Epic Research

Patients with Diabetes, with a Rural Residence, or Who Are Black Experience Higher Risk of Stillbirth

Kersten Bartelt, RN; Grant Keane; Anna Miller, RN; Emily Higgs — Thu, 16 Oct 2025 11:00:00 +0000

Stillbirth (fetal death at 20 or more weeks gestation) is a major cause of perinatal loss, with long-term impacts on families and public health.¹ While certain risk factors are well-documented, less is known about whether they are specific to early, late, or term stillbirth. We aimed to further understand timing-specific patterns, highlighting opportunities for targeted prevention.

We studied 246,775 pregnancies that occurred between January 1, 2017, and May 1, 2025, including those that had a miscarriage and those that did not, and matched pregnancies based on maternal age, gravidity, prior neonatal or fetal demise, and whether the pregnancy had more than one fetus. We accounted for demographics, BMI, smoking, rurality, census region, residence in a socially vulnerable area, multiple gestation status, maternal conditions, obstetric history, and prenatal care timing. Stillbirths were classified as early (20 to 27 weeks), late (28 to 36 weeks), or term (≥37 weeks).

Mothers who are Black experience markedly higher likelihood of stillbirths at each stage of stillbirth—up to 87% more likely compared to those who are White—as seen in Figure 1. A 9% increase in early pregnancy stillbirth was observed for Hispanic mothers. For other non-White mothers, representation was too low to establish statistical significance.

Figure 1. The likelihood of stillbirth by maternal race and ethnicity.

Mothers living in more rural areas are up to 35% more likely to experience a stillbirth compared to those living in more urban areas, as seen in Figure 2.

Figure 2. The likelihood of stillbirth by rurality.

We evaluated 20 maternal conditions that could potentially influence the risk of stillbirth. Figure 3 shows those with the strongest correlation. Patients with diabetes consistently had increased likelihood of stillbirth across all stages. Mothers who had thrombophilia, severe obesity, hypertension, or chronic kidney disease (CKD), on the other hand, had varying relationships with the likelihood of stillbirth at different stages. For the results of all studied factors, see the tables in the PDF version of the brief.

Figure 3. The likelihood of stillbirth by maternal conditions.

These data come from Cosmos, a dataset created in collaboration with a community of Epic health systems representing more than 300 million patient records from 1,800 hospitals and more than 41,000 clinics from all 50 U.S. states, Canada, Lebanon, and Saudi Arabia. This study was completed by two teams that worked independently, each composed of a clinician and research scientists. The two teams came to similar conclusions. Graphics by Brian Olson.

American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. Management of stillbirth: Obstetric care consensus no, 10: Obstetric care consensus no, 10. Obstet Gynecol. 2020;135(3):e110-e132. doi:10.1097/AOG.0000000000003719

GLP-1 Use in Non-Diabetics Associated with Trivial Increase in Creatinine

Kersten Bartelt, RN; Eric Barkley; Joel Jones, PharmD; Joe Deckert, PhD — Tue, 14 Oct 2025 11:00:00 +0000

GLP-1s are increasingly prescribed for weight management and metabolic health in patients without diabetes. While renal benefits of these medications have centered on diabetic populations,^2,3 limited data exist on kidney function changes in non-diabetic patients using GLP-1s. Lab tests to measure creatinine levels are often used to measure kidney function, and higher levels indicate poorer kidney function.³

To understand the relationship between GLP-1 medications and kidney function, as measured by creatinine lab results, we studied 108,439 adult patients who started semaglutide, liraglutide, or tirzepatide between 2021 and 2024 and had one or more creatinine labs in the months leading up to and following the new medication. Their change in creatinine was compared to patients with no GLP-1 exposure who had office visits in the same period. Patients prescribed GLP-1s were compared to patients who did not take GLP-1s but had similar patient demographics, baseline creatinine levels, follow-up period durations, and BMIs.

