comparisons of pharmacokinetic parameters. RESULTS: For subjects with the *1/*2 genotype, the mean steady-state apparent oral clearance (CL/Fss) of indomethacin was 13.5 ± 7.7 L/h (n = 4) and the mean metabolic ratio (AUCDMI/AUCindomethacin) was 0.291 ± 0.133. For subjects with the *1/*1 genotype, these values were 12.4 ± 2.7 L/h and 0.221 ± 0.078, respectively (n = 14). Of note, we identified one subject who was a carrier of both the *3 and *4 alleles, resulting in an amino acid change (I359P) which has not been reported previously. This subject had a metabolic ratio of 0.390 and a CL/Fss of indomethacin (24.3 L/h) that was nearly double the wild-type clearance. CONCLUSION: Although our results are limited by sample size and are not statistically significant, these data suggest that certain genetic polymorphisms of CYP2C9 may lead to an increased metabolic ratio and an increase in the clearance of indomethacin. More data are needed to assess the impact of CYP2C9 genotype on the effectiveness of indomethacin as a tocolytic agent.

Cervical Ripening Using Foley Balloon with or without Oxytocin: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess available evidence regarding the use of oxytocin in conjunction with Foley balloon (FB) for cervical ripening. METHODS: Databases from MEDLINE (U.S. National Library of Medicine, 1980-May 12, 2017), MEDLINE (Ovid, 1980-June 30, 2017), the Cochrane Library Controlled Trials Register, ClinicalTrials.gov, and Web of Science were queried for studies on FB cervical ripening with or without oxytocin in pregnant women. Search terms included: "balloon dilatation" OR "mechanical methods" OR "mechanical method" OR "mechanical dilation" OR "mechanical dilatation" OR "mechanical dilations" OR "mechanical dilatations" OR "balloon" OR "Foley" AND "Pitocin" OR "oxytocin." All relevant references were reviewed. Literature for inclusion and methodological quality were reviewed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. RESULTS: Out of 344 citations, six randomized clinical trials (1,133 patients) fulfilled our inclusion criteria. The pooled estimate showed that the cesarean delivery (CD) rate did not differ (relative risk [RR]: 0.91 (95% confidence interval [CI] [0.76-1.10]; p = 0.23) between patients who underwent preinduction cervical ripening with FB alone versus those who received oxytocin in addition to FB. Heterogeneity was not significant among studies (I 2 0.0%; p = 0.64). Furthermore, no differences in other outcomes such as composite and maternal outcomes were detected between these two groups. Compared with simultaneous use of oxytocin with FB, the Foley alone cervical ripening group had a longer induction to delivery time, and lower deliveries within 12 and 24 hours. Subgroup analysis showed that only multiparous women in the Foley alone group had lower rate of vaginal delivery within 24 hours (RR: 0.74, 95% CI [0.61-0.89], p = 0.002) along with a trend toward higher CD rates. CONCLUSION: Adding oxytocin to FB at the time of preinduction cervical ripening does not reduce cesarean rates nor improve maternal or neonatal outcomes. Multiparous women who received FB alone seem to have lower rates of vaginal deliveries within 24 hours, but these results should be interpreted with caution.

Medical management of postpartum hemorrhage: An update.

Obstetrical hemorrhage is the most common cause of maternal mortality worldwide. Together with adequate surgical control and judicious transfusion of blood products, the use of pharmacological agents (e.g., tranexamic acid) and clotting factor concentrates (e.g., fibrinogen concentrates and prothrombin complex concentrates) results in improved hemostasis and decreased bleeding-associated mortality. Guidance in the administration of these agents with the use of viscoelastic testing will likely become standard of care in the near future.

Progressive Devascularization: A Novel Surgical Approach for Placenta Previa.

Background The gold standard for antenatal diagnosis of placenta previa is the transvaginal ultrasonography. In placenta previa cases, separation of placental and uterine tissues is challenging even for the most experienced surgeons. Life-threatening obstetrical complications from cesarean deliveries with placenta previa include peripartum hemorrhage, coagulopathy, blood transfusion, peripartum hysterectomy, and multiple organ failure. Cases We detailed the 3 cases of placenta previa that underwent bilateral uterine artery ligation; if hemostasis was not achieved, horizontal mattress sutures were placed in the lower uterine segment. All patients were discharged with minimal morbidity. Conclusion For patients with placenta previa and low risk for placenta creta, counseling should include the risk for maternal morbidity and criteria for pursuing peripartum hysterectomy. Our devascularization, a stepwise surgical approach, shows promising outcomes in placenta previa cases. Précis We propose a novel surgical approach, using a progressive devascularization surgical technique, for management of women with placenta previa, undergoing cesarean delivery.

Damage-Control Surgery for Obstetric Hemorrhage.

