Anesthetic management with labor epidural analgesia of the parturient with severe factor VII deficiency: a case report.

BACKGROUND: Factor VII deficiency is considered a contraindication to neuraxial anesthesia due to the risk of an epidural hematoma. CASE REPORT: A 32 year old G1P0 parturient with severe factor VII deficiency presented for an anesthesiology consultation at 32 weeks gestation. Initial coagulation studies were significant for an elevated INR (2.0) and a low factor VII level of 6%. After interdisciplinary discussion, it was decided that neuraxial analgesia could be offered if her coagulation studies corrected after administration of recombinant activated factor VII (rFVIIa). The patient presented at 36 weeks gestation for a rFVIIa challenge. She received 22 mcg/kg rFVIIa and coagulation studies were analyzed 20 minutes later which showed complete correction of the coagulopathy. The patient presented to the hospital at 39 weeks and 3 days for delivery, received 2 mg rFVIIa and 20 minutes later, successfully received an epidural catheter. Her INR was monitored every 3 hours during her labor course and rFVIIa was given if the INR was 1.3 or greater. She required three additional doses over 22 hours. No bleeding or thrombotic events occurred, and the patient was discharged home without complications. CONCLUSION: This case highlights the safe management of an epidural catheter in a parturient with severe factor VII deficiency.

History of Cholestasis is not Associated with Worsening Outcomes in Subsequent Pregnancy with Cholestasis.

OBJECTIVE: Intrahepatic cholestasis of pregnancy is associated with adverse pregnancy outcomes including intrauterine fetal demise, spontaneous preterm labor, and meconium-stained amniotic fluid. Studies have yet to determine if patients with a history of pregnancy complicated by cholestasis had an association with more severe adverse outcomes in a subsequent pregnancy complicated by cholestasis. STUDY DESIGN: Retrospective cohort study of multiparous, singleton, nonanomalous live gestations complicated by cholestasis at Elmhurst Hospital Center from 2005 to 2019. We compared rates of adverse outcomes in multiparous pregnancies complicated by cholestasis with versus without prior cholestasis. Our primary outcome was rates of spontaneous preterm labor. Our secondary outcomes included rates of iatrogenic preterm birth, meconium-stained amniotic fluid, cesarean delivery for nonreassuring fetal heart tracing. Chi-square and multivariate regression tests were used to determine the strength of association. In all analyses, a p-value less than 0.05 and 95% confidence interval not crossing 1.00 indicated statistical significance. Mount Sinai Icahn School of Medicine Institutional Review Board approval was obtained for this project. RESULTS: Of the 795 multiparous pregnancies complicated by cholestasis, 618 (77.7%) had no prior history of cholestasis and 177 (23.3%) had prior history of cholestasis. Multiparous pregnancies with history of cholestasis had higher rates of prior preterm birth, earlier gestational age at diagnosis and delivery, and were more likely to receive ursodeoxycholic acid therapy. Pregnancies with history of cholestasis were not associated with spontaneous preterm labor in subsequent pregnancies with cholestasis, but history of cholestasis was associated with iatrogenic preterm birth and neonatal intensive care unit (NICU) admission. After adjusting for confounders, the association with iatrogenic preterm birth and NICU admission were no longer statistically significant. There was no significant association between history of cholestasis and other adverse obstetric outcomes. CONCLUSION: Findings suggests that history of prior cholestasis is not associated with worsening outcomes in subsequent pregnancies complicated by cholestasis. KEY POINTS: · Prior cholestasis may not alter risk in subsequent pregnancies.. · Unclear relationship between cholestasis and hepatobiliary disease.. · Studies needed to develop cholestasis screening protocol..

Mid-trimester sonographic placenta previa thickness and persistence at delivery.