Among patients diagnosed with CKD, no statically significant changes in creatinine were seen for any of the medications, as shown in Figure 1. Among patients without CKD, minimal increases in serum creatinine were observed for patients on a GLP-1 compared to those who were not prescribed a GLP-1: 0.01 mg/dL for semaglutide, 0.01 mg/dL for liraglutide, and 0.02 mg/dL for tirzepatide. Normal creatinine levels are 0.5 to 1.1 mg/dL for females and 0.6 to 1.2 mg/dL for males.¹

Figure 1. The change in creatinine levels from the three months before GLP-1 was started compared to levels one to three months after, split by whether the patient had pre-existing CKD.

Devkota, B. P. (2024, June 28). Creatinine. Medscape. https://emedicine.medscape.com/article/2054342-overview. Accessed August 1, 2025.
Li X, Song Y, Guo T, Xiao G, Li Q. Effect of glucagon-like peptide 1 receptor agonists on the renal protection in patients with type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab. 2022;48(5):101366. doi:10.1016/j.diabet.2022.101366
Simental-Mendía M, Linden-Torres E, Sánchez-García A, Sahebkar A, Simental-Mendía LE. Effect of glucagon-like peptide-1 receptor agonists on renal function: A meta-analysis of randomized controlled trials. Br J Clin Pharmacol. 2022;88(8):3566-3576. doi:10.1111/bcp.15304

Cardiovascular Event Risk Increases More Sharply for Men Than Women at Very Low Average Blood Pressure

Kersten Bartelt, RN; Ted Stamp; Dave Little, MD; Joe Deckert, PhD — Wed, 08 Oct 2025 11:00:00 +0000

Blood pressure (BP) is a key modifiable risk factor for cardiovascular disease (CVD). Prior research has highlighted that both low BP and high BP can increase risk of adverse cardiovascular events, but less is known about whether this risk differs between men and women.¹ Sex-based physiological differences, including vascular stiffness and hormonal factors, may contribute to different susceptibility to myocardial infarction (MI) and stroke.²

To better understand whether there are differing cardiovascular outcomes between sexes, we studied 22,070,072 patients aged 18 to 95 who had at least one outpatient BP measurement between May 1, 2019, and April 30, 2022, to calculate a historical average BP. An additional outpatient BP measurement between May 1, 2022, and April 30, 2023, served as the index value for stratifying patients by systolic BP levels. Patients were observed for one year for MI and stroke. We accounted for demographics, comorbidities, historical average BP, and medication use. Outcomes were defined as the first occurrence of MI, ischemic stroke, or hemorrhagic stroke.

Relative risk for MI increased at both BP extremes for men and women, but the increase was more pronounced in men for very low average systolic BP. Men with an average systolic BP <90 mmHg had a 142% greater risk of MI compared to men with an average systolic BP of 115–119 mmHg. For women, the risk was 102% greater at an average systolic BP <90 mmHg compared to women with an average systolic BP of 115–119 mmHg. At ≥160 mmHg, risks were similar between men (56% greater risk) and women (55% greater risk).

Figure 1. The risk of a patient experiencing an MI stratified by their average systolic BP and sex.

Similarly, both sexes showed higher ischemic stroke risk at both BP extremes, with a greater increase in men at very low average systolic BP. At <90 mmHg, the risk was 142% higher for men and 106% higher for women (compared with an average systolic BP of 115–119). The difference between sexes was smaller at ≥160 mmHg (71% greater for men and 59% greater for women).

Figure 2. The risk of a patient experiencing an ischemic stroke by their average systolic BP and sex.

Men had a sharper increase in hemorrhagic stroke risk at low average systolic BP than women. At an average systolic BP <90 mmHg, men had a 166% greater risk, versus a 67% greater risk for women, compared to those with an average systolic BP of 115–119 mmHg. At the highest average BP (≥160 mmHg), risk converged (24% for men, 26% for women).

Figure 3. The risk of a patient experiencing a hemorrhagic stroke by their average systolic BP and sex.

Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: Executive summary. Hypertension. 2018;71(6):1269-1324. doi:10.1161/HYP.0000000000000066
Ji H, Kwan AC, Chen MT, et al. Sex differences in myocardial and vascular aging. Circ Res. 2022;130(4):566-577. doi:10.1161/CIRCRESAHA.121.319902.

