Trends and Disparities in the Utilization of Low-Dose Aspirin for Pregnancies with Moderate or High-Risk of Preeclampsia: A National Study

Abstract

Background and Objective:

Preeclampsia (PE), a hypertensive disorder of pregnancy, is a leading cause of maternal morbidity and mortality globally. Low-dose aspirin (LDA) is recommended for PE prevention in high- and moderate-risk women. Despite clinical trial evidence, adherence to LDA guidelines and disparities in usage remain underexplored in real-world settings. This study assesses LDA initiation rates among high- and moderate-risk pregnant women, examining disparities by race, geography, and hospital characteristics.

Methods:

We conducted a retrospective cross-sectional analysis of the U.S. Nationwide Inpatient Sample (2016–2021). Pregnancy-associated hospitalizations were identified using International classification disease-10 (ICD-10) codes, and PE risk factors were classified as high or moderate based on the United States Preventive Services Task Force and American College of Obstetricians and Gynecologists criteria. Statistical analyses included descriptive statistics, bivariate analyses, and joinpoint regression to evaluate temporal trends and disparities in LDA use.

Results:

Among 23,163,717 hospitalizations, 8.2% were high-risk and 13.3% moderate-risk for PE. LDA use increased across all groups from 2016 to 2021, but remained lower among moderate-risk women. Racial disparities were evident, with Black and Hispanic women in the moderate-risk group demonstrating lower LDA utilization compared with White women. Geographic disparities revealed the Midwest and Northeast leading in LDA use, whereas rural hospitals consistently reported the lowest rates. Urban teaching hospitals had higher LDA use compared with rural and nonteaching hospitals.

Conclusion:

LDA use for PE prevention has improved, but significant disparities persist by race, region, and hospital type. Provider education, capacity-building in underserved areas, and enhanced documentation are essential to ensure equitable access to this evidence-based intervention.

Keywords

high-risk of preeclampsia moderate-risk of preeclampsia low-dose aspirin maternal health equity evidence-based intervention

Introduction

Preeclampsia (PE), a hypertensive disorder of pregnancy, is a multisystem inflammatory syndrome and a leading cause of maternal morbidity and mortality globally. It typically presents after 20 weeks of gestation in women with previously normal blood pressure, defined by persistent hypertension (systolic/diastolic blood pressure ≥140/90 mm Hg) and proteinuria (≥300 mg/24 hours).¹ In the United States, PE affects about 4% of pregnancies, contributing to 6% of all preterm births and 19% of medically indicated preterm deliveries.²

Current national and international guidelines recommend that high-risk women receive low-dose aspirin (LDA) for the prevention of PE, including the World Health Organization,³ American College of Obstetricians and Gynecologists (ACOG),⁴ and the National Institute for Health and Care Excellence.³ Based on a systematic review and meta-analysis finding that LDA was associated with absolute risk reductions of 2–5%, The United States Preventive Services Task Force (USPSTF) updated their recommendations regarding the use of LDA for PE prevention for pregnant women at increased risk for PE in 2021 strengthened by new evidence from additional trials demonstrating reduced risks of perinatal mortality with aspirin use.¹ The current recommendation is for initiation of LDA 81 mg/day at >12 weeks’ gestation in asymptomatic pregnant persons who at high risk for PE and have no prior adverse events with LDA and the consideration of initiation for those with multiple moderate-risk factors.⁴ Similarly, ACOG’s guidelines for LDA extended eligibility to a large proportion of pregnant women in the United States (U.S.) in 2018.⁴ Since the publication of these recommendations, multiple meta-analyses have suggested an observable and significant impact of initiation of LDA for the prevention of PE and accompanying adverse maternal and neonatal outcomes.^5–9

While the benefits of LDA for the prevention of PE have been well established in clinical trials and meta-analyses, little is known about LDA protocol initiation per existing guidelines.¹⁰ Physician adherence to guidelines and variations in real-world populations cannot be assessed in the intentionally highly selective and tightly regulated environment necessary for randomized controlled trials. Additionally, adherence to treatment guidelines for LDA supplementation for the prevention of PE in high- and moderate-risk populations and the determinants of LDA initiation have not been well-studied using nationally representative datasets.¹¹ This study provides a descriptive analysis of national trends in LDA use during pregnancy, aiming to evaluate initiation rates among women at high and moderate risk for PE and to identify potential disparities by race, geographic region, and hospital characteristics, including urbanicity and teaching status.

Methods

We conducted a retrospective cross-sectional analysis of the U.S. Nationwide Inpatient Sample (NIS) of inpatient hospitalization within the U.S. from 2016 to 2021. All pregnancy-associated hospitalizations among women aged 13 to 49 during the study period were included in the analysis. The study was deemed exempt by the Institutional Review Board. We utilized the ICD-10-CM-based published algorithm developed by Adman et al. 2022 to identify pregnancy-associated hospitalizations.¹² For each pregnancy-related hospitalization, we scanned all diagnosis and procedure fields in the dataset to identify ICD-10 codes representing LDA utilization, as well as other relevant pregnancy and nonpregnancy-related clinical variables and behavioral variables such as tobacco and alcohol use. We translated the USPSTF moderate- and high-risk criteria into variables and ICD-10 codes for use in administrative datasets.¹ The NIS dataset contains all six high-risk factors for which LDA is definitively recommended: history of PE, chronic hypertension, diabetes mellitus, antiphospholipid syndrome, systemic lupus erythematosus, multifetal gestation, and renal disease. High-risk conditions (e.g., chronic hypertension, diabetes) were mapped to specific ICD-10 codes, whereas moderate-risk factors (e.g., obesity, low socioeconomic status) were aligned with dataset variables such as Body mass index or median household income for patients’ Zip code (ZIP) code. Among individuals without a documented high-risk factor, we assessed moderate-risk factors, including obesity, African American maternal race, maternal age 35 years or older, more than a 10-year interval since last birth, low socioeconomic status (defined using the interquartile range), and in vitro fertilization. Due to the nature of the data, moderate risk factors such as nulliparity, personal history of low birth weight, being small for gestational age, and family history of PE were not used in the assessment of moderate risk of PE. The primary outcomes were the frequencies of each risk factor alone and in combinations that would lead to recommendations for LDA. For estimation purposes, missing data on a given risk factor were assumed to be not present. The full list of all ICD-10 diagnoses and procedure codes used in the current study is listed in Supplementary Table S1.