OBJECTIVE: Increasing placental thickness is associated with adverse outcomes including earlier gestational age at delivery, lower birthweight, and lower umbilical artery pH. We aim to determine whether mid-trimester placenta previa thickness is associated with persistence of previa at time of delivery. STUDY DESIGN: Single-center retrospective cohort study of singleton gestations with previa diagnosed at 18-24 weeks delivering between 2015 and 2019. The thickest portion of the placenta was measured in a longitudinal plane on transabdominal imaging to determine placental thickness. We defined three cohorts: 1) thick placenta (>1 standard deviation above the mean), 2) thin placenta (>1 standard deviation below the mean), and 3) average placenta (within 1 standard deviation above or below the mean). Primary outcome was previa persistence at time of delivery. Secondary outcomes included postpartum hemorrhage, cesarean delivery, placenta accreta spectrum, and maternal morbidity composite (use of Bakri balloon, B-lynch, or O'Leary, peripartum hysterectomy, blood transfusion, ICU admission, or death). In all analyses, average thickness was used as the base comparator. RESULTS: Of 239 pregnancies with mid-trimester previa there were 34 thin, 166 average, and 39 thick placentas. Patients with thick placenta were older, more likely to have prior cesarean delivery, fibroid uterus, and delivery at an earlier gestational age. After adjusting for confounders, thick placenta was associated with persistent previa (aOR 6.85 [3.13-15.00]) and cesarean delivery (aOR 2.76 [1.26-6.08]). CONCLUSION: At diagnosis of mid-trimester previa, thick placenta is associated with persistence at time of delivery and delivery by cesarean section. This suggests placental thickness may assist with risk stratification and coordination of care.

Fetal Arrhythmia Leading to a Diagnosis of Congenital Long QT Syndrome Type II.

We describe the case of an asymptomatic young pregnant woman with a diagnosis of congenital long QT syndrome type II in the context of in utero fetal 2:1 heart block and ventricular tachycardia. The presentation, clinical considerations, and management of the mother and baby in the antepartum and postpartum periods are discussed.

Severe cholestasis-associated coagulopathy diagnosed by routine screening: a case report.

Recent case reports suggest an association between severe intrahepatic cholestasis of pregnancy and fat-soluble vitamin deficiencies, including vitamin K deficiency. Screening for coagulopathy and fat-soluble vitamin deficiency has been proposed as a possible strategy to identify pregnancies at additional risk of adverse outcomes and allow for earlier risk-reducing iatrogenic preterm delivery. This report highlights a case of routine screening that resulted in the detection of subclinical coagulopathy that allowed for earlier intervention and delivery of a healthy neonate at 34 weeks of gestation. Further prospective studies are needed to determine the clinical use of routine screening in detecting coagulopathy and fat-soluble vitamin deficiency in cases of severe cholestasis.

Association Between Obesity and Fetal Acidosis at Scheduled Cesarean Delivery.

OBJECTIVE: To evaluate whether patients with obesity who undergo scheduled cesarean delivery under neuraxial anesthesia are at increased risk for umbilical artery pH less than 7.1 and base deficit 12 mmol or greater. METHODS: We conducted a multicenter, retrospective cohort study of individuals who delivered a term, singleton, nonanomalous neonate at one of four academic medical centers in New York City from 2013 to 2019 by scheduled cesarean under neuraxial anesthesia for whom fetal cord blood gas results were available. The primary study outcome was rate of fetal acidosis , defined as umbilical artery pH less than 7.1. This was compared between patients with obesity (body mass index [BMI] 30 or higher) and those without obesity (BMI lower than 30). Base deficit 12 mmol or greater and a composite of fetal acidosis and base deficit 12 mmol or greater were also compared. Secondary outcomes included neonatal intensive care unit admission rate, 5-minute Apgar score less than 7, and neonatal morbidity. Associations between maternal BMI and study outcomes were assessed using multivariable logistic or linear regression and adjusted for age, race and ethnicity, insurance type, cesarean delivery order number, and neuraxial anesthesia type. RESULTS: Of the 6,264 individuals who met inclusion criteria during the study interval, 3,098 had obesity and 3,166 did not. The overall rate of umbilical artery cord pH less than 7.1 was 2.5%, and the overall rate of umbilical artery base deficit 12 mmol or greater was 1.5%. Patients with obesity were more likely to have umbilical artery cord pH less than 7.1 (adjusted odds ratio [aOR] 2.7, 95% CI 1.8-4.2) and umbilical artery base deficit 12 mmol or greater (aOR 3.2, 95% CI 1.9-5.3). This association was not significantly attenuated after additional adjustments for potential mediators, including maternal medical comorbidities. We found no differences in secondary outcomes between groups. CONCLUSION: Maternal obesity is associated with increased odds of arterial pH less than 7.1 and base deficit 12 mmol or greater at the time of scheduled cesarean delivery under neuraxial anesthesia.

Perioperative dexamethasone with neuraxial anesthesia for scheduled cesarean delivery and neonatal hypoglycemia.

