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.

Routine screening for gestational diabetes: a review.

PURPOSE OF REVIEW: Rates of gestational diabetes mellitus (GDM) throughout the world continue to increase associated with the increasing rates of obesity. Given this epidemiologic burden, the importance of proper screening, diagnosis, and management cannot be understated. This review focuses on the current screening guidelines utilized throughout the world and new data recently published regarding the most optimal screening techniques and future directions for research. RECENT FINDINGS: Despite unanimous opinion that GDM warrants screening, the optimal screening regimen remains controversial. Notably, in the United States per the consensus recommendation by the American College of Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine, a 2-step screening approach is often used. Recently, there have been multiple studies published that have compared the 1-step and 2-step screening process with respect to GDM incidence and perinatal outcomes. These new findings are summarized below. SUMMARY: Utilization of the 1-step screening as opposed to the 2-step screening results in an increased diagnosis of GDM without significant population level benefit in outcomes. However, these studies remain underpowered to allow for meaningful comparison of outcomes in those diagnosed with GDM.

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.

Influence of Neighborhood Socioeconomic Status on Adverse Outcomes in Pregnancy.

PURPOSE: To evaluate whether ZIP-code level neighborhood socioeconomic status (SES) is associated with adverse pregnancy outcomes. METHODS: A retrospective study of 2009-2014 Oregon Health and Science University (OHSU) births with maternal ZIP codes in one of 89 Portland metropolitan area ZIP codes. Deliveries with ZIP codes outside of the Portland metro area were excluded. Deliveries were stratified by SES based on ZIP code median household income: low (below 10th percentile), medium (11th-89th percentile), and high (above 90th percentile). Univariate analysis and multivariable logistic regression with medium SES as the reference group evaluated perinatal outcomes and strength of association between SES and adverse events. RESULTS: This study included 8118 deliveries with 1654 (20%) classified as low SES, 5856 (72%) medium SES, and 608 (8%) high SES. The low SES group was more likely to be younger, have a higher maternal BMI, have increased tobacco use, identify as Hispanic or Black, and less likely to have private insurance. Low SES was associated with a significantly increased risk of preeclampsia (RR 1.23 95% CI 1.01-1.49), but this was no longer significant after adjusting for confounders (aRR 1.23 95% CI .971-1.55). High SES was negatively associated with gestational diabetes mellitus (GDM), even after adjusting for confounders (aRR 0.710, 95% CI 0.507-0.995). CONCLUSION: In the Portland metropolitan area, high SES was associated with a lower risk of GDM. Low SES was associated with a higher risk of preeclampsia before accounting for covariates. ZIP code-based risk assessment may be a useful indicator in detecting healthcare disparities.

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.

Intravenous immunoglobulin induced pancytopenia while preventing development of gestational alloimmune liver disease: A case report.

Gestational alloimmune liver disease is a rare complication associated with reactive maternal immunoglobulins resulting in neonatal liver pathology. The mainstay treatment for prevention in future pregnancies is intravenous immunoglobulins. Although relatively well tolerated, adverse reactions may occur. In this report, we highlight a case of intravenous immunoglobulin induced pancytopenia diagnosed by exclusion after thorough work-up. The patient was counseled on options and an informed decision was made to proceed with re-trial of intravenous immunoglobulin without systemic prednisone. This resulted in the delivery of a healthy neonate. We propose that future adverse reactions to intravenous immunoglobulin in pregnancy may warrant the trial of a new medication lot and use of systemic steroids only if subsequently indicated.

Fetal growth restriction with abnormal individual biometric parameters at second trimester ultrasound is associated with small for gestational age neonate at delivery.

