Faculty Bibliography

OBJECTIVE:Mood disturbances-including depressed mood, irritability, anxiety, and mental exhaustion-are common during the menopause transition, affecting up to 68% of women. While menopausal hormone therapy (HT) is FDA-approved for vasomotor and genitourinary symptoms, its role in managing mood symptoms remains less well understood. This retrospective, comparative study evaluated the impact of systemic HT on mood in a cohort of HT-naive individuals. METHODS:We included 260 patients presenting to an urban, academic menopause center between 2023 and 2025 who completed the Menopause Rating Scale (MRS) before and after initiating systemic HT for FDA-approved indications. MRS psychological subdomain scores covering depressive mood, irritability, anxiety, and mental exhaustion were analyzed. Most patients (96.5%) received transdermal estradiol, had an average age of 52.1 years, and a mean follow-up of 4.5 months. Notably, 51% had a history of anxiety or depression, and 24% were on antidepressant therapy at baseline. RESULTS:Results showed a significant reduction in MRS psychological subdomain scores from baseline to follow-up (P<0.001). The proportion of patients with severe mood symptoms (score ≥7) decreased from 62.3% to 24.6%. Improvement was greatest in those with severe baseline symptoms (mean change: -3.85, SE: 0.223). Treatment response did not differ by psychiatric history, age, menopausal stage, or antidepressant use. CONCLUSIONS:These findings suggest systemic HT may improve mood symptoms in midlife, especially among those with elevated baseline severity, independent of prior mental health diagnosis, antidepressant use, or menopause stage. These findings support further investigation of HT's impact on mood in midlife women.

BACKGROUND:Preterm birth (PTB, < 37 weeks of gestation) is the leading cause of child mortality in the United States (U.S.) and worldwide, and has substantial short- and long-term health consequences for mothers and infants. Each year, > 350,000 infants in the U.S. are born preterm, and rates continue to rise in parallel with maternal risk factors such as hypertension, diabetes, anemia, asthma, and mental health conditions. Evidence-based interventions exist for many of these conditions and are associated with improved pregnancy outcomes, including low-dose aspirin for preeclampsia prevention in individuals with chronic hypertension or pregestational diabetes, inhalers for asthma, iron for anemia, and therapy or medication for mental health disorders, but fewer than half of eligible individuals receive them, reflecting persistent gaps in use. To address this, we developed the PTB Actionable Risk Index (PTB-ARIx), which leverages factors with known evidence-based interventions to identify individuals who are pregnant and are at increased risk for PTB. This study evaluates performance of the PTB-ARIx throughout pregnancy with respect to risk determination and characterization of actionable risk factors, including their combined contributions to PTB. METHODS:A retrospective cohort study was conducted using linked data for 1.9 million singleton live births in California in 2016-2020, divided into training and testing sets. Poisson regression estimated associations between 18 candidate risk factors for PTB with evidence-based interventions spanning clinical, behavioral, and social risks, including preeclampsia risk composites (≥ 1 high-risk or ≥ 2 moderate-risk factors based on U.S. Preventive Services Task Force (USPSTF) criteria), maternal conditions (e.g., gestational hypertension, asthma), substance use, and social adversity. Beta coefficients were combined to construct the PTB-ARIx, evaluated by per-unit associations with PTB and by area under the receiver operating characteristic curve (AUC) overall, by early (< 32 weeks), late (32-36 weeks), spontaneous, and medically-indicated PTB, and by PTB co-occurring with preeclampsia. FINDINGS/RESULTS:All risk factors were found to be associated with increased PTB risk. Having ≥ 1 high-risk or ≥ 2 moderate-risk factors for preeclampsia (based on composites) was most strongly related to PTB (relative risk (RR) 6.73, 95% confidence interval (CI) 6.57, 6.89). Each unit increase in PTB-ARIx was associated with > 60% higher PTB risk (RRs 1.66-1.72) across training and testing samples, with consistent findings across PTB and race/ethnicity-insurance subgroups. Model performance was modest for late PTB (AUC ≈ 0.63), stronger for early PTB (0.69-0.72), and especially high for early PTB with preeclampsia (AUCs up to 0.97). Over 70% of individuals with PTB-ARIx scores ≥ 3.00 experienced PTB or another adverse outcome such as low birth weight (< 2,500 grams). CONCLUSIONS:The PTB-ARIx is a well-performing metric for identifying individuals at increased risk for PTB and other adverse pregnancy outcomes. By centering on modifiable risks, the PTB-ARIx combines risk identification with opportunities for intervention. Demonstrating strong performance across subgroups, including for early PTB and PTB with preeclampsia, the PTB-ARIx provides a potential pathway to improve patient-provider communication and uptake of equitable, evidence-based care. Further validation, including integration with treatment data, is needed to confirm its potential to reduce PTB risk and rates.

