Epidemiology and Outcomes of Hepatitis E Virus-Associated Hospitalisations in the United States With a Focus on Pregnancy: A Nationwide Population Study, 1998-2020.

Hepatitis E virus (HEV) is typically asymptomatic in developed countries but can be more severe in certain populations. We aim to describe the epidemiology of HEV-associated hospitalisations from 1998 to 2020 in the United States, investigate risk factors for inpatient mortality and describe outcomes in pregnant women. We utilised the National Inpatient Sample and extracted cases of HEV-associated hospitalisations using ICD-9/10 diagnostic codes. Demographic, clinical and pregnancy data were extracted and analysed by chi-square and logistic regression. We identified 3354 cases of HEV-associated hospitalisations; 1689 (50.4%) were female and 1425 (42.5%) were non-Hispanic White. The median age was 50 (IQR: 37-59) years. Hospitalisation rates for HEV ranged from 2.5 per 10,000,000 in 2008 to a peak of 9.6 per 10,000,000 people in the general U.S. population in 2004. The mortality rate was 5.2%. Age ≥ 40 years (OR: 7.73; 95% CI: 1.57-38.09; p = 0.012), HIV infection (OR: 4.63; 95% CI: 1.26-16.97; p = 0.021), and coagulopathy (OR: 7.22; 95% CI: 2.81-18.57; p < 0.001) were associated with increased odds of mortality within the HEV cohort. There were 226 pregnant women with HEV. Rates of maternal death, stillbirth and preterm birth were similar between HEV and non-HEV pregnant cohorts. Hepatitis B and hepatitis C co-infection were significantly more common in the HEV pregnant cohort (p < 0.05). HEV-associated hospitalisations are uncommon in the United States, but likely underdiagnosed. Certain risk factors can be used to predict prognosis of these hospitalised patients. Pregnant women with HEV appear to have favourable maternal and fetal outcomes despite hepatitis B and C co-infection.

Temporary mechanical support in the peripartum patient as a bridge to postpartum recovery: A report of three cases.

Cardiogenic shock (CS) is a severe complication of peripartum cardiomyopathy (PPCM). Patients with deteriorating CS often require temporary mechanical circulatory support. In PPCM, this can be used as a bridge to postpartum recovery or bridge to decision. The outcomes are unclear, especially if prolonged utilization is required. We present a case series of three patients with PPCM in deteriorating CS who were successfully supported with a ventricular assist device or veno-arterial extracorporeal membrane oxygenation as a bridge to postpartum recovery.

A nationwide study of Stevens-Johnson syndrome and toxic epidermal necrolysis in hospitalized pregnant women in the United States, 2009-2020.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rarely described in the pregnant population, and knowledge of their impact on the mother/fetus is limited. Objective: To describe SJS/TEN in pregnant women and to investigate the risk factors for developing SJS/TEN in pregnancy. Methods: We utilized hospitalization data from the 2009-2020 National Inpatient Sample. Pregnancy hospitalizations and SJS/TEN involvement were identified by ICD-9/10 codes and analyzed by chi-square and logistic regression. Results: We identified 650 pregnancies complicated by SJS/TEN requiring hospitalization. The median age was 28 years, and most were non-Hispanic White (55.2%). There were ≤10 cases associated with mortality. Most SJS/TEN cases (73.9%) occurred during the third trimester. HIV infection (OR = 9.49; P = .030), herpes simplex virus infection (OR = 2.49; P = .021), genitourinary tract infections (OR = 3.80; P < .001), malignant neoplasm (OR = 8.67; P = .031), and lupus erythematosus (OR = 41.94; P < .001) were associated with increased odds of developing SJS/TEN in pregnancy. Rates of preterm births were higher in the SJS/TEN cohort, 16.9% versus 8.2% (P < .001). Rates of pre-eclampsia, stillbirths, and post-term births were similar between the SJS/TEN versus non-SJS/TEN pregnancy cohorts. Limitations: Limited cohort size. Conclusions: SJS/TEN in pregnancy appears to be mild and is associated with favorable maternal-fetal outcomes, except for increased preterm birth.

