Our study investigated the extent to which pregnancy imposes the risk of severe COVID-19 complications among COVID-19 associated patients and COVID-19 positive patients, and examined the association across the range of prior comorbidity. We focused on five principal outcomes: maximum length of hospital stays, moderate ventilator dependence, invasive ventilator dependence, and death. In the COVID-19 identified group, we found significant differences in COVID-19 outcomes among COVID-19 identified pregnant women, and non-pregnant COVID-19 identified women. Notably, our findings showed that COVID-19 identified pregnant women were more than 12 times as likely to be hospitalized, more than twice as likely to moderately dependent on a ventilator and had a maximum LOS of less than 1 Day two times greater than that of COVID-19 identified non-pregnant. Perhaps most importantly, we did not observe an increased risk for invasive ventilator dependence or increased risk of death among pregnant COVID-19 identified women. We observed similar results after stratifying by age and other demographic or clinical characteristics. We further restricted our analysis to confirmed COVID-19 positive patients and found comparable results. In the COVID-19 confirmed group, pregnant COVID-19 pregnant women were more than ten times as likely to be hospitalized, nearly three times as likely to be moderately dependent on a ventilator and had a maximum LOS of less tha 1 Day almost two times greater that of COVID-19 confirmed non-pregnant women.
Our findings parallel results from CDC’s initial report on SARS-CoV-2 infection among pregnant women16 yet contradicts certain findings from CDC’s updated report25 on COVID-19 and pregnancy. For instance, similar to our results, CDC’s previous report showed that although pregnancy was associated with a heightened risk of hospitalization, intensive care admission, and mechanical ventilator receipt, pregnancy was not linked to increased risk of death among reproductive aged women with confirmed COVID-19 illness.16 However, CDC’s newest study on COVID-19 and pregnancy reported that pregnant COVID-19 diagnosed women were nearly twice as likely to die compared to non-pregnant COVID-19 diagnosed women.25 In comparison to the CDC studies, our study is strengthened by a more complete assessment of demographic variables, clinical characteristics, and prior comorbidities.
The current recommended standards of care for pregnant COVID-19 patients might explain our observed results. For instance, the CDC, the American College of Obstetricians and Gynecologists (ACOG), and the Society for Maternal-Fetal Medicine (SMFM) urge special considerations for the management of COVID-19 during pregnancy.26–28 Examples of these guidelines include hospitalization of pregnant women diagnosed with COVID-19 in facilities with maternal and fetal monitoring capabilities when warranted and the use of multispecialty team based approach during treatment.29 We argue that because of these recommendations and the limited scientific knowledge on COVID-19 and pregnancy, providers are likely taking precautionary measures in caring for their pregnant COVID-19 patients. Therefore, the fact that pregnancy was linked to increased hospitalization, higher LOS of less than 1 Day, moderate dependence on a ventilator but not invasive ventilator receipt or death lends additional support to the notion that the observed results may in part reflect provider behavior or current clinical recommendations. The additional attention provided for pregnant women may reduce their risk of severe morbidity or death, but this cannot be definitively identified in these observational data. Further studies are needed to examine the contribution of provider behavior on COVID-19 health outcomes for pregnant women. Even so, the effects of specific physiologic changes during pregnancy such as decreased lung capacity, reduced cell-mediated immunity, and increased heart rate on the outcome of viral infections such as SARS-COV-2 infections cannot be overlooked. 30,31
Other clinical factors associated with adverse COVID-19 outcomes were increasing comorbidity index score and being on Medicare or Medicaid. Several recent COVID-19 studies have reported a link between increasing comorbidities with increasing COVID-19 complications.32–34 Similarly, being on Medicare or Medicaid has also been associated with poor COVID-19 outcomes35. In particular, Medicaid can be used as a proxy for lower socioeconomic status as Medicaid eligibility is based on federal poverty level guidelines.36 Medicare beneficiaries who are under the age of 65 such as those present in our study may have disabilities or severe medical conditions such as end-stage renal disease.37Taken together, lower socioeconomic status and underlying medical conditions have critical implications on worsening COVID-19 outcomes32,38−40.
Concerning racial and ethnic differences, we found that the risk of hospitalization and higher LOS of < 1 Day among pregnant patients, compared to those who are not pregnant, to be significant and comparable across race/ethnicity groups (aOR ranges from 11.77–15.14 and eβˆ ranges from 1.55–2.22 across races) (Table 4). However; NH Black and NH other race pregnant patients had significantly higher odds of moderate ventilator dependence than those that were not pregnant; a finding that was not statistically significant among white and Hispanic/Latino patients. Current literature has uncovered the disproportionate overall burden of COVID-19 on minority populations, including Blacks and Native Americans41,42. Several reasons, including higher prevalence of underlying conditions, disproportionate representation in essential worker occupations, housing, and living conditions, and structural racism, have been identified as reasons for poor outcomes observed among minority populations.43–45 When focusing on pregnant women only, racial disparities in pregnancy complications persist among women of color when compared to whites with some exceptions for hispanic women which is consistent with our observation. For example, an investigation of racial disparity in pregnancy outcomes at a tertiary care medical center found that while black women were more likely, compared to whites, to remain in the hospital for > 4 days, have higher rates of preterm birth, small-for-gestationalage infants, preeclampsia, and stillbirths, hispanic women were found to have lower odds for preterm birth and when compared to black women, hispanic women were less likely to experience any adverse pregnancy events, with the exception of gestational diabetes mellitus.46 Here, we refer to the Hispanic paradox; the positive health outcomes observed among Hispanic populations despite risks associated with lower SES47 as a likely explanation while acknowledging that other COVID-19 studies have reported adverse effects in Hispanic populations48 in general but not among pregnant women in particular.
Finally, our stratified sensitivity analysis indicated a nearly fourfold increased risk for moderate ventilator dependence among COVID-19 associated pregnant women aged 35 to 44 years. However, the risk of moderate ventilator dependence among pregnant women aged 18 to 24 years did not yield significant results. In comparison, CDC’s newest study reported a heightened risk of invasive ventilator dependence among COVID-19 pregnant women of all ages, with the highest risk observed among older pregnant women aged 35–44 years old.25 Given that advanced maternal age has been associated with a host of adverse pregnancy outcomes49 our findings highlight the need for providers to pay close attention to pregnant women of advanced ages who contract COVID-19.
Our analysis has several limitations. First, our data were limited to only participating health systems, and may not fully represent the general population. Second, our study only included individuals who sought medical care for COVID-19 and may under-represent medically underserved minority populations such as Hispanics/Latinos and NH Blacks who may not seek treatment due to lack of health insurance. Further, all cases and many of our outcomes and predictors were identified using ICD and LOINC EHR codes, thereby limiting the study's specificity. Moreover, data from patient EHR is subject to ICD coding errors, may not include all relevant patient diagnoses, and may only capture primary patient complaints, resulting in lower estimates of vital patient health history components. Despite these limitations, our study has several strengths. We utilized a large sample size (8000-22,000), sufficient to capture important trends, and conduct informative stratified analyses for a wide variety of characteristics. Our large sample size also allowed for analyses of rare patient population (i.e. pregnant women with COVID-19) that may be incredibly difficult to identify using alternative means. Finally, to counter the effects of ICD coding limitations, we applied other methods such as text matching to capture every possible indication in the data.