The Cost of Developing and Implementing an Antepartum Referral Program for Penicillin Allergy Evaluation at a Single Academic Tertiary Care Hospital.

OBJECTIVE: Approximately 10% of pregnant individuals report a penicillin allergy, yet most are not truly allergic. Allergy verification during pregnancy is safe and recommended; however, many hospitals lack the infrastructure to execute testing. Our aim was to evaluate the cost of developing and implementing a penicillin allergy referral program for pregnant individuals at an academic institution and to compare costs of care between patients who were referred and not referred through the program. STUDY DESIGN: We conducted an economic analysis of our institution's antepartum penicillin allergy referral program. We prospectively collected detailed resource utilization data and conducted the analysis from the program's perspective, accounting for costs related to program development, allergy verification, antibiotic cost, and delivery hospitalization. Costs were compared between patients who were referred for evaluation versus patients who were not referred using bivariate tests as well as quantile regression adjusting for baseline differences. A sensitivity analysis was performed for allergy testing cost. All cost estimates were inflation adjusted to 2021 U.S. dollars. RESULTS: The startup cost of program development and educational initiatives was $19,920, or 86 per patient. The median allergy evaluation cost was $397 (interquartile range: $303-663). There was no significant difference in maternal (median: $13,579 vs. 13,999, p = 0.94) or neonatal (median: $3,565 vs. 3,577, p = 0.55) delivery hospitalization cost or antibiotic cost (median: $1.57 vs. 3.87, p = 0.10) between referred and nonreferred patients. Overall, the total cost per person did not differ significantly between study groups (median: $18,931 vs. 18,314, p = 0.69). CONCLUSION: The cost of developing a penicillin allergy referral program in pregnancy was modest and did not significantly alter short-term cost of care with potential for long-term cost benefit. Verification of a reported penicillin allergy is an integral part of antibiotic stewardship, and the pregnancy period should be utilized as an important opportunity to perform this evaluation. KEY POINTS: · The cost of developing and implementing an antepartum penicillin allergy referral program is modest.. · Program cost did not significantly alter short-term cost with a potential for long-term cost benefit.. · Penicillin allergy verification is an important part of antibiotic stewardship and should be expanded..

Intravenous iron for treatment of iron deficiency anemia during pregnancy and associated maternal outcomes.

BACKGROUND: More than 40% of pregnant patients worldwide are anemic, with at least half resulting from iron deficiency anemia (IDA). Anemia in pregnancy is linked with adverse maternal and neonatal outcomes. Treatment for IDA is iron supplementation; however, the optimal route of administration remains unclear. We sought to investigate whether patients with IDA who received intravenous iron (IVI) had decreased odds of maternal morbidity compared to patients who did not. METHODS: This is a retrospective cohort study of pregnant patients with presumed IDA with term deliveries at a tertiary hospital from 2013-2021. Data were extracted from the hospital's electronic medical record using standardized definitions and billing codes. Patients who received antepartum IVI were compared to patients who did not. The primary outcome was a maternal morbidity composite inclusive of receipt of blood transfusion, hysterectomy, admission to the intensive care unit or death. Bivariate analyses and multivariable logistic regression modelling were performed adjusting for potential confounders. RESULTS: Of 45,345 pregnancies, 5054 (11.1%) met eligibility criteria. Of these, 944 (18.7%) patients received IVI while 4110 (81.3%) did not. Patients who received IVI had higher risk baseline characteristics. They experienced a greater increase in hematocrit from pregnancy nadir to delivery admission (4.5% vs. 3.3%, p < .01). Despite this, patients who received IVI had higher odds of the maternal morbidity composite (OR 1.47, 95%CI 1.11-1.95). This finding persisted after adjusting for potential confounders, although the strength of the association became attenuated (aOR 1.37, 95%CI 1.02-1.85). Odds of the morbidity composite were not elevated among patients who received a full IVI treatment course (OR 1.2, 95% CI 0.83-1.90). DISCUSSION: Odds of the maternal morbidity composite were increased among patients who received IVI despite greater increases in hematocrit. The effect was attenuated after adjusting for potential confounders and was not significant among patients who completed a full treatment course.

