Study population and setting
This study compared COVID-19 disease severity outcomes between pregnant and non-pregnant women aged 15-44 years with symptomatic PCR-confirmed SARS-CoV-2 infections reported through national COVID-19 case surveillance or the National Notifiable Diseases Surveillance System from January 22 to October 3, 2020. The surveillance data included 1.3 million female cases aged 15-44 years, and pregnancy status was documented on a third of these case report forms (461,825). Among those with known pregnancy status, COVID-19 symptoms were documented in 409,462 case reports, yielding a study sample of 23,434 pregnant and 386,028 nonpregnant women. All outcomes and other data were ascertained from the case reports, reported by public health agencies and health care providers according to local procedures for reporting and investigating cases. The analyses incorporated all updates to these case reports submitted by October 28, 2020.
Summary of Main Findings
Pregnant women with symptomatic COVID-19 were more likely than nonpregnant women of reproductive age to be admitted to the intensive care unit (ICU) (10.5 v 3.9 per 1,000 cases), receive invasive ventilation (2.9 v 1.1 per 1,000 cases), or receive extracorporeal membrane oxygenation (ECMO) (0.7 versus 0.3 per 1,000 cases). In multivariable Poisson regression adjusted for age, race/ethnicity, and underlying comorbidities, the risk among pregnant compared to nonpregnant women was 3 times higher for ICU admission (adjusted RR [aRR] 3.0; 95% CI 2.6–3.4), 2.9 times higher for mechanical ventilation (95% CI=2.2–3.8), and 2.4 times higher for ECMO (95% CI 1.5–4.0). There were 34 deaths reported among pregnant women and 447 deaths among nonpregnant women, corresponding to an adjusted risk ratio of 1.7 (aRR 1.77 95% CI 1.2-2.4; 1.5 v 1.2 per 1,000 cases). The risk of death was highest among black women, independent of their pregnancy status.
This is the largest study of COVID-19 severity among pregnant women in the US, and the surveillance data captures cases outside of hospital settings. Importantly, these data include a comparison group of nonpregnant women of reproductive age with whom to directly compare COVID-19 outcomes by pregnancy status. The large sample size enabled the researchers to explore subgroup analyses by age group and race/ethnicity.
The primary limitation of this study was the high proportion of missing data (including data on outcomes, pregnancy status, underlying comorbidities, and race/ethnicity) and the variable data quality within the passive surveillance system. The majority (65%) of COVID-19 cases among women aged 15-44 years had unknown pregnancy status and were excluded from analysis; if these women differed systematically from those with known pregnancy status, results could be substantially biased. Resource constraints and heterogenous procedures likely limited outcome ascertainment, particularly for outcomes which may occur weeks after the case was originally reported. The assumption that missing outcome data (25-70%) were non-outcomes likely underreported outcomes and may have biased the associations. The inferences about the risk of death were most susceptible to this misclassification bias given their small numbers. The authors do not comment on whether obstetric settings might be more likely to report outcome data than non-obstetric settings, which would inflate risks associated with pregnancy. Though the analyses adjusted for important variables affecting disease severity, there may be residual confounding in the association between pregnancy and disease severity due to misclassification of underlying comorbidities (e.g. 50% missing) and other covariates in the case reports. Finally, it is possible that health care providers may have had a lower threshold for interventions in symptomatic pregnant women (e.g., ICU admission) relative to non-pregnant women with otherwise similar clinical presentations.
This large study included a comparison group of nonpregnant women with COVID-19 and adds to the limited evidence on whether COVID-19 severity differs by pregnancy status, much of which has been conducted in hospital samples and without an appropriate nonpregnant comparison group.
This review was posted on: 22 January 2021