In addition to clinical and behavioral factors, we used demographic variables to describe the study population. Self-reported race and ethnicity were first grouped by Hispanic or non-Hispanic. The non-Hispanic group was further classified based on race, including White, African American or Black, and other (i.e., Asian or Pacific Islander, Native American, multiple races, and others). Participants’ ages were divided into five categories (13–24, 25–29, 30–34, 35–39, and 40–49 years). The insurance status (primary payer for the hospitalization) was grouped into three categories: government (i.e., Medicare/Medicaid), private, and other (e.g., self-pay and charity). ZIP-code level estimates of median household income based on the patient’s residence were grouped into quartiles to serve as a proxy for community-level socioeconomic status. Hospital characteristics and the geographic distribution of participants, based on the census regions and divisions of the United States, were used to further describe the study population and outcomes.

Statistical analysis

Descriptive statistics including frequencies and percentages were used to describe the distribution of patient and hospital characteristics by PE risk status stratified by race group. The prevalence of LDA use per 1,000 pregnancy-associated hospitalizations among pregnant women at moderate- or high-risk of PE was calculated, and the rate was stratified by maternal race. We assessed the distribution of demographic, behavioral, and clinical characteristics of pregnancy-associated hospitalizations by PE risk status stratified by race group.

Using joinpoint regression, we estimated temporal trends in LDA use from 2016 to 2021 by maternal race, geographic region, and urbanicity/teaching status stratified by PE-risk. This method first assumes the observed annual prevalence of LDA use follows a straight line, reflecting a model with no changes in the trend in the rate and having zero joinpoints. Then, joinpoints are iteratively added to the model, with each joinpoint reflecting a change in the rate of LDA use, and a Monte Carlo permutation test is used to assess whether the added joinpoint improves model fit. Once a best-fitting model is selected, each joinpoint is a statistically significant change in LDA use trend and is characterized using a metric called annual percent change.

All statistical analyses were performed with Statistical Analysis System (SAS), version 9.4 (SAS Institute, Inc., Cary, NC) and the Joinpoint Regression Program, version 4.8.0.1. All statistical tests were two-sided with a 5% type-I error rate. Counts based on 10 or fewer events are suppressed in tables and figures in accordance with the data suppression rules established by the Healthcare Cost and Utilization Project.¹³

Results

The analysis included a total of 23,163,717 pregnancy-associated hospitalizations. Participants were categorized based on their risk of PE: low risk (78.5%, n = 18,204,214), moderate risk (13.3%, n = 3,072,094), and high risk (8.2%, n = 1,887,409). The majority of pregnancy-associated hospitalizations were White (43.8%, n = 10,146,933), followed by Hispanic (16.8%, n = 3,901,148), Black (5.1%, n = 1,172,495), and other racial groups (9.4%, n = 2,178,349). In the high-risk group, Black participants were disproportionately represented (24.3%) compared with their total population proportion. Conversely, White individuals comprised a lower percentage in the high-risk group (46.3%), considering their total population proportion. A similar pattern was observed for the moderate-risk group, where Black individuals were highly represented (63.1%).

Table 1 provides results from a bivariate analysis of demographic, behavioral, and hospital characteristics of the study cohort and its association with PE across different PE-risk and racial categories. Age distribution showed a significant association with PE risk. Compared with the reference group (13–24 years), women aged 25–29 had elevated odds of being at high risk for PE across all racial groups (ORs ranging from 1.3 to 1.6). The highest odds were observed in the 40–49 age group (OR = 5.8; 95% CI: 5.4, 6.3 for White participants in the low-PE-risk group and OR = 10.2; 95% CI: 9.2, 11.4 for Black participants in the low-PE-risk group). Behavioral risk factors showed inconsistent associations with PE across racial and risk groups. Among White women, these factors were generally associated with reduced odds of PE. For example, tobacco use was linked to lower odds in both the no-risk (OR = 0.81; 95% CI: 0.77–0.86) and high-risk (OR = 0.77; 95% CI: 0.68–0.88) groups, whereas cannabis use showed a similar pattern (e.g., OR = 0.76; 95% CI: 0.66–0.88 in the high-risk group). In contrast, among Hispanic women, tobacco use in the no-risk group (OR = 1.5; 95% CI: 1.2–1.8) and cannabis use in the moderate-risk group (OR = 1.9; 95% CI: 1.3–2.9) were associated with significantly increased odds of PE. Associations for other racial groups and risk categories were largely nonsignificant. White and Hispanic women with low household incomes had a lower risk of PE irrespective of their PE-risk category. Hospital bed size and region also varied by PE risk. Small and medium-sized hospitals had slightly lower odds of treating PE cases compared with large hospitals, whereas urban teaching hospitals were more likely to treat patients with PE across all risk categories and racial groups, with odds ranging from 1.3 to 2.0.

Table 1.