Survey of Obstetric Providers to Assess the Knowledge and Management of a Reported Penicillin Allergy in Pregnant Women.

OBJECTIVE: Penicillin allergy is the most commonly reported drug allergy in the United States; however, less than 10% of individuals labeled with a penicillin allergy are truly allergic. A reported penicillin allergy in pregnancy is associated with adverse maternal and perinatal outcomes. Despite recommendations for penicillin allergy testing in pregnancy, limited literature regarding obstetric providers' comfort and knowledge in addressing penicillin allergy and referral patterns exists. The objective of this study is to survey obstetric providers to assess their clinical practice patterns and baseline penicillin allergy knowledge, identify potential knowledge gaps in the management of pregnant patients with reported penicillin allergy, and measure the impact of an educational intervention on provider knowledge and practice patterns. STUDY DESIGN: An anonymous, electronic 23-question survey administered to all obstetric providers at a single academic medical center assessed obstetric provider characteristics, self-reported antibiotic practice patterns, and antibiotic allergy knowledge before (June 19, 2020) and after (September 16, 2020) a penicillin allergy educational intervention, which consisted of multiple small-group educational sessions and a culminating departmental educational session. Discrete knowledge comparison by provider type and experience level of pre- and postintervention was performed using chi-square tests. RESULTS: Of 277 obstetric providers invited, 124 (45%) responded preintervention and 62 (22%) postintervention. In total, 27% correctly identified the percentage of patients labeled penicillin allergic who would tolerate penicillins, 45% identified cephalosporin cross-reactivity, 59% understood penicillin allergies can wane, and 54% identified penicillin skin testing (PST) as a valid allergy verification tool. Among 48 respondents who attended educational sessions and responded postintervention, their knowledge of penicillin allergy waning (79% preeducation vs. 98% posteducation, p < 0.01) and PST as a valid tool for penicillin allergy verification (50% preeducation vs. 83% posteducation, p < 0.01) improved. CONCLUSION: Knowledge gaps related to penicillin allergy exist among obstetric providers. Educational initiatives may improve provider knowledge, help in the identification of patients requiring penicillin allergy evaluation, and reduce referral barriers. KEY POINTS: · Obstetric providers lack adequate knowledge of penicillin allergy.. · Educational interventions can improve discrete knowledge.. · Limited knowledge is a barrier to allergy referral for penicillin allergy delabeling..

Maternal Outcomes in Subsequent Pregnancies After Classical Cesarean Delivery.

OBJECTIVE: To compare maternal outcomes in subsequent pregnancies of patients who had a prior classical cesarean delivery with those with a prior low transverse cesarean delivery. METHODS: We conducted a cross-sectional analysis of patients with live singleton births at or after 24 weeks of gestation who had a prior classical cesarean delivery or a low transverse cesarean delivery in the 2016-2019 National Inpatient Sample database. Outcome measures included mode of delivery, uterine rupture, and severe maternal morbidity (SMM), as defined by the Centers for Disease Control and Prevention. Maternal outcomes were compared using the χ2 test and the propensity score method, accounting for differences in patients' clinical risk factors. Multivariable regressions further assessed how patients' sociodemographic and hospital characteristics might influence the differences in maternal outcomes between the two groups. RESULTS: The sample included 1,671,249 patients: 25,540 with prior classical cesarean delivery and 1,645,709 with prior low transverse cesarean delivery. Cesarean delivery occurred in 95.5% of patients with prior classical cesarean compared with 91.3% of those with prior low transverse delivery (P<.001; propensity score method: odds ratio [OR] 0.99, 95% CI 0.85-1.16) and uterine rupture occurred in 1.1% and 0.3%, respectively (P<.001; propensity score method: OR 2.17, 95% CI 1.40-3.36). Among patients with prior classical cesarean delivery, uterine rupture occurred in 10.6% of those who underwent labor compared with 0.3% of those who did not (P<.001). Rates of SMM were 5.9% and 2.0% in the two groups, respectively (P<.001; propensity score method: OR 1.87, 95% CI 1.53-2.29). After adjustment of maternal sociodemographic and hospital characteristics, differences in the risk of uterine rupture and SMM between the two groups were attenuated but remained significant. CONCLUSION: Prior classical cesarean delivery was associated with a higher risk of uterine rupture and SMM in subsequent pregnancies, compared with prior low transverse cesarean delivery, even after accounting for patients' clinical, sociodemographic, and hospital characteristics.

