Abstracts from the NIH Office of Research on Women's Health 2019 Annual BIRCWH Meeting – Building Interdisciplinary Research Careers in Women's Health December 11,2019

Introduction to the Scientific Abstracts from the 2019 Annual Meeting National Institutes of Health (NIH)

The period 2019‐2020 represents a landmark for the program called BIRCWH, Building Interdisciplinary Research Careers in Women's Health. The program, funded via NIH institutional career development grants, was created by the Office of Research on Women's Health (ORWH), with the first grant awards made in September 2000. The program has been continuously funded and coordinated by ORWH for nineteen years. The beginning of the 20^th anniversary year for the BIRCWH Program will be celebrated as part of the December 11, 2019 Annual BIRCWH meeting.

The BIRCWH Program was created to increase the number of women's health researchers working in an interdisciplinary environment, and is built around three pillars: strong mentoring, interdisciplinary research, and career development. The trainees supported by these awards are known as BIRCWH Scholars, have recently completed clinical training or postdoctoral fellowships, and hold the academic rank of assistant professor. As part of BIRCWH, the Scholars are paired with experienced, senior‐level investigators comprising interdisciplinary mentoring teams. These teams guide the Scholars in their career development to conduct basic, translational, clinical, or health services research related to women's health and, where appropriate, the use of both sexes to better understand the influence of sex as a variable on health and disease.

The 2019 Annual BIRCWH Meeting will open with the Ruth L. Kirschstein Memorial Keynote address that honors the life and achievements of Dr. Ruth L. Kirschstein, who was an exceptional scientist, mentor, and health administrator. In 1974, she became the first woman to direct an NIH institute, the National Institute of General Medical Sciences, a post she held until 1993. She then served as Principal NIH Deputy Director, and twice served as NIH acting director. In recognition of her leadership and support of NIH‐funded training programs, the National Research Service Award (NRSA) Program was renamed to honor Dr. Kirschstein's career, service to the nation, and commitment to future generations of scientists. Dr. Kirschstein was also a member of the Institute of Medicine, and a Fellow of the American Academy of Arts and Sciences.

The Keynote address will be followed by a panel discussion on how to mentor young researchers in dynamic fields like Artificial Intelligence/Machine Learning. The panel will be composed of BIRCWH Principal Investigators and other subject matter experts and will include NIH‐related resources for career development in this area.

To showcase the research achievements of the BIRCWH Programs, three BIRCWH Scholars were selected to present their research at the podium following the panel session. Their abstracts are listed first in the compendium below and represent the highly significant work of the BIRCWH Scholars overall. The topics of the oral/podium presentations range from a presentation about body composition and markers of cardiometabolic health in transgender youth, to sex differences in the cardiovascular events among patients with coronary health disease, with the third oral/podium talk focusing on sex differences in asthma. This exciting diversity of research projects are in areas crucial to the overall advancement of the health of women and reflect the high caliber of investigators being trained in these BIRCWH Programs.

The remaining BIRCWH Scholar abstracts will be presented during an afternoon Poster session. These posters represent many scientific areas that broadly fall within women's health and sex differences research, and include public health topics, basic, clinical, and translational science projects. These are highly meritorious projects, and their presentation should provide an important scientific networking opportunity. Additional guidance on grantsmanship issues and ways that Scholars can advance their research careers are provided in a mentoring session, attended by a number of program directors and scientists from the NIH institute, centers and offices affiliated with the BIRCWH Program. ORWH includes these abstracts below in advance of the 2019 Annual BIRCWH Meeting.

The full list of the NIH‐funded BIRCWH programs and additional information about the 2019 Annual BIRCWH Meeting can be found at: https://orwh.od.nih.gov/about/newsroom/events/building-interdisciplinary-research-careers-womens-health-bircwh-annual_19

Dr. Begg is a Senior Research Program Officer in the NIH Office of Research on Women's Health, overseeing the BIRCWH Program. For further information about the BIRCWH Program, please contact Dr. Begg at: beggl@od.nih.gov.

O‐1: Body Composition and Markers of Cardiometabolic Health in Transgender Youth on Gonadotropin‐releasing Hormone Agonists Compared to Cisgender Youth

Natalie J. Nokoff (presenting author),¹ Sharon L. Scarbro,^2,3,4 Elizabeth Juarez‐Colunga,^3,5 Kerrie L. Moreau,^6,7,8 Kristen J. Nadeau,¹ Philip Zeitler,¹ and Megan M. Kelsey¹

¹Department of Pediatrics, University of Colorado Anschutz Medical Campus; ²Department of Community and Behavioral Health, University of Colorado Denver Colorado School of Public Health; ³Adult and Child Consortium for Health Outcomes Research and Delivery Science (ACCORDS), University of Colorado Anschutz Medical Campus; ⁴Rocky Mountain Prevention Research Center, University of Colorado Denver Colorado School of Public Health; ⁵Department of Biostatistics and Informatics, University of Colorado Denver Colorado School of Public Health; ⁶Department of Medicine, University of Colorado Anschutz Medical Campus; ⁷Department of Medicine, Denver Veterans Administration Medical Center; ⁸Geriatric Research Education and Clinical Center

Background: 1.8% of youth identify as transgender; many will be treated with a gonadotropin‐releasing hormone agonist (GnRHa) to block endogenous puberty. The impact of GnRHa on insulin sensitivity (IS) and body composition in transgender youth is understudied.

Objective: To evaluate differences in IS and body composition in transgender youth on a GnRHa compared to cisgender youth.

Methods: Transgender females (MTF, n = 8, ages 12.6–16.1 years) on GnRHa (mean ± SD; 11.3 + 7 months) were compared to cisgender males (CM, n = 17, ages 12.5–15.5). Transgender males (FTM, n = 9, ages 10.1–16.0) on GnRHa (20.9 + 19.8 months) were compared to cisgender females (CF, n = 14, ages 10.6–16.2). Transgender participants were matched to cisgender participants on age, BMI and sex. Differences in IS (1/[fasting insulin]) and body composition (dual‐energy X‐ray absorptiometry) were performed using a mixed linear regression model.

Results: MTF were less IS (0.076 ± 0.029 vs. 0.135 ± 0.049, p = 0.028) and had a higher HbA1c (5.4 ± 0.1% vs. 5.1 ± 0.2%, p = 0.007) than CM. MTF had a higher % body fat (31 ± 9 vs. 24 ± 10%, p = 0.002) and lower % lean (66 ± 8 vs. 74 ± 10%, p < 0.001) than CM. FTM were less IS than CF (0.067 ± 0.020 vs. 0.103 ± 0.049, p = 0.031). FTM had a higher glucose (88 ± 5 vs. 78 ± 14 mg/dL, p = 0.018) and HbA1c (5.4 ± 0.2 vs. 5.2 ± 0.2%, p = 0.039) than CF. FTM had a higher % body fat (36 ± 7 vs. 32 ± 5%, p = 0.042) than CF.

Conclusions: Transgender youth on a GnRHa have lower IS and higher body fat than controls with similar characteristics. Longitudinal studies are needed to understand the significance of these changes, as well as the effect of subsequent introduction of testosterone or estradiol.

O‐2: Inflammatory Response to Acute Psychological Stress and Risk of Major Adverse Cardiovascular Events Among Patients with Coronary Heart Disease: Sex Differences

Samaah M. Sullivan (presenting author),¹ An Young,^1,2 Muhammad Hammadah,² Bruno B. Lima,^1,2 Yi‐An Ko,³ Brad D. Pearce,¹ Amit Shah,^1,2,5 Jeong Hwan Kim,² Kasra Moazzami,² Nancy Murrah,¹ Emily G. Driggers,^1,4 Belal Kaseer,² Oleksiy Levantsevych,¹ Ammer Haffar,¹ Laura Ward,³ Allison Hankus,¹ Tené T. Lewis,¹ Puja K. Mehta,² J. Douglas Bremner,^4,5 Paolo Raggi,⁶ Arshed Quyyumi,² and Viola Vaccarino^1,2

¹Departments of Epidemiology, ²Medicine, ³Biostatistics and Bioinformatics, ⁴Psychiatry and Behavioral Sciences, Emory University; ⁵Atlanta VA Medical Center; ⁶ Mazankowski Alberta Heart Institute, University of Alberta, Canada

Background: Stress may contribute to the progression of coronary heart disease (CHD) through inflammation, especially among women.

Objective: To examine whether increased inflammation in response to mental stress is associated with a greater risk of cardiovascular events and whether this risk is higher in women.

Methods: We examined inflammatory biomarkers known to increase with mental stress (speech task), including interleukin‐6 (IL‐6), monocyte chemoattractant protein‐1 (MCP‐1), and matrix metallopeptidase‐9 (MMP‐9) among 615 patients with stable CHD. Inflammatory response, the difference between post‐stress and resting values, was examined as a predictor of major adverse cardiovascular events (MACE) using subdistribution hazards models for competing risks adjusting for demographics, cardiovascular risk factors, and medications. MACE was defined as a composite endpoint of cardiovascular death, myocardial infarction, unstable angina with revascularization, and heart failure.

Results: During a median follow‐up of 3 years, 82 patients experienced MACE. Overall, there was no significant association between inflammatory response to stress and risk of MACE, but there were sex‐based interactions for IL‐6 (p = 0.001) and MCP‐1 (p = 0.008). Each unit increase in IL‐6 (pg/mL) with stress was associated with a 41% greater risk of MACE among women (HR: 1.41; 95% CI: 1.14, 1.75), but not among men (HR: 0.86; 95% CI: 0.71, 1.04). Each 10‐unit increase in MCP‐1 (pg/mL) with stress was associated with a 13% increase in risk of MACE among women only (HR: 1.13, 95% CI 1.06, 1.19).

Conclusions: Increased inflammation in response to stress is associated with future adverse cardiovascular outcomes among women with CHD.

O‐3: The Association Between Testosterone and Asthma is Mediated Through Eosinophils in Both Males and Females

Kedir N. Turi (presenting author),¹ Dawn Newcomb,¹ Tebeb Gebretsadik,² Brittney M. Donovan,¹ William D. Dupont,² and Tina V. Hartert¹

¹Division of Allergy, Pulmonary, Critical Care Medicine, Vanderbilt University Medical Center; ²Department of Biostatistics, Vanderbilt University Medical Center

Background: The pre‐ and post‐puberty switch in asthma prevalence among the sexes suggests a role for sex hormones in asthma pathogenesis.

Objective: To determine if the direct and eosinophil mediated association between testosterone and asthma is different among sexes.

Methods: Testosterone concentrations and peripheral blood eosinophil count was measured from participants in the 2016 National Health and Nutrition Examination Survey (age 6–80 years, n = 7,116). We estimated the effect of testosterone on the asthma status adjusted for age, sex, race, and body mass index and stratified by sex. We explored sex‐stratified and adjusted mediation analysis to estimate the direct and absolute eosinophil count mediated effects of testosterone on asthma status.

Results: Upper tertile testosterone levels are associated with 31% decreased odds of asthma (adjusted odds ratio [aOR] 0.69; 95% confidence interval [CI] 0.51, 0.91) compared to the lower tertile, but not statistically significant in the sex‐stratified analysis. Ten percent increase in testosterone level will decrease the absolute blood eosinophil count by 0.8 percent (β = −0.08, p < 0.001). In mediation analysis, elevated testosterone levels were associated with decreased odds of asthma directly (aOR 0.92, 95% CI 0.86, 0.98) and indirectly through reduced absolute eosinophil numbers (aOR 0.96; 95% CI 0.95, 0.97). The association between testosterone and asthma was mediated through reduced absolute eosinophil count in males (aOR 0.95; 95% CI 0.93, 0.97) and in females (aOR 0.94; 95% CI 0.92, 0.97), respectively.

Conclusions: Although the association of testosterone with asthma through eosinophils is consistent with other studies, the quantified mediated effect appears to be similar between sexes, thus, it may not explain the disparity in asthma prevalence observed.

P‐1: The Prevalence of Endometrial Cancer Symptoms in Overweight and Obese Women Presenting to a Multidisciplinary Weight Management Clinic

Anna L. Beavis (presenting author),¹ Larry Cheskin,² Rohan Mangel,³ and Amanda Nickles Fader¹

¹The Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Hospital; ²the Johns Hopkins Weight Management Center, Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health; ³Johns Hopkins University

Background: Fifty percent of endometrial cancer (EC) cases are attributable to obesity, but most women are unaware of the relationship between their weight and EC risk.

Objective: To determine the prevalence of symptoms of endometrial hyperplasia (EH) or cancer in women presenting to the Johns Hopkins Weight Management Center (JHWMC).