Progesterone Use Associated with 18% Reduction in Miscarriage Risk Among Women with History of Miscarriages

Kersten Bartelt, RN; Eric Barkley; Christopher Alban, MD; Jacob Gasser — Tue, 30 Sep 2025 11:00:00 +0000

Miscarriage is a common and often emotionally devastating outcome of pregnancy. Women with prior pregnancy losses often seek interventions that might improve their chances of a healthy birth. Because progesterone plays a critical role in maintaining early pregnancy, progesterone supplementation has been considered a treatment for women with recurrent miscarriages. However, evidence from clinical trials and reviews has been mixed, leaving uncertainty for both patients and clinicians.^1,2

To further understand the relationship between progesterone supplementation and miscarriages, we studied 84,009 pregnancies among women who had at least one prior miscarriage or fetal demise. We accounted for maternal age, BMI, race and ethnicity, social vulnerability, comorbidities, fertility treatments, and count of prior pregnancies. Women who were started on progesterone after the pregnancy began were excluded to avoid confounding by indication, since clinicians are more likely to prescribe progesterone to pregnancies already perceived as threatened.

We found that women who received progesterone prior to pregnancy were 18% less likely to experience a miscarriage compared to those who did not receive progesterone.

Figure 1. The likelihood of an expectant mother experiencing a miscarriage by whether she was prescribed progesterone.

A sensitivity analysis analyzing the type of progesterone used, based on the pharmaceutical class, found similar results.

These data come from Cosmos, a dataset created in collaboration with a community of Epic health systems representing more than 300 million patient records from 1,700 hospitals and more than 40,000 clinics from all 50 U.S. states, Canada, Lebanon, and Saudi Arabia. This study was completed by two teams that worked independently, each composed of a clinician and research scientists. The two teams came to similar conclusions. Graphics by Brian Olson.

Coomarasamy A, Devall AJ, Cheed V, et al. A randomized trial of progesterone in women with bleeding in early pregnancy. N Engl J Med. 2019;380(19):1815-1824. doi:10.1056/NEJMoa1813730
Devall AJ, Papadopoulou A, Podesek M, et al. Progestogens for preventing miscarriage: a network meta-analysis. Cochrane Database Syst Rev. 2021;4(4):CD013792. doi:10.1002/14651858.CD013792.pub2

Cardiac Event Risk Similar Among Patients on One or Two QT-Prolonging Medications

Kersten Bartelt, RN; Neil Sandberg; Matthew Gracianette, MD; Eric Barkley — Thu, 25 Sep 2025 11:00:00 +0000

Certain medications can affect the electrical activity of the heart, including lengthening a part of the heartbeat known as the QT interval. This change can increase the risk of dangerous rhythms, such as a rare but potentially fatal condition called torsades de pointes. Many widely used medications, particularly some used to treat heart conditions, infections, and mental health disorders, are known to carry this risk. Current clinical guidelines advise caution when prescribing more than one of these QT-prolonging medications at the same time, especially in patients with underlying heart problems.¹ However, there is limited real-world data quantifying the risk of combining these medications.

We evaluated the rate of serious heart rhythm and cardiac complications among 3,283,463 patients who initiated a new QT-prolonging drug between 2021 and 2024 and had at least one year of follow-up after starting the medication. Patients were categorized based on whether they were prescribed one or two QT-prolonging medications, which were classified as high or low-to-moderate risk.²

Ventricular tachycardia and myocardial infarction were the most common adverse outcomes observed, as shown in Figure 1. Rates were similar for patients prescribed either one or two high-risk medications.

Cardiac arrest, while uncommon, was more frequent among those on one high-risk QT-prolonging drug, occurring in 10.3 per 10,000 patients. Rates of torsades de pointes were very low across all groups regardless of the number of medications prescribed.

Figure 1. The rate of cardiac events by the combinations of QT-prolonging drugs.

Farzam K, Tivakaran VS. QT prolonging drugs. In: StatPearls. StatPearls Publishing; 2025.
Berul, C. I. (2024, November 21). Acquired long QT syndrome: Definitions, pathophysiology, and causes. UpToDate. https://www.uptodate.com/contents/acquired-long-qt-syndrome-definitions-pathophysiology-and-causes. Accessed March 20, 2025.

