BACKGROUND AND PURPOSE:

• Recent studies have not found a link between prenatal exposure to antipsychotics and childhood neurodevelopmental disorders
• However, longer follow-up times are required to assess outcomes like attention deficit hyperactivity disorder (ADHD)
• Wang et al. (JAMA, Internal Medicine, 2021) sought to determine the association between prenatal antipsychotics exposure and the risk of birth and neurodevelopmental problems

METHODS:

• Population-based cohort study
• Population
  • Children born between January 2001 and January 2015
  • Exclusion: Pregnancies with prenatal antidepressant/lithium exposure
• Exposure
  • Gestational exposure to antipsychotics
• Study design
  • Propensity score (PS) weighting used to account for differences in baseline covariates
  • Sibling matched analysis used to evaluate confounding by indication
• Minimum follow-up
  • ASD: 3 years
  • ADHD: 6 years
• Primary outcomes
  • Preterm birth: <37 gestational weeks
  • Small for gestational age (SGA): Birth weight <2 SD below the mean for gestational age
  • First diagnosis of ADHD and autism spectrum disorder (ASD)

RESULTS:

• 333,749 mother-child pairs for ADHD
  • Mean (SD) maternal age at delivery: 31.46 (5.03) years
• 411,251 pairs for ASD
  • Mean (SD) maternal age at delivery: 31.56 (5.01) years
• No difference in ADHD or ASD diagnoses, or SGA between the exposed and non-exposed cohorts
  • ADHD frequency: 3.95%
    • Weighted hazard ratio (wHR) 1.16 (95% CI, 0.83 to 1.61)
  • ASD frequency: 8.24%
    • wHR 1.06 (95% CI, 0.70 to 1.60)
  • Small for gestational age frequency: 1.70%
    • Weighted odds ratio (wOR) 1.36 (95% CI, 0.86 to 2.14)
• There was a small increased risk of preterm birth
  • wOR 1.40 (95% CI, 1.13 to 1.75)
• Additional analyses showed no association between gestationally exposed vs past maternal exposure for any outcome
  • ADHD: wHR 0.99 (95% CI, 0.60 to 1.61)
  • ASD: wHR 1.10 (95% CI, 0.58 to 2.08)
  • Small for gestational age: wOR 1.21 (95% CI, 0.66 to 2.20)
  • Preterm birth: wOR 0.93 (95% CI, 0.70 to 1.24)
• Sibling-matched analyses also revealed no association between antipsychotic exposure and the primary outcomes
  • ADHD: wHR 0.41 (95% CI, 0.04 to 4.93)
  • ASD: wHR 0.90 (95% CI, 0.40 to 2.01)
  • Small for gestational age: wOR 0.86 (95% CI, 0.32 to 2.31)
  • Preterm birth: wOR 1.25 (95% CI, 0.85 to 1.82)

CONCLUSION:

• There was no link found between prenatal antipsychotic exposure and increased risk of ADHD, ASD, or SGA
• Small risk for preterm birth disappeared when past maternal exposure was included in the analysis, indicating that maternal psychiatric disorder may be associated with higher risk rather than gestational exposure
• The authors conclude

This study’s findings do not suggest an association between prenatal exposure to antipsychotics and the risk of ADHD, ASD, preterm birth, and small for gestational age

Given that maternal psychiatric disorders may increase neurodevelopmental disorder risk in children clinicians should inform individual patients about the benefits and potential risks of using antipsychotics during pregnancy

Learn More – Primary Sources:

Association Between Prenatal Exposure to Antipsychotics and Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Preterm Birth, and Small for Gestational Age

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