Hepatitis C Prevalence and Birth Outcomes among Pregnant Women in the United States: A 2010-2020 Population Study.

BACKGROUND: The rates of hepatitis C virus (HCV) infection have increased in the pregnant population. We aim to describe the age-stratified clinical outcomes and trends for inpatient pregnant women with HCV in the U.S. METHODS: We utilized hospitalization data from the 2010-2020 National Inpatient Sample. Pregnancy and HCV were identified according to their ICD-9/ICD-10 codes. Demographic and clinical data including cirrhosis, mortality, preterm birth, and stillbirth were extracted. The age groups were defined as ≤18, 19-25, 26-34, and ≥35 years. RESULTS: We identified 195,852 inpatient pregnant women with HCV, among whom 0.7% were ≤18, 26.7% were 19-25, 57.9% were 26-34, and 14.8% were ≥35 years of age. The hospitalization rates of pregnant women with HCV increased overall between 2010 and 2020, with the highest velocity in the 26-34 age group. The 26-34 age group had the highest HCV burden, with an age-standardized hospitalization rate of 660 per 100,000 in 2020. The rates of mortality and cirrhosis were significantly higher in the HCV cohort and increased further with age (p < 0.05). Among the HCV pregnant cohort, 151,017 (77.1%) delivered during hospitalization. Preterm births and stillbirths were significantly higher in the HCV pregnant cohort compared to the controls across multiple age groups (p < 0.05). Minority race/ethnicity was associated with increased mortality, cirrhosis, preterm birth, and stillbirth (p < 0.001). HIV co-infection, hepatitis B co-infection, and diabetes increased the odds of cirrhosis (p < 0.001). CONCLUSIONS: Hospitalizations of pregnant women with HCV are escalating, and these women are at increased risk of mortality, cirrhosis, preterm birth, and stillbirth with modifying factors, exacerbating risks further.

A Composite Score for Predicting Vertical Transmission of Hepatitis C: A Multicenter Study.

BACKGROUND: Prevention of the vertical transmission of the hepatitis C virus (HCV) presents an obstetric challenge. There are no approved antiviral medications for the treatment or prevention of HCV for pregnant patients. OBJECTIVE: We aimed to create a composite score to accurately identify a population of pregnant patients with HCV who have high potential for vertical transmission. STUDY DESIGN: In a retrospective, multicenter cohort study, we identified pregnant patients with hepatitis C with linked data to their infants who have had HCV RNA or HCV antibody testing. Demographic data, including age and race/ethnicity, as well as clinical and laboratory data, including tobacco/alcohol use, infections, liver function tests, the HCV RNA titer, HCV antibody, HCV genotype, absolute lymphocyte count, and platelet count, were collected. Data were analyzed using logistic regression and receiver operating characteristics (ROCs) and internally validated using the forward selection bootstrap method. RESULTS: We identified 157 pregnant patients and 163 corresponding infants. The median maternal delivery age was 29 (IQR: 25-33) years, and the majority (141, or 89.8%) were White. A high HCV RNA titer, high absolute lymphocyte count, and high platelet count were associated with vertical transmission. A high HCV RNA titer had an AUROC of 0.815 with sensitivity, specificity, a positive predictive value, and a negative predictive value of 100.0%, 59.1%, 17.6%, and 100.0%, respectively. A composite score combining the three risk factors had an AUROC of 0.902 (95% CI = 0.840-0.964) but with a risk of overfitting. CONCLUSIONS: An HCV RNA titer alone or a composite score combining the risk factors for HCV vertical transmission can potentially identify a population of pregnant patients where the rate of vertical transmission is high, allowing for potential interventions during antepartum care.

Efficacy of the NICHD vaginal birth after cesarean delivery calculator: a single center experience.