Methods: A menstrual history questionnaire was integrated into the JHWMC intake form from July 2018 to May 2019. Heavy, irregular, and inter‐menstrual bleeding, as well as postmenopausal bleeding were considered symptoms of EH/EC. Frequency of these symptoms, and the prevalence of prior gynecologic work‐up was calculated using descriptive statistics.

Results: Seventy‐six women were surveyed; median age was 47 years (range: 23–72), and median BMI was 36 kg/m²(range: 26–60). Most women were white (65%, n = 49) or black race (19%, n = 15), premenopausal (n = 41, 54%), and had not undergone a hysterectomy (n = 62, 82%). 5% (n = 3) had a history of EH. Of the 62 women with an intact uterus, 34% (n = 26) reported ≥1 symptom of EH/EC. In 42 premenopausal women, 42% (n = 18) reported heavy menstrual bleeding, 31% (n = 13) irregular periods, and 14% (n = 6) intermenstrual spotting or anovulatory cycles. In 20 postmenopausal women, 15% (n = 3) reported postmenopausal bleeding/discharge. In symptomatic women, 50% (n = 13) had discussed the symptoms with a gynecologist, and 31% (n = 8) had undergone an endometrial biopsy.

Conclusions: In this at‐risk population, symptoms of EH/EC are prevalent, but only half of these women have ever sought gynecologic evaluation. Interventions to increase awareness of EH/EC symptoms in obese women are needed to aid in early detection of this disease.

P‐2: Sex Impacts Autoreactive B Lymphocyte Function in Type 1 Diabetes‐prone Mice

Rachel H. Bonami (presenting author),^1,2 Bryan A. Joosse,¹ and James W. Thomas^1,2

¹Division of Rheumatology and Immunology, Department of Medicine, ²Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN

Background: Study of pancreas‐infiltrating lymphocytes in human type 1 diabetes (T1D) is complicated by pancreas tissue inaccessibility. These challenges are circumvented by the non‐obese diabetic (NOD) mouse model, which spontaneously develops T1D. B lymphocyte activation drives proliferation, germinal center formation, isotype switch, and islet autoantibody production.

Objective: T1D is more penetrant in female NOD mice (80% vs. 50%), thus the hypothesis was tested that immunologic changes in B lymphocytes underlie this increased T1D development.

Methods: Flow cytometry was used to measure isotype‐switched (IgG⁺), germinal center (GL7^high FAS^high) and proliferating (Ki67⁺) B lymphocytes in spleen, pancreas, pancreatic draining lymph nodes, and mesenteric(irrelevant) lymph nodes of n ≥ 4 male and female NOD or VH125^SD/NOD mice.

Results: Female NOD mice have a higher proportion of proliferating IgG1 class‐switched B lymphocytes in the pancreas (p = 0.006). An increased percentage of anti‐insulin B lymphocytes enter germinal centers, class switch to IgG1, and proliferate relative to non‐insulin binding B cells in VH125^SD/NOD mice, but these increases occur independently of sex. However, female VH125^SD/NOD mice show increased class switching of non‐insulin‐binding B lymphocytes to the IgG2b isotype (the predominant insulin autoantibody isotype) in pancreas and draining lymph nodes of VH125^SD/NOD mice (p = 0.046 and p = 0.0095, respectively) but not spleen or mesenteric lymph nodes.

Conclusions: As lymphocyte proliferation tracks with recent activation, these data suggest IgG1 class‐switched B lymphocytes are more actively recruited into autoimmune responses in female NOD mice, but that insulin‐reactive B lymphocytes become activated independently of sex.

P‐3: Gender‐specific Predictors of Weight Loss in Diverse Adolescents with Obesity

Kanika A. Bowen‐Jallow (presenting author),¹ Claire B. Cummins,¹ Alex Wright,² John D. Prochaska,³ Ravi S. Radhakrishnan,¹ Oscar Suman,¹ and Debbe Thompson⁴

¹Department of Surgery, University of Texas Medical Branch, Galveston, TX; ²School of Medicine, University of Texas Medical Branch, Galveston, TX; ³Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TX; ⁴USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine. Houston, TX

Background: The prevalence of pediatric obesity has grown with a striking increase in adolescents. Societal, cultural, and gender differences can impact weight loss in a positive or negative way, depending on an individual's experiences.

Objective: The purpose of this study was to determine gender differences in survey responses among a diverse group of adolescents with obesity.

Methods: Participants 12–19 years of age with an aged‐matched BMI ≥95th percentile are eligible for our multidisciplinary adolescent weight loss clinic. Participants were seen every 4–6 weeks. A behavioral questionnaire focused on goal setting, home environment, socioeconomic information, and lifestyle behaviors was collected at the initial visit.

Results: A total of 189 adolescents had an initial visit. Sex was split evenly at the initial visit, with 51% female and 49% male. The plurality of participants was Hispanic (47%), followed by White (31%), Black (21%), and Other race (1%). Both female and male participants were less likely to have lost weight if participants reported receiving free or reduced cost meals at school (p = 0.031 and p = 0.016, respectively). Male participants were significantly less likely to lose weight if participants reported they were too tired to lose weight (p = 0.045) or if they reported previous testing for sleep apnea (p = 0.019). Female participants were significantly more likely to report feeling unhappy when looking in the mirror compared to male participants (p = 0.002).

Conclusions: Gender‐specific experiences impact adolescents with obesity in challenging ways. Tailoring weight loss interventions to target these differences could increase successful and sustainable lifestyle change.

P‐4: A Sex‐specific Examination of Psychosocial Factors Related to Alcohol Use Among American Indians

Catherine E. Burnette (presenting author),¹ Soonhee Roh,² and Yeon‐Shim Lee³

¹School of Social Work, Tulane University; ²Department of Social Work, University of South Dakota; ³School of Social Work, San Francisco State University

Background: The top causes of death for American Indians (AIs) include heart disease, cancer, unintentional injuries, diabetes, and alcohol‐induced death. These causes are often interrelated, yet extant research fails to investigate the sex differences that affect sex‐specific intervention development.

Objective: The purpose of this study was to examine sex differences in physical, behavioral, and mental risk and protective factors associated with alcohol use among AIs.

Methods: Data were drawn from a cross‐sectional survey with 479 AI adults residing in South Dakota. We employed overall and sex‐stratified multiple regression analyses to assess the associations of demographic, physical (Body Mass Index and cardiovascular risk), behavioral (smoking and health practices self‐efficacy) and mental (depressive symptoms) factors with alcohol use (frequency and severity of use). Effect modification of the association between depression and alcohol use by sex was tested by inclusion of a depressive symptoms‐by‐sex interaction term in the overall model.

Results: Prevalence of alcohol use among males was three times that of females. Sex remained a significant predictor for alcohol use across all models, with the exception of depressive symptoms, which was a risk factor for higher alcohol use among both sexes. Each model explained distinct amounts of the variance (R²): 1. males only = 29%; 2. females only = 7%; 3. interaction for females and depressive symptoms = 48%; and 4. both sexes = 22%.

Conclusions: Given sex differences in physical, behavioral, and mental factors related to alcohol use, the development and testing of sex‐specific holistic prevention and intervention approaches that promote wellness is warranted.

P‐5: Gender Differences in Acceptability of Social Risk Screening and Desire for Social Assistance

Elena Byhoff (presenting author),¹ Emilia De Marchis,² Karen M. Freund,¹ and Laura Gottlieb²

¹Institute for Clinical Research and Health Policy Studies, Tufts Medical Center; ²Department of Family and Community Medicine, University of California San Francisco

Background: Nationally representative studies have demonstrated that women have higher prevalence of social risks compared to men. Little research has explored gender‐specific perspectives on social risk screening in healthcare settings.

Objectives: The aim of this study is to compare acceptability in social needs screening and desire for help between women and men in diverse healthcare settings.

Methods: We conducted a cross‐sectional survey of 1035 adult patients and caregivers of pediatric patients recruited from primary care and emergency departments across the U.S. Surveys included the Accountable Health Communities' social risk screening tool and questions about screening acceptability and desire for help with social risks. We used logistic regressions to assess predictors of desire for assistance by gender.

Results: 70% of survey respondents were female (n = 729). Women respondents were younger, more likely to be Black or Hispanic, low income, and responding as a pediatric caregiver. Women and men were equally likely to find screening for social risks acceptable (77% vs. 81%; p = 0.2). In the adjusted analysis by gender, number of reported social risks, trust in healthcare provider, and having been previously screened for social risks were associated with higher odds of seeking help in men. For women, only the number of reported risks was significantly associated with seeking help.

Conclusions: Acceptability of social risk screening was high for men and women. Understanding patient characteristics who are interested in help addressing social risk factors can facilitate effective use of limited clinical resources.

P‐6: Providers' Perspectives on Racism and Black Women's Maternal and Infant Health: What are the Issues, and What Can We Do About It?

Brittany D. Chambers (presenting author),^1,2 Brianne Taylor,² Tamara Nelson,³ Jessica Harrison,⁴ Arielle Bell,³ Allison O'Leary,^2,5 Karen A. Scott,³ Andrea V. Jackson,⁵ Tina Raine‐Bennett,⁶ Miriam Kuppermann,^2,5 and Monica R. McLemore³

¹Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco; ²California Preterm Birth Initiative, School of Medicine, University of California, San Francisco; ³Family Health Care Nursing Department, School of Nursing, University of California, San Francisco; ⁴Department of Social and Behavioral Sciences, School of Nursing, University of California, San Francisco; ⁵Department of Obstetrics, Gynecology and Reproductive Sciences, School of Medicine, University of California, San Francisco; ⁶Division of Research, Kaiser Permanente Northern California

Background: Racism contributes to the medical mistreatment of Black women and plays a role in disparities in maternal morbidity and mortality.

Objective: In preparation for developing a comprehensive racial equity training, we explored healthcare providers' perceptions of how racism affects patients' experiences, health services provision, and maternal and neonatal outcomes among Black women during pregnancy and birth.

Methods: We conducted 25 semi‐structured interviews [range: 30‐60 minutes] among a group of prenatal care providers in the San Francisco Bay Area [8 certified nurse midwives, 13 physicians, 4 learners]. Constant comparative method was used to analyze transcribed data.

Results: Four themes emerged: History of Medical/Institutional Racism (e.g., history of medical racial experimentation); Differential Care and Treatment Options (e.g., I had a woman who had a massive complication during her labor course and felt like she wasn't being treated seriously); Over‐reporting of Black Patients and Families (e.g., urine tox screen on the black baby even though it was not indicated, and they didn't do it on the white baby when in fact, it was indicated); and Provider Implicit Bias (e.g., Black women are assumed to be less compliant because of their race).

Conclusion: Providers' observations and experiences support ways in which racism is operating in healthcare institutions. Racism in the healthcare setting affects provider decision‐making and behavior and has negative implications for Black women and infants' health. Findings from this study will be used to develop a racial equity training for prenatal care providers in collaboration with Black women and providers.

P‐7: Pharmacokinetic and Safety Study of Ledipasvir/Sofosbuvir Treatment in Pregnant Women with Chronic Hepatitis C Virus Infection

Catherine A. Chappell (presenting author)¹, Kimberly K. Scarsi,² Brian J. Kirby,³ Vithika Suri,³ Anuj Gaggar,³ Elizabeth E. Krans,¹ Ingrid S. Macio,¹ Leslie A. Meyn,¹ Debra L. Bogen,⁴ Katherine E. Bunge,¹ and Sharon L. Hillier¹

¹Department of Obstetrics, University of Pittsburgh; ²Department of Pharmacy Practice, University of Nebraska Medical Center; ³Gilead Sciences, Foster City; ⁴Department of Pediatrics, University of Pittsburgh

Background: Hepatitis C virus (HCV) treatment during pregnancy could cure maternal infection and prevent perinatal HCV transmission. Physiologic changes during pregnancy require pharmacokinetic (PK) evaluation.

Objective: To compare the PK of ledipasvir/sofosbuvir (LDV/SOF) in pregnant versus nonpregnant women, and to assess safety and viral response.

Methods: In this phase 1 study, pregnant women with chronic genotype 1 HCV infection were enrolled between 23–24 weeks' gestation and began LDV/SOF for 12 weeks. Three PK visits were performed at 25–26, 29–30, and 33–34 weeks' gestation. Plasma was collected at timed intervals to measure LDV, SOF and GS‐331007 (inactive SOF metabolite) by validated HPLC‐MS/MS methods. PK parameters were compared between participants and non‐pregnant women from LDV/SOF trials by geometric mean ratio. Adverse events, delivery outcomes, and viral clearance were assessed.