Damage-control surgery (abdominopelvic packing followed by a period of medical stabilization in the intensive care unit) is a life-saving intervention usually reserved for critically injured patients who may not survive an attempt to achieve hemostasis and complete repair of the damage in the operating room. Most obstetricians have little or no experience in this area, although the use of damage-control surgery in selected cases may be life-saving. This approach should be considered when arterial bleeding has been controlled and persistent bleeding is deemed to be secondary to coagulopathy that is refractory to blood product replacement, particularly in the presence of hypothermia, acidosis, and vasopressor requirement. A prototypical (albeit hypothetical) case is described here in which damage-control surgery is indicated.

Genetic Variation, Magnesium Sulfate Exposure, and Adverse Neurodevelopmental Outcomes Following Preterm Birth.

OBJECTIVE: To evaluate the association of magnesium sulfate (MgSO4) exposure and candidate gene polymorphisms with adverse neurodevelopmental outcomes following preterm birth. STUDY DESIGN: We performed a nested case-control analysis of a randomized trial of maternal MgSO4 before anticipated preterm birth for the prevention of cerebral palsy (CP). Cases were children who died within 1 year of life or were survivors with abnormal neurodevelopment at age 2 years. Controls were race- and sex-matched survivors with normal neurodevelopment. We analyzed 45 candidate gene polymorphisms in inflammation, coagulation, and vascular regulation pathways and their association with (1) psychomotor delay, (2) mental delay, (3) CP, and (4) combined outcome of death/CP. Logistic regression analyses, conditional on maternal race and child sex, and adjusted for treatment group, gestational age at birth and maternal education, were performed. RESULTS: Four hundred and six subjects, 211 cases and 195 controls, were analyzed. The strongest association was for IL6R (rs 4601580) in which each additional copy of the minor allele was associated with an increased risk of psychomotor delay (adjusted odds ratio 3.3; 95% confidence interval, 1.7-6.5; p < 0.001). CONCLUSION: Candidate gene polymorphisms are associated with death and adverse neurodevelopmental outcomes following preterm birth. MgSO4 may abrogate this genotype association for some loci.

Stroke Volume Recruitability during the Third Trimester of Pregnancy.

OBJECTIVE: It is unknown whether the heart operates in the ascending or flat portion of the Starling curve during normal pregnancy. Pregnant women do not respond to the passive leg-raising maneuver secondary to mechanical obstruction of the inferior vena cava by the gravid uterus. Our objective was to evaluate if administration of a fluid bolus increases baseline stroke volume (SV) among healthy pregnant patients during the third trimester. STUDY DESIGN: Healthy pregnant women who underwent elective term cesarean sections were included. A noninvasive cardiac output monitor was used to measure hemodynamic variables at baseline and after administration of a 500-mL crystalloid bolus. RESULTS: Forty-five women were included in the study. Fluid administration was associated with a statistically significant increase in SV from a baseline value of 71 ± 11 to 90 ± 19 mL (95% confidence interval [CI]: 13.67-21.49; p < 0.01) and a significant decrease in maternal heart rate from a baseline of 87 ± 9 beats per minute to 83 ± 8 after the fluid bolus (95% CI: -6.81 to -2.78; p = 0.03). No changes in peripheral vascular resistances or any other measured hemodynamic parameters were noted with volume expansion. CONCLUSION: In healthy term pregnancy, the heart operates in the ascending portion of the Starling's curve, rendering it fluid responsive.

Extracorporeal membrane oxygenation (ECMO) during pregnancy and postpartum.

Extracorporeal membrane oxygenation (ECMO) can provide respiratory support (VV-ECMO) or both respiratory and circulatory support (VA-ECMO). The use of ECMO has increased dramatically as a result of simpler technology. No level I evidence is yet available reflecting improved outcomes with ECMO. The use of this technology during pregnancy may be indicated in very select cases and should be delivered in centers with dedicated ECMO specialized units.

Tranexamic Acid for the Management of Obstetric Hemorrhage.

Obstetric hemorrhage remains the most common cause of maternal mortality worldwide. It is believed that increased fibrinolytic activity, secondary to release and activation of endothelial tissue plasminogen activator, is involved in its pathogenesis. Tranexamic acid (TXA), an antifibrinolytic agent, has been shown to be beneficial in trauma patients if used within 3 hours of injury. A recent large randomized controlled trial showed that TXA given to hemorrhaging women within 3 hours after delivery was associated with decreased risk of death resulting from bleeding with no increase in thromboembolic complications. Limited evidence suggests that prophylactic TXA reduces blood loss at the time of delivery and decreases transfusion rates in the obstetric population. Tranexamic acid appears to be a safe and effective option in the treatment of obstetric hemorrhage. In addition, the limited available evidence supports the need for a well-designed adequately powered clinical trial to test its benefit as a prophylactic agent.