Faculty Bibliography

BACKGROUND/UNASSIGNED:Cryptococcosis is the most common opportunistic fungal infection in people with human immunodeficiency virus. On a global scale, it causes 15% of acquired immunodeficiency syndrome-related mortality. CASE SUMMARY/UNASSIGNED:We report the case of a 21-year-old cisgender pregnant woman living with human immunodeficiency virus who presented with headache and photophobia. Her clinical course was complicated by recurrent hospital admissions for disseminated cryptococcosis and a life-threatening reaction to liposomal amphotericin B, the mainstay of treatment. A desensitization protocol was implemented, allowing for continuation of therapy during pregnancy. CONCLUSION/UNASSIGNED:The management of cryptococcosis in pregnancy is challenging due to the potential teratogenic effects of antifungals used and the limited therapeutic options available. This case highlights the complexities of treatment in pregnancy and demonstrates successful desensitization to liposomal amphotericin B during pregnancy.

OBJECTIVES/OBJECTIVE:Novel biologic agents targeting the neonatal Fc receptor (FcRn) offer a promising strategy to prevent cardiac neonatal lupus (cardiac-NL) in pregnant patients with high-titre anti-SSA/Ro52 kD or 60 kD autoantibodies via dual effects: reducing serum immunoglobin G (IgG) levels and inhibiting placental transfer. This study was initiated to assess the feasibility of FcRn blockade as prophylactic therapy for recurrent cardiac-NL. METHODS:A 34-year-old pregnant patient with systemic lupus erythematosus and 3 prior consecutive pregnancies complicated by neonatal lupus (1 cutaneous, 1 fatal cardiac-NL at 20 weeks, 1 cardiac-NL delivered at 32 weeks and neonatal cutaneous NL), each despite hydroxychloroquine 400 mg daily, was treated with weekly subcutaneous infusions of 560 mg rozanolixizumab (humanised IgG4 monoclonal antibody against FcRn) from gestational weeks 14 to 28 (to cover the vulnerable period of fetal cardiac injury) through a compassionate use designation. The patient performed home fetal heart rhythm monitoring thrice daily with weekly echocardiograms. RESULTS:Maternal anti-SSA/Ro52 kD and 60 kD autoantibodies, total IgG, and subclasses IgG1, 2, 3 decreased by about 65% at gestational week 22, with a return to near baseline levels by week 34. The pregnancy was uncomplicated, resulting in a spontaneous vaginal delivery of a healthy neonate at 37 weeks. At delivery, cord blood and maternal IgG levels were normal, obviating the need for rescue intravenous immune globulin. The neonate had a normal echocardiogram and electrocardiogram but developed a rash consistent with neonatal lupus at 5 weeks of life. There were no serious adverse events. CONCLUSIONS:The successful application of FcRn blockade to prevent recurrent cardiac-NL sets a precedent for a multicentre study.

OBJECTIVE:To determine whether administration of antenatal corticosteroids to patients with twin gestations at risk for late preterm delivery is associated with reduced risk for neonatal respiratory morbidity compared with unexposed twins. METHODS:This was a multicenter, retrospective cohort study in a large, urban health network (2013-2022) of patients with twin gestations at risk for preterm delivery between 34 0/7 and 36 6/7 weeks of gestation. Patients were excluded if they received antenatal corticosteroids before 34 weeks of gestation or had pregestational diabetes, single-twin death before 34 weeks, or oral steroid exposure during pregnancy. Neonates were excluded if they had major congenital anomalies. The primary outcome was a composite of neonatal respiratory morbidity requiring respiratory support within 72 hours of birth, including continuous positive airway pressure (CPAP) or high-flow nasal cannula for 2 hours or more, supplemental oxygen of 30% for 2 hours or more, extracorporeal membrane oxygenation, mechanical ventilation, and fetal or neonatal death. Secondary outcomes included neonatal hypoglycemia and indications for neonatal intensive care unit (NICU) admission. Adjusted and unadjusted relative risks with 95% CIs were calculated. RESULTS:During the study period, 366 twin gestations and 722 patient-neonate dyads were included: 162 gestations (321 neonates) in the exposed group and 204 (401 neonates) in the unexposed group. There was no difference in the composite outcome of respiratory morbidity in those exposed to antenatal corticosteroids (23.4% vs 20.4%, P=.40, adjusted relative risk [RR] 1.00, 95% CI, 0.71-1.42). The composite was driven mostly by rates of CPAP use (21.2% vs 18.5%, P=.41, adjusted RR 1.05, 95% CI, 0.73-1.53) and high-flow nasal cannula use (6.2% vs 2.2%, P=.02, RR 2.77, 95% CI, 1.16-6.66). Antenatal corticosteroid exposure was associated with a lower risk of need for supplemental oxygen (0.6% vs 3.5%, P=.02, RR 0.18, 95% CI, 0.04-0.79) and mechanical ventilation (0.6% vs 3.2%, P=.03, RR 0.19, 95% CI, 0.04-0.87). Although antenatal corticosteroids exposure was not associated with higher rates of hypoglycemia (44.2% vs 41.7%, P=.57, adjusted RR 0.99, 95% CI, 0.82-1.19), exposure was associated with a higher risk of having hypoglycemia as the only indication for NICU admission (10.3% vs 5.2%, P=.03, RR 1.96, 95% CI, 1.07-3.59). CONCLUSION/CONCLUSIONS:In a large, multicenter, network-wide retrospective cohort study of patients with twin gestations at risk for late preterm birth, antenatal corticosteroid use was not associated with a decrease in overall respiratory morbidity but was associated with a decreased risk of need for supplemental oxygen and mechanical ventilation, as well as a higher risk of NICU admission for hypoglycemia. These results underscore the ongoing need to elucidate the risks and benefits of late preterm antenatal corticosteroids for patients with twin gestations at risk for late preterm birth.