Results: Of 29 women screened, 20 were excluded due to genotype 2 or 3 infection (n = 10), ongoing drug use (n = 4), declining participation (n = 3), off‐site delivery (n = 2), and thrombocytopenia (n = 1). Eight women were HCV infected by drug use; one by perinatal transmission. Similar LDV and SOF, but lower GS‐331007 PK exposure was observed between pregnant and non‐pregnant women. All nine participants were cured. All adverse events related to LDV/SOF were ≤ grade 2.

Conclusions: In this first study of HCV treatment during pregnancy, LDV/SOF was safe and effective with similar LDV/SOF PK exposure. Lower GS‐331007 exposure is due to increased glomerular filtration rate during pregnancy. Given the high prevalence of genotype 2 and 3 infection, evaluation of a pan‐genotypic regimen is needed prior to larger studies.

P‐8: Preterm Birth Prevention in Appalachian Kentucky: Adopting a Dissemination and Implementation Science Approach

Niraj R. Chavan (presenting author),¹ Cynthia Cockerham‐Morris,¹ Mairead Moloney,² John M. O'Brien,¹ and Jing Li³

¹Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Kentucky College of Medicine; ²Department of Sociology, University of Kentucky; ³Center for Health Services Research, University of Kentucky College of Medicine

Background: Preterm birth represents an important health disparity across the state of Kentucky (KY). The best biomarker for the prediction of preterm birth is transvaginal ultrasound (TVU) measurement of cervical length. However, several unique provider‐ and patient‐related barriers for implementation limit the widespread uptake of this evidence‐based practice in Appalachian KY.

Objectives: The objective of this study is to understand provider and patient knowledge, attitudes and perceptions towards TVU screening and identify key barriers that have limited the widespread adoption of this evidence‐based technology in Appalachian KY.

Methods: Recruitment is currently underway at 3 community‐based sites (Hazard, Morehead and Ashland, KY) with a plan to recruit 5 practitioners from each site (N = 15), and 8 patients per site (N = 24). The Consolidated Framework for Implementation Research (CFIR) will be adopted as the guiding dissemination and implementation science framework for understanding key areas of knowledge deficits, attitudes, practices and perceived barriers towards TVU cervical length screening using a mixed methods design. Semi‐structured qualitative interviews will be supplemented with quantitative data collection using electronic medical record (EMR) systems at each study site to understand the current practice of TVU cervical length screening. This will be utilized to develop a multifaceted implementation strategy best suited for addressing and overcoming barriers identified by the target population.

Results: Qualitative and quantitative data analyses are pending. Until date, 8 participants have been enrolled, 6 (75%) females and 2 (25%) males. Of these participants, 6 (75%) are obstetric providers and 2 (25%) are patients.

Conclusions: Currently ongoing research study.

P‐9: Gender Differences in the Biological Mechanisms of Physical Frailty in Heart Failure: The Role of Body Composition and Metabolic Biomarkers

Quin E. Denfeld (presenting author),¹ Jonathan Q. Purnell,² Christopher S. Lee,³ Kerri Winters‐Stone,^1,4 James O. Mudd,⁵ Shirin O. Hiatt,¹ and Beth A. Habecker^2,6

¹Oregon Health and Science University School of Nursing; ²Oregon Health and Science University Knight Cardiovascular Institute; ³Boston College William F. Connell School of Nursing; ⁴Oregon Health and Science University Knight Cancer Institute; ⁵Providence Sacred Heart Medical Center; ⁶Department of Physiology and Pharmacology, Oregon Health and Science University

Background: In heart failure (HF), women have higher rates of physical frailty compared with men; however, the biological mechanisms of physical frailty in women versus men with HF are unclear.

Objective: To explore the role of body composition and metabolic biomarkers in explaining gender differences in the biological mechanisms of physical frailty in HF.

Methods: This was a preliminary analysis of data collected from a study of adults with HF. Physical frailty was measured with the Frailty Phenotype Criteria. Body composition was measured by dual‐energy x‐ray absorptiometry. Metabolic biomarkers were measured by enzyme‐linked immunosorbent assays (insulin‐like growth factor‐1 [IGF‐1] and insulin) and colorimetric assays (glucose). Comparative statistics were used to quantify differences in body composition and metabolic biomarkers by gender.

Results: The average age of the sample (n = 65) was 62.0 ± 16.6 years, and 35.3% were women. Physical frailty was identified in 43% of participants; more women than men were physically frail (p = 0.002). Physically frail men had significantly higher overall percent body (p = 0.03) and trunk (p = 0.03) fat, higher percent gynoid (p = 0.03) and android (p = 0.04) fat, and lower IGF‐1 (p = 0.002) compared with non‐physically frail men. There were no significant differences in body composition or metabolic biomarkers between physically frail and non‐physically frail women.

Conclusions: Select body composition and metabolic biomarkers differentiate physically frail versus non‐physically frail men, but not women, potentially indicating that fat distribution is a key gender difference in the biological mechanisms of physical frailty in HF.

P‐10: Changes in the T cell Repertoire of Human Placentae Diagnosed with Villitis of Unknown Etiology

Elizabeth Ann L. Enninga (presenting author),¹ Rodrigo Ruano,¹ Rana Chakraborty,^1,2 and Sarah E. Kerr³

¹Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN; ²Department of Pediatrics and Infectious Disease, Mayo Clinic, Rochester, MN; ³Department of Laboratory Pathology, Mayo Clinic, Rochester, MN

Background: During human pregnancy, inflammatory responses in the placenta can cause severe fetal complications, including growth restriction, preterm birth, and stillbirth. Villitis of unknown etiology (VUE), an inflammatory condition characterized by the non‐infectious infiltration of maternal T cells into the placenta, is hypothesized to be a tissue rejection response to the haploidentical fetus. As this condition is poorly understood, there are no methods to predict or treat VUE.

Objectives: Characterize the T cell profile and inflammatory environment of placentae diagnosed with VUE compared to unaffected gestational age matched control placentae.

Methods: 10 placentae with VUE were compared to 10 unaffected controls. Multiplex immunofluorescence was used to profile the interaction of CD4 and CD8 maternal T cells. ImmunoSEQ T cell receptor sequencing was completed to identify the most abundant T cell clones. Data were compared by two‐tailed Mann‐Whitney test.

Results: Placentae with VUE diagnosis demonstrate higher staining abundance of CD8+, but not CD4+, T cell infiltration into both the stem and distal villi compared to controls. Next‐generation deep sequencing of VUE T cell receptors showed a higher frequency of T cell clones (2,060 vs. 490; p = 0.002), and those clones were less diverse (more antigen specific) compared to control placentae (0.06 vs. 0.01; p = 0.0002).

Conclusions: VUE is a complex immunological disease that leads to the activation of maternal CD8+ T cells against fetal cells, which may resemble an allograft rejection response. Future studies into the mechanisms that activate T cells are required for the development of effective diagnostic and therapeutic tools.

P‐11: Detection of Endometrial Cancer DNA Through Vaginal Tampon Recovery

Britt K. Erickson (presenting author),¹ Melissa A. Geller,¹ Carol Lange,² Andrew Nelson,³ and Bharat Thyagarajan³

¹Department of Obstetrics Gynecology and Women's Health; ²Department of Medicine; ³Department of Laboratory Medicine and Pathology, University of Minnesota

Background: Endometrial cancer is the most common gynecologic malignancy and no effective screening strategy exists. Given that the endometrium communicates with the vagina through the endocervix, we sought to identify tumor DNA that descends into the vagina through tampon collection.

Objective: To determine whether genomic alterations of endometrial cancer cells as well as endometrial cancer specific proteins can be detected through vaginal tampon collection of DNA.

Methods: This is secondary outcome data from the parent vphase IIA, single‐arm ‘window of opportunity’ study of postmenopausal women with low grade endometrial adenocarcinoma who are candidates for hysterectomy. All participants received 24–31 days of oral exemestane, an aromatase inhibitor, from study entry until hysterectomy. Pre‐ and post‐treatment endometrial tissue was collected. Additionally, at two separate points during the trial, participants placed a vaginal tampon which was kept in place overnight and then removed by study personnel. DNA and protein were extracted from the tampons. DNA from the primary tumor was sequenced using a solid tumor assay. Microsatellite instability and hypermethylation were also assessed.

Results: Results to date include: (a) Fourteen patients have been enrolled in the study; (b) 14 patients have DNA and protein available from tampon collections; and (c) tumor and vaginal DNA sequencing is underway via a next generation sequencing (NGS) assay.

Conclusion: Collection of vaginal DNA through tampon collection is feasible, and we anticipate that the results of this pilot study will show that tumor DNA can be detected through NGS. Results of this study will have important implications for the future development of endometrial cancer screening tests.

P‐12: Gender Differences in the Relationship of Health Literacy and Help‐seeking to Maladaptive Coping Behaviors During Life Stressors in Adults

Sasha A. Fleary (presenting author)¹ and Karen M. Freund²

¹Eliot‐Pearson Department of Child Study and Human Development, Tufts University; ²Tufts Medical Center and Tufts University School of Medicine

Background: Using food, tobacco, and alcohol to cope with stressors negatively impact health. However, one's ability to access and utilize health resources (i.e., health literacy [HL]) and openness to seeking mental health help (help‐seeking) may be protective. Gender differences in the relationship between HL, help‐seeking, and maladaptive coping behaviors are unknown.

Objectives: To explore whether HL, help‐seeking, and two life stressors (food and housing insecurity) were related to maladaptive coping behaviors and determine the gender differences in these relationships.

Methods: Data (n = 590) were collected using Qualtrics Panel and online snowball sampling. Gender‐specific multiple logistic regressions predicting coping behaviors from HL, help‐seeking, and life stressors were computed. Maladaptive behaviors included depressed‐eating, anxious‐eating, stress‐smoking, and alcohol use to cope with anxiety/depression (emotional‐drinking), a bad mood (mood‐drinking), and problems (problem‐drinking). Gender differences were computed using chi‐square and independent‐sample t‐tests.

Results: Women reported greater housing and food insecurity than men, greater HL and help‐seeking, but also greater maladaptive eating and smoking behaviors. Housing insecurity was positively related to anxious‐ and depressed‐eating and emotional‐drinking for women and problem‐drinking for men. Food insecurity was positively related to stress‐smoking and mood‐drinking for women. HL was negatively related to mood‐drinking and anxious‐ and depressed‐eating for men. HL was not associated with reductions in maladaptive behaviors for women.

Conclusions: Though women had higher HL, HL may be more protective for men's maladaptive coping behaviors. Women's higher food and housing insecurity may be indicative of other stressors that contribute to maladaptive coping strategies and that may require more direct intervention.

P‐13: Exclusion from Participation in Vaccine Clinical Trials on Reproductive Characteristics

Erika L. Fuchs (presenting author),^1,2 Jeffrey S. Farroni,³ Abbey B. Berenson,¹ and Richard E. Rupp^2,4

¹Center for Interdisciplinary Research in Women's Health, Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston; ²Sealy Institute for Vaccine Sciences, University of Texas Medical Branch at Galveston; ³Institute for the Medical Humanities, University of Texas Medical Branch at Galveston; ⁴Department of Pediatrics, University of Texas Medical Branch at Galveston

Background: Two vaccines are recommended to occur during pregnancy, yet uptake remains low. Some pregnant women are hesitant to receive the vaccines due to the perception they have not been trialed in pregnant women. Historically, women have been excluded from participation in research, often due to pregnancy and reproductive potential. The American College of Obstetricians and Gynecologists and the National Institutes of Health recommend against the broad exclusion of pregnant women from clinical trials. The just inclusion of pregnant women may compel their participation in vaccine research and routine prenatal vaccination if it may lead to improved maternal and fetal outcomes.

Objectives: Examine current practices of participant exclusion in vaccine trials based on reproductive characteristics.

Methods: ClinicalTrials.gov was queried by search terms [vaccine/vaccination/ immunization] and filtered to include trials recruiting adults in the United States in June 2019. Interventional trials enrolling healthy participants were eligible for inclusion. Relevant criteria regarding pregnancy, breastfeeding, and contraceptives were abstracted. Descriptive analyses were conducted using Stata SE Version 15.1.

Results: Of 262 search results, 68 trials met inclusion criteria. Pregnancy was an exclusion in 66 (97.1%) studies while breastfeeding was an exclusion in 59 (79.4%) studies. Contraceptive use was required of females in 64.7% (44/68) of studies recruiting females and was required of males in 23.9% (16/67) of studies recruiting males.

Conclusions: Pregnancy, breastfeeding, and inadequate contraceptive use are frequently exclusion criteria in recruiting trials of vaccines. Excluding potential participants from these studies may create barriers to vaccination and warrants further investigation.

