Impact of COVID-19 on Pregnancy Outcomes across Trimesters in the United States

Pregnant individuals are considered high-risk for severe COVID-19 due to pregnancy-related physiological and immunologic adaptations that increase susceptibility to infection and complications. While prior studies show higher maternal morbidity and mortality with COVID-19 in pregnancy, trimester-specific risks and outcomes have been insufficiently characterized. This study investigates whether COVID-19 impacts maternal mortality and obstetric complications differently across trimesters and explores the role of comorbidities and social determinants (race/ethnicity, insurance, income, hospital characteristics) in shaping outcomes.

Early reports during the pandemic suggested mostly mild infections in pregnancy with limited evidence of increased mortality or vertical transmission. Subsequent studies, including the INTERCOVID multinational cohort, demonstrated higher maternal morbidity and mortality with COVID-19, and a possible association with preeclampsia. Tosseta et al. reported increased preeclampsia incidence among COVID-19-positive pregnancies. However, prior data often lacked high-quality, trimester-specific analyses and comprehensive population-based estimates by race/ethnicity and insurance status. The literature also indicates disproportionate COVID-19 impacts on racial/ethnic minorities and those with lower socioeconomic status, but trimester-specific stratification of these disparities has been limited.

Design: Retrospective case-control analysis using the US National Inpatient Sample (NIS) for calendar year 2020. Data Source: NIS (HCUP/AHRQ), a 20% stratified sample of US inpatient discharges; deidentified and IRB-exempt. Population: Hospitalizations of pregnant women aged ≥18 years. COVID-19-positive pregnancies identified via ICD-10-CM codes (COVID-19 as primary or secondary diagnosis). Controls were COVID-19-negative pregnant hospitalizations. Exclusions: Records with missing key information. Sample: Approximately 1.6 million hospitalizations in 2020 had COVID-19; 53,025 included a pregnancy diagnosis. Trimester-specific COVID-19-positive subgroups included 1,160 (first trimester), 3,495 (second), and 48,445 (third). Variables: Patient-level (age, race/ethnicity, insurance, median ZIP-code income, disposition), hospital-level (region/division, teaching status, bed size, location), illness severity (length of stay [LOS], mortality, total charges, comorbidities, mechanical ventilation, circulatory support/vasopressors). Outcomes: Primary—In-hospital mortality. Secondary—mechanical ventilation, vasopressor use, AKI, AKI requiring hemodialysis, venous thromboembolism (VTE); trimester-based obstetric outcomes (molar/ectopic/missed/threatened/spontaneous abortion, gestational HTN, GDM, preterm labor, preeclampsia, HELLP); and resource use (LOS, charges, disposition). Statistical analysis: Survey weights applied to generate national estimates. Descriptive statistics reported as mean±SD or n (%). Univariate logistic regression produced crude ORs; variables with p<0.20 entered multivariable logistic regression models adjusting for age, race, income, insurance, hospital size/teaching/location, and comorbidities. Continuous outcomes (LOS, charges) analyzed via multivariable linear regression. Significance set at two-tailed p≤0.05.