OBJECTIVES: To determine if early-onset fetal growth restriction with abnormal individual biometric parameters, defined as head circumference, abdominal circumference and femur length less than the 10th percentile, is associated with adverse neonatal outcomes compared to fetal growth restriction with normal biometric parameters. STUDY DESIGN: Retrospective cohort study including women diagnosed with fetal growth restriction between 16 and 24 weeks gestation who delivered a singleton, non-anomalous neonate at Mount Sinai Hospital from 2013 to 2019. The primary outcome was rate of small for gestational age neonate at delivery. Maternal, obstetric and neonatal outcomes were compared using multivariable regression analysis. RESULTS: Patients diagnosed with fetal growth restriction with abnormal biometric parameters were more likely to be nulliparous, diagnosed with severe growth restriction and to receive antenatal corticosteroids than those with normal biometric parameters. The rate of small for gestational age neonate at delivery was higher in those with abnormal parameters (OR 4.0, 95% CI 1.7-9.2, p < 0.01) when compared to normal parameters. The rate of resolution of fetal growth restriction was higher in the normal biometric parameter group compared to those with abnormal parameters (OR 3.3, 95% CI 1.4-8.1, p < 0.01). CONCLUSIONS: Fetal growth restriction and normal biometric parameters diagnosed at second trimester ultrasound is associated with an increased likelihood of resolution of growth restriction and decreased likelihood of delivering a small for gestational age neonate.

The Utility of Obtaining Postmobilization Imaging in Nonsurgical Pelvic Ring Injuries.

INTRODUCTION: Pelvic fractures are diverse injuries with varying degrees of severity. Treatment recommendations are determined by the associated instability. For likely stable patterns, postmobilization imaging is used to assess for occult instability. This study assesses the utility of postmobilization images and determines how often they alter the recommendations for treatment. METHODS: Records at a single level 1 trauma center from January 2007 through December 2014 were reviewed, and patients with Current Procedural Terminology codes and International Classification of Diseases, Ninth Revision codes for pelvic and acetabular fractures were identified. For those chosen for nonsurgical treatment at presentation, a detailed chart review was performed to identify patients who had postmobilization radiographs and to determine whether this imaging led to a change in treatment recommendations. RESULTS: Inclusion criteria were met by 762 patients whose average age was 50 years. Of 331 patients planned for nonsurgical treatment at presentation, 168 (51%) had postmobilization images. The postmobilization radiographs did not alter treatment recommendations in any of these patients; however, three of these patients underwent surgical stabilization based on the patients' report of pain with attempted mobilization. DISCUSSION: Routine postmobilization imaging has limited value for patients with pelvic injuries and a low likelihood for instability, such as those with incomplete sacral fractures. Eliminating this step would reduce cost and decrease radiation exposure. The need for change in treatment plan or further imaging should be based on the patient's clinical progress with weight bearing. LEVEL OF EVIDENCE: Level 4.

Constitutive expression of NF-κB inducing kinase in regulatory T cells impairs suppressive function and promotes instability and pro-inflammatory cytokine production.

CD4+Foxp3+ regulatory T cells (Tregs) are indispensable negative regulators of immune responses. To understand Treg biology in health and disease, it is critical to elucidate factors that affect Treg homeostasis and suppressive function. Tregs express several costimulatory TNF receptor family members that activate non-canonical NF-κB via accumulation of NF-κB inducing kinase (NIK). We previously showed that constitutive NIK expression in all T cells causes fatal multi-organ autoimmunity associated with hyperactive conventional T cell responses and poor Treg-mediated suppression. Here, we show that constitutive NIK expression that is restricted to Tregs via a Cre-inducible transgene causes an autoimmune syndrome. We found that constitutive NIK expression decreased expression of numerous Treg signature genes and microRNAs involved in Treg homeostasis and suppressive phenotype. NIK transgenic Tregs competed poorly with WT Tregs in vivo and produced pro-inflammatory cytokines upon stimulation. Lineage tracing experiments revealed accumulation of ex-Foxp3+ T cells in mice expressing NIK constitutively in Tregs, and these former Tregs produced copious IFNγ and IL-2. Our data indicate that under inflammatory conditions in which NIK is activated, Tregs may lose suppressive function and may actively contribute to inflammation.