COVID-19: Pregnant women are at risk for severe disease with an increased adverse perinatal outcomes

Two new studies released by the U.S.CDC shows that pregnant women who become infected with the delta variant are at increased risk of a stillbirth or dying during childbirth.

The studies were published on the CDC’s Online Journal: Morbidity and Mortality Weekly Report (MMWR)
https://www.cdc.gov/mmwr/volumes/70/wr/mm7047e1.htm?s_cid=mm7047e1_w
https://www.cdc.gov/mmwr/volumes/70/wr/mm7047e2.htm?s_cid=mm7047e2_w

regnant women are at increased risk for severe COVID-19–related illness, and COVID-19 is associated with an increased risk for adverse pregnancy outcomes and maternal and neonatal complications (1–3).

To date, studies assessing whether COVID-19 during pregnancy is associated with increased risk for stillbirth have yielded mixed results (2–4).

Since the B.1.617.2 (Delta) variant of SARS-CoV-2 (the virus that causes COVID-19) became the predominant circulating variant,* there have been anecdotal reports of increasing rates of stillbirths in women with COVID-19.† CDC used the Premier Healthcare Database Special COVID-19 Release (PHD-SR), a large hospital-based administrative database,§ to assess whether a maternal COVID-19 diagnosis documented at delivery hospitalization was associated with stillbirth during March 2020–September 2021 as well as before and during the period of Delta variant predominance in the United States (March 2020–June 2021 and July–September 2021, respectively).

Among 1,249,634 deliveries during March 2020–September 2021, stillbirths were rare (8,154; 0.65%): 273 (1.26%) occurred among 21,653 deliveries to women with COVID-19 documented at the delivery hospitalization, and 7,881 (0.64%) occurred among 1,227,981 deliveries without COVID-19.

The adjusted risk for stillbirth was higher in deliveries with COVID-19 compared with deliveries without COVID-19 during March 2020–September 2021 (adjusted relative risk [aRR] = 1.90; 95% CI = 1.69–2.15), including during the pre-Delta (aRR = 1.47; 95% CI = 1.27–1.71) and Delta periods (aRR = 4.04; 95% CI = 3.28–4.97). COVID-19 documented at delivery was associated with increased risk for stillbirth, with a stronger association during the period of Delta variant predominance. Implementing evidence-based COVID-19 prevention strategies, including vaccination before or during pregnancy, is critical to reducing the impact of COVID-19 on stillbirths.

Delivery hospitalizations were identified from PHD-SR using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic and procedure codes pertaining to obstetric delivery and diagnosis-related group delivery codes.¶ Deliveries with discharge dates during March 2020–September 2021 were included. Stillbirths, defined as fetal deaths at ≥20 weeks’ gestation, were identified using maternal ICD-10-CM diagnosis codes.**

Hospitalizations without ICD-10-CM codes indicating gestational age or with ICD-10-CM codes indicating gestational age <20 weeks were excluded to reduce misclassification of fetal deaths at <20 weeks’ gestation as stillbirths (1.5% of the overall sample).

Maternal demographic variables assessed included age, race/ethnicity (i.e., Hispanic, non-Hispanic Black, non-Hispanic White, non-Hispanic Asian, and non-Hispanic other), and primary payor (i.e., Medicaid, private insurance, self-pay, and other). Assessed hospital characteristics included urban or rural location and U.S. Census division. COVID-19†† and selected underlying medical conditions (i.e., obesity, smoking,§§ any diabetes,¶¶ any hypertension,*** and multiple-gestation pregnancy) were included if the relevant ICD-10-CM diagnosis code was documented during the delivery hospitalization (3).

In addition, among deliveries with documented COVID-19, indicators of severe illness (i.e., adverse cardiac event/outcome,††† placental abruption, sepsis, shock, acute respiratory distress syndrome, mechanical ventilation, and intensive care unit [ICU] admission) were considered present if the relevant ICD-10-CM diagnosis code was documented during the delivery hospitalization (3). Vaccination status was unable to be assessed in this analysis.

Poisson regression models with robust standard errors were used to calculate overall unadjusted and adjusted§§§ relative risks for stillbirth among deliveries with COVID-19 versus deliveries without COVID-19, accounting for within-hospital and within-woman correlation.

To better understand the potential biologic mechanism for stillbirth among women with COVID-19 at delivery, Poisson regression models with robust SEs were used to calculate unadjusted and adjusted¶¶¶ prevalence ratios for stillbirth for each underlying medical condition and indicator of severe illness among deliveries with documented COVID-19.

Relative risks and prevalence ratios were calculated overall as well as during the pre-Delta and Delta periods. Effect modification by period was assessed using adjusted models with interaction terms. For all models, p-values <0.05 were considered statistically significant. All analyses were performed using SAS software (version 9.4; SAS Institute). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.****

Among 1,249,634 deliveries at 736 hospitals during March 2020–September 2021, 53.7% of women were non-Hispanic White, and 50.6% had private insurance as the primary payor (Table 1). Overall, 15.4% had obesity, 11.2% had diabetes, 17.2% had a hypertensive disorder, 1.8% had a multiple-gestation pregnancy, and 4.9% had smoking (tobacco) documented on the delivery hospitalization record. Overall, 21,653 (1.73%) delivery hospitalizations had COVID-19 documented.

During March 2020–September 2021, a total of 8,154 stillbirths were documented, affecting 0.64% and 1.26% of deliveries without COVID-19 and with COVID-19, respectively (aRR = 1.90; 95% CI = 1.69–2.15) (Figure). During the pre-Delta period (March 2020–June 2021), 6,983 stillbirths were documented, involving 0.98% of deliveries with COVID-19 compared with 0.64% of deliveries without COVID-19 (aRR = 1.47; 95% CI = 1.27–1.71).

During the Delta period (July–September 2021), 1,171 stillbirths were documented, involving 2.70% of deliveries with COVID-19 compared with 0.63% of deliveries without COVID-19 (aRR = 4.04; 95% CI = 3.28–4.97).†††† Effect modification was present in the model; the risk for stillbirth was significantly higher during the period of Delta predominance than during the pre-Delta period (p<0.001).

Among deliveries with COVID-19, chronic hypertension, multiple-gestation pregnancy, adverse cardiac event/outcome, placental abruption, sepsis, shock, acute respiratory distress syndrome, mechanical ventilation, and ICU admission were associated with a higher prevalence of stillbirth (Table 2).

The associations for adverse cardiac event/outcome and ICU admission varied significantly between the periods before and during Delta predominance (p = 0.03 and p = 0.003, respectively); for each of these, the associations were stronger during the period of Delta predominance.