The Distribution of Demographic, Behavioral, and Hospital Characteristics of Participants by the Risk of Developing Preeclampsia Stratified by PE-Risk Group and Maternal Race (NIS 2016–2021)

Total N = 23,163,717	OR (95% CI)
	Low risk of PE (n = 18,204,214)				High risk of PE (n = 1,887,409)				Moderate risk of PE (n = 3,072,094)
	White (n = 10,146,933)	Black (n = 1,172,495)	Hispanic (n = 3,901,148)	Other (n = 2,178,349)	White (n = 873,500)	Black (n = 458,640)	Hispanic (n = 320,995)	Other (n = 166,715)	White (n = 573,564)	Black (n = 1,938,229)	Hispanic (n = 396,805)	Other (n = 119,875)
Age Group
13–24	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.
25–29	1.7† (1.6,1.7)	1.6† (1.4,1.8)	1.6† (1.5,1.7)	1.4† (1.2,1.6)	1.3† (1.2,1.4)	1.2† (1.1,1.3)	1.2† (1.1,1.3)	1.2 (1.0,1.5)	1.4† (1.1,1.6)	1.5† (1.4,1.7)	1.5† (1.2,1.9)	1.5 (0.88,2.5)
30–34	2.1† (2.0,2.3)	1.9† (1.7,2.1)	2.0† (1.9,2.2)	1.9† (1.7,2.2)	1.5† (1.4,1.6)	1.5† (1.4,1.6)	1.4† (1.3,1.5)	1.5† (1.2,1.8)	1.7† (1.4,2.0)	2.1† (1.9,2.3)	2.0† (1.7,3.0)	1.4† (0.79,2.3)
35–39	3.4† (3.1, 3.6)	5.2† (4.7,5.7)	3.4† (3.0,3.7)	3.8† (3.3,4.4)	1.7† (1.6,1.8)	1.6† (1.5,1.7)	1.6† (1.4,1.7)	1.7† (1.5,2.1)	1.6† (1.4,1.8)	2.7† (2.5,3.0)	1.6† (1.3,2.0)	1.4 (0.95,2.2)
40–49	5.8† (5.4, 6.3)	10.2† (9.2,11.4)	5.1† (4.5,5.8)	7.0† (5.9,8.2)	1.8† (1.6,1.9)	1.9† (1.7,2.1)	1.8† (1.6,2.0)	1.8† (1.5,2.2)	2.1† (1.8,2.5)	4.0† (3.6,4.6)	2.3† (1.8,2.9)	2.4† (1.5,3.7)
Alcohol use^a	0.97 (0.74, 1.3)	1.3 (0.56,2.8)	1.0 (0.49, 2.1)	1.1 (0.50,2.5)	0.57† (0.40,0.82)	0.62† (0.41,0.94)	0.97 (0.50,1.9)	0.42 (0.16,1.1)	1.1 (0.61,2.1)	0.94 (0.56,1.6)	1.4 (0.45,4.3)	0.70 (0.10,5.1)
Tobacco use^a	0.81† (0.77, 0.86)	1.2 (0.95, 1.4)	1.5† (1.2, 1.8)	0.99 (0.77,1.3)	0.77† (0.72,0.83)	1.0 (0.93,1.1)	0.98 (0.81,1.2)	1.1 (0.89,1.4)	0.82† (0.74,0.92)	1.1 (0.97,1.2)	1.3 (0.93,1.8)	0.88 (0.53,1.4)
Cannabis use^a	0.82† (0.73, 0.91)	1.2 (0.93, 1.5)	1.1 (0.76,1.5)	0.80 (0.52,1.2)	0.76† (0.66,0.88)	0.99 (0.88,1.1)	0.98 (0.74,1.3)	1.1 (0.80,1.6)	1.1 (0.89,1.4)	1.1 (0.96,1.3)	1.9 (1.3,2.9)	1.2 (0.56,2.5)
Substance use^a	0.73† (0.65, 0.81)	1.2 (0.88, 1.5)	1.0 (0.74, 1.4)	0.71 (0.47,1.1)	0.65† (0.57,0.74)	0.96 (0.84,1.1)	0.75 (0.57,1.0)	0.83 (0.59,1.2)	0.85 (0.67,1.1)	1.1 (0.97,1.3)	1.2 (0.78,2.0)	1.6 (0.84,2.9)
Opioid use^a	0.67† (0.59, 0.77)	1.6 (1.0, 2.7)	0.89 (0.54, 1.5)	0.61 (0.30,1.2)	0.58 (0.49,0.69)	0.59† (0.43,0.82)	0.53† (0.30,0.92)	0.86 (0.49,1.5)	0.77 (0.58,1.0)	1.5† (1.1,2.0)	0.57 (0.18,1.8)	0.67 (0.17,2.7)