P‐14: Cataloging Sex Differences in Clinical Diagnoses Using Electronic Health Records: A Phenome‐Wide Association Study (PheWAS)

Ayush Giri (presenting author),¹ Digna R. Velez Edwards,^1,2 Eric R. Torstenson,³ and Katherine Hartmann¹

¹Division of Quantitative Sciences, Department of Obstetrics and Gynecology, Institute for Medicine and Public Health, Vanderbilt University Medical Center; ²Department of Biomedical Informatics, Vanderbilt University Medical Center; Division of Epidemiology, ³Department of Medicine, Vanderbilt University Medical Center

Background: The prospect of combining informatics approaches with large electronic health records (EHR) to catalogue and understand sex differences in health is underexplored.

Objectives: To evaluate and catalogue sex differences in clinical diagnoses from EHRs with a phenome‐wide association study (PheWAS) approach.

Methods: We used diagnosis codes from deidentified EHRs of 202,857 non‐Hispanic white adults at Vanderbilt University Medical Center to derive 1,647 hierarchical/correlated phenotypes applicable to both sexes. Two or more diagnosis codes per patient were needed to diagnose cases per phenotype. We used logistic regression to evaluate associations between reported sex and phenotypes adjusted for age.

Results: Approximately 56.9% of adults identified as female. After Bonferroni correction (P‐value <0.05/1,647), 830 correlated phenotypes belonging to 334 distinct diagnosis groupings showed evidence of sex differences and 143 of these exhibited odds ratios of >2.0. As positive controls, men were more likely to have inguinal hernias (OR = 12) and HIV infection (OR = 10), while women were more likely to have conditions related to the breast, including breast cancer (OR = 57). Women were more likely to be diagnosed with osteoporosis (OR = 6), lupus (OR = 5.5), and thyroid disorders (Graves' [OR = 3], hypothyroidism [OR = 3]). Men were more likely to have conditions grouped to the circulatory system (myocardial infarction [OR = 2.9]), kidney disorders and diabetes.

Conclusions: The PheWAS approach efficiently captures a large proportion of sex differences in diagnoses, recapitulates previously reported associations and holds the potential to reveal previously undetected patterns between phenotypes. Network‐analyses and assessment of differences in age at diagnosis by sex and race/ethnicity are ongoing.

P‐15: Preeclampsia

Kathryn J. Gray (presenting author),^1,3,4 Mengxi Yang,² David E. Cantonwine,¹ Thomas F. McElrath,¹ Liming Liang,² and Richa Saxena^3,4

¹Division of Maternal‐Fetal Medicine, Brigham and Women's Hospital, Boston, MA; ²Harvard T.H. Chan School of Public Health, Boston, MA; ³Center for Genomic Medicine, General Hospital, Boston, MA; ⁴Broad Institute, Cambridge, MA

Background: Placental dysfunction and maternal endothelial damage precede clinically‐apparent PE. Mechanistic understanding of preeclampsia (PE) is needed for improved prediction and therapy.

Objective: To delineate alterations in the maternal metabolome in early pregnancy and provide insight into causal PE biologic pathways.

Methods: Maternal 1^st (T1; 12 weeks) and 2^nd (T2, 26 weeks) trimester plasma samples from 68 women who developed early‐onset PE (EO‐PE) were matched with 68 healthy, normotensive controls from the LIFECODES pregnancy cohort based on maternal age, race, BMI, smoking status, and gestational age at sample collection (T1, T2). Global metabolic profiling by liquid‐chromatography mass spectroscopy (LC‐MS) was performed using the Metabolon DiscoveryHD4^TM platform, identifying 955 metabolites. Data was normalized, log₂ transformed, and metabolite differences compared between matched case‐control samples using paired t‐tests with correction for multiple testing. Conditional logistic regression was performed to control for confounders.

Results: >600 metabolites were significantly different between cases and controls. Among the altered metabolites, a clear signature of dysfunctional mitochondrial β‐fatty acid oxidation (FAO) emerged, as demonstrated by a significant elevation in medium‐ and long‐chain fatty acids, acylcarnitines, and ketones in cases vs. controls at T2. This signature remained after adjustment for pregestational and gestational diabetes. As most of the EO‐PE cases (>80%) did not develop clinical features of PE until >30 weeks, the abnormal β‐FAO occurs many weeks prior to clinical disease.

Conclusions: Dysfunction in β‐FAO is an early event in PE pathogenesis that precedes clinically‐evident disease. This highlights mitochondrial β‐FAO as a pathway for further investigation.

P‐16: Recurrent Episodic Cortical Spreading Depressions Induce Trigeminal Allodynia and Anxiety Behavior in a Migraine Mouse Model

Andrea Harriott (presenting author),^1,2,3,4 David Chung,^1,2,4 Tsubasa Takizawa,^1,2,4 Tao Qin,¹ and Cenk Ayata^1,2,4

¹Neurovascular Research Laboratory, Department of Radiology, MA General Hospital, Charlestown, MA; ²Vascular Division, Headache and Neuropathic Pain Division, Department of Neurology, MA General Hospital, Boston, MA; ³John R. Graham Headache Center, Brigham and Women's Faulkner Hospital, Boston, MA; ⁴Harvard School of Medicine, Boston, MA

Background: Cortical spreading depression (CSD) is an intense propagating depolarization responsible for migraine aura. Cutaneous allodynia, anxiety, and cognitive disturbances can accompany migraine, but their association with CSD is unclear.

Objective: To test the hypothesis that recurrent CSD causes migraine‐phenotypic behavior.

Methods: Unilateral single event optogenetic CSDs were induced non‐invasively every other day for two weeks in male and female transgenic mice. CSD was detected by optical intrinsic signal imaging coincident with propagating oligemia. Behavioral testing was performed 24–72 hours after the last CSD. Mechanical allodynia of the periorbital and hindpaw regions was tested using von Frey monofilaments. Anxiety and working memory were tested with open field and Y maze respectively.

Results: Recurrent episodic CSDs reduced periorbital mechanical pain thresholds compared with sham mice (p < 0.001). Despite unilateral CSD inductions, decreases in mechanical force threshold for periorbital nocifensive behavior was bilateral. There was a significant main effect of sex on trigeminal mechanical pain thresholds with female mice showing lower thresholds than males (p = 0.025). Hindpaw mechanical sensitivity did not differ between sham and CSD groups (p = 0.149), or between males and females (p = 0.607). In an open field, mice with episodic CSDs spent more time clinging to the walls (i.e., thigmotaxis), suggesting anxiety behavior (p = 0.015). There was a significant main effect of sex on thigmotaxis scores (p = 0.027). There was no difference in Y maze testing between CSD and sham mice.

Conclusions: These data support a role for recurrent CSD in migraine related trigeminal allodynia and anxiety, with evidence for sexual dimorphism, using a non‐invasive model.

P‐17: Uterine Fibroids Polygenic Risk Score Identifies Differential Phenome Associations by Sex

Jacklyn N. Hellwege (presenting author),^1,2 Jacqueline A. Piekos,² Eric S. Torstenson,^2,3 Yanfei Zhang,⁴ Gail P. Jarvik,⁵ Ozan Dikilitas,⁶ Iftikhar J. Kullo,⁶ Daniel J. Schaid,⁷ Sarah A. Pendergrass,⁸ Dan M. Roden,^2,9 Joshua C. Denny,^2,10 Todd L. Edwards,^2,3 and Digna R. Velez Edwards^2,10,11

¹Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center; ²Vanderbilt Genetics Institute, Vanderbilt University; ³Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center; ⁴Genomic Medicine Institute, Geisinger, Danville, PA; ⁵Departments of Medicine (Medical Genetics) and Genome Sciences, University of Washington Medical Center, Seattle, WA; ⁶Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN; ⁷Department of Health Sciences Research, Mayo Clinic, Rochester, MN; ⁸Biomedical and Translational Informatics, Geisinger, Danville, PA; ⁹Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center; ¹⁰Department of Biomedical Informatics, Vanderbilt University Medical Center; ¹¹Division of Quantitative Sciences, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center

Background: Uterine leiomyoma, or fibroids, are benign smooth muscle growths common in women. Thirty genetic loci have been associated with fibroid risk. Although men and women both may have fibroid risk‐increasing alleles, males cannot develop uterine fibroids. However, it is possible that genetic factors that influence fibroids may also have pleiotropic effects impacting the risk of other diseases and outcomes in women and/or men.

Objective: We utilized a polygenic risk score (PRS) with phenome‐wide association study (PheWAS) approach to investigate a fibroid genetic contribution to diseases by sex.

Methods: We optimized the PRS in fibroid cases and controls and applied it to data from European ancestry participants from the Electronic Medical Records and Genomics (eMERGE) network. We performed PheWAS across 35,969 women and 33,246 men using the PRS as the predictor for 1,867 diagnoses, adjusted for age and 10 principal components.

Results: The optimal threshold for the PRS was P < 0.001 and included 4,448 variants. PheWAS in females identified 59 significant (P < 2.67x10⁻⁵) results, including uterine leiomyoma (P = 7.76x10⁻¹⁷⁷). In males, the top association was specific nonpsychotic mental disorders due to brain damage (P = 0.00063). Of the 59 significant results in females, 21 were diagnoses occurring in both sexes. Only tension headaches were consistently suggestive in men (P = 0.0038) and women (P = 1.9x10⁻⁶).

Conclusion: The top PheWAS result in females was uterine fibroids, confirming the PRS is valid. In males there were no strong association signals observed. These results suggest that genetic factors contributing to fibroids may not strongly predispose to disease conditions in men.

P‐18: Intergenerational Effects of Trauma Resulting from Torture and War: Associations Between Maternal Caregivers' Mental Health and Youth Psychosocial Adjustment

Sarah J. Hoffman, (presenting author),¹ Maria Vukovich,² Abigail Gewirtz,³ Joseph Gaugler,⁴ and Cheryl L. Robertson¹

¹School of Nursing, University of Minnesota; ²University of Denver; ³FSoS, University of Minnesota; ⁴School of Public Health, University of Minnesota

Background: Child attachment and psychosocial adjustment can be negatively impacted by parental trauma history. Depression and anxiety symptoms are reported at higher levels among children with traumatized parents. Factors such as family functioning and resilience strategies can influence these associations or function as protective factors. Children whose parents have experienced negative mental health outcomes resulting from torture and war may lead to long‐term consequences in youth psychosocial adjustment.

Objective: Examine relationships between maternal mental health and youth psychosocial adjustment as reported by maternal caregivers in a sample of 96 Karen refugee women where participants experienced torture versus war trauma alone.

Methods: Refugee maternal caregivers (with youth 11–23 years) completed self‐report instruments describing maternal mental health [5‐item Karen validated screener] and maternal war trauma/torture exposure [tool adapted from United Nations torture screening criteria], and perceived adjustment of youth [Strength and Difficulties Questionnaire].

Results: Results of multiple linear regression models indicated that self‐reported age, gender, maternal mental health and maternal torture status significantly predicted psychosocial adjustment in youth under 18, F(2, 166) = 6.111, p < .001, R² = .128, and youth over 18, F(4, 102) = 3.876, p = .006, R² = .132. Greater emotional, conduct, and hyperactivity behaviors in youth were reported by maternal caregivers with elevated mental health distress.

Conclusions: Results are an important contribution towards establishing mechanisms that influence the effects of trauma resulting from torture and war across generations.

P‐19: Telemedicine Breastfeeding Support Following Late Preterm Delivery: A Randomized Trial

Laura R. Kair (presenting author),¹ Eleanor B. Schwarz,² James P. Marcin,¹ Daniel J. Tancredi,¹ and Caroline J. Chantry¹

¹Department of Pediatrics, University of California Davis; ²Department of Internal Medicine, University of California Davis

Background: Late preterm (34 to 36^6/7 weeks gestation) mother‐infant dyads have shorter breastfeeding duration than other infants. Compared to term infants, late preterm infants are less physically mature and more ineffective at breastfeeding. Still, they are discharged from the hospital sooner than more premature infants, depriving these mothers of needed breastfeeding support.

Objective: Execute early‐phase trial to determine the extent to which breastfeeding support via home‐based telemedicine video visits may affect maternal satisfaction and breastfeeding duration among late preterm dyads.

Methods: We will randomize 56 late preterm dyads who initiate breastfeeding at the University of California Davis Medical Center to receive up to four video visits for breastfeeding support in the first month following discharge in addition to usual care, or simply usual care. We will follow dyads' infant feeding behaviors for 12 months and assess women's satisfaction with video visits using a modified, 16‐item Interactive Telehealth Satisfaction Scale. (Clinicaltrials.gov registration: NCT03901833)

Results: Assuming loss to follow up is less than 12% for each group, margins of error for group mean scores for infant feeding behavior and women's satisfaction will be ≤0.4 SD.

