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.

Serum from pregnant donors induces human beta cell proliferation.

Pancreatic beta cells are among the slowest replicating cells in the human body and have not been observed to increase in number except during the fetal and neonatal period, in cases of obesity, during puberty, as well as during pregnancy. Pregnancy is associated with increased beta cell mass to meet heightened insulin demands. This phenomenon raises the intriguing possibility that factors present in the serum of pregnant individuals may stimulate beta cell proliferation and offer insights into expansion of the beta cell mass for treatment and prevention of diabetes. The primary objective of this study was to test the hypothesis that serum from pregnant donors contains bioactive factors capable of inducing human beta cell proliferation. An immortalized human beta cell line with protracted replication (EndoC-ßH1) was cultured in media supplemented with serum from pregnant and non-pregnant female and male donors and assessed for differences in proliferation. This experiment was followed by assessment of proliferation of primary human beta cells. Sera from five out of six pregnant donors induced a significant increase in the proliferation rate of EndoC-ßH1 cells. Pooled serum from the cohort of pregnant donors also increased the rate of proliferation in primary human beta cells. This study demonstrates that serum from pregnant donors stimulates human beta cell proliferation. These findings suggest the existence of pregnancy-associated factors that can offer novel avenues for beta cell regeneration and diabetes prevention strategies. Further research is warranted to elucidate the specific factors responsible for this effect.

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.

Managing High Cardiac Output Failure in a Patient With Hereditary Hemorrhagic Telangiectasias During Pregnancy.

Hemorrhagic telangiectasias is a rare genetic vascular disorder that may complicate pregnancy. We report a case of a pregnant hemorrhagic telangiectasias patient with innumerable hepatic arteriovenous malformations that developed high output cardiac failure necessitating delivery. Postpartum, the patient was treated with bevacizumab that resulted in clinical improvement.

Serum from pregnant donors induces human beta cell proliferation and insulin secretion.

Pancreatic beta cells are among the slowest replicating cells in the human body. Human beta cells usually do not increase in number with exceptions being during the neonatal period, in cases of obesity, and during pregnancy. This project explored maternal serum for stimulatory potential on human beta cell proliferation and insulin output. Gravid, full-term women who were scheduled to undergo cesarean delivery were recruited for this study. A human beta cell line was cultured in media supplemented with serum from pregnant and non-pregnant donors and assessed for differences in proliferation and insulin secretion. A subset of pregnant donor sera induced significant increases in beta cell proliferation and insulin secretion. Pooled serum from pregnant donors also increased proliferation in primary human beta cells but not primary human hepatocytes indicating a cell-type specific effect. This study suggests stimulatory factors in human serum during pregnancy could provide a novel approach for human beta cell expansion.

Evaluation of a Maternal Plasma RNA Panel Predicting Spontaneous Preterm Birth and Its Expansion to the Prediction of Preeclampsia.

Preterm birth is the principal contributor to neonatal death and morbidity worldwide. We previously described a plasma cell-free RNA panel that between 16 and 20 weeks of pregnancy had potential to predict spontaneous preterm birth (sPTB) ≤ 32 weeks caused by preterm labor (PTL) or preterm premature rupture of membranes (PPROM). The present study had three objectives: (1) estimate the RNA panel prognostic accuracy for PTL/PPROM ≤ 32 weeks in a larger series; (2) improve accuracy by adding clinical characteristics to the predictive model; and (3) examine the association of the RNA panel with preeclampsia. We studied 289 women from Memphis TN prospectively sampled 16.0-20.7 weeks and found: (1) PSME2 and Hsa-Let 7g were differentially expressed in cases of PTL/PPROM ≤ 32 weeks and together provided fair predictive accuracy with AUC of 0.76; (2) combining the two RNAs with clinical characteristics improved good predictive accuracy for PTL/PPROM ≤ 32 weeks (AUC 0.83); (3) NAMPT and APOA1 were differentially expressed in women with 'early-onset preeclampsia' (EOP) and together provided good predictive accuracy with AUC of 0.89; and (4) combining the two RNAs with clinical characteristics provided excellent predictive accuracy (AUC 0.96). Our findings suggest an underlying common pathophysiological relationship between PTL/PPROM ≤ 32 weeks and EOP and open inroads for the prognostication of high-risk pregnancies.

