Association of Antipsychotic Drug Exposure in Pregnancy With Risk of Neurodevelopmental Disorders

Abstract

IMPORTANCE Although antipsychotic drugs cross the placenta and animal data suggest potential neurotoxic effects, information regarding human neurodevelopmental teratogenicity is limited.OBJECTIVE To evaluate whether children prenatally exposed to antipsychotic medication are at an increased risk of neurodevelopmental disorders (NDD). DESIGN, SETTINGS, AND PARTICIPANTSThis birth cohort study used data from the Medicaid Analytic eXtract (MAX, 2000(MAX, -2014 and the IBM Health MarketScan Research Database (MarketScan, 2003(MarketScan, -2015 for a nationwide sample of publicly (MAX) and privately (MarketScan) insured mother-child dyads with up to 14 years of follow-up. The MAX cohort consisted of 2 034 883 children who were not prenatally exposed and 9551 who were prenatally exposed to antipsychotic medications; the MarketScan consisted of 1 306 408 and 1221 children, respectively. Hazard ratios were estimated through Cox proportional hazards regression, using propensity score overlap weights for confounding control. Estimates from both cohorts were combined through meta-analysis.EXPOSURES At least 1 dispensing of a medication during the second half of pregnancy (period of synaptogenesis), assessed for any antipsychotic drug, at the class level (atypical and typical), and for the most commonly used drugs (aripiprazole, olanzapine, quetiapine, risperidone, and haloperidol). MAIN OUTCOMES AND MEASURESAutism spectrum disorder, attention-deficit/hyperactivity disorder, learning disability, speech or language disorder, developmental coordination disorder, intellectual disability, and behavioral disorder, identified using validated algorithms, and the composite outcome of any NDD. Data were analyzed from April 2020 to January 2022. RESULTSThe MAX cohort consisted of 2 034 883 unexposed pregnancies and 9551 pregnancies with 1 or more antipsychotic drug dispensings among women with a mean (SD) age of 26.8 (6.1) years, 204 (2.1%) of whom identified as Asian/Pacific Islander, 2720 (28.5%) as Black, 500 (5.2%) as Hispanic/Latino, and 5356 (56.1%) as White. The MarketScan cohort consisted of 1 306 408 unexposed and 1221 exposed pregnancies among women with a mean (SD) age of 33.1 (5.0) years; race and ethnicity data were not available. Although the unadjusted results were consistent with an approximate 2-fold increased risk for most exposure-outcome contrasts, risks were no longer meaningfully increased after adjustment (eg, pooled unadjusted vs adjusted hazard ratios [95% CI] for any NDD after any antipsychotic exposure

Exposure to psychotropic drugs before and during pregnancy: what has changed over the last two decades?

“…Considering that some pregnant women will be exposed to antipsychotic(s), the guidelines mention that the use of antipsychotic drugs is relatively safe concerning the development of congenital malformations, pregnancy, and birth complications (Federatie Medisch Specialisten 2020a ). Furthermore, antipsychotics do not seem to increase the risk of neurodevelopmental disorders in offspring like Attention Deficit-Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) (Wang et al 2021 ; Straub et al 2022 ). Although the knowledge about the long-term effects of antipsychotics is limited, NVOG recommends continuing its use during pregnancy since the benefits of a well-treated psychotic disorder may outweigh its potential risk to the mother and fetus (Federatie Medisch Specialisten 2020a ).…”

Association of Maternal Antipsychotic Prescription During Pregnancy With Standardized Test Scores of Schoolchildren in Denmark

“…These findings align with previous findings of no increased risk of diagnosed neurodevelopmental disorders, learning disability, or poorer intelligence quotients among children prenatally exposed to antipsychotics. [11][12][13][14][15] However, some children with more severe neurodevelopmental disorders may attend special education schools and thus may not have participated in the test program. However, this selection was less likely to bias the present associations because there was no association between prenatal antipsychotic exposure and offspring's overall neurodevelopmental disorders.…”

“…10 Four recent studies demonstrated little or no increased long-term risks associated with prenatal antipsychotic exposure in neurodevelopmental disorders. [11][12][13][14] One study has evaluated potential cognitive outcomes, which may capture more subtle neurodevelopmental impairment. 15 To our knowledge, school performance, which is associated with cognitive ability, has not been investigated in this context so far.…”

Do Not Panic About Prenatal Exposure to Antipsychotics Except for Aripiprazole?

“…To the Editor There were 3 confounders not highlighted in the excellent study by Dr Straub and colleagues . First, their study was extensively controlled for multiple important confounders, including maternal age.…”

“…A meta-analysis including 36 cohorts suggested that obesity was associated with increased risks for several neurodevelopmental outcomes, including ASD, ADHD, developmental delay, and emotional or behavioral problems . Hence, the study by Dr Straub and colleagues needed to control for these 3 confounding factors or address their omission in the study limitations …”