Conclusions: Home‐based telemedicine video visits for breastfeeding support may produce high levels of satisfaction with care and have the potential to benefit late preterm mother‐infant dyads via prolonged breastfeeding duration.

P‐20: Tailored Messages Addressing Mothers' HPV Vaccination Concerns: Differences in Response by Child Sex

Melanie L. Kornides (presenting author),⁵ Kristen A. Feemster,^1,2,3,4 Katherine J. Head,⁶ Gregory D. Zimet,⁷ and Catherine A. Panozzo⁸

¹Vaccine Education Center, Children's Hospital of Philadelphia, Philadelphia, PA; ²Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA; ³Department of Pediatrics, Perelman School of Medicine, University of Philadelphia, Philadelphia, PA; ⁴Philadelphia Department of Public Health Division of Disease Control, Philadelphia, PA; ⁵Department of Family and Community Health, University of Philadelphia School of Nursing, Philadelphia, PA; ⁶Department of Communication Studies, Indiana University School of Liberal Arts, Indianapolis, IN; ⁷Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN; ⁸Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA

Background: Interventions tailored to the concerns of vaccine‐hesitant parents may help to improve Human papillomavirus (HPV) vaccine uptake.

Objectives: To determine how supplementing a presumptive, bundled recommendation with tailored messaging that addresses one vs. all parental concerns improves HPV vaccination intent among mothers of girls versus boys.

Methods: We conducted a web‐based randomized controlled trial across 27 states with low HPV vaccine uptake. Participants were English‐speaking mothers who did not intend to vaccinate their 11 to 14‐year‐old child against HPV. Participants (n = 762) were randomized to: a) presumptive, bundled recommendation video (“control”); b) control + video addressing the top HPV vaccine concern; or c) control + ≥1 videos addressing all concerns. The primary outcome was HPV vaccination intent (1 = extremely unlikely and 10 = extremely likely) reported as the mean for each group.

Results: Half of the mothers had a female child (50.7%), and most children were white (81.8%) and non‐Hispanic (90.1%). Among mothers of boys, there was a significant difference in the mean intent to vaccinate post‐intervention between the control group (3.6, 95% CI:3.2–4.1) and the all concerns group (4.4, 95% CI:3.9–4.9, p. = 03) only. For mothers of girls, both intervention groups had higher mean intent (4.0, 95% CI:2.7–3.5, and 4.0, 95% CI:2.7–3.5, respectively) vs. the control group (3.3, 95% CI:2.4–2.9, p = .03).

Conclusions: Among mothers of both boys and girls who do not intend to vaccinate, tailored messages addressing all concerns improved HPV vaccination intent, while mothers of girls responded equally well to videos addressing their top concern.

P‐21: Longitudinal Trajectories of Mental Health Symptomatology and Psychosocial Functioning in Male and Female Iraq and Afghanistan Veterans

Karen A. Lawrence (presenting author),¹ Dawne S. Vogt,^2,3 Emily M. Slade,⁴ Adam J. Dugan,⁴ and Brian N. Smith^2,3

¹College of Social Work, University of Kentucky; ²National Center for PTSD Women's Health Sciences Division, VA Boston Healthcare System; ³Department of Psychiatry, Boston University School of Medicine; ⁴Department of Biostatistics, College of Public Health, University of Kentucky

Background: Relative to male veterans, female veterans are disproportionately at risk for depression and exhibit a more rapidly increasing suicide rate.

Objectives: Given these disparities, a clearer understanding of suicide risk factors in women veterans is needed. Suicide risk factors in female veterans include suicidal ideation, having a mental health diagnosis, and impaired psychosocial functioning. We sought to model within‐ and between‐group longitudinal trajectories of these factors in recently returned male and female Iraq and Afghanistan veterans.

Methods: This secondary data study utilized a 7.5‐year longitudinal Veterans Administration (VA)‐ funded study, which included a random sample of veterans (n = 1046), with women oversampled. Our study included n = 554 women and n = 481 men who responded to the gender question. Measures included the Posttraumatic Stress Disorder (PTSD) Checklist‐Military, modified Beck Depression Inventory‐Primary Care (BDI‐PC), Suicidal Ideation (BDI‐PC item), Alcohol Use Disorders Identification Test for Consumption, and scales of relationship, parental, and work functioning (Inventory of Psychosocial Functioning). Bivariate analyses and generalized linear mixed models were used.

Results: Significant gender differences were detected for initial status on PTSD severity, alcohol misuse, and work and parental functioning (p < .05). Scores for PTSD, depression, alcohol misuse, suicidal ideation, and relationship functioning changed significantly over time (p < .05) within groups. However, no significant gender by time interactions were observed to modify risk factor trajectories.

Conclusions: Within‐group but not between‐group longitudinal changes were observed on several key suicide risk factors in men and women veterans.

P‐22: The Importance of Early Diagnosis in Peripartum Cardiomyopathy

Jennifer Lewey (presenting author),¹ Lisa D. Levine,² Michal A. Elovitz,² Olga C. Irizarry,² and Zoltan Arany¹

¹Division of Cardiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; ²Maternal and Child Health Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA

Background: Peripartum cardiomyopathy (PPCM) can lead to long‐term cardiac dysfunction, especially among black women. Hypertensive disorders of pregnancy (HDP) are the strongest risk factor for PPCM, but controversy remains on whether HDP predict a favorable outcome. Women with HDP are also often diagnosed with PPCM earlier than those without HDP.

Objectives: To determine recovery of systolic function (ejection fraction, EF >50%) in patients with PPCM stratified by HDP, timing of diagnosis, and race.

Methods: We conducted a retrospective cohort study of patients diagnosed with PPCM between 1986 through 2016 at our institution.

Results: We identified 220 PPCM patients (55% black). Patients with PPCM and HDP were diagnosed earlier postpartum than patients without HDP (p = 0.013), an effect that was most pronounced in non‐black patients. Rates of recovery were similar among PPCM patients with and without HDP (68.4% vs. 62.6%, p = 0.425). In contrast, patients with PPCM diagnosed after 1 month postpartum had lower rates of recovery than patients diagnosed <1 month postpartum (53.7% vs. 69.9%, p = 0.035). EF at time of diagnosis is a strong predictor of recovery, and patients with PPCM diagnosed after 1 month postpartum had lower baseline EF compared to patients presenting within 1 month of delivery.

Conclusions: The presence of HDP does not correlate with recovery in our racially diverse cohort with PPCM. In contrast, early diagnosis does portend a favorable outcome and is associated with higher EF at presentation. These findings underscore the need for early monitoring and diagnosis, especially in at‐risk underserved populations.

P‐23: Genetic Associations of Perinatal Pain and Depression

Grace Lim (presenting author),¹ Lora McClain,² Lisa A. Pan,² and David Peters³

¹Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh; ²Department of Psychiatry, University of Pittsburgh; ³Department of Obstetrics and Gynecology, University of Pittsburgh

Background: Underlying genetic influences may affect perinatal pain, depression, or both. We investigated the role of 59 single nucleotide polymorphisms (SNP) on quantitative traits measured in perinatal women.

Objectives: To quantify genetic factors associated with perinatal pain and depression, identifying preliminary loci to target in larger genetic studies.

Methods: 183 pregnant women (28‐37 weeks) were prospectively genotyped for 59 SNPs with known prior associations with either pain or depression in non‐pregnant populations. Phenotypic data were gathered during prenatal, labor and delivery, and postpartum (six weeks and three months) periods, capturing labor pain, Edinburgh Postnatal Depression Score, and Brief Pain Inventories. Genotypes were used as predictors and phenotypes as dependent variables in multiple linear regression. Three statistical models were tested: additive allele effects, deviation from dominant allele effects, and the joint test of both.

Results: rs4633 (a synonymous SNP in COMT) associated with “pain right now” scores at six‐weeks postpartum, and rs1135349 (a SNP within non‐coding RNA with many associations for depression) with maximum pain unpleasantness score during labor (a measure of the emotional valence of labor pain), controlling for the Holm‐Bonferroni family‐wise error rate. Sensory dimensions of labor pain (i.e., pain intensity) and postpartum depression scores were not associated with genotyped SNPs.

Conclusions: SNPs in COMT, and in a non‐coding RNA transcript associated with depression, are linked to pain at six weeks postpartum and to the emotional valence of labor pain, respectively. Identifying genomic components of these perinatal complex disorders may produce insights into relevant pathways or novel treatment options.

P‐24: Effect of the Combination Conjugated Estrogens and Bazedoxifene on Energy Metabolism in Obese Postmenopausal Women

Dragana Lovre (presenting author),^1,2 Kara L. Marlatt,³ Chandra Tate,^1,2 Robbie A. Beyl,³ Eric Ravussin,³ and Franck Mauvais‐Jarvis^1,2

¹Department of Endocrinology, Tulane Health Sciences Center, New Orleans, LA;²Department of Endocrinology, Southeast Louisiana Veterans Health Care Systems, New Orleans, LA; ³Pennington Biomedical Research Center, Baton Rouge, LA

Background: Menopause increases risk for type 2 diabetes (T2D). Randomized controlled trials show that menopause hormone therapy reduces the incidence of T2D. A novel menopausal therapy, combining conjugated estrogens (CE) and a tissue‐selective estrogen complex, bazedoxifene (BZA), has been shown to increase fat oxidation in a mouse model. The effect of CE/BZA on energy metabolism in postmenopausal women is unknown.

Objective: To identify novel markers and metabolic pathways to provide new insights about CE/BZA's effect on energy metabolism in obese postmenopausal women.

Methods: A pilot randomized double blind, crossover trial – 8 weeks of CE/BZA treatment vs. placebo with an 8‐week washout in obese menopausal women. Outcomes included muscle and serum non‐targeted metabolites (by ultra‐performance liquid chromatography with tandem‐mass spectroscopy) and muscle and adipose mRNA expression (by Real‐Time Polymerase Chain Reaction).

Results: Eight females (mean age 53.4 ± 2.8 years, BMI 35.7 ± 3.2, years since last menstrual period 2.45 ± 0.69) completed the study. Treatment with CE/BZA resulted in significant decrease of serum medium‐ and long‐chain acylcarnitine species and advanced glycation end products, and an increase in diacylglycerols, triacylglycerols, phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, threonine, and homoarginine. Adipose tissue mRNA expression of adiponectin and lipase increased, while muscle mRNA expression was unchanged.

Conclusions: Eight‐week treatment of obese menopausal women with CE/BZA altered several serum and adipose markers of fat oxidation. Modulating the metabolomic profile with CE/BZA as means of treating estrogen‐deficiency driven diseases may have a large impact on metabolic health in postmenopausal women.

P‐25: Sex‐Differences in Persistent Opioid Use Following Burn Injury

Matthew C. Mauck (presenting author),¹ Andrew Tungate,¹ and Samuel A. McLean¹

¹Institute for Trauma Recovery, Department of Anesthesiology, University of North Carolina, Chapel Hill

Background: Annually, worldwide ∼11 million burn injuries occur. Following burn injury, chronic pain is a common, morbid outcome often severe enough to warrant persistent opioid therapy. Previous work indicates that a greater proportion of females experience chronic pain following burn injury; however, sex‐differences in persistent opioid use to treat post‐burn injury pain remains unknown.

Objective: To fill this gap, we performed a retrospective study using insurance claims data to elucidate sex‐differences in persistent opioid use following burn injury.

Methods: Using commercial insurance claims data (Truven MarketScan^®) from 2001–2017, we estimated the incidence of new persistent opioid use. Our study cohort includes patients continuously insured for 1 year prior to hospital admission for burn injury, no prior opioid prescriptions for 1year preceding injury (opioid naïve), and those with a burn injury identified by diagnostic billing codes. We defined persistent opioid use as receipt of ≥1 prescription 90 to 180 days following burn injury.

Results: Among 2,874 burn survivors identified (877 females and 1,997 males), persistent opioid use was more common in females compared to males [20 vs. 16%, OR 1.23, 95% CI: 1.01–1.50, P = 0.043].

Conclusions: Despite burn injury being less common in females, compared to males, females are more likely to require persistent opioids to manage ongoing pain and thus contribute a greater burden to public health. To address the increase in chronic opioid use in females, non‐opioid analgesic strategies are urgently needed to reduce both chronic pain and persistent opioid use among all burn injury survivors.

