BACKGROUND AND PURPOSE:

• Räikkönen et al. (JAMA, 2020) investigated whether antenatal corticosteroid treatment is associated with mental and behavioral disorders in children born at term and preterm

METHODS:

• Population retrospective cohort study
  • Data collected on deliveries ≥22 weeks and ≥500g
• Participants
  • All singleton live births in Finland surviving until 1 year (2006 through 2017)
• Exposures
  • Maternal antenatal corticosteroid treatment
  • Number and timing of treatments were not available in the database
• Finnish corticosteroid protocol
  • Betamethasone (12 mg) twice 24 hours apart
    • Until 2009: up to 34w0d
    • After 2009: Up to 34w6d and possibly later depending on clinical scenario
  • Repeat treatments
    • Until 2009: Not recommended
    • After 2009: 1 repeat course if risk of RDS high
• Within-sibpair comparison conducted to help address unmeasured familial confounding
  • Sibpairs discordant for treatment exposure were compared with sibpairs concordant for nonexposure
  • Multiple other potential confounders (e.g., maternal age, gestational age, mode of delivery, BMI etc.) were extracted from the database
• Primary outcome
  • Any childhood mental and behavioral disorder diagnosed in a specialized medical care setting

RESULTS:

• Total of 670,097 singleton births used in the analysis
  • Median length of follow-up: 5.8 (IQR 3.1-8.7) years
• Corticosteroid exposure and birth
  • Corticosteroid exposed children: 2.22% | 46.1% female
    • Born at term: 45.27%
    • Born preterm: 54.74%
  • Non-exposed children: 97.78% | 48.9% female
    • Born at term: 96.88%
    • Born preterm: 3.12%
• Eligible sibpairs: 241,621
  • Discordant for treatment exposure: 1.71%

Compared to non-exposure, exposure to corticosteroids was significantly associated with higher risk of any mental or behavioral disorder

• Entire cohort
  • Exposed: 12.01%
  • Non-exposed: 6.45%
  • Absolute difference 5.56% (95% CI, 5.04% to 6.19%)
  • Adjusted hazard ratio (HR) 1.33 (1.26 to 1.4)
• Term-born children
  • Exposed: 8.89%
  • Non-exposed: 6.31%
  • Absolute difference 2.58% (95% CI, 1.92% to 3.29%)
  • HR 1.47 (95% CI, 1.36 to 1.69)
• Term within-sibpair analysis
  • Exposure in sibling of discordant sibpair was associated with increased risk for mental and behavioral disorder
    • Exposed:6.56%
    • Unexposed: 4.17%
    • Absolute difference: 2.40% (95% CI, 1.67%-3.21%)
    • HR 1.38: (95% CI, 1.21-1.58)
• Preterm-born children
  • Cumulative incidence was significantly different but not the HR
    • Exposed: 14.59%
    • Non-exposed: 10.71%
    • Absolute difference 3.38% (95% CI, 2.95% to 4.87%)
    • HR 1.00 (95% CI, 0.92 to 1.09)

CONCLUSION:

• This study identified an association between antenatal exposure to corticosteroids for lung maturity and mental and behavioral disorders in offspring
• The authors acknowledge multiple limitations, including
  • The data reflecting association and not causation
  • The Finnish population is homogeneous and therefore results may not be generalizable to other populations
• The authors conclude

…exposure to maternal antenatal corticosteroid treatment was significantly associated with mental and behavioral disorders in children

These findings may help inform decisions about maternal antenatal corticosteroid treatment

Learn More – Primary Sources:

Associations Between Maternal Antenatal Corticosteroid Treatment and Mental and Behavioral Disorders in Children

Related ObG Topics:

Antenatal Corticosteroids – When to Administer?

Results from the PRECISE Study: Repeat Prenatal Corticosteroid Treatment for Preterm Birth

Are Topical Corticosteroids Safe During Pregnancy? 

In Women at Risk of Late Preterm Delivery, is Corticosteroid Therapy Still Cost-Effective?