INTRODUCTION/UNASSIGNED:Platelet hyperreactivity is linked to inflammation and cardiovascular risk in nonpregnant populations, but its relationship to placentally mediated pregnancy outcomes is undefined. We prospectively evaluated platelet hyperreactivity in pregnancy and subsequent ischemic placental disease (IPD), and examined aspirin's (ASA) effect on platelet activity by baseline platelet phenotype. METHODS/UNASSIGNED: RESULTS/UNASSIGNED:Of 66 pregnant participants recruited, 61 had first-trimester LTA; 20 (32.8%) had platelet hyperreactivity. Participants with hyperreactivity were more likely to develop IPD than those without (55% versus 24%, adjusted odds ratio [aOR] 3.77 (95% CI [1.05-13.53]), with consistent directionality across individual components despite low event frequencies. Participants with platelet hyperreactivity showed greater platelet aggregation to ADP, collagen, and low-dose AA. Platelet transcriptomic profiling distinguished participants with versus without platelet hyperreactivity and revealed differential expression of pathways related to platelet activity, energy metabolism, and immune regulation. Among 45 high-risk participants recommended ASA, those with hyperreactivity exhibited higher AA-induced aggregation (24% vs 12.5% platelet aggregation, p=0.01) despite similar serum TxB2 levels. CONCLUSION/UNASSIGNED:First-trimester platelet hyperreactivity was present in approximately one-third of participants and was independently associated with increased risk of IPD. Participants with platelet hyperreactivity demonstrated distinct transcriptomic signatures and greater platelet aggregation despite ASA use. Together, these findings support a contributory role for platelets in placental ischemic pathology and highlight the need to elucidate mechanisms and develop platelet-targeted preventive strategies.

OBJECTIVE:To evaluate the association between severe perioperative surgical morbidity with cesarean delivery and postpartum readmission. METHODS:This was a retrospective cross-sectional study using linked birth certificate and maternal discharge data for patients who underwent cesarean delivery in any California hospital between October 2015 and October 2021. Severe perioperative surgical morbidity is an index characterized by severe surgical complications occurring during hospitalization for cesarean delivery, identified using International Classification of Diseases, Tenth Revision diagnosis and procedure codes for severe surgical complications. The primary outcome was all-cause postpartum readmission within 42 days after hospital discharge. Readmission rates were quantified for patients with and without severe perioperative surgical morbidity, and generalized estimating equations were used to estimate adjusted relative risks (aRRs), adjusted risk differences (aRD), and 95% CIs, accounting for patient- and hospital-level factors. In secondary analysis, the association was assessed separately for prelabor and intrapartum cesarean deliveries. RESULTS:The study population included women who had undergone 703,079 cesarean deliveries. The readmission rate was higher among those with severe perioperative surgical morbidity compared with those without severe perioperative surgical morbidity (469.4/10,000 [95% CI, 428.0-511.0] vs 165.3/10,000 [95% CI, 162.3-168.3]). Severe perioperative surgical morbidity was associated with a twofold increased risk of readmission (aRR 2.22; 95% CI, 2.00-2.46). The aRD for patients with severe perioperative surgical morbidity was an excess of two readmissions (2.5; 95% CI, 2.1-3.0/100 cesarean deliveries) compared with patients without severe perioperative surgical morbidity. Wound infection was the most common diagnosis at readmission among patients with severe perioperative surgical morbidity (77/10,000; 95% CI, 60.5-95.3). The risk of readmission was similar among patients with severe perioperative surgical morbidity and without severe perioperative surgical morbidity who underwent intrapartum cesarean delivery (aRR 2.35; 95% CI, 2.09-2.65) and prelabor cesarean delivery (aRR 2.03; 95% CI, 1.72-2.40). CONCLUSION/CONCLUSIONS:Nearly 1 in 20 patients undergoing cesarean delivery who experience severe perioperative surgical morbidity undergoes postpartum readmission, with a twofold increased readmission risk at 42 days after discharge. Patients with severe perioperative surgical morbidity may benefit from targeted follow-up to reduce postpartum admission.

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.