Two Years After Stopping GLP-1s, Most Patients Sustain at Least Some Weight Loss

Kersten Bartelt, RN; Joe Deckert, PhD; Blaine Franklin, PT, DPT; Eric Barkley — Tue, 09 Sep 2025 11:00:00 +0000

GLP-1 medications, including semaglutide, liraglutide, and tirzepatide, are increasingly used for weight loss. While effective during treatment, their long-term benefit hinges on whether weight loss persists after discontinuation. We previously showed promising one-year outcomes,¹ but questions remain about longer-term trends.

To understand the durability and stability of weight outcomes after stopping GLP-1s, we studied 188,722 patients who stopped using a GLP-1 medication after being on it for at least 90 days and who lost at least 5 pounds while on it. Patients were grouped based on whether they regained weight, maintained their weight loss, or experienced further weight reduction.

Two years after stopping GLP-1 treatment, most patients had sustained at least some of their weight loss. For semaglutide, 25.9% doubled their weight loss, 15.6% had some additional weight loss, and 14.6% maintained their initial loss, totaling 56.1% in the sustained or improved categories.

Figure 1. The proportion of patients by amount of weight regained or lost after stopping semaglutide.

For liraglutide, 21.8% of patients doubled their weight loss, 15.9% lost some additional weight, and 14.2% maintained their loss, with 51.9% in total maintaining or losing more weight.

Figure 2. The proportion of patients by amount of weight regained or lost after stopping liraglutide.

Among patients who stopped taking tirzepatide, 31.0% doubled their weight loss after two years, 15.2% lost some additional weight, and 9.0% maintained their initial loss, with 55.2% in total maintaining or losing more weight.

Figure 3. The proportion of patients by amount of weight regained or lost after stopping tirzepatide.

Across all groups, proportions in each weight category stabilized after 12 months, with small variations between months 12 and 24, suggesting long-term weight trajectories are largely set by one-year post-cessation. Stratification by patient sex and age showed similar distributions.

These data come from Cosmos, a dataset created in collaboration with a community of Epic health systems representing more than 300 million patient records from 1,700 hospitals and more than 40,000 clinics from all 50 U.S. states, Lebanon, and Saudi Arabia. This study was completed by two teams that worked independently, each composed of a clinician and research scientists. The two teams came to similar conclusions. Graphics by Brian Olson.

Bartelt K, Mast C, Deckert J, Gracianette M, Joyce B. Many Patients Maintain Weight Loss a Year After Stopping Semaglutide and Liraglutide. Epic Research. https://epicresearch.org/articles/many-patients-maintain-weight-loss-a-year-after-stopping-semaglutide-and-liraglutide. Accessed on August 4, 2025.

Sepsis in Infants: Less Common, More Deadly

Thu, 04 Sep 2025 11:00:00 +0000

Neonatal sepsis is a leading cause of morbidity and mortality in the first weeks of life and is a critical marker of neonatal care quality. Neonatal sepsis can come from pathogen exposure in utero, during delivery, or in the hospital or community. Studies have shown disparities in neonatal sepsis by race and ethnicity, but less is known about how that has evolved over recent years.¹

To understand trends in neonatal sepsis and subsequent mortality in the first year of life, we studied 7,710,439 babies born between 2015 and 2023. Neonatal sepsis rates declined steadily from 2015 to 2023, as seen in Figure 1a. Black infants had the highest sepsis rate at the beginning of the study period (2.4%) and experienced a sharper decline than infants of other races, reaching 1.3% in 2023. White, Hispanic, and infants of another race followed similar downward trends, though had lower rates than Black patients throughout.

In contrast to diagnosis rates, all-cause mortality by the first birthday among infants diagnosed with neonatal sepsis rose substantially over the study period. Black infants experienced an increase from 5.5% in 2015 to 8.9% in 2023. White infants had a similar trend, rising from 3.9% to 7.3%. Despite this, the proportion of all babies who received both a sepsis diagnosis and then died before age one remained the same among Hispanic infants and White infants and decreased among Black infants and those of another race or ethnicity. Of note, neonatal sepsis followed by all-cause death in the first year of life remains uncommon, occurring in fewer than 0.15% of infants.