OBJECTIVE: While the use of dexamethasone for cesarean delivery to prevent post-operative nausea and vomiting has become routine, the impact on fetal glucose metabolism is unknown. We aim to examine whether perioperative dexamethasone administration prior to scheduled non-labor cesarean delivery is associated with neonatal hypoglycemia. STUDY DESIGN: Multi-institution retrospective cohort study of singleton, full-term, non-anomalous pregnancies delivered by scheduled non-labor cesarean delivery with neuraxial anesthesia from 2013 to 2019. The exposure was intravenous dexamethasone after neuraxial anesthesia placement. Primary outcome was neonatal hypoglycemia and secondary outcomes included low Apgar, umbilical artery pH < 7.1, NICU admission, and meconium-stained amniotic fluid. A subgroup analysis was performed on pregnancies complicated by diabetes (both gestational and pre-gestational). Multivariate regression adjusting for baseline differences and potential confounders was used to the determine the strength of association between dexamethasone and adverse outcomes. RESULTS: Of the 4991 women in the study, 2719 (54.5%) received dexamethasone. Compared to non-receipt, women receiving dexamethasone were older, more likely to be White, non-Hispanic, have private insurance, and less likely to have diabetes. Perioperative dexamethasone receipt was not associated with neonatal hypoglycemia (adjusted OR 0.90, 95% CI 0.71-1.14). In a subgroup analysis of the 466 (9.3%) pregnancies complicated by pre-gestational and gestational diabetes, 219 (47.0%) received dexamethasone and receipt was associated with a significantly increased rate of neonatal hypoglycemia (adjusted OR 1.96, 95% CI 1.28-3.00). No significant associations were found between perioperative dexamethasone and other outcomes. CONCLUSIONS: Dexamethasone administration after neuraxial anesthesia placement for scheduled non-labor cesarean delivery is associated with altered neonatal glucose metabolism only in pregnancies complicated by diabetes.

Beyond stillbirth: association of intrahepatic cholestasis of pregnancy severity and adverse outcomes.

BACKGROUND: Intrahepatic cholestasis of pregnancy is associated with adverse pregnancy outcomes, including sudden fetal cardiac arrhythmias, resulting in stillbirth. This association has been correlated with the total bile acid levels, which are a marker for disease severity. Studies are yet to determine if intrahepatic cholestasis of pregnancy severity is also associated with increased rates of other adverse neonatal outcomes. OBJECTIVE: This study aimed to determine whether pregnancies complicated by intrahepatic cholestasis of pregnancy show a bile acid severity-based relationship with other adverse obstetrical outcomes beyond stillbirth alone. STUDY DESIGN: This was a retrospective cohort study of singleton, nonanomalous gestations complicated by intrahepatic cholestasis of pregnancy at the Elmhurst Hospital Center from 2005 to 2019. Severity was defined by the peak total bile acid levels (µmol/L): mild (10-19), low moderate (20-39), high moderate (40-99), and severe (>100). We examined the rates of spontaneous preterm labor, fetal growth restriction, preterm prelabor rupture of membranes, iatrogenic preterm birth, meconium-stained amniotic fluid, cesarean delivery for nonreassuring fetal heart tracing, umbilical artery pH, neonatal intensive care unit admission, and neonatal birthweight. The chi-square, Fisher exact, Student t, Mann-Whitney, and multivariate regression tests were used to determine the association of intrahepatic cholestasis of pregnancy severity and adverse neonatal outcomes. In all analyses, mild severity was used as the base comparator. A P value of <.05 and 95% confidence interval not crossing 1.00 indicated statistical significance. RESULTS: Of the 1202 pregnancies complicated by intrahepatic cholestasis of pregnancy, 306 (25.5%) were mild, 449 were low moderate (37.4%), 327 were high moderate (27.2%), and 120 were severe (10.0%). After adjusting for confounders, progressive intrahepatic cholestasis of pregnancy severity was associated with an increased risk of spontaneous preterm labor (low moderate adjusted odds ratio, 1.60; 95% confidence interval, 0.76-3.38; high moderate adjusted odds ratio, 3.49; 95% confidence interval, 1.69-7.22; severe adjusted odds ratio, 6.58; 95% confidence interval, 2.97-14.55), iatrogenic preterm birth (low moderate adjusted odds ratio, 1.54; 95% confidence interval, 0.95-2.52; high moderate adjusted odds ratio, 3.11; 95% confidence interval, 1.91-5.06; severe adjusted odds ratio, 4.94; 95% confidence interval, 2.81-8.71), and meconium-stained amniotic fluid (low moderate adjusted odds ratio, 1.33; 95% confidence interval, 0.75-2.36; high moderate adjusted odds ratio, 2.63; 95% confidence interval, 1.48-4.65; severe adjusted odds ratio, 3.91; 95% confidence interval, 1.98-7.69). There was no significant association between intrahepatic cholestasis of pregnancy severity and other adverse outcomes. CONCLUSION: The findings suggest that intrahepatic cholestasis of pregnancy disease severity is associated with an increased risk of spontaneous preterm labor, iatrogenic preterm birth, and meconium-stained amniotic fluid. These findings provide valuable insight toward patient anticipatory counseling.

