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

Pregnant women are considered a high-risk group for severe COVID-19 due to pregnancy-related physiological changes in the respiratory and immune systems. These changes, including modifications in the maternal immune system, alterations in functional residual capacity and cardiovascular function, and variations in coagulation, increase susceptibility to infections and potentially lead to severe maternal-fetal complications. The 2002 SARS-CoV-1 pandemic highlighted the vulnerability of pregnant women to severe outcomes from coronavirus infections. While previous studies have shown increased maternal morbidity and mortality in pregnant women with COVID-19, understanding of trimester-specific effects remains limited. Initial data suggested only mild infections and no definitive evidence of worsened mortality or morbidity. However, later studies showed higher incidences of preeclampsia in COVID-19 positive pregnancies. This study aimed to investigate trimester-specific outcomes in pregnant patients with COVID-19 using the large National Inpatient Sample (NIS) database to analyze in-hospital mortality and the impact of pre-existing comorbidities, social factors, and regional influences, as well as trimester-specific maternal and fetal complications.

Existing literature on the impact of COVID-19 on pregnancy outcomes showed conflicting results. Early studies reported mild infections with no significant increase in mortality or morbidity, while others highlighted increased risk of maternal morbidity and mortality, but lacked a detailed understanding of trimester-specific outcomes. Some studies demonstrated a higher incidence of preeclampsia in COVID-19 positive pregnancies. However, these studies often lacked high-quality data or sufficient sample sizes to draw robust conclusions, and limited population-based estimates of COVID-19 diagnoses in pregnancy, segmented by race, ethnicity, and insurance status. This study aimed to fill these gaps by providing a comprehensive analysis using a large, nationally representative dataset.

This retrospective case-control study used the US National Inpatient Sample (NIS) database from 2020. The NIS is a large all-payer healthcare database containing data on approximately 20% of all US hospital discharges. The study identified hospitalizations in 2020 with a primary or secondary diagnosis of pregnancy complicated by COVID-19 using ICD-10-CM codes. Hospitalizations with missing information were excluded. The study population included pregnant women aged 18 years or older admitted to the hospital with COVID-19 infection. Variables included patient-related factors (age, race, insurance status, income), hospital-related factors (location, teaching status, size), and illness severity indicators (length of stay, mortality, comorbidities, mechanical ventilation). The primary outcome was in-hospital mortality, while secondary outcomes included intubation, vasopressor use, acute kidney injury (AKI), hemodialysis, venous thromboembolism, and trimester-specific complications (preeclampsia, HELLP syndrome, preterm birth, etc.). Statistical analysis was performed using Stata version 17.0, employing sample weights from NIS to calculate national estimates. Descriptive statistics, univariate regression, and multivariate logistic and linear regression models were used to analyze the data, adjusting for potential confounders. The study excluded cases with missing information. A two-tailed p-value of ≤0.05 was considered statistically significant.

The study analyzed data from 53,025 hospitalizations of pregnant women with COVID-19 in 2020, categorized by trimester. **Trimester-Specific Findings:** * **First Trimester:** COVID-19 positive patients showed significantly higher rates of obesity compared to the negative cohort. There was a higher percentage of African Americans, Hispanics, and Asians in the COVID-19 positive group compared to Caucasians. In-hospital mortality was not statistically significant, although there was an elevated rate of mechanical ventilation in the COVID-19 positive group. * **Second Trimester:** COVID-19 positive patients had significantly higher rates of mechanical ventilation, while the rate of AKI was also higher but not as strongly significant. Smoking and drug abuse were less prevalent among COVID-19 positive individuals in this trimester. The COVID-19 negative group exhibited higher rates of preeclampsia and missed abortion. * **Third Trimester:** The most significant findings were observed in the third trimester. COVID-19 positive patients had significantly higher in-hospital mortality rates compared to the negative cohort. They also showed significantly higher rates of preeclampsia, HELLP syndrome, mechanical ventilation, and AKI requiring hemodialysis. Preterm labor was also significantly higher. Hispanic women represented the largest percentage of COVID-19 infections across all trimesters. COVID-19 positive patients also had higher hospital charges and longer lengths of stay compared to those negative for COVID-19 across the second and third trimesters. No significant difference was found between the two groups regarding the mode of delivery across the second and third trimesters. **Demographic Disparities:** Hispanic women consistently showed the highest prevalence of COVID-19 infection across all trimesters, followed by African American women. Lower household income (< USD 49,999) was strongly associated with higher rates of COVID-19 infection, along with Medicaid insurance coverage.

The study's findings highlight the significant impact of COVID-19 on pregnancy outcomes, particularly in the third trimester, where maternal mortality and several severe complications were significantly elevated among COVID-19 positive patients. The increased incidence of preeclampsia and HELLP syndrome in the third trimester among COVID-19 positive women aligns with existing research on the shared pathological underpinning of endothelial damage in both conditions. The higher rates of AKI and the need for renal replacement therapy further demonstrate the multi-organ involvement of severe COVID-19 in pregnant women. The study also underscores the importance of considering pre-existing comorbidities, particularly obesity, as risk factors for severe COVID-19 outcomes in pregnancy. The significant racial and socioeconomic disparities observed highlight the need for equitable healthcare access and interventions to mitigate the disproportionate impact of COVID-19 on vulnerable populations. The lack of a significant difference in the mode of delivery between the groups suggests that other factors are predominant in determining the birth method.

This study demonstrates the increased risk of maternal mortality and severe complications associated with COVID-19 infection during pregnancy, particularly in the third trimester. Significant racial and socioeconomic disparities in COVID-19 prevalence and pregnancy outcomes were also identified. These findings underscore the crucial need for equitable healthcare strategies focusing on preventative measures and improved care for diverse and socioeconomically disadvantaged groups to reduce adverse maternal and fetal outcomes. Future research should focus on the timing and severity of COVID-19 infection, viral variants, vaccination status, and the impact of specific treatments on pregnant women and their fetuses, including the possibility of vertical transmission.

The study's reliance on the NIS database limits its ability to assess the timing of COVID-19 diagnosis, disease severity, viral variants, and vaccination status, all factors potentially influencing outcomes. The lack of information on COVID-19-specific medications and their effects on both mother and fetus is another limitation. The use of ICD-10 codes for diagnoses introduces the potential for coding errors and biases. While multivariate analysis was used to adjust for confounders, residual confounding may still exist. Finally, data were limited to index hospitalization, precluding assessment of long-term outcomes.