Household income
Low	0.55† (0.51, 0.59)	1.9† (1.7,2.1)	0.51† (0.46,0.57)	0.44† (0.37,0.51)	0.84† (0.78,0.90)	0.92 (0.83,1.0)	0.84† (0.74,0.94)	0.91 (0.80,1.0)	0.44† (0.39,0.50)	0.43† (0.38,0.49)	0.38† (0.30,0.48)	0.36† (0.38,0.47)
2nd Quartile	0.85† (0.80,0.91)	0.99 (0.86,1.1)	0.89† (0.80,0.98)	0.74† (0.66,0.84)	0.95 (0.89,1.0)	1.0 (0.90,1.1)	0.87† (0.77,0.98)	0.95 (0.84,1.1)	1.0 (0.90,1.2)	0.98 (0.86,1.1)	0.87 (0.66,1.2)	1.1 (0.78,1.6)
3rd Quartile	0.97 (0.92,1.1)	1.0 (0.91,1.2)	0.95 (0.87,1.0)	0.84† (0.76,0.93)	1.0 (0.95,1.1)	1.0 (0.90,1.1)	0.96 (0.86,1.1)	0.96 (0.86,1.1)	1.0 (0.89,1.4)	1.1 (0.95,1.2)	0.78 (0.59,1.0)	0.88 (0.63,1.3)
High Quartile	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.
Hospital Bed size
Small	0.85† (0.76,0.95)	0.70† (0.57,0.86)	0.91 (0.79,1.1)	0.91 (0.79,1.1)	0.85† (0.77,0.94)	0.78† (0.68,0.89)	0.92 (0.80,1.1)	0.84† (0.72,0.98)	0.94 (0.80,1.1)	0.81† (0.68,0.97)	0.90 (0.68,1.2)	0.84 (0.61,1.2)
Medium	0.90† (0.82,0.99)	0.68† (0.57,0.82)	0.65† (0.57,0.75)	0.84† (0.73,0.96)	0.86† (0.78,0.95)	0.75† (0.66,0.86)	0.69† (0.61,0.79)	0.75† (0.66,0.86)	0.95 (0.83,1.1)	0.80† (0.68,0.95)	0.63† (0.50,0.79)	0.84 (0.65,1.1)
Large	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.
Hospital region
Northeast	1.3† (1.1,1.5)	1.5† (1.1,1.9)	1.6† (1.4,1.9)	1.1 (0.89,1.3)	1.2† (1.1,1.4)	1.1 (0.90,1.3)	1.2 (1.0,1.4)	0.69† (0.58,0.82)	1.3† (1.1,1.6)	1.4† (1.1,1.7)	1.7† (1.3,2.3)	0.82 (0.58,1.1)
Midwest/North Central	1.3† (1.1,1.4)	1.6† (1.2,2.0)	2.0† (1.6,2.4)	1.3† (1.1,1.6)	1.3† (1.1,1.4)	1.6† (1.3,1.8)	1.6† (1.3,1.9)	1.2 (1.0,1.4)	1.4† (1.2,1.6)	1.3† (1.1,1.6)	2.5† (1.9,3.2)	1.1 (0.79,1.5)
South	1.1 (0.96,1.2)	1.3 (1.1,1.6)	0.99 (0.87,1.1)	1.3 (1.1,1.5)	1.1 (0.98,1.2)	1.1 (0.98,1.3)	1.1 (0.94,1.2)	1.0 (0.90,1.2)	0.95 (0.82,1.1)	1.0 (0.87,1.2)	1.0 (0.81,1.2)	1.0 (0.77,1.3)
West	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.
Hospital Location/Teaching
Rural	0.71† (0.63,0.80)	0.56† (0.3,0.96)	0.83 (0.65,1.1)	0.57† (0.42,0.76)	0.83† (0.73,0.95)	0.74† (0.59,0.91)	0.91 (0.68,1.2)	0.90 (0.67,1.2)	0.76† (0.63,0.92)	0.44† (0.35,0.56)	1.1 (0.66,1.7)	0.56† (0.35,0.92)
Urban teaching	1.5† (1.3,1.6)	1.7† (1.4,2.0)	1.7† (1.4,1.9)	1.3† (1.1,1.5)	1.5† (1.4,1.6)	1.6† (1.4,1.9)	1.7† (1.4,2.0)	1.3† (1.1,1.5)	1.4† (1.2,1.6)	1.5† (1.2,1.7)	2.0† (1.5,2.6)	1.1 (0.80,1.4)
Urban nonteaching	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.