Severe fat-soluble vitamin deficiency suspected secondary to intrahepatic cholestasis of pregnancy: A case report.

Intrahepatic cholestasis is the most common hepatobiliary complication of pregnancy. Worsening cholestasis, measured by total bile acid levels, has been associated with an increased incidence of adverse fetal outcomes; however, maternal morbidity remains rare. This report highlights a case of severe fat-soluble vitamin deficiency suspected to be secondary to severe cholestasis. Active management with weekly vitamin supplementation and close outpatient follow-up resulted in the delivery of a 32-week healthy neonate. We propose consideration of screening for fat-soluble vitamin deficiency for patients whose pregnancy is complicated by severe cholestasis or early-onset cholestasis.

From Pruritus to Cholestasis: Building a Statistical Model and Online Application to Predict a Diagnosis Prior to Bile Acid Determination.

OBJECTIVE: This study aimed to create a statistical model using clinical and laboratory parameters to predict which patients presenting with pruritus in pregnancy will have elevated total bile acids (TBA) and thus, have a high risk of intrahepatic cholestasis of pregnancy (ICP). STUDY DESIGN: Retrospective cohort study of patients presenting with pruritus in pregnancy and had TBA sent from a single public hospital from January 1, 2017, to December 31, 2017. Primary outcome is TBA ≥ 10 µmol/L. Multivariate logistic regression with stepwise and backward variable selection were used to create predictive models. Four models were compared using Akaike information criterion (AIC), C-statistic, and the DeLong nonparametric approach to test for differences between area under the curve (AUC) of receiver operating characteristic (ROC) curves. Internal validation was performed via fivefold cross-validation technique on the best-fitting, most parsimonious model. RESULTS: Of the 320 patients with pruritus, 153 (47.8%) had elevated bile acid levels ≥10 µmol/L. Sixty-nine variables were assessed for association with the primary outcome. Five variables were significantly associated with elevated TBA: pruritus of palms and soles (adjusted odds ratio [aOR]: 2.35 [95% confidence interval, CI: 1.22, 4.54]), gestational hypertension (aOR: 0.10 [95% CI: 0.02, 0.60]), log of total bilirubin (aOR: 4.71 [95% CI: 2.28, 9.75]), systolic blood pressure (aOR: 0.97 [95% CI: 0.94, 0.99]), and alanine aminotransferase (aOR: 1.05 [95% CI: 1.02, 1.07]). The final model was chosen for being parsimonious while having the lowest AIC with highest AUC (0.85; 95% CI: 0.81, 0.89). Internal validation using a probability threshold of 50% demonstrated a sensitivity of 65.5%, specificity of 83.5%, and accuracy of 75.1%. CONCLUSION: We provide a predictive model using five simple variables to determine the probability that a patient presenting with pruritus in pregnancy carries the diagnosis of ICP. This tool, available via a web app, is designed to aid providers and enhance clinical judgment in difficult triage situations. KEY POINTS: · Currently, no standard method to triage pruritus in pregnancy exists.. · We present a predictive statistical model using five readily available clinical variables.. · Final calculator yields probability of having intrahepatic cholestasis of pregnancy..

Burden of Future Liver Abnormalities in Patients With Intrahepatic Cholestasis of Pregnancy.