Objective: As the cesarean delivery rate has risen future pregnancy outcomes are impacted including the decision to undergo a repeat cesarean or a vaginal birth after cesarean (VBAC) in the subsequent pregnancy. A calculator was developed by the maternal fetal medicine units (MFMUs) network in 2007 to estimate the chance of successful VBAC and is used widely. The purpose of this study was to investigate the calculator's validity on our obstetric patient population.Study design: This was a retrospective study of patients attempting a VBAC delivery at a single center from January 2012 to June 2014. Chances for success were estimated using the MFMU network VBAC calculator in 201 evaluable patients. We then compared the calculator's results with the outcomes observed. In order to determine if the MFMU VBAC calculator was accurately predicting successful vaginal deliveries, we discretized our dataset by binning into MFMU score deciles. Each decile was then tested for significant deviations from the predicted success rate using an exact binomial test. Significance was determined at 0.05 levels.Results: Two hundred and one patients were included. Our results demonstrated higher actual VBAC success than anticipated by using the MFMU network calculator for patients with scores in the 40-80% decile range. When stratified by race, we found the calculator to be a better predictor of success in African-American patients, as the calculator appears to underestimate success in white and Hispanic patients.Conclusion: Calculators are helpful to facilitate patient counseling and shared decision-making regarding the patient's choice for VBAC. When providing such counseling, the potential for reduced predicted VBAC success in the mid-decile range with the MFMU calculator should be recognized.

New Antiviral Agents for Treatment of Hepatitis C.

Between 70 and 170 million people worldwide are infected with hepatitis C virus (HCV) which frequently causes chronic liver disease and cirrhosis. There are several genotypes and many subtypes of HCV. Direct-acting antiviral agents are effective at eradicating HCV in the vast majority of patients, producing much higher cure rates than were seen with interferon and ribavirin regimens only a few years ago. The chapter reviews the epidemiology and virology of HCV infection. Treatment regimens are complex but a straightforward approach to selection of patients, choice of direct-acting antiviral agents and follow-up is presented.

Perinatal outcomes after adopting 1- versus 2-step approach to diagnosing gestational diabetes.

OBJECTIVE: The American College of Obstetricians and Gynecologists (ACOG) and the IADPSG (International Association of Diabetes and Pregnancy Study Groups) proposed distinct approaches to diagnosing gestational diabetes mellitus (GDM). We sought to analyze these paradigms: (1) ACOG 2-step approach where screening is followed by diagnostic testing, (2) IADPSG 1-step diagnostic testing. STUDY DESIGN: We reviewed data from pregnant women (24-28 wks) screened for GDM over two periods: (1) November 2011-May 2012 (2) November 2012-May 2013. Period 1: 2-step approach (screening 1-h glucose challenge test (GCT) followed by a diagnostic 3-h 100-g glucose tolerance test (GTT) when abnormal (≥140 mg/dl)). Period 2: an abnormal value after a 2-h 75-g GTT result was diagnostic of GDM. We compared the incidence of GDM and perinatal outcomes using either approach. RESULTS: Out of 471 patients screened by ACOG 2-step approach, 72 (15.3%) had an abnormal 1-h screening and underwent the 3-h diagnostic GTT, and 26 (5.5%) developed GDM. The 1-step approach resulted in 53 (15.96%) with GDM of a total 332 evaluated. There was no statistically significant difference in perinatal outcomes between the two cohorts. Maternal weight at the start and the end of pregnancy was greater for patients diagnosed by the ACOG 2-step approach. CONCLUSION: Adopting 1-step approach (ADA) to diagnose GDM resulted in a 3-fold increase in prevalence of GDM with no differences in perinatal outcomes.

Autonomic and Enteric Nervous System Dysfunction May Play a Role in Hyperemesis Gravidarum.

BACKGROUND: Nausea and vomiting, seen in 70-85% of all pregnancies, becomes intractable in hyperemesis gravidarum (HG). We aimed to investigate the relationship between HG and autonomic nervous system functioning and gastric electrical activity. METHODS: Twenty-seven pregnant patients, 21 with HG and six normal, were studied with sympathetic adrenergic; percent vasoconstriction (%VC) and postural adjustment ratio (PAR); parasympathetic vagal cholinergic functions by R-to-R intervals (RRIs), a total autonomic score; and enteric nervous system measured by electrogastrography (EGG). RESULTS: Significant differences were found in parasympathetic measures (RRI for HG 29.98 ± 2.95 vs. control 40.91 ± 2.38, P < 0.05); sympathetic PAR was significantly lower in patients (PAR for HG 24.5 ± 5.0 vs. 67.6 ± 11.4 for controls, P < 0.01); mean total autonomic score was significantly lower in HG (131.75 ± 9.61 vs. 196.87 ± 12.8, P < 0.05). EGG results were borderline different (normal < 3.3, HG 3.4 vs. controls 3.0, P = 0.07). CONCLUSION: Autonomic and enteric nervous system dysfunction may play a role in the pathophysiology of HG.