Variations in Awareness of Association Between Adverse Pregnancy Outcomes and Cardiovascular Risk by Specialty.

INTRODUCTION: Cardiovascular disease (CVD) remains the leading cause of death among women. Adverse pregnancy outcomes (APOs), including pre-eclampsia (PE), gestational diabetes mellitus (GDM) and pre-term birth (PTB) are associated with future maternal CVD risk. However, data on awareness of the association between APOs and long-term CVD risk among physicians in different specialties are lacking. This study assessed awareness of this association and whether this knowledge varies by specialty. METHODS: An anonymous web-based voluntary survey was sent to physicians in internal medicine (IM), family medicine (FM), obstetrics-gynecology (Ob-Gyn) and cardiology. The questions aimed to assess a physician's knowledge regarding identification of APOs and their association with future CVD risk and knowledge of CVD risk factor screening in women with APOs and future CVD risk. RESULTS: The survey was completed by 53 physicians, of whom 21% were in IM, 26% in FM, 23% in Ob-Gyn and 30% in cardiology. Based on the responses, cardiologists screened most frequently for APOs, with 56% always screening a female patient and 31% often screening. Only half of the IM and FM physicians acknowledged awareness of the association between APOs and CVD risk. Respondents in all specialties recognized PE and GDM as APOs linked to long-term maternal CVD risk, but failed to associate PTB as an APO. The majority of physicians in IM, FM and cardiology also lacked the knowledge of how often to appropriately screen for CVD risk factors associated with APOs. CONCLUSION: Awareness of the association between APO and future maternal CVD risk varies by specialty. A significant percentage of the physicians who responded to the survey did not routinely ask about APOs when assessing CVD risk and failed to identify PTB as a risk factor for APOs. Education on this topic and targeted efforts to improve screening for APOs are needed within all specialties to help reduce CVD morbidity and mortality.

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.

Relationship between non-alcoholic fatty liver disease during pregnancy and abnormal glucose metabolism during and after pregnancy.

While non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of impaired glucose tolerance and type 2 diabetes mellitus (DM) in non-pregnant patients, the clinical significance of NAFLD during pregnancy is still unclear. We hypothesized that sonographic findings of NAFLD during pregnancy would be associated with gestational diabetes mellitus (GDM) and predict abnormal postpartum glucose metabolism. NAFLD was assessed by ultrasound during and after pregnancy. Standard 2-hour 75 g oral glucose tolerance test (OGTT) was used during pregnancy and post partum to establish GDM and the diagnosis of normal, impaired fasting glucose, or DM. We also measured plasma insulin, C peptide, and free fatty acids (FFA) concentration during an OGTT to evaluate glucose tolerance, insulin secretion and insulin resistance. Of the 84 subjects, 12 had sonographic evidence of NAFLD (5 of whom had OGTT post partum). There was a non-significant trend toward higher mean weight and body mass index during and after gestation in the NAFLD group, but no statistically significant differences in mean age, ethnicity, prepregnancy and postpregnancy hemoglobin A1C values, and postpartum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, insulin, or FFA. We did not find an association between sonographic evidence of NAFLD during the third trimester of pregnancy and abnormal glucose metabolism during or after pregnancy. This study also suggests that while AST and ALT are not reliable diagnostic tools for NAFLD during the postpartum period, ultrasound is a reasonably safe, practical, and cost-effective modality to assess maternal hepatic fat during pregnancy.

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.

Diabetes and pregnancy: Risks and opportunities.

Diabetes in pregnancy increases the risk of adverse maternal, obstetric, fetal, and neonatal outcomes. Internists can reduce these risks by optimizing glycemic control before conception and providing effective counseling on strategies to reduce the risks associated with pregnancy and diabetes. Routine screening of reproductive-age women with diabetes should include a comprehensive physical examination and laboratory tests to identify at-risk patients and begin strategic management. A review of medications for teratogenic potential is also needed.

Paroxysmal Nocturnal Hemoglobinuria in Pregnancy: A Dilemma in Treatment and Thromboprophylaxis.