INTRODUCTION: There are limited data on the incidence, predictors, and time to future liver abnormalities in patients with intrahepatic cholestasis of pregnancy (ICP). METHODS: Single-center retrospective study of pregnant women with and without ICP who delivered from 2005 to 2009 evaluating incidence and time to future liver abnormalities. Women returning for care with liver function tests at a minimum of 6 months postpartum were included. Liver disease diagnoses and liver functions test abnormalities were compared. Time to development of alanine aminotransferase (ALT) >25 U/L, alkaline phosphatase (ALP) >140 U/L, and diagnosis of liver disease (through imaging or clinical evaluation) were compared between women with and without ICP using Kaplan-Meier methods and Cox regression models. RESULTS: A total of 255 women with ICP and 131 age-matched control subjects with delivery during the same period were identified. Subjects in both groups were similar in follow-up time, age at pregnancy, prepregnancy body mass index, and ethnicity (≥75% were Hispanic in both groups). On univariate analyses, ICP was associated with increased incidence of ALT >25 U/L P < 0.01 ALP >140 U/L (P < 0.01) and liver disease (P = 0.03). Adjusting for metabolic factors, ICP diagnosis was associated with risk of future liver abnormalities: postpartum ALT >25 U/L (hazard ratio [HR] 1.9, P < 0.01), ALP >140 U/L (HR 3.4, P < 0.01), and liver disease (HR 1.5, P = 0.05). DISCUSSION: In our cohort of urban women, ICP diagnosis predicted risk of future liver disease and abnormal liver tests. Women with pregnancies complicated by ICP may benefit from surveillance for postpartum liver abnormalities.

Pregnant women with severe or critical coronavirus disease 2019 have increased composite morbidity compared with nonpregnant matched controls.

BACKGROUND: In March 2020, as community spread of severe acute respiratory syndrome coronavirus 2 became increasingly prevalent, pregnant women seemed to be equally susceptible to developing coronavirus disease 2019. Although the disease course usually appears mild, severe and critical cases of coronavirus disease 2019 seem to lead to substantial morbidity, including intensive care unit admission with prolonged hospital stay, intubation, mechanical ventilation, and even death. Although there are recent reports regarding the impact of coronavirus disease 2019 on pregnancy, there is a lack of information regarding the severity of coronavirus disease 2019 in pregnant vs nonpregnant women. OBJECTIVE: We aimed to describe the outcomes of severe and critical cases of coronavirus disease 2019 in pregnant vs nonpregnant, reproductive-aged women. STUDY DESIGN: This is a multicenter, retrospective, case-control study of women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection hospitalized with severe or critical coronavirus disease 2019 in 4 academic medical centers in New York City and 1 in Philadelphia between March 12, 2020, and May 5, 2020. The cases consisted of pregnant women admitted specifically for severe or critical coronavirus disease 2019 and not for obstetrical indications. The controls consisted of reproductive-aged, nonpregnant women admitted for severe or critical coronavirus disease 2019. The primary outcome was a composite morbidity that includes the following: death, a need for intubation, extracorporeal membrane oxygenation, noninvasive positive pressure ventilation, or a need for high-flow nasal cannula O2 supplementation. The secondary outcomes included intensive care unit admission, length of stay, a need for discharge to long-term acute care facilities, and discharge with a home O2 requirement. RESULTS: A total of 38 pregnant women with severe acute respiratory syndrome coronavirus 2 polymerase chain reaction-confirmed infections were admitted to 5 institutions specifically for coronavirus disease 2019, 29 (76.3%) meeting the criteria for severe disease status and 9 (23.7%) meeting the criteria for critical disease status. The mean age and body mass index were markedly higher in the nonpregnant control group. The nonpregnant cohort also had an increased frequency of preexisting medical comorbidities, including diabetes, hypertension, and coronary artery disease. The pregnant women were more likely to experience the primary outcome when compared with the nonpregnant control group (34.2% vs 14.9%; P=.03; adjusted odds ratio, 4.6; 95% confidence interval, 1.2-18.2). The pregnant patients experienced higher rates of intensive care unit admission (39.5% vs 17.0%; P<.01; adjusted odds ratio, 5.2; 95% confidence interval, 1.5-17.5). Among the pregnant women who underwent delivery, 72.7% occurred through cesarean delivery and the mean gestational age at delivery was 33.8±5.5 weeks in patients with severe disease status and 35±3.5 weeks in patients with critical coronavirus disease 2019 status. CONCLUSION: Pregnant women with severe and critical coronavirus disease 2019 are at an increased risk for certain morbidities when compared with nonpregnant controls. Despite the higher comorbidities of diabetes and hypertension in the nonpregnant controls, the pregnant cases were at an increased risk for composite morbidity, intubation, mechanical ventilation, and intensive care unit admission. These findings suggest that pregnancy may be associated with a worse outcome in women with severe and critical cases of coronavirus disease 2019. Our study suggests that similar to other viral infections such as severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, pregnant women may be at risk for greater morbidity and disease severity.