Outpatient penicillin allergy evaluation during pregnancy and associated clinical outcomes.

BACKGROUND: Beta-lactam antibiotics are often clinically indicated in the peripartum period, posing a challenge for pregnant women who report a penicillin allergy. Allergy verification testing is rarely performed during pregnancy, even though most women do not have a true allergy. OBJECTIVE: This study aimed to evaluate a hospital-wide multidisciplinary program introduced in August 2020 to identify, refer, evaluate, and test pregnant women with unverified penicillin allergies and assess its association with maternal and neonatal outcomes. STUDY DESIGN: We conducted a retrospective cohort study at a large academic hospital of all pregnant women with a penicillin allergy documented in the electronic medical record who delivered from September 2020 to October 2021. Data were abstracted by medical record review. Women referred for penicillin allergy evaluation were compared with those who were not. Maternal outcomes were alternative antibiotic (clindamycin or vancomycin) use, postpartum infection, and maternal length of postpartum hospital stay. Neonatal outcomes were intensive care unit admission, postnatal blood draw, antibiotic treatment, and birth hospitalization length of hospital stay. Bivariate and multivariable analyses were performed. RESULTS: Of 689 women with a documented penicillin allergy, 232 (33.7%) were referred for allergy evaluation during the study period. Of those referred, 175 (75.4%) underwent allergy consultation, and of these patients, 167 (95.4%) were considered appropriate for allergy verification testing. Of note, 117 women (70.1%) underwent skin testing with or without graded oral amoxicillin drug challenge, and all but 1 woman (99.1%) were found to be penicillin tolerant. Moreover, 5 additional women were delabeled of their penicillin allergy based on history and pharmacy confirmation of penicillin tolerance subsequent to index reaction. Referred women had a 62% lower likelihood of receiving an alternative antibiotic than those who were not referred, and this significance persisted even after adjusting for potential confounders (adjusted odds ratio, 0.49; 95% confidence interval, 0.27-0.89). Other maternal and neonatal adverse outcomes were less frequent in those referred, but these associations did not reach statistical significance. CONCLUSION: This study documented the feasibility, safety, and clinical benefit of an outpatient penicillin allergy referral program for pregnant women. Referred patients were significantly less likely to receive alternative antibiotics; however, more patients are needed to assess whether there are additional clinical benefits.

Aberrant H19 Expression Disrupts Ovarian Cyp17 and Testosterone Production and Is Associated with Polycystic Ovary Syndrome in Women.

As one of the most common endocrine disorders affecting women, polycystic ovary syndrome (PCOS) is associated with serious conditions including anovulation, endometrial cancer, infertility, hyperandrogenemia, and an increased risk for obesity and metabolic derangements. One contributing etiology to the pathophysiology of hyperandrogenemia associated with PCOS is an intrinsic alteration in ovarian steroidogenesis, leading to enhanced synthesis of androgens including testosterone. Studies have suggested that the increased testosterone synthesis seen in PCOS is driven in part by increased activity of CYP17A1, the rate-limiting enzyme for the formation of androgens in the gonads and adrenal cortex, which represents a critical factor driving enhanced testosterone secretion in PCOS. In this work, we evaluated the hypothesis that dysregulation of the noncoding RNA H19 results in aberrant CYP17 and testosterone production. To achieve this, we measured Cyp17 in ovarian tissues of H19 knockout mice, and quantified serum testosterone levels, in comparison with wild-type controls. We also evaluated circulating and ovarian H19 expression and correlated results with the presence or absence of PCOS in a group of women undergoing evaluation and treatment for infertility. We found that the loss of H19 in a mouse model results in decreased ovarian Cyp17, along with decreased serum testosterone in female mice. Moreover, utilizing serum samples and cumulus cells from women with PCOS, we showed that circulating and ovarian levels of H19 are increased in women with PCOS compared to controls. Findings from our multimodal experimental strategy, involving both a mouse model of dysregulated H19 expression and clinical serum and ovarian cellular samples from women with PCOS, suggest that the loss of H19 may disrupt androgen production via a Cyp17-mediated mechanism. Conversely, excess H19 may play a role in the pathogenesis of PCOS-associated hyperandrogenemia.