Thyroid function and 3,3'-diiodothyronine sulfate cross-reactive substance (compound W) in maternal hyperthyroidism with antithyroid treatment.

OBJECTIVE: To test whether the serial measurement of maternal levels of compound W, a 3,3'-diiodothyronine sulfate cross-reactive substance, can serve as a potential indicator of fetal thyroid function in pregnant women receiving antithyroid medication. METHODS: Compound W was measured repeatedly in serum of pregnant women with hyperthyroidism treated with antithyroid medication. Free thyroxine levels of mothers and serum thyroid-stimulating hormone levels of 1-day-old neonates were analyzed by local clinical or state laboratories. RESULTS: Use of minimal antithyroid medication impaired the progressive increase of compound W seen in euthyroid mothers during pregnancy. At term, depressed compound W levels in maternal serum were found in 7 of 22 pregnancies; in 1 case, maternal compound W was suppressed and newborn thyroid-stimulating hormone was elevated. Seven mothers with treated hyperthyroidism failed to show an increase in serum levels of compound W after midterm. CONCLUSION: Normal progression of maternal serum compound W may be an index of normal fetal thyroid development in mothers with hyperthyroidism treated with necessary antithyroid medication.

Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length.

OBJECTIVE: The objective of the study was to assess cerclage to prevent recurrent preterm birth in women with short cervix. STUDY DESIGN: Women with prior spontaneous preterm birth less than 34 weeks were screened for short cervix and randomly assigned to cerclage if cervical length was less than 25 mm. RESULTS: Of 1014 women screened, 302 were randomized; 42% of women not assigned and 32% of those assigned to cerclage delivered less than 35 weeks (P = .09). In planned analyses, birth less than 24 weeks (P = .03) and perinatal mortality (P = .046) were less frequent in the cerclage group. There was a significant interaction between cervical length and cerclage. Birth less than 35 weeks (P = .006) was reduced in the less than 15 mm stratum with a null effect in the 15-24 mm stratum. CONCLUSION: In women with a prior spontaneous preterm birth less than 34 weeks and cervical length less than 25 mm, cerclage reduced previable birth and perinatal mortality but did not prevent birth less than 35 weeks, unless cervical length was less than 15 mm.

Perinatal outcomes in pregnancies managed with antenatal insulin glargine.

We compared perinatal outcomes in pregnancies in which insulin glargine was used in the management of patients with pregnancies in which standard insulin therapy was used at a single institution. A retrospective analysis of 114 pregnant patients with diabetes (pregestational or gestational) managed at a single center between January 2004 and August 2006 was undertaken. Sixty-five patients managed with insulin glargine were compared with 49 patients managed with neutral protamine Hagedorn (NPH) insulin. Both groups were also treated with short-acting insulin (either regular, lispro, or aspart insulin). Maternal age, parity, prepregnancy weight, body mass index, duration of diabetes, hemoglobin A (1C) (at entry and final recorded) and gestational age at entry were similar for each group (glargine and NPH). Thirty patients had gestational diabetes (18 glargine and 12 NPH); there were no differences in numbers of patients in higher-order White's classification between the two groups. Cesarean section for obstetric reasons included labor abnormalities, malpresentation, fetal distress, and suspected macrosomia. There were no differences in gestational age at delivery, birth weight, preeclampsia, or frequency of cesarean section (total or for obstetric reasons). The frequency of shoulder dystocia was higher in the NPH group. Regarding neonatal outcomes, gestational age at delivery, birth weight, Apgar scores, admission to the neonatal intensive care unit, respiratory distress syndrome, hypoglycemia, and congenital anomalies were similar between the two groups. From this retrospective analysis, no adverse maternal or neonatal effects were seen from maternal administration of insulin glargine. A larger multicenter study is needed to confirm these findings. This preliminary report suggests that use of insulin glargine during pregnancy can be considered if maternal metabolic control is suboptimal using the standard split-mix regimen.