Contained aortic rupture in a term pregnant patient during the COVID-19 pandemic.

Aortic dissection and rupture is a rare occurrence in pregnant and postpartum patients. This case discusses the presentation and diagnosis of a patient with an acute contained thoracic aortic aneurysm rupture at 38 weeks of gestation, after presenting with throat pain and syncope during the COVID-19 pandemic. The patient underwent emergent caesarean delivery for non-reassuring fetal heart tracing, following which continued syncope workup revealed an aortic aneurysm and pericardial effusion. Diagnosis in this case was finalised with multimodality imaging, including transthoracic echocardiogram, and the patient underwent surgical aortic repair.

Clinical improvement of severe COVID-19 pneumonia in a pregnant patient after caesarean delivery.

The clinical implications of COVID-19 in pregnancy remain unknown. While preliminary reports demonstrate that pregnant patients have a similar symptomatic presentation to the general population, the appropriate management and timing of delivery in these patients is still unclear, as pregnancy may impose additional risk factors and impede recovery in gravid patients. In this brief report, we present a case of COVID-19 in a pregnant patient with severe respiratory compromise, whose clinical status significantly improved after caesarean delivery. We also address the potential benefits of experimental therapy, including tocilizumab, a monoclonal antibody that targets interleukin-6 receptors.

Characteristics and Outcomes of 241 Births to Women With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection at Five New York City Medical Centers.

OBJECTIVE: To describe the characteristics and birth outcomes of women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as community spread in New York City was detected in March 2020. METHODS: We performed a prospective cohort study of pregnant women with laboratory-confirmed SARS-CoV-2 infection who gave birth from March 13 to April 12, 2020, identified at five New York City medical centers. Demographic and clinical data from delivery hospitalization records were collected, and follow-up was completed on April 20, 2020. RESULTS: Among this cohort (241 women), using evolving criteria for testing, 61.4% of women were asymptomatic for coronavirus disease 2019 (COVID-19) at the time of admission. Throughout the delivery hospitalization, 26.5% of women met World Health Organization criteria for mild COVID-19, 26.1% for severe, and 5% for critical. Cesarean birth was the mode of delivery for 52.4% of women with severe and 91.7% with critical COVID-19. The singleton preterm birth rate was 14.6%. Admission to the intensive care unit was reported for 17 women (7.1%), and nine (3.7%) were intubated during their delivery hospitalization. There were no maternal deaths. Body mass index (BMI) 30 or higher was associated with COVID-19 severity (P=.001). Nearly all newborns tested negative for SARS-CoV-2 infection immediately after birth (97.5%). CONCLUSION: During the first month of the SARS-CoV-2 outbreak in New York City and with evolving testing criteria, most women with laboratory-confirmed infection admitted for delivery did not have symptoms of COVID-19. Almost one third of women who were asymptomatic on admission became symptomatic during their delivery hospitalization. Obesity was associated with COVID-19 severity. Disease severity was associated with higher rates of cesarean and preterm birth.

Comparing pregnancy outcomes and loss rates in elective twin pregnancy reduction with ongoing twin gestations in a large contemporary cohort.