Paroxysmal nocturnal hemoglobinuria (PNH) is a hematologic disorder characterized by an acquired somatic mutation in the phosphatidylinositol glycan class A gene which leads to a higher risk for increased venous and arterial thrombosis. Current treatment for PNH includes eculizumab. Pregnant patients who have PNH have higher risk for thrombosis and hemorrhage with both pregnancy and their underlying PNH. Treatment frequently poses conundrum. The safety and efficacy of eculizumab during pregnancy and breast feeding have not been extensively studied and contraception has been recommended due to potential for teratogenicity. We present a case of a patient who was safely on both eculizumab and modest prophylactic anticoagulation for 6 weeks post-partum.

Transient Fetal Tachycardia After Intravenous Diphenhydramine Administration.

BACKGROUND: Fetal tachycardia is attributable to a variety of etiologies, including an untreated maternal medical condition or an indicator of potential fetal compromise. Maternal medication administration may also affect the fetal heart rate. CASE: A 28-year-old nulliparous patient at 41 weeks of gestation was treated for pruritus with intravenous diphenhydramine after epidural administration of fentanyl. Within 14 minutes, the fetal heart rate increased from a baseline of 155 beats per minute (bpm) to more than 200 bpm while maintaining moderate variability. This was accompanied by an increase in uterine contractions occurring every 1.5 minutes. The fetal tachycardia lasted 51 minutes; several hours later, a healthy neonate was delivered. CONCLUSION: Diphenhydramine may produce transient fetal tachycardia as well as increased maternal uterine activity.

Combining adverse pregnancy and perinatal outcomes for women exposed to antiepileptic drugs during pregnancy, using a latent trait model.

BACKGROUND: Application of latent variable models in medical research are becoming increasingly popular. A latent trait model is developed to combine rare birth defect outcomes in an index of infant morbidity. METHODS: This study employed four statewide, retrospective 10-year data sources (1999 to 2009). The study cohort consisted of all female Florida Medicaid enrollees who delivered a live singleton infant during study period. Drug exposure was defined as any exposure to Antiepileptic drugs (AEDs) during pregnancy. Mothers with no AED exposure served as the AED unexposed group for comparison. Four adverse outcomes, birth defect (BD), abnormal condition of new born (ACNB), low birth weight (LBW), and pregnancy and obstetrical complication (PCOC), were examined and combined using a latent trait model to generate an overall severity index. Unidimentionality, local independence, internal homogeneity, and construct validity were evaluated for the combined outcome. RESULTS: The study cohort consisted of 3183 mother-infant pairs in total AED group, 226 in the valproate only subgroup, and 43,956 in the AED unexposed group. Compared to AED unexposed group, the rate of BD was higher in both the total AED group (12.8% vs. 10.5%, P < .0001), and the valproate only subgroup (19.6% vs. 10.5%, P < .0001). The combined outcome was significantly correlated with the length of hospital stay during delivery in both the total AED group (Rho = 0.24, P < .0001) and the valproate only subgroup (Rho = 0.16, P = .01). The mean score for the combined outcome in the total AED group was significantly higher (2.04 ± 0.02 vs. 1.88 ± 0.01, P < .0001) than AED unexposed group, whereas the valproate only subgroup was not. CONCLUSIONS: Latent trait modeling can be an effective tool for combining adverse pregnancy and perinatal outcomes to assess prenatal exposure to AED, but evaluation of the selected components is essential to ensure the validity of the combined outcome.

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.

Conservative management of maternal cervical vertebral hemangioma complicating pregnancy.

BACKGROUND: Although vertebral hemangiomas are found in 10% of the population, they rarely become symptomatic. We describe management of an enlarging cervical vertebral hemangioma during pregnancy. CASE: A primiparous woman at 33 weeks of gestation presented with neck pain and paresthesias. She had a known cervical hemangioma. Imaging revealed a C6-C7 hemangioma with extradural extension. Her symptoms fluctuated, and she was delivered by cesarean at 36 weeks of gestation. Improvement occurred after delivery, and radiographic regression of the hemangioma was demonstrated. CONCLUSION: Hormonal and vascular changes of pregnancy may exacerbate spinal hemangiomas. Depending on the location, these may lead to profound neurologic disability and management depends on the degree of myelopathy. Surgical intervention may be necessary to avoid neurologic injury, but amelioration after delivery is possible.

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.