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The topics of neonatal encephalopathy and cerebral palsy, as well as hypoxic-ischemic encephalopathy, are of paramount importance to anyone who ventures to deliver infants. Criteria sufficient to define an acute intrapartum hypoxic event as sufficient to cause cerebral palsy have been advanced previously by both The American College of Obstetricians and Gynecologists (ACOG) and the International Cerebral Palsy Task Force. ACOG convened a task force that over the past 3 years reviewed these criteria based upon advances in scientific knowledge. In this review, we cover the slow but steady progression toward defining the pathogenesis and pathophysiology of neonatal encephalopathy and cerebral palsy. Four essential criteria are also advanced as prerequisites if one is to propose that an intrapartum hypoxic-ischemic insult has caused a moderate to severe neonatal encephalopathy that subsequently results in cerebral palsy. Importantly, all four criteria must be met: 1) evidence of metabolic acidosis in fetal umbilical cord arterial blood obtained at delivery (pH less than 7 and base deficit of 12 mmol/L or more), 2) early onset of severe or moderate neonatal encephalopathy in infants born at 34 or more weeks' gestation, 3) cerebral palsy of the spastic quadriplegic or dyskinetic type, and 4) exclusion of other identifiable etiologies, such as trauma, coagulation disorders, infectious conditions, or genetic disorders. Other criteria that together suggest intrapartum timing are also discussed. [ABSTRACT FROM AUTHOR]

The rate of cerebral palsy has not decreased in developed countries over the past 30 years, despite the widespread use of electronic fetal heart rate monitoring and a 5-fold increase in the cesarean delivery rate over the same period of time. However, neonatal survival has improved during these decades. These observations have lead to the hypothesis that increased survival of premature, neurologically impaired infants may have masked an actual reduction in cerebral palsy among term infants as a result of the use of electronic monitoring and the avoidance of intrapartum asphyxia. A review of the medical literature, as well as a demographic analysis of term and preterm birth rates in the United States, refutes this hypothesis on four grounds. First, cerebral palsy prevalence has been separately analyzed in term infants and shows no change over 30 years. Second, the prevalence of cerebral palsy is the same or lower in underdeveloped countries than in developed nations; in the former, the availability of emergency cesarean delivery based on electronic monitor data is limited or absent. Third, the increase in prevalence of cerebral palsy among low-birth-weight infants and the increase in cesarean sections based on presumed fetal distress were not simultaneous events-the former preceded the latter by a decade. Improved neonatal survival since the 1980s has been associated with a stable or decreasing rate of neurologic impairment and thus could not have obscured improvement from reduced term asphyxia. Finally, compared with the number of infants born by cesarean section for fetal distress, there are simply not enough infants born in the most vulnerable weight groups to make any impact on even a minimal improvement of outcome in the group delivered by cesarean section for presumed fetal distress. Except in rare instances, cerebral palsy is a developmental event that is unpreventable given our current state of technology. [ABSTRACT FROM AUTHOR]

Adopting a universal definition of stillbirth and linking the results of a placental examination and autopsy to the fetal death certificate can help us collect the accurate data needed to address this major public health problem. Two experts in maternal fetal medicine include these recommendations in their list of imperatives. [ABSTRACT FROM AUTHOR]

Defined as any blood loss that cannot be compensated for physiologically, PPH can sometimes be prevented with prostaglandins. An effective treatment strategy may include IV fluids, packed RBCs, oxytocin, and/or surgery [ABSTRACT FROM AUTHOR]

With an associated maternal mortality rate of 61 and long-term neurologic complications in most surviving women and infants, AFE warrants special vigilance in evaluating symptoms and instituting treatment. This review describes a wide range of diagnostic and therapeutic modalities. [ABSTRACT FROM AUTHOR]

Experts walk you through the steps in successfully turning around a risky breech presentation--in hopes of avoiding a cesarean. [ABSTRACT FROM AUTHOR]