†Bolded values: Estimates that are statistically significant at p ≤ 0.05 are bolded.

Reference group is absence of the behavior/condition.

Table 2 provides results from a bivariate analysis investigating the association of selected clinical comorbidities and indicators of severe maternal morbidity with PE across various PE-risk and racial categories. The bivariate analysis revealed significant associations between PE risk and certain clinical comorbidities, with notable variations across racial groups and PE risk categories. Statistically significant results were observed for anxiety, depression, asthma, and obesity, which consistently elevated PE risk across racial groups and risk categories, particularly among Hispanic women in the high or moderate PE risk groups. Obstructive sleep apnea and ischemic stroke were significantly associated with markedly higher odds of PE, especially among Black and Hispanic women. Conversely, conditions such as diabetes and hypertension showed nonsignificant or weak associations with PE across most groups. Notably, several conditions, including eclampsia and sepsis, demonstrated nonsignificant associations in many groups, suggesting that their contributions to PE risk may be limited or context dependent.

Table 2.

The Distribution of Obstetric and Clinical Morbidities by the Risk of Developing Preeclampsia Stratified by PE-Risk Group and Maternal Race (NIS 2016–2021)

Clinical or obstetric morbidities	OR (95% CI
	Low risk of PE (n = 18,204,214)				High risk of PE (n = 1,887,409)				Moderate risk of PE (n = 3,072,094)
	White (n = 10,146,933)	Black (n = 1,172,495)	Hispanic (n = 3,901,148)	Other (n = 2,178,349)	White (n = 873,500)	Black (n = 458,640)	Hispanic (n = 320,995)	Other (n = 166,715)	White (n = 573,564)	Black (n = 1,938,229)	Hispanic (n = 396,805)	Other (n = 119,875)
Bipolar disorder^a	1.4† (1.2,1.6)	1.4 (1.0,2.0)	2.1† (1.6,2.8)	1.4 (0.88,2.2)	1.1 (0.94,1.2)	0.94 (0.79,1.1)	1.0 (0.74,1.3)	0.91 (0.56,1.5)	1.1 (0.86,1.4)	1.4† (1.2,1.7)	2.0† (1.2,3.4)	1.2 (0.36,3.8)
Anxiety^a	2.2† (2.2,2.3)	2.4† (2.1,2.9)	2.7† (2.4,3.0)	2.6† (2.2,3.0)	1.6† (1.6,1.7)	1.4† (1.3,1.6)	1.6† (1.4,1.8)	1.8† (1.5,2.1)	1.8† (1.7,2.0)	2.4† (2.0,3.0)	2.4† (2.0,3.0)	2.4† (1.7,3.4)
Depression^a	2.1† (2.0,2.2)	2.6† (2.2,3.1)	2.6† (2.3,3.0)	2.2† (1.8,2.6)	1.6† (1.5,1.7)	1.4† (1.3,1.6)	1.7† (1.5,1.9)	1.5† (1.3,1.8)	1.8† (1.6,2.0)	2.2† (2.0,2.5)	2.3† (1.8,2.8)	2.1† (1.4,3.1)
COPD flag^a	1.8† (1.8,1.9)	2.0† (1.8,2.3)	2.4† (2.1,2.6)	1.9† (1.7,2.2)	1.3† (1.2,1.4)	1.4† (1.3,1.4)	1.4† (1.3,1.6)	1.4† (1.2,1.7)	1.5† (1.4,1.7)	1.8† (1.7,2.0)	2.0† (1.6,2.4)	1.9† (1.4,2.5)
Asthma^a	1.8† (1.8,1.9)	2.0† (1.8,2.3)	2.3† (2.1,2.6)	2.0† (1.7,2.2)	1.3† (1.3,1.4)	1.4† (1.3,1.5)	1.4† (1.3,1.6)	1.4† (1.2,1.7)	1.5† (1.4,1.7)	1.8† (1.7,2.0)	2.0† (1.6,2.4)	1.9† (1.4,2.5)
OSA^a	4.9† (3.9,6.1)	5.2† (2.3,11.7)	10.7† (7.3,15.7)	7.9† (4.4,14.1)	1.7† (1.4,2.0)	1.9† (1.6,2.2)	1.9† (1.4,2.6)	2.9† (2.0,4.3)	2.7† (2.0,3.7)	5.5† (4.3,7.0)	6.6† (4.3,10.1)	1.5 (0.36,6.0)
DM flag^a	1.0 (0.69,1.5)	1.0 (0.61,1.6)	1.0 (0.52,1.9)	1.0 (0.56,1.8)	1.1 (1.0,1.1)	1.1 (1.0,1.2)	1.0 (0.94,1.1)	1.1 (1.0,1.3)	1.0 (0.87,1.1)	1.0 (0.76,1.3)	1.0 (0.78,1.3)	1.0 (0.79,1.3)
HPN^a	1.0 (0.70,1.4)	1.0 (0.62,1.6)	1.0 (0.53,1.9)	1.0 (0.57,1.8)	1.6† (1.5,1.7)	1.8† (1.7,1.9)	1.9† (1.7,2.0)	2.1† (1.9,2.3)	1.0 (0.88,1.1)	1.0 (0.77,1.3)	1.0 (0.79,1.3)	1.0 (0.80,1.3)
Hemorrhage stroke^a	1.2 (0.40,3.9)	***	3.4 (0.83,13.6)	***	0.29 (0.07,1.2)	0.35 (0.11,1.1)	0.26 (0.04,1.9)	0.69 (0.17,2.9)	***	1.9 (0.62,6.1)	***	***
Isch stroke^a	7.6† (4.8,12.0)	11.7† (2.7,50.7)	9.0† (3.3,24.5)	14.9† (5.3,41.9)	1.4 (0.83,2.5)	1.8† (1.1,3.0)	0.82 (0.25,2.6)	***	3.7 (0.85,16.0)	6.6† (2.9,15.5)	18.8† (3.8,93.7)	24.3† (2.2,269.8)
CAD flag^a	8.1† (6.1,10.8)	13.2† (6.4,27.1)	14.1† (8.3,23.7)	4.4† (1.4,14.0)	3.0† (2.4,3.8)	2.7† (2.2,3.4)	3.4† (2.3,5.2)	3.2† (1.7,6.0)	7.0† (4.1,12.0)	9.0† (6.0,13.5)	28.9† (15.1,55.2)	40.5† (14.3,114.2)