BACKGROUND: As compared with singleton gestations, twin pregnancies are associated with a significantly higher risk of preterm birth and maternal complications as well as fetal and neonatal morbidity and mortality. Multifetal pregnancy reduction is a technique developed in the 1980s to reduce the fetal number in higher-order multiple pregnancies to reduce the risk of adverse pregnancy outcomes, most importantly preterm birth. OBJECTIVE: The objective of the study was to compare pregnancy outcomes and loss rates in elective twin pregnancy reduction to ongoing twin gestations in a large contemporary cohort. STUDY DESIGN: This was a retrospective review of dichorionic diamniotic twin gestations that underwent first-trimester ultrasound at our institution from January 2008 to September 2016. Planned elective 2-to-1 multifetal pregnancy reductions at less than 15 weeks' gestation were compared with ongoing dichorionic diamniotic twin gestations. Data were collected via chart review. Demographics between 2-to-1 reduced singletons and ongoing twins were assessed using a Student t test or a Wilcoxon rank-sum test, as appropriate, for continuous variables and χ2 or Fisher exact tests, as appropriate, for categorical variables. Univariable and multivariable logistic regressions were used to compare pregnancy outcomes between ongoing twins and reduced singletons adjusting for maternal age, body mass index, race, in vitro fertilization, use of chorionic villus sampling, prior term birth, and prior preterm birth. RESULTS: Of 1070 dichorionic diamniotic twin pregnancies identified, completed follow-up data were available and analyzed for 855 patients (79.9%). Among those, 250 (29.2%) were 2-to-1 singletons and 605 (70.8%) were ongoing twins. Reduced singleton patients were slightly older, more likely white, and had lower body mass index. They were also more likely to have undergone in vitro fertilization (63.6% vs 48.8%), had chorionic villus sampling (92% vs 37.5%), and had prior term births (54% vs 35.7%). Compared with 2-to-1 singletons, the adjusted odds of having preterm delivery at 37 weeks for ongoing twins were 5.62 times (95% confidence interval, 3.67-8.61; P < .001) and 2.22 times (95% confidence interval, 1.20-4.11; P < .001) at 34 weeks. While intrauterine growth restriction, placental abruption, and gestational diabetes were not significant, ongoing twins were more likely to have a cesarean delivery (odds ratio, 5.53, 95% confidence interval, 3.60-8.49; P < .001) and preeclampsia (odds ratio, 3.33, 95% confidence interval, 1.60-6.96; P < .001) after adjusting for maternal characteristics. There were also significant differences between groups for preterm premature rupture of membranes and low birthweight at less than the fifth and 10th percentiles. Total pregnancy loss (at 24 and 20 weeks) was similar between singleton and ongoing twins (4% vs 2.5%, P = .23, and 3.6% vs 1.7%, P = .09 for respective weeks). There were no significant differences in the rate of unintended pregnancy loss (2.4% vs 2.3%; P = .94) and the rate of intrauterine fetal death greater than 24 weeks (1.2% vs 0.7%; P = .43) in reduced singleton versus ongoing twin group, respectively. CONCLUSION: In our study, patients who elected to reduce to a singleton pregnancy had a higher gestational age of delivery and lower rates of preterm birth and pregnancy complications without an increased risk of pregnancy loss.

Outcome after implementation of a modern management strategy for intrahepatic cholestasis of pregnancy.

OBJECTIVE: The aim of this study was to determine whether the institution of a modern management strategy affected pregnancy outcomes for intrahepatic cholestasis of pregnancy (ICP). METHODS: We performed a retrospective cohort study of women diagnosed with ICP at one hospital from 2005 to 2013. A new management protocol for ICP was instituted in 2009 for women with total bile acids >40 µmol/L at <36 weeks. This strategy included inpatient admission, continuous fetal heart rate monitoring, with delivery between 36 and 37 weeks. We compared maternal and neonatal outcomes prior and subsequent to the institution of this protocol. RESULTS: We identified 186 singleton gestations with bile acids >40 µmol/L and diagnosis <36 weeks. Patient demographics were similar between the groups, with the exception of greater maternal age and gestational diabetes in the newer cohort. The newer cohort demonstrated a significant reduction in the incidence of stillbirth 0% versus 3.4%, p= 0.035). There was no difference in the age at delivery, cesarean delivery rates or NICU admissions. CONCLUSION: Application of our management strategy for ICP reduced the stillbirth rate without adversely affecting other maternal and neonatal outcomes.