Neonatal sepsis trends: proportion of newborns diagnosed with sepsis, proportion of sepsis-diagnosed infants who died by first birthday, and proportion of all babies who were both diagnosed with sepsis and died by their first birthday.

These data come from Cosmos, a dataset created in collaboration with a community of Epic health systems representing more than 300 million patient records from 1,700 hospitals and more than 40,000 clinics from all 50 U.S. states, Lebanon, and Saudi Arabia. This study was completed by two teams that worked independently, each composed of a clinician and research scientists. The two teams came to similar conclusions. Graphics by Brian Olson.

Nandakumar V, Hazzaa S, Saker F, Aly H, Mohamed MA. Racial and Ethnic Disparities in Neonatal Sepsis. Pediatr Infect Dis J. 2025;44(3):e85-e89. doi:10.1097/INF.0000000000004572

Post-Discharge Opioid Prescriptions for New Mothers Down 43% Since 2017

Dave Little, MD; Emily Higgs; Matthew Gracianette, MD; Neil Sandberg — Tue, 26 Aug 2025 17:00:00 +0000

Effective pain management during childbirth is essential for maternal comfort and recovery, yet the use of opioids for this purpose has raised clinical concerns regarding dependency and safety.¹ The American College of Obstetricians and Gynecologists encourages cautious opioid prescribing in obstetric care to reduce misuse and neonatal complications.²

To understand pain medication patterns around the time of delivery, we studied more than 7 million deliveries that occurred between 2017 and 2024. We analyzed how discharge prescriptions for opioids have changed over time. We found that there has been a substantial decline during the studied period in the proportion of women who received an opioid prescription upon discharge, as seen in Figure 1. In 2017, more than half of all patients were prescribed an opioid upon discharge. By 2024, that figure had dropped to roughly a quarter of deliveries, representing a 43% decrease.

Figure 1. The annual rate of opioids being prescribed for mothers upon discharge after delivery by year.

We also analyzed how the use of pain medications varies throughout the delivery admission. We categorized the stages as pre-labor (in hospital), labor and delivery, and post-delivery (in hospital). Opioid medications included those administered orally, intravenously, intramuscularly, subcutaneously, sublingually, transdermally, or epidurally. Data on patient-controlled analgesics (PCAs), which are used during labor and delivery in some situations,¹ were not available for analysis.

Opioid use varied by whether the mother had an opioid prescription in the 30 days prior. 76% of women with a recent opioid prescription received an opioid during labor compared to 65% of those without such a history, as seen in Figure 2. This trend was similar for before and after labor as well.

Figure 2. The rate of opioids being administered by delivery stage by whether the patient had a prescription for an opioid in the 30 days before the admission.

These data come from Cosmos, a dataset created in collaboration with a community of Epic health systems representing more than 300 million patient records from 1,700 hospitals and more than 40,000 clinics from all 50 U.S. states, Lebanon, and Saudi Arabia. This study was completed by two teams that worked independently, each composed of a clinician and research scientists. The two teams came to similar conclusions. Graphics by Brian Olson.

Reale S. Pharmacologic management of pain during labor and delivery. UpToDate. February 26, 2024. https://www.uptodate.com/contents/pharmacologic-management-of-pain-during-labor-and-delivery. Accessed May 5, 2025.
Committee Opinion No. 711: Opioid Use and Opioid Use Disorder in Pregnancy. Obstet Gynecol. 2017;130(2):e81-e94. doi:10.1097/AOG.0000000000002235

RSV Vaccine Effectiveness Declines After 12 Months in Older Adults

Tue, 19 Aug 2025 11:00:00 +0000

Respiratory syncytial virus (RSV) is a common and potentially severe respiratory pathogen in older adults. We previously found the vaccine to be effective at preventing infections, ED visits, and hospitalizations in the season it was administered.¹ However, limited data are available on longer-term protection, particularly beyond one year after vaccination.

To further understand RSV vaccine effectiveness in older adults, we studied 1,204,649 patients aged 60 and older who had an RSV lab test during the 2024/2025 RSV season. Patients were matched based on the month of their RSV lab test, age, and factors that indicate increased risk of complications from an RSV infection. Patients were grouped based on the time elapsed between RSV vaccination and RSV lab testing.