Neurocritical care of the pregnant patient.

INTRODUCTION: An estimated 0.1%-0.8% of obstetric patients require admission to an intensive care unit (ICU) during pregnancy or the puerperium. When neurologic emergencies occur in pregnancy, collaboration between the neurointensivist, obstetric anesthesiologist, and obstetrician is key in minimizing morbidity and mortality. PRINCIPLES: Care of the critically ill pregnant patient mirrors that of the critically ill nonpregnant patient with some minor exceptions. Special care must be taken to consider the normal physiologic changes of pregnancy as well as possible fetal exposure to medical interventions. Timing and method of delivery must be carefully considered when caring for patients with neurologic emergencies. Common neurologic emergencies in pregnancy include hypertensive disorders of pregnancy, intracranial neoplasms, noneclamptic seizures, cerebrovascular disorders, and ventriculoperitoneal shunt malfunctions. CONCLUSION: While neurologic emergencies in pregnancy are overall rare, when they do occur, they can be devastating. As in the nonpregnant population, prompt recognition and rapid intervention are crucial in optimizing patient outcomes. When neurologic emergencies occur in pregnancy, maternal and fetal care is optimized through a multidisciplinary care team.

The relationship between H19 and parameters of ovarian reserve.

CONTEXT: The H19 long noncoding RNA (lncRNA) belongs to a highly conserved, imprinted gene cluster involved in embryonic development and growth control. We previously described a novel mechanism whereby the Anti-mullerian hormone (Amh) appears to be regulated by H19. However, the relationship between circulating H19 and markers of ovarian reserve including AMH not been investigated. OBJECTIVE: To determine whether H19 expression is altered in women with decreased ovarian reserve. DESIGN: Experimental study. SETTING: Yale School of Medicine (New Haven, USA) and Gazi University School of Medicine (Ankara, Turkey). PATIENTS OR OTHER PARTICIPANTS: A total of 141 women undergoing infertility evaluation and treatment. INTERVENTION: Collection of discarded blood samples and cumulus cells at the time of baseline infertility evaluation and transvaginal oocyte retrieval, respectively. MAIN OUTCOME MEASURE: Serum and cumulus cell H19 expression. RESULTS: Women with diminished ovarian reserve (as determined by AMH) had significantly lower serum H19 expression levels as compared to controls (p < 0.01). Serum H19 was moderately positively correlated with serum AMH. H19 expression was increased 3.7-fold in cumulus cells of IVF patients who demonstrated a high response to gonadotropins, compared to low responders (p < 0.05). CONCLUSION: In this study, we show that downregulation of H19 in serum and cumulus cells is closely associated with decreased ovarian reserve, as measured by decreased AMH levels and reduced oocyte yield at oocyte retrieval. Further study with expanded sample sizes is necessary to determine whether H19 may be of use as a novel biomarker for diminished ovarian reserve.

Accurate diagnosis of endometriosis using serum microRNAs.