HF flag^a	4.7† (3.7,6.0)	4.6† (2.5,8.7)	5.5† (3.0,9.9)	5.3† (2.7,10.2)	1.3† (1.1,1.5)	1.5† (1.3,1.7)	1.5† (1.1,2.0)	1.3 (0.92,2.0)	2.8† (1.7,4.7)	6.9† (5.3,8.9)	4.6† (1.9,11.5)	3.5 (0.82,14.7)
PVD flag^a	7.9† (5.8,10.7)	10.9† (4.8,24.9)	10.7† (5.0,22.9)	12.3† (5.1,29.4)	3.6† (2.6,4.9)	3.6† (2.8,4.7)	4.2† (2.5,7.1)	2.9† (1.3,6.6)	9.1† (4.8,17.3)	20.7† (14.3,30.0)	3.9 (0.53,29.8)	***
AMI^a	4.9† (2.7,9.0)	12.8† (3.9,42.5)	12.6† (5.5,29.1)	6.7† (1.6,27.5)	1.3 (0.76,2.3)	1.7† (1.1,2.6)	1.5 (0.57,3.7)	4.0† (1.6,9.9)	***	11.8† (6.7,21.0)	8.7† (1.9,39.0)	24.4† (4.4,133.8)
Obesity^a	2.6† (2.5,2.7)	1.0 (0.82,1.2)	2.9† (2.6,3.1)	2.5† (2.2,2.8)	1.7† (1.6,1.8)	1.7† (1.6,1.8)	1.7† (1.6,1.8)	1.8† (1.6,2.0)	2.0† (1.8,2.2)	2.6† (2.4,2.8)	1.8† (1.6,2.0)	2.5† (2.0,3.0)
Aneurysm^a	5.7† (3.2,10.2)	***	***	***	2.4† (1.4,4.1)	1.7 (0.71,4.0)	3.0 (0.84,10.4)	***)	2.1 (0.28,15.9)	4.7† (1.1,19.9)	***	24.3† (2.2,268.7)
ARF^a	1.5 (0.88,2.6)	2.5 (0.79,7.7)	1.9 (0.71,5.1)	0.7 (0.1,4.8)	0.6† (0.5,0.8)	0.7† (0.7,0.9)	0.6† (0.5,0.8)	0.70 (0.52,1.0)	0.7 (0.2,2.9)	1.8 (0.9,3.5)	***	3.0 (0.4,23.0)
Amniotic embolism^a	***	10.1† (1.3,78.2)	5.6 (0.74,42.8)	***	0.84 (0.20,3.5)	***	***	***	***	***	***	***
ARDS^a	2.3† (1.9,2.8)	1.6 (0.79,3.2)	3.4† (2.4,4.9)	1.8 (1.0,3.1)	0.67† (0.5,0.8)	0.73† (0.6,0.9)	0.98 (0.7,1.3)	0.83 (0.5,1.3)	1.6† (1.1,2.5)	2.0† (1.4,2.7)	2.1† (1.2,3.9)	1.2 (0.3,4.8)
vFIB^a	1.6 (0.6,4.2)	3.2 (0.4,23.2)	2.6 (0.4,18.6)	***	0.50 (0.20,1.2)	0.55 (0.26,1.2)	0.63 (0.15,2.6)	***	***	2.1 (0.68,6.8)	2.8 (0.38,21.0)	***
Cardiac conversion^a	0.45 (0.07,3.1)	***	10.8† (3.9,29.8)	2.9 (0.40,21.3)	1.1 (0.55,2.3)	0.66 (0.29,1.5)	1.2 (0.38,4.1)	***	5.0† (1.5,16.8)	2.2 (0.70,7.0)	***	***
DIC^a	3.2† (2.7,3.8)	3.6† (2.3,5.9)	2.0† (1.3,3.1)	1.4 (0.8,2.5)	0.93 (0.73,1.2)	1.0 (0.75,1.3)	0.96 (0.64,1.4)	0.94 (0.56,1.6)	2.2 (1.4,3.5)	2.3 (1.7,3.2)	2.7 (1.4,5.4)	0.64 (0.09,4.6)
Eclampsia^a	1.3 (0.87,1.9)	0.88 (0.28,2.7)	1.8 (0.88,3.5)	0.78 (0.19,3.1)	0.54 (0.34,0.86)	0.79 (0.53,1.2)	0.97 (0.55,1.7)	0.58 (0.21,1.6)	0.65 (0.16,2.6)	0.89 (0.49,1.6)	1.1 (0.28,4.7)	2.1 (0.28,15.7)
HF arrest surgery^a	***	***	***	***	***	***	***	***	***	***	1.0 (0.1,7.5)	***
Puerperal CVD^a	6.3† (5.0,8.0)	6.2† (3.3,11.6)	7.1† (4.5,11.2)	8.4† (4.7,14.9)	1.9† (1.5,2.6)	1.2 (0.85,1.6)	1.3 (0.78,2.1)	1.0 (0.52,2.0)	2.9† (1.3,6.1)	5.1† (3.4,7.6)	8.1† (3.0,21.4)	6.1† (1.4,26.6)
Pulmonary edema AHF^a	3.7† (2.8,4.7)	2.7† (1.3,5.7)	2.8† (1.4,5.6)	2.4† (1.1,5.5)	0.95 (0.79,1.2)	1.2 (1.0,1.4)	0.96 (0.68,1.4)	1.2 (0.82,1.8)	1.9 (1.0,3.3)	4.2† (3.1,5.7)	0.66 (0.09,4.7)	1.2 (0.17,9.1)
Sepsis^a	1.0 (0.79,1.3)	0.5 (0.2,1.3)	1.1 (0.8,1.6)	1.3 (0.8,2.1)	0.4† (0.3,0.5)	0.5† (0.4,0.7)	0.4† (0.3,0.6)	0.7 (0.4,1.1)	0.7 (0.4,1.4)	1.2 (0.8,1.7)	1.3 (0.7,2.6)	***
Shock^a	2.0† (1.4,2.7)	1.8 (0.67,4.8)	2.2† (1.3,3.9)	1.1 (0.5,2.7)	0.5† (0.4,0.7)	0.6† (0.45,0.9)	0.4† (0.2,0.7)	0.6 (0.3,1.2)	0.7 (0.26,1.9)	2.2† (1.3,3.6)	2.4 (1.0,5.4)	1.0 (0.1,7.5)
Air/Thrombotic embolism^a	1.4 (1.0,2.1)	2.0 (0.8,4.9)	1.5 (0.6,4.1)	5.4† (2.6,10.9)	0.4† (0.2,0.7)	0.47† (0.3,0.8)	1.1 (0.6,2.2)	0.48 (0.1,2.0)	1.1 (0.5,2.4)	1.5 (0.9,2.7)	2.1 (0.7,6.6)	***
Temporary tracheostomy^a	2.3† (1.8,3.1)	1.5 (0.48,4.7)	2.5† (1.5,4.1)	1.0 (0.4,2.6)	0.9 (0.6,1.3)	0.7 (0.4,1.1)	0.7 (0.4,1.3)	1.0 (0.5,1.9)	1.0 (0.5,2.0)	0.9 (0.5,1.8)	1.2 (0.5,3.0)	0.7 (0.1,4.7)
Ventilation^a	1.5 (0.9,2.3)	0.6 (0.1,3.9)	1.5 (0.6,3.7)	1.0 (0.24,3.8)	0.5† (0.3,0.7)	0.6† (0.4,0.8)	0.6 (0.3,1.1)	0.3† (0.1,0.8)	1.2 (0.4,3.5)	1.8† (1.1,3.1)	1.4 (0.4,5.8)	***
Severe anesthesia complication^a	1.4 (0.34,5.6)	***	3.0 (0.4,21.4)	5.5 (0.7,40.5)	0.9 (0.2,3.8)	0.4 (0.1,3.2)	0.8 (0.1,5.6)	***	***	***	0.7 (0.1,4.7)	1.2 (0.17,9.1)
Died^a	***	5.6 (0.8,41.3)	2.5 (0.4,17.9)	***	0.1 (0.0,0.8)	0.4 (0.2,1.1)	0.3 (0.0,2.3)	***	***	***	***	***

