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The InPreSS data: Are β-Blockers Associated with Increased Risk of Congenital Malformations?


  • Bateman et al. (Annals of Internal Medicine, 2018) assessed whether β-blocker exposure in first-trimester was associated with greater risk for birth defects 


  • Cohort study 
    • InPreSS safety consortium (registries from US, Denmark, Finland, Iceland, Norway, and Sweden) 
    • Prospectively collected data 
  • Participants 
    • Data collected on pregnant women with a diagnosis of hypertension and their offspring 
  • First-trimester exposure to β-blockers was assessed 
  • Data on covariates were also obtained  
  • Outcomes 
    • Major congenital malformation | Cardiac malformations | Cleft lip or palate | CNS 


  • 3,577 women in the Nordic cohort | 14,900 women were included in the U.S. cohort 
    • 682 (Nordic) and 1668 (US) women were exposed to β-blockers in the first trimester  
  • There was no overall increased risk attributed to β-blocker exposure  
    • Relative risk (RR): 1.07 (95% CI, 0.89 to 1.30)  
    • Risk difference per 1000 persons (RD1000): 3.0 (95% CI, -6.6 to 12.6)  
  • There was no increased risk for cardiac defects 
    • RR: 1.12 (95% CI, 0.83 to 1.51)  
    • RD1000: 2.1 (95% CI, -4.3 to 8.4)  
  • There was no increased risk for cleft lip  
    • RR: 1.97 (95% CI, 0.74 to 5.25) 
    • RD1000: 1.0 (95% CI, -0.9 to 3.0) 
  • There was no increased risk for CNS malformations  
    • RR: 1.37 (95% CI, 0.58 to 3.25)  
    • RD1000: 1.0 (CI, -2.0 to 4.0)  
  • The above results were adjusted for confounders  


  • Even using the upper bound of the 95% CIs, β-blocker exposure in the first trimester is not associated with a large increase in the risk for overall malformations and cardiac defects 
  • The results were similar for cleft lip and CNS disorders, but smaller ‘n’  
  • The authors state 

Our analysis was able to exclude a large increase in the relative and absolute risks for overall major malformations and for the most common class of birth defects, cardiac malformations. 

Learn more – Primary Sources: 

β-Blocker Use in Pregnancy and the Risk for Congenital Malformations: An International Cohort Study