BACKGROUND: Endometriosis, a chronic disease that afflicts millions of women worldwide, has traditionally been diagnosed by laparoscopic surgery. This diagnostic barrier delays identification and treatment by years, resulting in prolonged pain and disease progression. Development of a noninvasive diagnostic test could significantly improve timely disease detection. We tested the feasibility of serum microRNAs as diagnostic biomarkers of endometriosis in women with gynecologic disease symptoms. OBJECTIVE: The objective of the study was to validate the use of a microRNA panel as a noninvasive diagnostic method for detecting endometriosis. STUDY DESIGN: This was a prospective study evaluating subjects with a clinical indication for gynecological surgery in an academic medical center. Serum samples were collected prior to surgery from 100 subjects. Women were selected based on the presence of symptoms, and laparoscopy was performed to determine the presence or absence of endometriosis. The control group was categorized based on absence of visual disease at the time of surgery. Circulating miRNAs, miR-125b-5p, miR-150-5p, miR-342-3p, miR-451a, miR-3613-5p, and let-7b, were measured in serum by quantitative real-time polymerase chain reaction in a blinded fashion without knowledge of disease status. Receiver-operating characteristic analysis was performed on individual microRNAs as well as combinations of microRNAs. An algorithm combining the expression values of these microRNAs, built using machine learning with a random forest classifier, was generated to predict the presence or absence of endometriosis on operative findings. This algorithm was then tested in an independent data set of 48 previously identified subjects not included in the training set (24 endometriosis and 24 controls) to validate its diagnostic performance. RESULTS: The mean age of women in the study population was 34.1 and 36.9 years for the endometriosis and control groups, respectively. Control group subjects displayed varying pathologies, with leiomyoma occurring the most often (n = 39). Subjects with endometriosis had significantly higher expression levels of 4 serum microRNAs: miR-125b-5p, miR-150-5p, miR-342-3p, and miR-451a. Two serum microRNAs showed significantly lower levels in the endometriosis group: miR-3613-5p and let-7b. Individual microRNAs had receiver-operating characteristic areas under the curve ranging from 0.68 to 0.92. A classifier combining these microRNAs yielded an area under the curve of 0.94 when validated in the independent set of subjects not included in the training set. Analysis of the expression levels of each microRNA based on revised American Society of Reproductive Medicine staging revealed that all microRNAs could distinguish stage I/II from control and stage III/IV from control but that the difference between stage I/II and stage III/IV was not significant. Subgroup analysis revealed that neither phase of the menstrual cycle or use of hormonal medication had a significant impact on the expression levels in the microRNAs used in our algorithm. CONCLUSION: This is the first report showing that microRNA biomarkers can reliably differentiate between endometriosis and other gynecological pathologies with an area under the curve >0.9 across 2 independent studies. We validated the performance of an algorithm based on previously identified microRNA biomarkers, demonstrating their potential to detect endometriosis in a clinical setting, allowing earlier identification and treatment. The ability to diagnose endometriosis noninvasively could reduce the time to diagnosis, surgical risk, years of discomfort, disease progression, associated comorbidities, and health care costs.

Acute Herpes Simplex Virus Hepatitis in Pregnancy.

BACKGROUND: Herpes simplex virus (HSV) causes only 2-4% of all acute hepatitis but has high morbidity and mortality. Pregnancy is a risk factor for HSV hepatitis. We describe a case of gestational HSV hepatitis. CASE: A 32-year old woman, gravida 2 para 1, presented at 38 2/7 weeks of gestation with back pain and fetal tachycardia. She became febrile after admission, had spontaneous rupture of membranes, and was delivered by cesarean for malpresentation. Postpartum, she became persistently febrile and developed transaminitis, symptomatic hypotension, and pancytopenia despite antibiotics. Imaging revealed acute liver injury, splenomegaly, pleural effusions, and cardiomyopathy. Serum polymerase chain reaction (PCR) screening identified HSV-1 infection. The patient recovered on acyclovir. There was no evidence of neonatal seroconversion. CONCLUSION: Herpes simplex virus hepatitis causes significant morbidity, and pregnant women are susceptible to severe infections. Pregnant or peripartum women with acute febrile hepatitis require prompt evaluation for HSV with serum PCR screening.