During the 2024/2025 RSV season, patients vaccinated two weeks to six months prior had a positive RSV infection rate of 1.1%, while those vaccinated more than a year prior had rates more than twice as high and those who have never received the RSV vaccine had rates nearly four times as high. Similar patterns were observed for ED visits and hospitalizations, as seen in Figure 1.

Figure 1. The rate of RSV infections, RSV-related ED visits, and RSV-related hospitalizations in the 2024/2025 RSV season by time since RSV vaccination.

Vaccine effectiveness (VE) declined steadily over time. For RSV infection, VE was 71% at 4 months, decreasing to 40% by month 19. Effectiveness against RSV-related ED visits followed a similar pattern, dropping from 71% in month 4 to 46% by month 19. Hospitalization protection declined from 73% to 44% over the same period.

Figure 2. Vaccine effectiveness against RSV infection, RSV-related ED visit, or an RSV-related hospitalization by months since the patient received their RSV vaccine.

These findings suggest that while protection against severe outcomes persists into the next season, it is significantly reduced compared to the initial vaccination season.

These data come from Cosmos, a dataset created in collaboration with a community of Epic health systems representing more than 300 million patient records from 1,700 hospitals and more than 40,000 clinics from all 50 U.S. states, Lebanon, and Saudi Arabia. This study was completed by two teams that worked independently, each composed of a clinician and research scientists. The two teams came to similar conclusions. Graphics by Brian Olson.

Bartelt K, Deckert J, Gracianette M, Barkley E. RSV Vaccine Can Prevent More Than 70% of RSV Infections, ED Visits, and Admissions Among Older Adults. Epic Research. https://epicresearch.org/articles/rsv-vaccine-can-prevent-more-than-70-of-rsv-infections-ed-visits-and-admissions-among-older-adults. Accessed on June 30, 2025.

SSRI Antidepressants Associated with Lower Risk of Blood Cancers

Thu, 14 Aug 2025 11:00:00 +0000

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for depression and anxiety disorders. Previous studies suggest SSRIs may enhance T-cell activity, potentially improving immune surveillance against cancers,¹ however, other studies have found mixed associations, including potential increased risk of some cancer types.^2,3

To further explore the relationship between SSRI use and cancer diagnoses across various cancer types, we studied 627,964 adult patients, including patients with no history of SSRI use and those with three to eight years of SSRI use. Patients were matched 1:1 based on legal sex and age, and we accounted for other factors such as demographics, smoking history, BMI, use of other antidepressants, and comorbidities in our analysis.

We found that SSRI use did not significantly change the overall risk of developing cancer, as seen in Figure 1. Similarly, no significant associations were observed for lung, breast, colorectal, prostate, pancreatic, or melanoma cancers. However, patients on SSRIs had an 18% lower risk of hematologic cancers compared to those not on an SSRI. This aligns with prior animal studies suggesting SSRIs may enhance immune surveillance by modulating T-cell activity.¹

Figure 1. Cancer risk for patients with three to eight years of SSRI use compared to those with no SSRI use.

These data come from Cosmos, a dataset created in collaboration with a community of Epic health systems representing more than 300 million patient records from 1,700 hospitals and more than 40,000 clinics from all 50 U.S. states, Lebanon, and Saudi Arabia. This study was completed by two teams that worked independently, each composed of a clinician and research scientists. The two teams came to similar conclusions. Graphics by Brian Olson.

Li B, Elsten-Brown J, Li M, et al. Serotonin transporter inhibits antitumor immunity through regulating the intratumoral serotonin axis. Cell. Published online 2025. doi:10.1016/j.cell.2025.04.032
Boursi B, Lurie I, Mamtani R, Haynes K, Yang YX. Anti-depressant therapy and cancer risk: a nested case-control study. Eur Neuropsychopharmacol. 2015;25(8):1147-1157. doi:10.1016/j.euroneuro.2015.04.010
Ashbury JE, Lévesque LE, Beck PA, Aronson KJ. A population-based case-control study of Selective Serotonin Reuptake Inhibitors (SSRIs) and breast cancer: the impact of duration of use, cumulative dose and latency. BMC Med. 2010;8:90. Published 2010 Dec 22. doi:10.1186/1741-7015-8-90