†Bolded values: Estimates that are statistically significant at p ≤ 0.05 are bolded.

Reference group is absence of the behavior/condition.

***

Due to low numbers, some factor estimates were inestimable and thus not included in the mode.

OSA, Obstructive sleep apnea; PE, preeclampsia; AMI, Acute myocardial infarction; ARF, Acute renal failure; ARDS, Acute respiratory distress syndrome; CAD, Coronary artery disease; COPD, Chronic obstructive pulmonary disease; DIC, Disseminated intravascular coagulation; DM, Diabetes mellitus; HF, Heart failure; HPN, Hypertension; pCVD, Puerperal cerebrovascular disorder; PVD, Peripheral vascular disease; vFIB, Ventricular fibrillation.

Figure 1 illustrates the annual rates of LDA use per 1,000 pregnancy-related hospitalizations, stratified by PE risk (high versus moderate) and race group from 2016 to 2021. Across all racial groups, LDA use increased steadily over the study period for both high- and moderate-risk cohorts. Among high-risk individuals, Black and White women consistently demonstrated higher rates of LDA use compared with Hispanic women, with the highest rates observed in Black women by 2021 (approximately 160 per 1,000). In contrast, LDA use in the moderate-risk group remained substantially lower than in the high-risk group. However, usage also increased over time, with White women showing the highest moderate-risk LDA use by 2021. Notably, Black women shifted from having the highest rates in the high-risk group to the lowest in the moderate-risk group. Hispanic women consistently had lower rates of LDA use compared with Black and White women in both high-risk and moderate-risk groups throughout the study period.

FIG. 1.

Rate of LDA use stratified by preeclampsia risk (high versus moderate) and maternal race group (NIS 2016–2021). LDA, low-dose aspirin; NIS, Nationwide Inpatient Sample.

The rates of LDA use among pregnant women at moderate and high risk of PE varied by the U.S. geographic region between 2016 and 2021, as shown in Figure 2. The Midwest and Northeast consistently led in LDA prescribing across risk groups, whereas western hospitals lagged. For high-risk women, the Midwest demonstrated the highest rate of LDA prescription by 2021, reaching 181 per 1,000 pregnancy-related hospitalizations. For moderate-risk women, the LDA prescription rates were substantially lower than their high-risk counterparts across regions. The absolute rate of LDA use for moderate-risk women was approximately half of that observed in the high-risk group. The South and West showed similar trends, with gradual increases from 2016, but remained below 100 prescriptions per 1,000 pregnancy-related hospitalizations. All regions experienced a marked upward trend in LDA use from 2016 to 2021, indicating increased adherence to guidelines recommending LDA for PE prevention. However, notable regional disparities were observed, with the Midwest and Northeast regions showing the highest rates of prescription for both moderate- and high-risk groups, whereas the West exhibited the lowest rates, particularly for moderate-risk women.

FIG. 2.

Rate of LDA use stratified by preeclampsia risk (high versus moderate) and U.S. geographic region (NIS 2016–2021).LDA, low-dose aspirin; NIS, Nationwide Inpatient Sample.

The rates of LDA prescription among women at moderate and high risk of PE were analyzed based on hospital location and teaching status between 2016 and 2021, as shown in Figure 3. Urban teaching hospitals showed the highest LDA use for both moderate- and high-risk women. Rural hospitals had persistently lower prescribing rates. Among high-risk women, urban teaching hospitals demonstrated the highest rates of LDA prescriptions during the study period, increasing from approximately 25.6 per 1,000 pregnancy-related hospitalizations in 2016 to 162.4 in 2021. This was followed by urban nonteaching hospitals (137.5 per 1,000 in 2021) and rural hospitals (99.9 per 1,000 in 2021). Similar to high-risk groups, urban teaching hospitals had the highest rates for moderate-risk women by 2021, reaching just above 50 per 1,000 pregnancy-related hospitalizations, followed by urban nonteaching hospitals and rural hospitals, with rural hospitals again showing the lowest rates of LDA prescription. A steady increase in LDA use was observed in all hospital types and for both risk groups over time, highlighting a growing adherence to guideline-based preventive measures for PE. However, the rate of increase was more pronounced in urban teaching hospitals for both high- and moderate-risk women. A notable disparity persisted between urban and rural hospital settings, with rural hospitals lagging behind in LDA prescription rates across the entire study period.

FIG. 3.

Rate of LDA use stratified by preeclampsia risk (high versus moderate) and hospital location and teaching status (NIS 2016–2021). LDA, low-dose aspirin; NIS, Nationwide Inpatient Sample.