Objective: It has been shown that the level of soluble fms-like tyrosine kinase-1 (sFlt-1) is elevated in pregnant women who are destined to have preeclampsia, and a role for sFlt-1 in its pathogenesis has been suggested. Our objective was to determine the effect of the over-expression of sFlt-1 on blood pressure and the occurrence of other manifestations of preeclampsia in pregnant mice. Study Design: At day 8 of gestation CD-1 mice were allocated randomly to an injection of an adenovirus carrying sFlt-1 (10(9) plaque-forming units; sFlt-1 group), adenovirus carrying the murine immunoglobulin G2alpha Fc fragment (10(9) plaque-forming units; mFc group used as a control for the virus) or saline solution (100 microL; saline group). At day 10 of gestation, blood pressure catheters were inserted through the left carotid artery into the aortic arch and tunneled to a telemetric transmitter. Blood pressure was monitored continuously in the conscious unrestrained animals until day 18. Blood was collected from the pregnant mice at different gestational times, and plasma sFlt-1 was measured by enzyme-linked immunosorbent assay. Pups and placentae were weighed, and maternal platelet counts were determined at death on day 18. Results: Plasma levels of sFlt-1 increased significantly in the sFlt-1 mice and were significantly higher than the 2 control groups. The mean blood pressure in the sFlt-1 mice was significantly higher on days 17 and 18 of gestation, compared with the mFc and saline solution groups. The time-course of blood pressure rise mirrored that of the sFlt-1 levels. The average pup weight, placental weight, and maternal platelet counts were significantly lower in the sFlt-1 group, compared with the controls. Conclusion: SFlt-1 induces hypertension and fetal growth restriction in pregnant mice, which supports its hypothesized role in the pathogenesis of preeclampsia. This animal model minimizes the need for manipulation or the administration of various compounds to induce the condition. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to determine whether fetal programming of adult blood pressure is altered in a previously characterized mouse model of preeclampsia that was induced by sFlt-1. STUDY DESIGN: CD-1 mouse mothers at day 8 of gestation were injected with an adenovirus carrying Flt 1-3 (10(9) plaque-forming units) or with an adenovirus carrying mFc as control (10(9) plaque-forming units). The resulting pups were followed until 6 months of age, at which time blood pressure (BP) was recorded continuously for 6 days. The offspring weight was also recorded from weaning until adulthood. RESULTS: BP was significantly higher in the male offspring that were born to sFlt-1-treated mothers compared with the controls. Male offspring from sFlt-1-treated mothers were significantly smaller from weaning until adulthood. However, there were no significant differences in BP and postweaning weight in female offspring between the 2 groups. CONCLUSION: Our findings highlight the role of the intrauterine environment in the developmental origin of adult disease. [ABSTRACT FROM AUTHOR]

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 (AUC 0-6h ) and clearance of indomethacin in nonpregnant women and pregnant women are similar to the clinical observations. AUC 0-6h 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., (© 2021 British Pharmacological Society.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

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%.

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/F ss ) of indomethacin was 13.5 ± 7.7 L/h (n = 4) and the mean metabolic ratio (AUC DMI /AUC indomethacin ) 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/F ss 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.

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., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To evaluate the association of magnesium sulfate (MgSO 4 ) 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 MgSO 4 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. MgSO 4 may abrogate this genotype association for some loci., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