- Mortality: COVID-19-positive pregnant patients showed significantly higher in-hospital mortality in the third trimester vs COVID-19-negative (0.093% vs 0.0039%; aOR 24.4, 95% CI 10.7–55.63; p<0.001). Mortality differences were not statistically significant in first and second trimesters after adjustment. - Respiratory support: Mechanical ventilation was higher with COVID-19 in all trimesters—first: 2.15% vs 0.64% (aOR 3.31, 95% CI 1.31–8.38; p=0.01); second: 4.15% vs 0.55% (aOR 5.63, 95% CI 3.51–9.03; p<0.001); third: 0.84% vs 0.05% (aOR 14.8, 95% CI 11.1–19.8; p<0.001). - Renal outcomes: AKI increased with COVID-19 in second (2.29% vs 1.02%; aOR 1.79, 95% CI 1.04–3.09; p=0.03) and third trimesters (0.34% vs 0.15%; aOR 1.71, 95% CI 1.18–2.47; p=0.004). AKI requiring hemodialysis was higher in second (0.43% vs 0.058%; aOR 4.60, 95% CI 1.13–18.64; p=0.03) and third trimesters (0.031% vs 0.002%; aOR 14.33, 95% CI 3.69–55.69; p<0.001). - Hypertensive disorders: Third-trimester COVID-19 associated with higher preeclampsia (9.0% vs 7.05%; aOR 1.17, 95% CI 1.09–1.26; p<0.001) and HELLP (0.45% vs 0.24%; aOR 1.78, 95% CI 1.30–2.44; p<0.001). In the second trimester, preeclampsia and missed abortion were less frequent in COVID-19-positive vs negative (preeclampsia 2.86% vs 6.06%; aOR 0.39, 95% CI 0.24–0.61; p<0.001; missed abortion 2.0% vs 5.89%; aOR 0.35, 95% CI 0.2–0.6; p<0.001). - Preterm labor: Third trimester preterm labor was higher with COVID-19 (1.22% vs 0.76%; aOR 1.29, 95% CI 1.05–1.58; p=0.01). No significant difference in second trimester (aOR 0.79; p=0.30). - Gestational diabetes and hypertension: No significant increase with COVID-19 in third trimester for GDM (aOR 0.98; p=0.68); gestational HTN slightly lower (aOR 0.88; p=0.005). - Resource utilization: COVID-19 associated with higher mean total charges (second trimester adjusted +USD 16,213; third trimester adjusted +USD 4,454; both p<0.001). LOS longer in third trimester (adjusted +0.27 days; p<0.001). Most (>90%) discharged home in all trimesters; small increases in home health and AMA discharges among COVID-19-positive. - Disparities: COVID-19-positive cohorts had higher proportions of Hispanic patients across trimesters (e.g., third trimester 43.1% vs 21.2%; p<0.001), greater Medicaid coverage (third 60.3% vs 43.0%; p<0.001), and lower household income (largest share in <$49,999 group; third 35.2% vs 27.5%; p<0.001). COVID-19-positive patients were more often treated in large, urban teaching hospitals. - Comorbidities: Obesity was consistently higher among COVID-19-positive across trimesters (first 18.1% vs 7.9%; second 18.0% vs 11.8%; third 13.8% vs 11.2%). Smoking and drug misuse were lower among COVID-19-positive than negative in second and third trimesters.

The study addresses the research question by demonstrating that COVID-19 risk and severity vary by trimester. The third trimester is associated with markedly increased maternal mortality risk, greater need for mechanical ventilation, higher rates of preeclampsia/HELLP, and more AKI requiring dialysis. These findings align with physiologic stressors and hypertensive disorders that cluster in late pregnancy and peripartum, suggesting that COVID-19 may exacerbate endothelial dysfunction and inflammatory pathways contributing to these conditions. Elevated preterm labor in the third trimester underscores potential fetal risks and healthcare resource implications. Disparities by race/ethnicity, insurance, and income indicate structural and social determinants significantly influence exposure and outcomes, with Hispanic and lower-income patients disproportionately affected. Recognizing obesity as a prevalent comorbidity further refines risk stratification and supports targeted preventive strategies (e.g., vaccination, early monitoring for hypertensive disorders and renal complications). Overall, trimester-specific risk profiling can inform clinical surveillance, triage, and equitable care delivery for pregnant patients with COVID-19.

COVID-19 in pregnancy is associated with increased maternal complications that vary by trimester, with the third trimester showing the highest risks for mortality, mechanical ventilation, preeclampsia/HELLP, AKI requiring dialysis, and preterm labor. Significant racial and socioeconomic disparities in COVID-19 prevalence and outcomes were observed, particularly affecting Hispanic and low-income patients cared for at urban teaching hospitals. These findings support implementing equitable, trimester-tailored preventive and clinical management strategies, including vigilant monitoring for hypertensive and renal complications and addressing social determinants of health. Future research should incorporate timing and severity of infection, variant and vaccination status, treatment effects, and post-discharge maternal–infant outcomes to optimize care and reduce adverse events.

Key limitations include absence of data on timing of infection during pregnancy, disease severity, viral variant, and vaccination status; lack of details on COVID-19-specific treatments and fetal/neonatal outcomes (including vertical transmission); analyses limited to index hospitalization without longitudinal follow-up; potential ICD-10 coding inaccuracies; and residual confounding despite multivariable adjustment. The database also lacks granularity to stratify outcomes by infection severity, which may influence relationships (e.g., with preeclampsia).