OBJECTIVE:To investigate the relationship between platelet indices (count, size and production/immaturity) and hypertensive disorders of pregnancy. STUDY DESIGN/METHODS:This was a secondary analysis of a prospective cohort of pregnant individuals followed from first trimester through delivery at an academic tertiary care institution. Routine platelet indices obtained prospectively during prenatal care and delivery were compared between those who developed a hypertensive disorder of pregnancy and those who did not. We assessed platelet count (by trimester), mean platelet volume, and immature platelet fraction measured as percent (%) and absolute count. Data were analyzed using Fisher's Exact test, chi-square test, and multivariable logistic regression. P < 0.05 was considered statistically significant. RESULTS: = 0.01) compared to those without a hypertensive disorder of pregnancy, after adjusting for age, race/ethnicity, obesity, nulliparity, and chronic hypertension. The prevalence and likelihood of a hypertensive disorder of pregnancy increased with increasing mean platelet volume, as well as with both the percent and absolute immature platelet fraction. There was no difference between groups in platelet count in the first trimester, second trimester, or at delivery. CONCLUSIONS:An increase in platelet size and immaturity was observed in those with a hypertensive disorder of pregnancy. These data support further investigation of platelets in the mechanisms of the development of hypertensive disorders of pregnancy and the use of platelet indices to better identify high risk groups in pregnancy.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Healthcare is increasingly being delivered in the outpatient setting, but robust quality improvement programs and performance metrics are lacking in ambulatory care, particularly specialty-based ambulatory care. METHODS:To promote quality improvement in ambulatory care, we developed an infrastructure to create specialty-specific quality measures and dashboards that could be used to display providers' performance across relevant measures to individual providers and institutional leaders. RESULTS:The products of this program include a governance and infrastructure for specialty-specific ambulatory quality metrics as well as two distinct dashboards for data display. One dashboard is provider-facing, displaying provider's performance on specialty-specific measures as compared to institutional standards. The second dashboard is a leadership dashboard that provides overall and provider-level information on performance across measures. CONCLUSIONS:The Specialty-based Ambulatory Quality program reflects a systematic, institutionally-supported quality improvement framework that can be applied across diverse ambulatory specialties. As next steps, we plan to evaluate the program's impact on provider performance across measures and expand this program to other specialties practicing in the outpatient setting.

OBJECTIVE:Preterm induction of labor can be necessary for maternal and fetal wellbeing. Duration of cervical ripening balloon (CRB) use has been studied in only term inductions. Our study investigated duration of time in hours for CRB expulsion and vaginal delivery in preterm inductions of labor. METHODS:This was a single-institution retrospective cohort study of preterm (< 37 weeks) and term (≥ 37 weeks) inductions with CRB between 2010 and 2021. Cesarean deliveries were excluded. Primary outcome was insertion to expulsion time of CRB. Secondary outcomes included induction to delivery time, cervical dilation after expulsion, misoprostol, and Pitocin use. Institutional review board (IRB) approval was obtained prior to the study. RESULTS:Ninety-eight patients with vaginal delivery after preterm CRB use were identified and matched 1:1 on baseline characteristics (p > 0.05) to term patients with vaginal delivery after CRB use. Mean insertion to expulsion time was significantly shorter for term than preterm inductions (mean 7.2 ± 3.09 h versus 8.5 ± 3.38 h; p < 0.01). Mean induction to delivery time was significantly shorter for term than preterm inductions (18.4 ± 7.6 h versus 22.5 ± 9.01 h; p < 0.01). Increased use of misoprostol, Pitocin, and second CRB were noted among the preterm cohort. Among term patients, more CRB placement at start of induction and greater cervical dilation post-balloon were found in comparison to preterm patients. CONCLUSION/CONCLUSIONS:Among patients undergoing preterm induction, longer insertion to expulsion time of CRB, longer induction to delivery time, and increased interventions should be expected. Different standards for labor management should be considered for achieving vaginal delivery in preterm inductions.

BACKGROUND/UNASSIGNED:Coronary artery spasm is an established mechanism of myocardial infarction with non-obstructive coronary arteries (MINOCA). Various mechanisms have been proposed, ranging from vascular smooth muscle hyperreactivity to endothelial dysfunction, to autonomic nervous system dysregulation. CASE SUMMARY/UNASSIGNED:We report a case of a 37-year-old woman who presented with recurrent non-ST elevation myocardial infarction (NSTEMI), coinciding with her menstrual periods. Intracoronary acetylcholine provocation testing resulted in coronary spasm in the left anterior descending artery (LAD) that was relieved with nitroglycerine. Initiating calcium channel blockade and suppressing cyclical variation in sex hormones resulted in improvement of her symptoms and cessation of monthly NSTEMI events due to coronary spasm. DISCUSSION/UNASSIGNED:Initiating calcium channel blockade and suppressing cyclical variation in sex hormones resulted in improvement of her symptoms and cessation of monthly NSTEMI events due to coronary spasm. Catamenial coronary artery spasm is a rare, but clinically important, presentation of myocardial infarction with non-obstructive coronary arteries (MINOCA).