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., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Bupropion (BUP) has a potential to be an effective pharmacotherapy for smoking cessation during pregnancy. Smoking during pregnancy stimulates placental carbonyl reductases that catalyze the biotransformation of BUP. 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) is a potent carcinogen of cigarette smoke. Carbonyl reduction of NNK into 4- methylnitrosamino-1-(3-pyridyl)-1-butanol (NNAL) constitutes a major step in NNK detoxification. Thus, placentas of pregnant smokers on BUP therapy can become a site of drug-drug interaction. Therefore, we investigated the effect of continuous exposure to BUP and cigarette smoke on the activity of placental carbonyl reductases in the formation of NNAL from NNK., Methods: The reductive metabolism of NNK was determined using microsomal and cytosolic subcellular fractions of placentas obtained from non-smoking women treated with BUP for depression, and women not exposed to BUP: non-smokers (control) and smokers. The effect of BUP and its metabolites on the reductive metabolism of NNK was investigated using subcellular fractions of control placentas., Results: The formation of NNAL from NNK by placental cytosolic fractions of heavy smokers (≥20 cigarettes per day) was lower than that of control (12.1±3.5 nmol.mgP-1 vs 16.5±6.0 nmol.mgP-1, P<0.05). While being exposed to BUP, the activity of placental carbonyl reductases remained unaffected, the formation of NNAL in the placental cytosolic fraction decreased only in the presence of high concentrations of BUP metabolites., Conclusion: Smoking during pregnancy decreases the detoxifying capacity of soluble carbonyl reductases towards NNK. Given the experimental conditions, exposure to BUP and its metabolites should not impede the reductive metabolism of NNK by placenta in vivo., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

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.

