BACKGROUND AND PURPOSE:

• Lai et al. (AJOG, 2021) assessed whether the severity of SARS-CoV-2 infection increased the likelihood of preeclampsia, potentially indicating causality  

METHODS:

• Retrospective observational study 
• Population 
  • Pregnant women from 14 NHS hospitals in the UK 
• Exposures 
  • SARS-CoV-2 diagnosis by severity 
    • Asymptomatic 
    • Mild: Non-respiratory symptoms of COVID-19 
    • Moderate: Evidence of lower respiratory disease 
    • Severe: Requiring high dependency or intensive care for respiratory impairment or multiorgan dysfunction 
• Study design 
  • The effect of severity of infection on the rate of preeclampsia were assessed using Poisson regression models  
• Primary outcome 
  • Occurrence of preeclampsia 
• Secondary outcome 
  • Preterm birth  

RESULTS:

• 1223 pregnant women with SARS-CoV-2 infection  
  • Preeclampsia: 4.2% 
  • Miscarriages: 1.3% 
  • Fetal deaths: 0.81% 
  • Preterm birth: 17.6% 
• Preeclampsia diagnoses 
  • Diagnosed after infection: 23 cases 
  • Median interval from infection to diagnosis: 16 (IQR 7 to 61) days 
  • 43% of preeclampsia diagnosed after SARS-Cov-2 infection was preterm preeclampsia (< 37 weeks) 
• Severity of COVID-19 was associated with increasing risk of developing preeclampsia (P for trend=0.0017) 
  • A non-infected cohort: ~1% 
  • Asymptomatic: 1.9% 
  • Mild: 2.2% 
  • Moderate: 5.7% 
  • Severe: 11.1% 
• Compared to those with asymptomatic disease, there was a higher risk of preeclampsia with severe COVID-19 
  • aRR 4.9 (95% CI, 1.48 to 7.38) 
• There was also a trend towards an increased risk of developing moderate or severe COVID-19 after a diagnosis of preeclampsia (P=0.14) 
  • RR 2.28 (95% CI, 0.92 to 5.61) 
  • aRR 1.96 (95% CI, 0.80 to 4.84) 
• The risk of preterm birth increased as a function of the severity of COVID-19 (P for trend<0.0001) 
  • Asymptomatic: 11.7% (rate of preterm birth) 
  • Mild: 12.8% 
  • Moderate: 29.9% 
  • Severe: 69.4% 
• Compared to those with asymptomatic disease, there was a higher risk of preterm birth with moderate and severe COVID-19 
  • Moderate: aRR 2.47 (95% CI, 1.61 to 3.78) 
  • Severe: aRR 5.64 (95% CI, 4.09 to 7.79) 

CONCLUSION:

• The relationship between COVID-19 and risk of preeclampsia is dose dependent, with more severe disease having a significantly increased risk for preeclampsia 
• Patients with severe COVID-19 have a five-fold higher risk of preeclampsia than those who have asymptomatic COVID-19 
• The authors state that dose dependency is a criterion for causality 

SARS-CoV-2 infection can lead Journal to endothelial dysfunction, intravascular inflammation, proteinuria, activation of thrombin, and hypertension, which are all features of preeclampsia Therefore, a causal relationship must be considered 

AJOG, 2021

Learn More – Primary Sources: 

SARS-CoV-2 and the subsequent development of preeclampsia and preterm birth: evidence of a dose response relationship supporting causality 

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