P‐26: Association of Right Versus Left Hemisphere Stroke on Rehabilitation Outcomes

Jamila Minga, (presenting author),^1,2 Gabrielle Harris,³ Qing Yang,³ Mark A. Hirsch,⁴ Vu Q.C. Nguyen,⁴ and Janet Prvu Bettger^3,5

¹Communication Disorders Program, Department of Allied Professions, North Carolina Central University; ²Department of Obstetrics and Gynecology, School of Medicine Duke University; ³School of Nursing, Duke University; ⁴Carolinas Rehabilitation, Atrium Health; ⁵Duke Clinical Research Institute, Duke University

Background: Hemisphere specific variability in deficits on which outcomes are based suggest that patient outcomes should be distinguished based on the hemisphere of stroke, yet these differences are infrequently explored.

Objective: To determine if rehabilitation outcomes are associated with the hemisphere of stroke.

Methods: Main outcome measures of discharge disposition, motor, and cognitive function (Functional Independence Measure scores (FIM)) of adults with unilateral stroke (n = 904) admitted to an accredited acute rehabilitation facility were examined.

Results: Of the 904 patients with unilateral stroke (mean age, 65.2 ± 13.9, 48.1% female, 35.1% non‐white), 432 (47.8%) were right hemisphere stroke (RHS) and 472 (52.2%) were left (LHS). On admission, patients with RHS had slightly higher total FIM (more independent) (RHS, 51.4 ± 17.5; LHS, 49.1 ± 18.2, p = .047) and cognitive FIM scores (RHS 19.5 ± 6.8; LHS 16.6 ± 7.2, p < 0.001) but similar motor FIM function. Both groups demonstrated clinically meaningful functional improvements over the inpatient rehabilitation stay (18 days for both groups). After adjusting for patient demographic and clinical characteristics, discharge total FIM scores were lower for RHS when compared with LHS (β = ‐2.2, p = 0.028) and lower for motor FIM (β = ‐1.5, p = 0.046). Differences in cognition attenuated and were no longer significant after adjusting for covariates (unadjusted β = 2.48, p = 0.001; adjusted β = ‐0.35, p = 0.266). The adjusted probability of discharge home was similar for RHS and LHS patients (OR = 0.739, p = 0.107).

Conclusions: Patients with RHS had higher cognitive functioning than LHS but other clinical characteristics documented during the inpatient rehabilitation stay indicate more research is needed to delineate impact of stroke on daily activities and participation after discharge.

P‐27: Prospective Study of 3 Draction Pencil‐beam Scanning Proton Accelerated Partial Breast Irradiation (APBI): Early Provider and Patient Reported Outcomes of a Novel Regimen

Robert W. Mutter,¹ Krishan R. Jethwa,¹ Karthik Gonuguntla,¹ Nicholas B. Remmes,¹ Thomas J. Whitaker,¹ Tina J. Hieken,² Kathryn J. Ruddy,³ Lisa A. McGee,⁴ Kimberly S. Corbin,¹ and Sean S. Park¹

¹ Department of Radiation Oncology Mayo Clinic, Rochester, MN; ²Department of Surgery, Mayo Clinic, Rochester, MN; ³Division of Medical Oncology Mayo Clinic, Rochester, MN, ⁴Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ

Background: Proton therapy has unique physical properties which enable greater normal tissue sparing than x‐rays. Condensing treatment could improve access to this promising technology.

Objective: To report dosimetry and early adverse effects, aesthetic, and patient‐reported outcomes of a prospective study of 3‐fraction proton APBI.

Methods: Eligibility included women age ≥50 years with estrogen receptor positive, sentinel lymph node negative invasive or in‐situ breast cancer measuring ≤2.5 cm. The prescription was 21.9 Gy (RBE 1.1) in 3 daily fractions using pencil‐beam scanning. Patient reported outcomes collected included 10‐point Linear Analog Scale Assessment, Patient‐Reported Outcomes Version of the CTCAE, and the Harvard Breast Cosmesis Scale.

Results: 76 women were treated between 2015 and 2017. Median mean heart, mean ipsilateral lung, and maximum skin dose were 0 Gy, 0.1 Gy, and 20.6 Gy, respectively. With a median follow‐up of 12 months, no treatment‐related toxicity grade ≥2 has been observed. Most common grade 1 adverse events were dermatitis (68%) and skin hyperpigmentation (18%). At 12 months, the only persistent toxicities were one patient with grade 1 breast edema and one patient with a grade 1 seroma. 90% of patients reported quality of life as ≥7 out of 10 (0 indicating “as bad as it can be” and 10 indicating “as good as it can be”), and 98% of patients reported excellent or good cosmesis.

Conclusions: 3‐fraction PBS proton APBI is well tolerated with low rates of physician and patient reported early adverse effects. Follow‐up is ongoing to assess late treatment outcomes. Further investigation of this novel strategy is warranted.

P‐28: Mechanisms of Preterm Infant Retinopathy Protection in Maternal Preeclampsia

Leah A. Owen (presenting author),¹ Kinsey Shirer,² Blair Wood,¹ Denise J. Morgan,¹ Benjamin Haaland,³ Lakshmi D. Katikaneni,⁴ and Margaret M. DeAngelis^1,5

¹Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT; ²Department of Ophthalmology, Medical University of South Carolina, Charleston, SC; ³Department of Population Health Sciences, University of Utah, Salt Lake City, UT; ⁴Department of Pediatrics, Division of Neonatology, Medical University of South Carolina, Charleston, SC; ⁵Department of Pharmacotherapy, the College of Pharmacy, University of Utah, Salt Lake City, UT

Background: Maternal preeclampsia and retinopathy of prematurity (ROP) exist along a spectrum of ischemic aberrancy. Both conditions lack adequate risk and prevention due to incomplete understanding of molecular disease mechanisms. A novel paradigm of ROP protection found in the setting of maternal preeclampsia may allow for greater disease insight.

Objectives: We hypothesize that angiogenesis mediators facilitate ROP‐protection.

Methods: We analyzed peripheral or cord blood expression of candidate proteins with suggested roles in preeclamptic and ROP pathophysiology and with a direct or indirect angiogenesis function, using ELISA (HTRA1, sFLT1, IGF1) or Luminex (TGFβ‐1 and VEGF‐A). Placental expression was assessed using IHC. Pathologic function was analyzed in vivo using established murine models of ROP and preeclampsia.

Results: We recruited maternal‐infant pairs (n = 39) ± preeclampsia and preterm infants (GA <32 weeks) (n = 75) from two institutions. HTRA1 expression was decreased in a statistically significant fashion in women with preeclampsia and infants without ROP at birth and throughout the post‐natal period. No other candidate proteins were significantly different in both conditions. Placental HTRA1 expression was similarly decreased in preeclamptic pregnancies versus control. A murine model of preeclampsia demonstrated less ROP in the oxygen induced retinopathy (OIR) model of ROP, which correlated with less retinal HtrA1 expression by RT‐PCR. Transgenic mice with elevated HtrA1 expression demonstrate greater disease severity in the OIR model.

Conclusions: HTRA1 may be a systemic marker of disease for preeclampsia and ROP, but also mediate pathology. Thus, our work may allow for better risk stratification and disease prevention, which does not currently exist.

P‐29: Familial Hypermobile Ehlers‐Danlos Syndrome and Comorbid Dysautonomia May Have a Genetic Neuroimmunologic Origin

Laura A. Pace (presenting author),¹ Bing‐Jian Feng,² James Hemp,¹ and Matt Velinder³

¹Department of Internal Medicine, Division of Gastroenterology; ²Department of Dermatology; ³USTAR Center for Genetic Discovery, University of Utah

Background: Hypermobile Ehlers‐Danlos Syndrome (hEDS) is a rare genetic connective tissue disorder that presents with a sex‐dependent phenotype, with affected females having a more disabling clinical course. They are also more likely to have profound manifestations of comorbid dysautonomias, such as POTS (Postural Orthostatic Tachycardia Syndrome), and immune mediated disorders, such as Sjögren's syndrome, and mast cell activation syndrome (MCAS). In addition, there appears to be a wide spectrum of clinical presentations beyond the observed sex differences. While hEDS, dysautonomia, and immune disorders commonly co‐associate in these individuals, they also tend to cluster in families in an inheritance pattern suggestive of an autosomal dominant disorder. However, the genetic underpinnings of these disorders remain to be elucidated. For this study we leveraged the power of whole genome sequencing (WGS) coupled with extended pedigrees to identify the genetic determinants of this comorbid spectrum disorder.

Methods: We recruited affected individuals from a large extended family, with participants out to the 10^th cousin level. WGS was performed using the 10X Chromium and Illumina NovaSeq platforms. This allowed for haplotype phasing of single nucleotide variants, small insertions‐and‐deletions and provided access to large structural variants that extend over >10 Mb segments including deletions, insertions, duplications, copy‐number variants, inversions, and translocations. Variants were prioritized using multiple prioritization algorithms.

Results: We identified several candidate pathological variants associated with either the immune or neurological systems, suggesting this comorbid spectrum disorder may be of neuroimmunological origin.

Conclusions: We are working to verify these findings in additional affected individuals.

P‐30: Activity‐regulated Cytoskeleton‐associated Protein (arc/arg3.1) Differentially Regulates Mood‐related Behavior in the Male and Female Nucleus Accumbens

Rachel D. Penrod (presenting author)¹ and Christopher W. Cowan¹

¹Department of Neuroscience, Medical University of South Carolina, Charleston, SC

Background: Anxiety disorders are highly prevalent and increased anxiety is a common symptom in numerous neuropsychiatric diseases.

Objectives: There is a need for novel therapeutic strategies requiring a better understanding of the underlying neurobiology mediating anxiety disorders. Furthermore, despite the significant sex differences in anxiety (and other stress‐related) disorders, we have little understanding of the molecular mediators driving these differences. Recent work from our laboratory has identified activity‐regulated cytoskeleton associated protein (Arc) in the adult nucleus accumbens (NAc) as a potential mediator of sex differences in anxiety‐like behavior.

Methods: Male and female wild‐type mice received intra‐NAc infusions of Arc shRNA (shArc) or control shRNA (shCntrl). Following surgical recovery and Arc knockdown, mice were assessed for anxiety and drug‐related behaviors mediated by the NAc.

Results: We find that NAc shArc reduces anxiety‐like behavior in males, but not in females. Interestingly, Arc expression is induced following an anxiety‐associated experience in the male, but not female, NAc. Similar to anxiety‐related behavior, NAc shArc reduces male, but not female, sensitivity to the rewarding and locomotor activating effects of cocaine. Not all NAc shArc effects are sex‐specific as both male and female NAc shArc mice show deficits in novelty preference for objects and social partners.

Conclusions: These preliminary findings indicate a potential sex‐specific role for Arc in mediating anxiety. Future work is focused on examining how Arc expression/induction may be regulated by sex hormones and determining the cell‐types and molecular mechanisms mediating Arc's effect on male anxiety behavior.

P‐31: Effects of Sugar‐sweetened Beverage Consumption on Insulin Sensitivity in African‐American and White Women

Candice Allister Price (presenting author),¹ Valentina Medici,² Vivien Lee¹, Marinelle V. Nunez¹, Nancy L. Keim,³ and Kimber L. Stanhope¹

¹Department of Molecular Biosciences, School of Veterinary Medicine (CAP, KLS, VL) the Department of Nutrition (KLS, MVN, NLK); ²The Division of Gastroenterology and Hepatology, School of Medicine (VM); ³U.S. Department of Agriculture, Western Human Nutrition Research Center, Davis, CA (NLK)

Background: African‐American (AA) women are the highest consumers of sugar‐sweetened beverages (SSB): (1) and are one of the most high‐risk groups for type 2 diabetes (T2D), (2) High SSB consumption is associated with increased T2D in adults, (3,4), but clinical studies to demonstrate a direct link between SSB intake and T2D in African‐American women, specifically, has not been demonstrated.

Objective: To evaluate biomarkers of cardiometabolic risk in AA and white women after consumption of SSBs and to determine whether circulating microRNAs correspond to differential metabolic responses between these two groups.

Methods: Healthy AA (n = 7) and white (n = 7) women (mean BMI 30.4 ± 3.4 kg/m²; mean age 30.1 ± 6.0 years) consumed SSBs provided at 25% of their daily energy‐requirement for 2 weeks.

Results: After 2 weeks of SSB consumption in AA women (n = 7), we observed greater increases in glucose (p < 0.05) and greater reductions in insulin sensitivity (p = 0.08), both measured by an oral glucose tolerance test (OGTT), compared to white women (n = 7). We found differences in the fold change of miR100‐5p after 2 weeks of SSB between AA and white women, −0.11 ± 0.1 vs. 0.34 ± 0.1, respectively and these changes correlated with absolute changes in insulin sensitivity, regardless of race (r² = 0.53, p = 0.005).