Background  Massive transfusion protocols (MTPs) have been examined in trauma. The exact ratio of packed red blood cells (PRBC) to other blood replacement components in hemostatic resuscitation in obstetrics has not been well defined. Objective  The objective of this study was to evaluate hemostatic resuscitation in peripartum hysterectomy comparing pre- and postinstitution of a MTP. Study Design  We conducted a retrospective, descriptive study of women undergoing peripartum hysterectomies from January 2002 to January 2015 who received ≥ 4 units of PRBC. Individuals were grouped into either a pre-MTP institution group or a post-MTP institution group. The post-MTP group was subdivided into those who had the protocol activated (MTP) versus not activated (no MTP). Primary outcomes were estimated blood loss (EBL) and need for blood product replacement. The secondary outcome was a composite of maternal morbidity, including need for mechanical ventilation, venous thromboembolism, pulmonary edema, acute kidney injury, and postpartum infection. A Mann-Whitney U test was used to compare continuous variables, and a chi-squared test was used for categorical variables with significance of p  < 0.05. Results  Of the 165 women who had a peripartum hysterectomy during the study period, 62 received four units or more of PRBC. No significant differences were noted in EBL or blood product replacement between the pre-MTP ( n  = 39) and post-MTP ( n  = 23) groups. Similarly, the MTP ( n  = 6) and no MTP ( n  = 17) subgroups showed no significant difference between EBL and overall blood product replacement. Significant differences were seen in transfusion of individual blood products, such as fresh frozen plasma (FFP) (MTP = 4, no MTP = 2; p  = 0.02) and platelets (plts) (MTP = 6, no MTP = 0; p  = 0.03). The use of high ratio replacement therapy for both plasma and plts was more common in the MTP group (FFP/PRBC ratio [MTP = 0.5, no MTP = 0.3; p  = 0.02]; plts/PRBC ratio [MTP = 0.7, no MTP = 0; p  = 0.03]). There were no differences in the secondary outcome between pre- and post-MTP or MTP and no MTP. Conclusion  Initiation of the MTP did result in an increase in transfusion of FFP and plts intraoperatively. At our institution, the MTP is underutilized, but it appears that providers are more cognizant of the use of high transfusion ratios., Competing Interests: Conflict of Interest: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Women with polycystic ovary syndrome (PCOS) are often presented with hyperandrogenemia along with vascular dysfunction and elevated blood pressure. In animal models of PCOS, anti-androgen treatment decreased blood pressure, indicating a key role for androgens in the development of hypertension. However, the underlying androgen-mediated mechanism that contributes to increased blood pressure is not known. This study determined whether elevated androgens affect endothelium-derived hyperpolarizing factor (EDHF)-mediated vascular relaxation responses through alteration in function of gap junctional proteins. Female rats were implanted with placebo or dihydrotestosterone (DHT) pellets (7.5 mg, 90-day release). After 12 weeks of DHT exposure, blood pressure was assessed through carotid arterial catheter and endothelium-dependent mesenteric arterial EDHF relaxation using wire myograph. Connexin expression in mesenteric arteries was also examined. Elevated DHT significantly increased mean arterial pressure and decreased endothelium-dependent EDHF-mediated acetylcholine relaxation. Inhibition of Cx40 did not have any effect, while inhibition of Cx37 decreased EDHF relaxation to a similar magnitude in both controls and DHT females. On the other hand, inhibition of Cx43 significantly attenuated EDHF relaxation in mesenteric arteries of controls but not DHT females. Elevated DHT did not alter Cx37 or Cx40, but decreased Cx43 mRNA and protein levels in mesenteric arteries. In vitro exposure of DHT to cultured mesenteric artery smooth muscle cells dose-dependently downregulated Cx43 expression. In conclusion, increased blood pressure in hyperandrogenic females is due, at least in part, to decreased EDHF-mediated vascular relaxation responses. Decreased Cx43 expression and activity may play a role in contributing to androgen-induced decrease in EDHF function., (© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Bupropion is used to treat depression during pregnancy. However, its usefulness as a smoking cessation aid for pregnant women is not fully known., Objective: The objective of the study was to evaluate the preliminary efficacy of bupropion sustained release for smoking cessation during pregnancy., Study Design: We conducted a randomized, prospective, double-blind, placebo-controlled, pilot trial. Pregnant women who smoked daily received individualized behavior counseling and were randomly assigned to a 12 week, twice-a-day treatment with 150 mg bupropion sustained release or placebo. The primary study objectives were to determine whether bupropion sustained release reduces nicotine withdrawal symptoms on the quit date and during the treatment period compared with placebo and whether it increases 7 day point prevalence abstinence at the end of the treatment period and at the end of pregnancy., Results: Subjects in the bupropion (n = 30) and placebo (n = 35) groups were comparable in age, smoking history, number of daily smoked cigarettes, and nicotine dependence. After controlling for maternal age and race, bupropion sustained release reduced cigarette cravings (1.5 ± 1.1 vs 2.1 ± 1.2, P = .02) and total nicotine withdrawal symptoms (3.8 ± 4.3 vs 5.4 ± 5.1, P = .028) during the treatment period. Administration of bupropion sustained release reduced tobacco exposure, as determined by levels of carbon monoxide in exhaled air (7.4 ± 6.4 vs 9.1 ± 5.8, P = .053) and concentrations of cotinine in urine (348 ± 384 ng/mL vs 831 ± 727 ng/mL, P = .007) and increased overall abstinence rates during treatment (19% vs 2%, P = .003). However, there was no significant difference in 7 day point prevalence abstinence rates between the 2 groups at the end of medication treatment (17% vs 3%, P = .087) and at the end of pregnancy (10% vs 3%, P = .328)., Conclusion: Individual smoking cessation counseling along with the twice-daily use of 150 mg bupropion sustained release increased smoking cessation rates and reduced cravings and total nicotine withdrawal symptoms during the treatment period. However, there was no significant difference in abstinence rates between groups at the end of medication treatment and at the end of pregnancy, likely because of the small sample size. A larger study is needed to confirm these findings and to examine the potential benefit/ risk ratio of bupropion sustained release for smoking cessation during pregnancy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Few conditions in medicine are plagued with as confusing and anachronistic terminology as the clinical variants of pregnancy-induced hypertension and preeclampsia. We propose a simple system of nomenclature that reflects both actual pathophysiology and standard 21st century medical terminology. Such a change would facilitate both rational, evidence-based clinical care, collaboration with other specialties, and research.