Hypertensive disease in pregnancies complicated by systemic lupus erythematosus.

OBJECTIVE: The purpose of this study was to assess the percentage of hypertensive disease in pregnancies complicated by systemic lupus erythematosus at a single institution. STUDY DESIGN: We conducted a retrospective analysis of medical records between 1992 and 2003 of 68 pregnancies that were complicated by systemic lupus erythematosus from 48 parturients. Patients were categorized into 3 groups: no chronic hypertension (n = 49 women), chronic hypertension-no medication (n = 6 women) and chronic hypertension-treated (n = 13 women). Analyses of variance (with Tukey-Kramer adjusted follow-up evaluation) and chi-squared/Fisher's exact tests were used for the analyses of continuous and categoric variables, respectively. Significance was defined by a probability value of < or = .05. RESULTS: Chronic hypertension complicated 28% of systemic lupus erythematosus pregnancies. Mean systolic blood pressures at intake were significantly different between the normotensive and no chronic hypertension groups and between the chronic hypertension-no medication and chronic hypertension-treated groups; the differences in diastolic pressures reached significance only between the no chronic hypertension and the chronic hypertension-treated groups. Maternal age, gestational age at delivery, birth weight, lowest platelet count, and highest serum creatinine levels were similar between the hypertensive and the nonhypertensive groups. There were no differences in the percentage of aspirin or heparin treatments among the groups, but the percentage of the chronic hypertension-treated group who received steroids was significantly greater than the percentage of women who received steroids in the other 2 groups (P < .05). Preeclampsia developed in 23% of the no chronic hypertension pregnancies and in 32% of the hypertensive pregnancies (P = .54). When pregnancies that were treated with prednisone (n = 34 pregnancies) were compared with those pregnancies that were managed with other agents (n = 34 pregnancies), the percentages of preeclampsia were similar (26% and 24%, respectively; P = .78). CONCLUSION: The percentage of parturients with systemic lupus erythematosus in whom preeclampsia develops is increased, regardless of the presence of underlying chronic hypertension. Prednisone therapy was not associated with a higher risk of preeclampsia in this series.

Sonographic visualization of ovarian veins during the puerperium: an assessment of efficacy.

OBJECTIVE: The purpose of this study was to determine the ability to visualize ovarian veins by sonography in postpartum patients as well as to assess the frequency of ovarian vein thrombosis in these patients. STUDY DESIGN: Seventy subjects were recruited from either the postpartum ward or labor and delivery unit after vaginal delivery between November 1, 2000, and March 1, 2001. Patients were excluded if they had a previous or current history of venous thrombosis or recently underwent cesarean delivery. Demographic data were recorded. Transabdominal ultrasonography was performed with gray scale or color Doppler imaging for visualization of the right and left ovarian veins. Either power Doppler or pulsed Doppler imaging with spectral analysis was used for verification of the ovarian veins. Logistic regression was used for univariate analysis. RESULTS: Of the 70 parturients studied, both ovarian veins were visualized in 55 women (78.6%). Of the remaining subjects, either the right (n = 6) or the left (n = 6) ovarian vein could not be visualized. In 3 subjects, neither ovarian vein could be visualized (4.3%). An isolated, asymptomatic right ovarian vein thrombus was identified in one subject (1/55, 1.8%) after bilateral tubal ligation was performed. Maternal age, parity, body mass index, gestational age, spontaneous versus operative vaginal delivery, neonatal sex, or sonographer (radiologist versus perinatologist) did not correlate with ability to visualize the ovarian veins; however, increasing birth weight tended positively toward significance (P =.064). CONCLUSION: Most ovarian veins can be visualized sonographically during the early puerperium. Additional imaging studies should be considered when a diagnosis is unclear. The presence of an asymptomatic ovarian vein thrombus is unusual and is of uncertain importance.