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Association Between Prenatal Exposure to Antipsychotics and Attention-Deficit/Hyperactivity Disorder, Autism Spectrum
Zixuan Wang1, Adrienne Y L Chan2,3,4, David Coghill5,6
1Research Department of Practice and Policy, UCL School of Pharmacy, London, England.
Insights
Prenatal exposure to antipsychotics did not increase the risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD). While a small risk of preterm birth was observed initially, further analysis did not confirm this association, supporting continued antipsychotic treatment during pregnancy.
Area of Science:
- Perinatal Psychiatry
- Neurodevelopmental Disorders
- Pharmacovigilance
Background:
- The safety of antipsychotic use during pregnancy is a significant concern for both clinicians and patients.
- Existing data on the association between prenatal antipsychotic exposure and adverse birth or neurodevelopmental outcomes are limited and often conflicting.
Purpose of the Study:
- To investigate the association between prenatal exposure to antipsychotics and the risk of specific birth complications and neurodevelopmental disorders in children.
- To differentiate between gestational exposure and other potential confounding factors through robust analytical methods.
Main Methods:
- A large population-based cohort study utilizing the Hong Kong Clinical Data Analysis and Reporting System.
- Inclusion of mother-child pairs with exclusion of pregnancies exposed to antidepressants or lithium.
- Primary analysis using propensity score fine stratification, with additional analyses including past exposure comparisons and sibling-matched designs.
Main Results:
- No increased risk was found for attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) in children exposed prenatally to antipsychotics.
- A statistically significant increased risk for preterm birth was observed in the primary analysis (wOR, 1.40; 95% CI, 1.13-1.75), but not supported by sibling-matched or past exposure analyses.
- No significant associations were identified for small for gestational age.
Conclusions:
- Prenatal antipsychotic exposure does not appear to elevate the risk for ADHD, ASD, or small for gestational age.
- The observed increased risk for preterm birth in the primary analysis was not consistently supported across different analytical approaches.
- Findings suggest that the benefits of antipsychotic treatment for maternal mental health during pregnancy outweigh the potential risks, and discontinuation is not recommended.
Importance:
The risk of birth and neurodevelopmental complications with prenatal exposure to antipsychotics is unclear.
Objective:
To evaluate the association between prenatal antipsychotics exposure and the risk of birth and neurodevelopmental problems.
Design, Setting, And Participants:
This population-based cohort study included children born between January 2001 and January 2015 with follow-up to December 2019 who were identified by the Hong Kong Clinical Data Analysis and Reporting System. Pregnancies with maternal antidepressant/lithium exposure were removed. Primary analyses compared gestationally exposed and gestationally nonexposed individuals with propensity score fine stratification. Additional analyses included gestationally exposed individuals vs those with past exposure and a sibling-matched analysis to evaluate the effect of confounding by indication.
Exposures:
Prenatal antipsychotic exposure.
Main Outcomes And Measures:
Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 standard deviations below the mean for gestational age), and first diagnosis of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children.
Results:
The cohorts included 333 749 mother-child pairs for ADHD (mean [SD] maternal age at delivery, 31.46 [5.03] years) and 411 251 pairs for ASD, preterm birth, and small for gestational age analyses (mean [SD] maternal age at delivery, 31.56 [5.01] years). There were 13 196 children (3.95%) with a diagnosis of ADHD, 8715 (2.12%) with ASD, 33 891 (8.24%) preterm, and 7009 (1.70%) who were small for gestational age. The weighted hazard ratio (wHR) was 1.16 (95% CI, 0.83-1.61) for ADHD and 1.06 (95% CI, 0.70-1.60) for ASD, while the weighted odds ratio (wOR) was 1.40 (95% CI, 1.13-1.75) for preterm birth and 1.36 (95% CI, 0.86-2.14) for small for gestational age when comparing gestationally exposed with gestationally nonexposed individuals. Additional analyses showed no association when comparing gestationally exposed individuals with those with past exposure (ADHD: wHR, 0.99; 95% CI, 0.60-1.61; ASD: wHR, 1.10; 95% CI, 0.58-2.08; preterm birth: wOR, 0.93; 95% CI, 0.70-1.24; small for gestational age: wOR, 1.21; 95% CI, 0.66-2.20) and in a sibling-matched analysis (ADHD: wHR, 0.41; 95% CI, 0.04-4.93; ASD: wHR, 0.90; 95% CI, 0.40-2.01; preterm birth: wOR, 1.25; 95% CI, 0.85-1.82; small for gestational age: wOR, 0.86, 95% CI, 0.32-2.31).
Conclusions And Relevance:
In this cohort study, the findings did not suggest that prenatal antipsychotics exposure increased the risk of ADHD, ASD, or small for gestational age. In the primary analysis, there was a small increased risk of preterm birth, but additional analyses comparing gestationally exposed individuals with those with past exposure and comparing gestationally exposed with gestationally nonexposed siblings did not support an increased risk. Given the benefits of treating psychosis during pregnancy, our findings do not support a recommendation for women to discontinue receipt of their regular antipsychotic treatment during pregnancy.
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