BACKGROUND:Physical exam indicated-cerclage is an intervention offered to prolong pregnancy in the setting of painless cervical dilation prior to 24 weeks. One randomized clinical trial (RCT) showed an increased incidence of pregnancy prolongation by at least 28 days among participants who received perioperative indomethacin and cefazolin in the setting of a physical exam-indicated cerclage compared to those who did not receive those perioperative medications. Prospective studies suggest that prophylactic azithromycin may increase latency in the setting of cervical shortening, but this has not been studied in a controlled manner in patients undergoing physical exam-indicated cerclage. OBJECTIVE:The aim of our study is to determine whether the addition of perioperative azithromycin to cefazolin and indomethacin for physical exam-indicated cerclage increases latency to delivery compared to perioperative cefazolin and indomethacin alone. STUDY DESIGN/METHODS:This was an open-label multicenter RCT of individuals with singleton gestations who were undergoing a physical exam-indicated cerclage between December 2021 and September 2023 at four sites across the United States. The study was IRB approved and registered at clinicaltrials.gov (NCT05132829). Participants were randomized 1:1 via a computer-generated randomization sequence stratified by site to standard of care (cefazolin 1-2 gm IV and indomethacin 50mg preoperatively followed by 2 additional doses at 8 and 16 hours postoperatively, control arm) or standard of care plus azithromycin (azithromycin 1000mg IV in addition to cefazolin and indomethacin described in the control group, azithromycin arm). The primary outcome was gestational latency (days) from cerclage placement to delivery. Secondary outcomes include preterm birth, gestational age at delivery, chorioamnionitis, and neonatal morbidity and mortality. RESULTS:A total of 82 pregnant individuals were assessed for eligibility and 54 participants were randomized, 27 to control and 27 to the azithromycin arm. In the primary intention-to-treat analysis, the median gestational latency from cerclage placement to delivery did not differ between the intervention and control groups (92 [45-118] vs 85 [20-123] days p=0.93). Furthermore, there were no statistically significant differences found in any of the secondary obstetric or neonatal outcomes. CONCLUSION/CONCLUSIONS:A single perioperative dose of azithromycin in addition to standard of care cefazolin and indomethacin does not improve latency to delivery or other perinatal outcomes compared to standard of care alone in singleton gestations undergoing a physical exam-indicated cerclage.

IMPORTANCE/UNASSIGNED:Insomnia and obstructive sleep apnea (OSA) are associated with pregnancy complications. OBJECTIVE/UNASSIGNED:To evaluate the association of insomnia and OSA during pregnancy with the risk of ischemic placental disease (IPD) and severe morbidity (SM) and to compare these risks between the 2 sleep disorders. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cross-sectional study included a statewide population-based sample of liveborn singleton births with linked birth certificates for birthing people and their infants in California from January 1, 2011, through December 31, 2020. The analysis was performed on July 22, 2024. EXPOSURES/UNASSIGNED:Insomnia and OSA. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The main outcomes were IPD, defined as preeclampsia, placental abruption, and birth of a neonate small for gestational age (SGA), and SM, defined according to the Centers for Disease Control and Prevention definition. RESULTS/UNASSIGNED:During the study period, there were 4 145 096 singleton live births among birthing people aged 13 to 55 years; 4783 (0.1%) had insomnia, 5642 (0.1%) had OSA, and 4 134 671 (99.7%) had neither condition. The prevalence of insomnia and OSA was 116 and 136 cases per 1000 live births, respectively. Compared with patients without insomnia or OSA (738 660 [17.9%]), the adjusted relative risk (ARR) of any IPD was 1.42 (95% CI, 1.35-1.50) for those with insomnia (1406 patients [29.4%]) and 1.57 (95% CI, 1.50-1.64) for those with OSA (1848 [32.8%]). Compared with patients with neither disorder, the ARR of birth of an SGA neonate was higher for those with insomnia (1.23; 95% CI, 1.13-1.35) than for those with OSA. The ARR of preterm birth was 1.81 (95% CI, 1.68-1.95) for insomnia (711 patients [14.9%]) and 1.73 (95% CI, 1.62-1.85) for OSA (870 [15.4%]) vs neither disorder (279 364 [6.8%]). The ARR of SM was 2.26 (95% CI, 2.03-2.50) for insomnia (366 patients [7.7%]) and 2.81 (95% CI, 2.58-3.06) for OSA (545 [9.7%]) vs neither disorder (93 857 [2.3%]). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cross-sectional study of singleton live births, pregnant individuals with insomnia or OSA were at increased risk for IPD, SM, and preterm birth compared with those without these sleep disorders. Further study is needed to determine the biological mechanisms for these risks and whether early identification and targeted preventive interventions may improve pregnancy outcomes.