Discussion

This study assessed national trends in LDA use during pregnancy from 2016 to 2021, in the context of updated clinical recommendations, and examined disparities across key population and hospital characteristics. We observed a steady increase in documented LDA use over the study period, which aligns with the release and dissemination of national guidelines. However, the data also reveal persistent disparities in LDA use by race and ethnicity, geographic region, and hospital type. Key findings include: (1) racial disparities in LDA use, with White women in the moderate-risk group having the highest rates and high-risk Black women showing higher LDA use compared with moderate-risk Black women; (2) significant regional differences, with the Midwest and Northeast leading in LDA prescription rates; and (3) hospital-level variations, where urban teaching hospitals showed significantly higher rates of LDA use than rural and urban nonteaching hospitals.

In the moderate-risk group, White women consistently exhibited the highest LDA use rates over the study period, with Black and Hispanic women showing significantly lower utilization. This finding aligns with prior studies indicating systemic barriers, including limited access to care, implicit biases, and inequitable health care delivery, that disproportionately affect minority groups in accessing evidence-based maternal health interventions.^12–14 For Hispanic women, LDA use was consistently lower than that of White women in both moderate- and high-risk groups, underscoring a concerning gap in preventive treatment for this population. Previous research similarly highlights that Hispanic women often face language barriers, limited health care access, and cultural obstacles, which may contribute to these disparities.^15,16 While Black women in the high-risk group demonstrated relatively higher LDA use rates compared with their moderate-risk counterparts, the observed disparities suggest that both high- and moderate-risk groups, particularly Black and Hispanic women, are not consistently receiving LDA in accordance with guidelines.¹⁷

LDA use varied significantly by region, with the Midwest and Northeast demonstrating the highest prescription rates across both risk groups, whereas the South and West consistently lagged behind. Geographic disparities were most pronounced in the high-risk group, where the gap between regions was particularly wide, suggesting variation in guideline uptake. These findings align with prior studies highlighting significant regional variations in the utilization of maternal health services.^18,19 A consistently low rate of LDA use among moderate-risk groups across all regions suggests an underutilization of preventive care, even in regions with higher uptake. Previous research also indicates that rates of PE are disproportionately higher in regions like the South and West, creating an inverse relationship between the use of preventive measures such as LDA and maternal health outcomes.^20,21

Hospital location and teaching status significantly influenced LDA use, with disparities more pronounced in the high-risk group. Urban teaching hospitals consistently reported higher LDA utilization compared with rural and urban nonteaching hospitals. The disparity between hospital types was far wider among high-risk women, suggesting that rural and nonteaching hospitals may lack infrastructure or support to deliver and document this care. These findings parallel prior studies showing relatively stronger adherence to clinical guidelines in teaching hospitals.^22,23 Equally concerning is the consistently low rate of LDA use among moderate-risk women across all hospital categories. Rural hospitals showed the lowest rates of LDA use overall, reflecting ongoing challenges in maternal health care in rural areas.

Our study suggests that many pregnant individuals who may benefit from LDA are not documented as receiving it, despite current USPSTF recommendations supporting its use among populations at elevated risk for PE. Although administrative coding may not fully capture prescribing trends, the observed patterns align with clinical data reported following the updated guidelines,²⁴ indicating that trends in LDA uptake, although steadily increasing, remain well below the recommended levels across various data sources. Bivariate analysis of clinical comorbidities also highlights significant links between less commonly associated risk factors such as anxiety, depression, asthma, obesity, and PE risk, especially in Hispanic and Black women. In contrast, factors such as diabetes, hypertension, eclampsia, and sepsis showed weak or nonsignificant associations, suggesting limited or context-specific impacts for PE risk. These findings emphasize the need to focus on statistically significant factors in PE risk stratification whereas acknowledging that nonsignificant associations may warrant further investigation to explore potential context-specific or subgroup effects.

This study had several limitations. First, reliance on ICD-10 codes for LDA identification likely underestimated actual usage due to inconsistent coding practices. Retrospective secondary data analyses are inherently limited by coding variability, inaccuracies, and missing data, which can bias the results. LDA may also be under-recorded in inpatient settings due to variability in documentation, coding practices, and the fact that LDA is an over-the-counter medication. Documentation is highly dependent on provider practices and institutional Electronic medical record protocols, which may vary by hospital type and region. Additionally, the NIS database does not capture the timing of entry into prenatal care, which may influence the reporting of LDA initiation and use, potentially leading to underreporting in the current study. The NIS also does not include key obstetric history variables such as nulliparity or interpregnancy interval, which are known risk factors for PE and used to guide LDA eligibility. Although stratified bivariate comparisons allowed for exploration of disparities, findings may be influenced by unmeasured confounding and variability in documentation. However, it is reasonable to assume that this under-reporting was consistent across racial and geographic regions. Therefore, the findings related to disparities are likely to reflect true disparities rather than artifacts of inconsistent data capture. The data also did not capture unmeasured factors, such as provider attitudes, patient preferences, and health care system barriers, potentially influencing the observed trends. Finally, the cross-sectional nature of the analysis precludes causal inferences, limiting our ability to identify underlying drivers of the disparities observed.

Conclusion

This study identifies significant disparities in LDA use for PE prevention across racial, geographic, and hospital factors. While progress has been made in increasing LDA use over time, persistent gaps remain. Within the limits of administrative data, our findings suggest three priority areas: improving LDA use among moderate-risk Black and Hispanic women, addressing lower uptake in the South and West, and supporting rural and nonteaching hospitals where utilization was lowest. Improved documentation in both clinical and administrative datasets is also critical, as accurate capture of LDA use will strengthen monitoring of adherence and better inform quality improvement. To close these gaps, efforts should ensure that both high- and moderate-risk groups are systematically offered LDA in line with guidelines. Targeted strategies may include provider education to support consistent prescribing, culturally tailored counseling to reduce barriers among minority women, and region-specific initiatives such as patient outreach and resource allocation in low-performing areas.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Supplemental Material

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