Risk of congenital malformations associated with first-trimester exposure to antipsychotics: a propensity score-weighted population-based cohort study

Abstract

Background: There is growing concern regarding reproductive-safety of antipsychotics, especially teratogenic effect. Previous research assessing association between antipsychotics and congenital- malformations yielded mixed results and were all derived from Western-countries. We aimed to examine risk of major and organ/system-specific congenital-malformations associated with prenatal antipsychotic exposure in predominantly-Chinese population in Hong-Kong. Methods: This population-based study identified women aged 15-50 years who delivered their first/singleton child between 2003-2018, using data from medical-record database of Hong-Kong public-healthcare services. Propensity-score-(PS)-weighted logistic-regression analyses were performed to examine risk of congenital-malformations following first-trimester exposure to antipsychotic classes (second- and first-generation antipsychotic; SGA and FGA) and six most frequently-prescribed individual-antipsychotics. Results: Of 465,069 women, 419 and 420 redeemed =1 prescription of SGA and FGA during first- trimester, respectively. Prevalence of any major malformations was 4.9% (95%CI:4.9%-5.0%) in unexposed-infants, 9.1% (6.7%-12.3%) in SGA-exposed infants, and 6.2% (4.3%-9.0%) in FGA- exposed infants. Exposure to SGA (adjusted-odds-ratio: 2.11 [95%CI:1.19-3.86]) was associated with increased risk of major malformations. This finding was consistent with sensitivity-analyses addressing exposure-misclassification and confounding by treatment-indication, but not with PS-matched sensitivity-analysis. Elevated risk of major malformations was also observed in infants exposed to high- dose olanzapine (7.50 [1.65-36.13]) and high-dose quetiapine (15.03 [4.86-56.72]), but with wide-CIs. Organ/system-specific malformations were not associated with SGA, FGA or individual-antipsychotics. Conclusion: We observed a small increased risk of major malformations associated with SGA, but was not consistently-affirmed in sensitivity-analyses, precluding firm conclusions. Research with large sample size clarifying comparative safety of individual antipsychotics on specific malformations is warranted.