BACKGROUND AND AIMS/OBJECTIVE:Pre-eclampsia confers increased risks of long-term cardiovascular disease (CVD). However, little is known about CVD risk among patients diagnosed with eclampsia, especially in the post-partum period. The aim of this study was to determine whether patients with eclampsia are at increased risk for readmission for CVD within the first year after delivery. METHODS:Using the Nationwide Readmissions Database from 2010 to 2018, readmissions for CVD events were identified during the calendar year after delivery in patients with eclampsia. Prevalence rates of CVD readmission (per 100 000 deliveries) were determined, and associations between eclampsia and CVD rehospitalization were based on a confounder adjusted hazard ratio (HR) with a 95% confidence interval (CI). A quantitative bias analysis addressed eclampsia misclassification and unmeasured confounding biases. RESULTS:Of over 27 million delivery hospitalizations, 20 478 (74.7 per 100 000) were complicated by eclampsia. CVD readmission rates among the eclampsia and normotensive patients were 854 and 147 per 100 000 delivery hospitalizations, respectively (rate difference 707, 95% CI 473-941; HR 6.9, 95% CI 4.5-10.4). HRs were high for specific heart disease types (range of adjusted HRs 4.8 to 15.5). Eclampsia was associated with a substantially high risk for stroke readmissions (adjusted HR 12.6, 95% CI 6.9-22.8). CONCLUSIONS:Eclampsia is associated with an increased risk for CVD complications compared with normotensive conditions, even as early as the first month following delivery. These data highlight the need for targeted short-term follow-up for CVD complications among patients whose pregnancies are complicated by eclampsia.

In this symposium, we introduce a collection of reviews that delve into the diverse clinically relevant aspects of the placenta and umbilical cord. The symposium addresses placenta previa and abruption; pathology, genetics, and imaging of the placenta; infections of the placenta; and ischemic placental disease. The umbilical cord's essential function as a fetal lifeline is explored, with an emphasis on the clinical repercussions of its dysfunction, including vasa previa and other umbilical cord abnormalities. This curated collection of reviews, which synthesizes the placenta's and umbilical cord's fundamental role in maternal-fetal health, underscores the clinical importance of these structures in pregnancy.

OBJECTIVE:The "39-week rule," implemented in August 2009, strongly discouraged early term deliveries before 39 weeks without accepted ACOG delivery indications. In this study, we evaluated fetal death rates before and after the 39-week rule in the United States (US) by review of published series. STUDY DESIGN/METHODS:Systematic literature searches were performed in PubMed, Cochrane Central Register of Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Scopus databases (January 2009-June 2023). Searches were focused on the 39-week rule and fetal death. Articles were excluded if they were non-English, included non-US population, or included multiple gestations. The articles were then exported to EndNote for reference management and uploaded to Rayyan for title and abstract screening by two independent reviewers. The study was prospectively registered in PROSPERO. RESULTS:Of 833 articles identified after initial search, 6 peer-reviewed studies met the inclusion criteria. After combining the data from these studies, there were 8713 fetal deaths/7,294,911 total births (0.12 %) post-implementation of the 39-week rule, and 8523 fetal deaths/7,705,422 total births (0.11 %) pre-implementation. Compared to pre-implementation, the odds of fetal death after implementation of the 39-week rule were 1.08 (95 % CI 1.05-1.11). CONCLUSIONS:Implementation of ACOG's 39-week rule resulted in an 8 % increased risk of fetal death compared to pre-implementation of the 39-week rule. This is alarming, but must be evaluated in the setting of decreased neonatal morbidity and mortality following the introduction of the 39-week rule.