Conclusions: These interim results suggest SSB consumption may differentially affect insulin sensitivity in AA as compared with white women and the epigenetic effects of SSB on insulin signaling in AA women may explain these findings.

P‐32: Timing of Pregnancy Confirmation: Adolescents Compared to Adults

Lauren J. Ralph (presenting author),¹ Diana G. Foster,¹ and Corinne H. Rocca¹

¹Bixby Center for Global Reproductive Health, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco

Background: Approximately one‐quarter of women discover pregnancy after 8 weeks gestation. This figure has not changed in the last two decades, possibly due to increased use of home pregnancy tests.

Objectives: Understanding timing of pregnancy testing, including barriers to home pregnancy testing, might facilitate earlier entry into pregnancy‐related care, particularly for adolescents.

Methods: We used survey data from 259 individuals of childbearing age with known or suspected pregnancies at eight primary care and family planning clinics across the U.S. (2016–2017). We used Chi‐square and Kruskal‐Willis tests to identify differences in timing of pregnancy testing by age.

Results: Most (74%) took a home test to confirm pregnancy. This figure was lower among adolescents than young adults (65% vs. 81%, p = 0.06). Two‐thirds (64%) reported delays in pregnancy testing, most often because they wanted to wait to see if they got their period (52%) or feared the result (35%). Adolescents more often reported experiencing delays; coupled with taking a longer time to suspect pregnancy, their average gestation at testing was 7.7 weeks [SD 3.7] vs. 5.7 weeks [SD 2.9] among adults, p = 0.03. Among participants who did not take a home pregnancy test, 43% cited concerns about accuracy. Logistical barriers such as cost, difficulty obtaining, or confidentiality concerns were less common (9–11% each).

Conclusions: Utilization of home pregnancy tests is high but varies by age. Adolescents may be most likely to experience delayed entry to desired pregnancy‐related care. Efforts to increase knowledge about the high accuracy of available tests may increase utilization.

P‐33: The Role of MKRN3 in Sex Differences in the Timing of Pubertal Onset

Stephanie A. Roberts (presenting author),^1,2 Soukayna Chouman,¹ Victor Navarro,¹ Rona S. Carroll,¹ and Ursula B. Kaiser¹

¹Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA; ²Division of Endocrinology, Boston Children's Hospital, Boston, MA

Background: Girls are at increased risk for central precocious puberty (CPP) while boys are at increased risk for delayed puberty; both have short‐ and long‐term health implications. Loss‐of‐function mutations in MKRN3, the most common genetic cause of CPP, affect girls more severely than boys. The impact of increased MKRN3 expression has not been reported.

Objectives: To explore the effects of Mkrn3 overexpression on puberty onset using a novel mouse model and characterize any sex differences in pubertal phenotype.

Methods: Wild type C57B6 mice were injected on postnatal day (PND) 1 using a recombinant adeno‐associated virus (rAAV‐Mkrn3‐IRES‐EGFP) that overexpresses Mkrn3 or a control virus (rAAV‐EGFP) and evaluated for puberty onset.

Results: Female neonatal mice injected intracerebroventricularly bilaterally at PND1 with rAAV‐Mkrn3‐IRES‐IEGFP had significantly delayed markers of pubertal onset, including vaginal opening and delayed first estrus (p < 0.005). Body weight was unaffected. Subsequent estrous cyclicity and fertility was normal. Injected male mice did not exhibit any difference in preputial separation, a marker of puberty onset. In addition to increased Mkrn3 mRNA levels, significantly increased mRNA levels of Kiss1, Tac2, and Pdyn, expressed by Kiss1 neurons in the mediobasal hypothalamus, an important area of pubertal onset, were observed in females at PND 28 and males at PND 60 injected rAAV‐Mkrn3‐IRES‐EGFP, while other key neuroendocrine genes were unaffected.

Conclusions: Overexpression of Mkrn3 leads to delayed puberty in female but not male mice. This may occur by targeted degradation of neuropeptides in Kiss1 neurons, with secondary upregulation of mRNA levels for these neuropeptides.

P‐34: Loss and Child Maltreatment: The Link to Cardiovascular Risk in Women

Leia Y. Saltzman (presenting author)

School of Social Work, Tulane University

Background: Cardiovascular disease disproportionally impacts adults exposed to trauma and loss. Similarly, women are at greater risk for cardiovascular disease, and traditionally report higher levels of exposure to trauma. Yet, few studies have examined the sex differences in the relationships between trauma. bereavement, and cardiovascular health.

Objectives: This study sought to compare sex differences in the role of bereavement and trauma in predicting ten‐year cardiovascular risk score, and to identify psychological factors that mediate these relationships.

Methods: The Midlife and Development in the United States (MIDUS) biomarker project includes 1255 adults. Predictors include: bereavement, child maltreatment, and sex. Mediators include: depression, anxiety, stress, positive affect, and social networks. Finally, a Framingham ten‐year cardiovascular risk score was calculated. A series of seemingly unrelated regression models were estimated to test a mediation model.

Results: Child maltreatment predicted depression (b = 0.17, p < 0.001), anxiety (b = 2.43, p < 0.001), stress (b = 3.83, p < 0.001), positive affect (b = ‐4.59, p < 0.001), and social networks (b = ‐0.45, p < 0.001), but did not predict cardiovascular risk. Being female and experiencing bereavement was associated with higher anxiety (b = 1.91, p < 0.001), stress (b = 1.283, p < 0.05), and cardiovascular risk (b = ‐6.32, p < 0.001) compared to males without loss. Anxiety mediated the relationships between maltreatment (b = 0.29, p < 0.01) and being female with loss (b = 0.23, p < 0.05) on cardiovascular risk.

Conclusions: Being female and experiencing loss both directly and indirectly predicted greater cardiovascular risk. This relationship was not found for males. While these findings offer preliminary insight, understanding the mechanisms that differentiate the impact of trauma and loss on cardiovascular risk for men and women requires further investigation.

P‐35: Examining the Effect of Age on the Anti‐Dipsogenic and Anti‐Natriorexigenic Effect of Estradiol

Jessica Santollo (presenting author)¹ and Andrea A. Edwards¹

¹Department of Biology, University of Kentucky, Lexington KY

Background: Estradiol (E2) inhibits fluid intake in several species, including humans. This effect helps defend fluid homeostasis by preventing excessive extracellular fluid volume. Although this phenomenon is well established using the rat model, it has exclusively been studied in young adults. Because aging can influence the neuronal sensitivity to E2, it is possible that this fluid intake effect of E2 is lost in older animals.

Objective: This study tested the hypothesis that aging influences the anti‐dipsogenic and anti‐natriorexigenic effect of E2.

Methods: Young (2–4 month), middle‐aged (10–12 month) and old (16–18 month) female rats were ovariectomized and implanted with a cannula aimed at the right lateral ventricle. After recovery, rats were treated with either oil or 10 μg estradiol benzoate (EB) once a day for two days. On day 3, all rats were treated with 100 ng angiotensin II to stimulated intake and 1 h water and 1.5% saline intake were measured. The following week the protocol was repeated with animals receiving the opposite hormone treatment.

Results: Regardless of age, EB‐treatment reduced water intake. However, saline intake was influenced by an interaction of age and EB‐treatment. While EB‐treatment reduced saline intake in young females, it did not influence saline intake in middle‐aged or old females.

Conclusions: These results suggest that the anti‐natriorexigenic, but not anti‐dipsogenic, effect of E2 is lost in older animals. This could contribute to the increased risk of hypertension in older females because increased salt intake causes fluid retention and thus an increase in extracellular fluid volume.

P‐36: Sex Differences of Motor Unit Characteristics Associated with Anterior Cruciate Ligament Injury and Arthrogenic Muscle Inhibition

Nathan D. Schilaty (presenting author),¹ April L. McPherson,¹ Takashi Nagai,¹ Nathaniel A. Bates,¹ and Timothy E. Hewett

¹Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN

Background: Females have 4–6x greater risk than males for an anterior cruciate ligament (ACL) injury. ACL injury induces a presynaptic reflex inhibition of joint musculature, termed arthrogenic muscle inhibition (AMI). Although initially protective, AMI prevents complete activation of the muscle and may impede recovery. AMI likely manifests differently between sexes and warrants exploration for improved, individualized rehabilitation.

Objectives: To determine the motor unit (MU) characteristics of thigh musculature [biceps femoris (BF), semitendinosus (ST), vastus lateralis (VL), vastus medialis (VM)] between sexes and determine MU adaptations from ACL injury and rehabilitation compared to healthy controls.

Methods: Decomposed electromyography (dEMG) was acquired with a four‐pin array sensor of four major thigh muscles from 56 subjects [Female (n = 32); Control (n = 25)]. Data was acquired from isometric contractions with force measured by a custom load cell apparatus (MLP‐300). Acquired dEMG data was analyzed with dEMG Analysis software. A mixed model analysis was performed in JMP 14.

Results: Females demonstrated significantly higher rate coding than males for the VL, BF, and ST (p < 0.001). In addition, females demonstrated higher rate coding than males for 25, 35, and 50% maximum voluntary contraction (MVC; p < 0.001). Females consistently recruited MUs at lower levels of MVC than males and fewer in quantity. Across rehabilitation, females at pre‐surgery recruited significantly less MUs than males (p < 0.001), however, this reversed at 12‐months post‐surgery (p < 0.001).

Conclusions: With controls, females have different recruitment and rate coding patterns than males. With rehabilitation, females demonstrated significantly worse MU characteristics 12‐months post‐surgery, potentially leading to worse outcomes and future risk.

P‐37: Biological Sex and Neuroimaging in Infancy Predict Later Autism Diagnosis

Mark D. Shen (presenting author),^1,2 Mahmoud Mostapha,³ Martin A. Styner,^1,2,3 and Joseph Piven^1,2

¹Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC; ²Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC; ³Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC

Background: Autism diagnosis is based on the subjective assessment of behavioral symptoms that are not diagnostic until 2–4 years of age. Girls are diagnosed four times less frequently than boys and, on average, two years later than boys. There is a need for objective biomarkers to identify autism in girls and boys in infancy, enabling earlier intervention.

Objective: To build a multifactorial prediction model using sex of the infant and a brain MRI at 6 months to predict autism diagnosis at 2 years.

Methods: 151 high familial‐risk infants (93 male/58 female) underwent a structural MRI at 6 months and diagnostic assessments at 2 years. We measured four features of infant brain anatomy: extra‐axial CSF, cortical shape, surface area, and cortical thickness. Sex and the brain features were entered into a fully cross‐validated, 10‐fold, deep‐learning prediction model to predict autism diagnosis.

Results: The combination of sex, extra‐axial CSF, and cortical shape at 6 months predicted autism at 2 years with 89% sensitivity, 96% specificity, 85% positive predictive value, and 97% negative predictive value. The model performed equally well in girls and boys.

Conclusions: A prediction model incorporating sex of the infant and a 6‐month MRI accurately predicted autism diagnosis at 2 years. Future directions include determining how sex differences in 6‐month brain measures may contribute to sex‐specific biomarkers for autism. Detection of autism in infancy, without waiting until children show behavioral symptoms at 2–4 years of age, raises the potential to initiate early intervention in infancy, and consequently, improve long‐term outcomes.

P‐38: Ovarian Endothelin‐2 Gene Expression is Dysregulated Across the Estrous Cycle with Chronic High‐Fat Diet Consumption

Malgorzata E. Skaznik‐Wikiel (presenting author),¹ Natalie M. Hohos,¹ Emily M. Elliott,¹ and Thomas Jansson¹

¹Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO

Background: We have previously shown that high‐fat diet (HFD) feeding in female mice causes abnormal estrous cyclicity and subfertility. We discovered that endothelin‐2 (Edn2), a gene critical to normal ovulation, was significantly downregulated in the ovaries of HFD mice. However, it is unknown how HFD affects ovarian Edn2 expression across the estrous cycle.

Objective: We tested the hypothesis that HFD feeding causes abnormal changes in ovarian Edn2 expression throughout the estrous cycle.

Methods: 5‐week‐old C57Bl/6J mice were fed a standard chow or 60% HFD for 10 weeks. Estrous cyclicity was evaluated daily for the last two weeks of feeding and ovaries were collected in each of the four estrous cycle stages (n = 9/group/stage). Edn2 expression was measured by qRT‐PCR. T‐test and chi‐square tests were used for statistical analysis.

Results: After 10 weeks of diet, HFD mice weighed more than chow controls and had a higher prevalence of abnormal estrous cycles (58.3% and 21.6% p = 0.0018). In chow controls, Edn2 was expressed with low levels during diestrus and proestrus, increased 11.6‐fold during estrus, and decreased to basal levels during metestrus. In HFD mice, Edn2 expression was increased 6.2‐fold and 10.9‐fold during diestrus and proestrus (p < 0.05). In contrast, Edn2 expression was lower in estrus (16% of chow‐fed controls) and metestrus (21% of chow‐fed controls) in HFD fed mice.