Mitochondrial gene expression profiles are associated with intrahepatic cholestasis of pregnancy.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) affects 0.2-2% of pregnant women. While the maternal clinical course of ICP is usually benign, the fetal effects can be severe spanning from spontaneous preterm birth to fetal demise to long term effects on the health of the progeny. ICP is characterized by high maternal serum levels of bile acids and placental and hepatic bile acids accumulation. Intrahepatic cholestasis, in the non-pregnant state, has been also linked to alterations of the mitochondrial activity attributed to high oxidative stress rates driven by high intracellular bile acids concentrations. Here we explored the hypothesis that elevated bile acid levels of ICP modify the placental mitochondrial activity. METHODS: By using a set of 12 ICP and 12 control placenta samples, we assessed the expression of all 13 mitochondrial-encoded protein-coding genes and the mitochondrial DNA (mtDNA) relative abundance by real-time PCR. We also assessed the oxidative stress status by measuring DNA damage by ELISA. RESULTS: We determined that: 1) the expression of MT-ND4L (+53% - p < 0.01), MT-ND4 (-19%-0.05 < p ≤ 0.01), MT-ND5 (+40% - p < 0.01), MT-CYTB (+35% - p < 0.01) is associated with ICP; 2) the mtDNA relative abundance is not associated with ICP (0.098 in ICP vs 0.118 in controls - p > 0.05); 3) the oxidative stress status is associated with ICP (4403.9 pM 8-oxo-dG/µg DNA in ICP vs 3809.8 pM 8-oxo-dG/µg DNA in controls - p < 0.01). DISCUSSION: This preliminary study suggests that mitochondria in placenta respond to high oxidative stress to modify their gene expression which may play an important role in the pathophysiology of ICP.

Predictive value of combined serum biomarkers for adverse pregnancy outcomes.

OBJECTIVE: To determine if a combination of first and second trimester serum biomarkers (pregnancy-associated plasma protein A (PAPP-A), free ßhCG, and maternal serum alpha-fetoprotein (msAFP)) may be utilized to develop a predictive model for adverse pregnancy outcomes. STUDY DESIGN: We conducted a retrospective analysis including all women who delivered at our institution between 2007 and 2010. We estimated the area under the ROC curve (AUC) to compare predictive abilities of PAPP-A, free ßhCG, and msAFP singularly, and in combination for adverse pregnancy outcomes. We sought to predict the risks of preeclampsia, preterm delivery (PTD, <37 weeks gestational age) and low birth weight (LBW, <2500g). Using logistic regression analysis, we created models that controlled for maternal age, race, parity, body mass index, and histories of chronic hypertension and tobacco use. RESULTS: The final sample included 2199 women. Determining the AUC and optimal cutoff probability values for each of the biomarkers, we found that for PTD and LBW, the combination of all three biomarkers was most predictive, while for preeclampsia the combination of msAFP and PAPP-A was most predictive. The AUC of the three biomarker combination to detect adverse pregnancy outcomes are as follows: LBW 67%, PTD 72%, and preeclampsia 77%. We created race-specific logistic regression models to predict the risk probabilities. To illustrate, the predictive probability for a 33-year-old African American, nullipara with a BMI of 50, chronic hypertension, tobacco use, PAPP-A 0.3, msAFP 2.0 and free ßhCG 0.98 MOMs are: PTD 59%, LBW 61% and Preeclampsia 91%. CONCLUSION: The combination of biomarkers currently utilized in Down syndrome screening may also be used to predict additional adverse pregnancy outcomes. Further studies are needed to determine optimal maternal and fetal surveillance, if and when increased risks are identified.

Epigenetics in women's health care.

Epigenetics refers to structural modifications to genes that do not change the nucleotide sequence itself but instead control and regulate gene expression. DNA methylation, histone modification, and RNA regulation are some of the mechanisms involved in epigenetic modification. Epigenetic changes are believed to be a result of changes in an organism's environment that result in fixed and permanent changes in most differentiated cells. Some environmental changes that have been linked to epigenetic changes include starvation, folic acid, and various chemical exposures. There are periods in an organism's life cycle in which the organism is particularly susceptible to epigenetic influences; these include fertilization, gametogenesis, and early embryo development. These are also windows of opportunity for interventions during the reproductive life cycle of women to improve maternal-child health. New data suggest that epigenetic influences might be involved in the regulation of fetal development and the pathophysiology of adult diseases such as cancer, diabetes, obesity, and neurodevelopmental disorders. Various epigenetic mechanisms may also be involved in the pathogenesis of preeclampsia and intrauterine growth restriction. Additionally, environmental exposures are being held responsible for causing epigenetic changes that lead to a disease process. Exposure to heavy metals, bioflavonoids, and endocrine disruptors, such as bisphenol A and phthalates, has been shown to affect the epigenetic memory of an organism. Their long-term effects are unclear at this point, but many ongoing studies are attempting to elucidate the pathophysiological effects of such gene-environment interactions.