Objective: Endogenous digoxin-like factor (EDLF) has been linked to vasoconstriction, altered membrane transport, and apoptosis. Our objective was to determine whether increased EDLF in the cord sera of preterm infants was associated with an increased incidence of necrotizing enterocolitis (NEC)., Study Design: Cord sera from pregnant women enrolled in a randomized trial of MgSO4 for fetal neuroprotection were analyzed for EDLF using a red cell Rb(+) uptake assay in which the inhibition of sodium pump-mediated Rb(+) transport was used as a functional assay of EDLF. Specimens were assayed blinded to neonatal outcome. Cases (NEC, n = 25) and controls (neonates not developing stage 2 or 3 NEC, n = 24) were matched by study center and gestational age. None of the women had preeclampsia. Cases and controls were compared using the Wilcoxon test for continuous and the Fisher exact test for categorical variables. A conditional logistic regression analysis was used to assess the odds of case vs control by EDLF level., Results: Cases and controls were not significantly different for gestational age, race, maternal steroid use, premature rupture of membranes, or MgSO4 treatment. In logistic models adjusted for treatment group, race, premature rupture of membranes, and gestational age, cord sera EDLF was significantly associated with development of NEC (P = .023)., Conclusion: These data demonstrated an association between cord sera EDLF and NEC., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: To estimate the effects of pravastatin on the altered vascular function in a mouse model of preeclampsia induced by overexpression of soluble fms-like tyrosine kinase-1 (sFlt-1)., Methods: Pregnant CD1 mice, at day 8 of gestation, were randomly allocated to injection using the tail vein of the adenovirus carrying sFlt-1 (10 plaque-forming units in 100 microliters; sFlt-1 group) or mFc (10 plaque-forming units) as virus control, and then to receive pravastatin (Pra; 5 mg/kg/d) dissolved in drinking water or control. The mice in four groups (sFlt-1, sFlt-1-pravastatin, mFc, and mFc-pravastatin; n=4-6 per group) were killed at day 18 of gestation and 2-mm segments of carotid artery were used for vascular reactivity studies. Serum sFlt-1 levels were also measured by enzyme-linked immunosorbent assay., Results: Mice in the sFlt-1 group had the highest responses to phenylephrine. Treatment with pravastatin decreased the contractile responses to phenylephrine (maximal effect [mean+/-standard error of the mean] 137.35+/- 27.70 compared with 42.24+/-8.76; P=.006) for sFlt-1 compared with sFlt-1-pravastatin, respectively. There were no differences in the contractile responses to thromboxane A2. The vasorelaxant responses to acetylcholine were significantly highest in the mFc-pravastatin group, with a maximal effect of 108.37+/-5.25 compared with 89.77+/-3.96 in the mFc group (P=.008), and those with sodium nitroprusside were not different across the four groups. Serum sFlt-1 levels were not different at baseline (day 8) but were significantly lower in sFlt-1-pravastatin compared with sFlt-1 at day 18 (59.42+/-5.31 compared with 102.59+/-15.15 ng/mL; P=.01)., Conclusion: Pravastatin improved the vascular reactivity in this murine model of preeclampsia by decreasing sFlt-1 levels. Statins should be evaluated for the prevention of the vascular abnormalities of preeclampsia.

Objective: To validate a previously developed vaginal birth after cesarean (VBAC) prediction model using a patient cohort different than that from which it was derived., Methods: We performed a cohort study of all term pregnant women (January 2002-August 2007) with one prior low transverse cesarean delivery attempting a trial of labor. Variables used in the final prediction model (maternal age, prepregnancy body mass index, ethnicity, prior vaginal delivery, prior VBAC, and indication for prior cesarean delivery) were extracted from medical records and used to calculate an individual woman's predicted VBAC success rate. These rates at the level of the study population then were partitioned into deciles and compared with the actual VBAC rates., Results: Of 545 women who fit the inclusion criteria, 502 had complete data available. A total of 262 (52.2%) had VBAC. The predicted probability of VBAC, as calculated by the regression equation, was significantly higher in those who had a successful trial of labor (median 78.4%, interquartile range 62.1-88.2) than in those who did not (median 59.7%, interquartile range 50.8-75.3, P<.001). The predictive model had an area under the receiver operating characteristic of 0.70 (95% confidence interval 0.65-0.74, P<.001), which was similar to that originally described. The actual VBAC rates did not differ from the predicted rates when the predicted chance of success was less than 50%. Above a 50% predicted success, the achieved success rates were consistently 10-20% lower., Conclusion: The published nomogram is predictive of VBAC success. It may help pregnant women contemplating a trial of labor reach a more informed decision., Level of Evidence: II.