Conclusions: Our data suggest that Edn2 is dysregulated across the estrous cycle in HFD feeding. Future studies are needed to confirm a cause‐and‐effect relationship between ovarian Edn2 expression and subfertility, which could provide a foundation for developing strategies to mitigate HFD‐induced ovulation defects.

P‐39: Exploring Resting State MRI in Adolescents with Anorexia Nervosa: The Relationship Between the Executive Control Network and Reward Network

C. Alix Timko (presenting author),^1,2 Anushua Bhattacharya,¹ Xin Niu,³ and John Herrington^1,2

¹Department of Child and Adolescent Psychiatry and Behavioral Sciences, Children's Hospital of Philadelphia; ²Department of Psychiatry, Perelman School of Medicine, University of PA; ³Department of Psychology, Drexel University

Background: The majority of work on the neurobiology of anorexia nervosa (AN) has focused on adults; however, AN begins in adolescence. Research elucidating the neurobiology of AN should occur during this period of significant brain development.

Objective: The purpose of this study is to gather preliminary resting state MRI (rsMRI) data examining the executive control network (ECN) and reward network (RN) in adolescents with AN. It is hypothesized that connectivity within the ECN will correlate with performance on set shifting tasks. The RN is disrupted in AN; it is expected that FC in the ECN will be positively correlated with the RN. The nucleus accumbens is hypothesized to be a connective node for these two networks.

Methods: Adolescents with restrictive eating disorders completed a neuroimaging scan, battery of neuropsychological measures, and diagnostic interview at three time points: T₁ (acutely ill, starting treatment), T₂ (four weeks after initial scan), and T₃ (6 months post initial scan).

Results: 142 eligible adolescents were identified and 40 enrolled. 17 completed a T₁ scan, 15 a scan at T₂, and 11 a scan at T₃. 6 participants are male. The average age was 185.28 ± 21.57 months. The majority were severely malnourished (92.6%). The average BMI z‐Score was −0.27 ± 0.9. MRI data analysis is ongoing.

Conclusions: Results have the potential to increase our knowledge about the neurobiology of AN and will inform future hypotheses regarding the role of executive control and reward mechanisms in this complex and severe psychiatric illness.

P‐40: Gender Differences in Smoking Latency Following Exposure to Stressful Images Administered in Naturalistic Settings

Rachel L. Tomko (presenting author),¹ Brett Froeliger,² Erin A. McClure,¹ Michael E. Saladin,^1,3 and Kevin M. Gray¹

¹Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina; ²Department of Neuroscience, Medical University of South Carolina; ³College of Health Professions, Medical University of South Carolina

Background: Women are more prone to smoking‐related disease and may have more difficulty quitting smoking than men. Laboratory research suggests that female smoking may be maintained by stress to a greater extent than male smoking. Female smokers report greater craving and stress than male smokers when shown stressful images during their typical daily routines (i.e., randomly administered via a mobile app). However, it is unclear whether this translates to a gender difference in stress‐related smoking behavior.

Objective: To examine gender differences in latency to smoke following stressful or smoking versus neutral cues presented in daily life via a mobile phone app. To evaluate feasibility of using an electronic smart lighter to track cigarette smoking.

Methods: Adult smokers (n = 22; 50% female) used an electronic, smart lighter to time‐stamp cigarettes smoked for two weeks. Smokers also provided ratings of mood and cigarette craving before and after viewing stressful, smoking, and neutral cues presented at random, four times daily on their mobile phones.

Results: An estimated 92% of cigarettes smoked were recorded via the lighter. Regardless of gender, stressful and smoking cues did not reduce latency to smoke relative to neutral cues.

Conclusions: Stressful images did not promote earlier smoking for either gender suggesting that these cues have minimal direct effect on smoking behavior in daily life. Further work should explore if cues elicit smoking when other risk factors are present. The electronic smart lighter is feasible for collecting data on patterns of smoking, though alternative designs may increase cigarettes captured.

P‐41: Sex Differences in Cognitive Control of Emotion and Their Contribution to Sex Differences in Schizophrenia Symptom Profiles

Laura M. Tully (presenting author),¹ Ana‐Maria Iosif,² Mary Blendermann,¹ Rajpreet Chahal,³ Amanda Guyer,³ and Cameron S. Carter¹

¹Department of Psychiatry and Behavioral Sciences, University of California, Davis; ²Department of Public Health Sciences, Division of Biostatistics, University of California, Davis; and ³Department of Human Ecology, Center for Mind and Brain, University of California, Davis

Background: Females with schizophrenia (SZ) exhibit more psychotic and mood symptoms; males exhibit more negative symptoms (avolition, anhedonia). Psychotic symptom severity relates to mood symptom severity in females, indicating a link between psychosis and emotion regulation not observed in males. Sex differences in cognitive control of emotion (CCoE), mediated by the frontal‐limbic network, may drive this but have not been examined.

Objectives: 1) Test the influence of biological sex on the frontal‐limbic network as captured by task‐based fMRI during CCoE in healthy control (HC) and SZ participants; 2) Test associations between frontal‐limbic activation during CCoE and sex‐specific symptom profiles in SZ.

Methods: During fMRI, 44 HC (26 female) and 24 SZ (14 female) participants completed the Social Evaluation Task, in which participants react to or down‐regulate their emotional responses to negative social evaluation (NSE). Participants also completed psychosocial symptom assessments.

Results: Preliminary results indicate HC females show higher NSE reactivity than HC males (estimated difference = 0.89, p = 0.002); this effect was attenuated in SZ (estimated difference = 0.44, p = 0.24). Regardless of sex, HC demonstrated greater NSE down‐regulation than SZ (estimated difference = 0.34, p < 0.0001). In SZ females, greater NSE down‐regulation was associated with lower anxiety symptoms (r = ‐0.53; p = 0.052); SZ males showed an opposite non‐significant association (r = 0.42, p = 0.23).

Conclusions: Preliminary analyses indicate SZ individuals have impaired CCoE, which may be specifically associated with anxiety symptoms in SZ females, suggesting treatments targeting CCoE could alleviate anxiety in females with SZ. Future analyses will utilize fMRI data to examine sex and diagnosis effects in the frontal‐limbic network during CCoE.

P‐42: Spontaneous Coronary Artery Dissection and Risk for Recurrence

Marysia S. Tweet (presenting author),¹ Rajiv Gulati,¹ and Sharonne N. Hayes¹

¹Department of Cardiovascular Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN

Background: Spontaneous coronary artery dissection (SCAD) causes myocardial infarction and sudden cardiac arrest due to a hematoma ± intimal tear in the coronary artery. SCAD often affects otherwise healthy women without atherosclerotic risk factors, and risk for recurrent SCAD remains variably reported.

Objective: We aimed to ascertain risk of SCAD recurrence.

Methods: We reviewed retrospective and prospective data of 876 patients with history of SCAD enrolled in the Mayo Clinic SCAD Registry from 8/30/2011‐12/31/2018.

Results: Most (96%) participants were female with a median age of 46 years (IQR 39–53) at time of SCAD. Median time to follow‐up from SCAD was 3.9 years (IQR 2.1–6.3). Ten percent of patients presented with cardiac arrest; all others presented with myocardial infarction. SCAD occurred during or within a year of pregnancy in 12% of patients. The estimated Kaplan‐Meier 5‐year rate of SCAD recurrence in the overall cohort was 16%; the majority (79%) of whom had only one recurrence. Among the 151 with SCAD recurrence, median time to second SCAD was 2 yrs (IQR 0.18, 5.3). All but two with recurrent SCAD were women, most (60%) presented as non‐ST‐elevation myocardial infarction, and one recurrence occurred at 20 years.

Conclusions: Recurrence is a notable concern after incident SCAD, the predictors of which remain to be better defined. These findings emphasize the need to further clarify contributing factors and underlying mechanisms for SCAD recurrence in order to identify strategies to reduce future adverse events.

P‐43: Gender Differences Across Health‐related Fitness Measures Among Elementary‐aged Children: A Cross‐sectional Study

Timothy J. Walker (presenting author),¹ Derek Craig,¹ Gregory Knell,^2,3 Andjelka Pavlovic,⁴ Shelby Thiele,⁴ and Harold W. Kohl⁵

¹University of Texas Health Science Center at Houston, School of Public Health; ²University of Texas Health Science Center at Houston, School of Public Health in Dallas; ³Children's Health Andrews Institute for Orthopedics and Sports Medicine; ⁴The Cooper Institute, Dallas; ⁵University of Texas Health Science Center at Houston, School of Public Health in Austin

Background: Research consistently shows girls are less likely than boys to meet the physical activity guideline recommendations. Yet little information exists about gender differences among health‐related fitness measures, which are strong predictors of overall health.

Objective: The purpose of this study was to compare health‐related fitness levels between elementary school‐aged girls and boys.

Methods: This cross‐sectional study used FitnessGram^® data collected in 2017‐2018 from 67 schools serving elementary students in the Dallas Metropolitan area participating in the Healthy Zone School Program. FitnessGram^® includes tests for: 1) aerobic capacity; 2) body composition; 3) upper‐body strength and endurance; 4) abdominal strength and endurance; 5) trunk extensor strength; and, 6) flexibility. Multivariable logistic regression models examined differences in odds for students who were in the Healthy Fitness Zone (HFZ) for each respective test. Age and sex‐specific cut points were used to define HFZ.

Results: There were 18,197 students in grades 3–5 (mean age = 9.5 years) included in the dataset. Girls had significantly lower odds for being in the HFZ for aerobic capacity (OR = 0.56, 95%CI = 0.50–0.63) and upper body strength (OR = 0.71, 95%CI = 0.66–0.77) compared to boys. Girls had similar odds for being in the HFZ for abdominal strength (OR = 1.04, 95%CI = 0.96–1.12) compared to boys. However, girls had significantly higher odds of being in the HFZ for BMI (OR = 1.21, 95%CI = 1.14–1.28), trunk extensor strength (OR = 1.26, 95%CI = 1.11–1.44), and flexibility (OR = 1.42, 95%CI = 1.11–1.81) compared to boys.

Conclusions: More physical activity opportunities need to be provided that better meet the interests of girls and target aerobic and upper body muscle strengthening physical activities.

P‐44: Sex‐dependent Regulation of Cardiomyocyte Function by Midkine in Pediatric Dilated Cardiomyopathy

Kathleen C. Woulfe (presenting author),¹ Cortney E. Wilson,¹ Shelley D. Miyamoto,³ Brian L. Stauffer,^1,2 and Carmen C. Sucharov¹

¹Department of Medicine, Division of Cardiology, University of Colorado Denver School of Medicine, Aurora, CO; ²Department of Medicine, Division of Cardiology, Denver Health and Hospital Authority, Denver, CO; ³Department of Pediatrics, Division of Cardiology, University of Colorado Denver School of Medicine and Children's Hospital Colorado, Aurora, CO

Background: Pediatric dilated cardiomyopathy (DCM) affects 1 in 100,000 children, and the prognosis for this disease is very poor. Evidence‐based therapies that help adult DCM patients are not effective in pediatric DCM patients. Interestingly, girls with DCM have worse outcomes than boys. It is not clear the mechanisms that lead to these differences. We have identified a cytokine, midkine (MDK) that is significantly upregulated in the serum from pediatric DCM patients. MDK is significantly higher in girls with DCM requiring a transplantation compared to girls with DCM who are stable.

Objective: The objective of this study is to determine if MDK impacts cardiomyocyte function differently in males and females.

Methods: Cardiomyocytes isolated from juvenile male and female rats were treated with 100ng MDK for 48 and 72 hours. Cardiomyocyte function and calcium dynamics were assessed using an IonOptix system. Myofibril mechanics, calcium sensitivity, and proteins involved in sarcomeric function and calcium handling were assessed.

Results: Male cardiomyocytes treated with MDK have prolonged calcium reuptake compared to untreated male cardiomyocytes. This response is absent in female cardiomyocytes treated with MDK. Further, myofibrils isolated from male cardiomyocytes treated with MDK decreased calcium sensitivity. Gene expression of sarcomeric reticulum ATPase 2 (SERCA) is increased in male cardiomyocytes treated with MDK but not in female cardiomyocytes.

Conclusions: This study demonstrates functional differences in response to MDK in male and female juvenile cardiomyocytes. These findings suggest that elevated circulating MDK in pediatric DCM patients may lead to different cardiac function in male and female patients.