In utero exposure to methylphenidate, amphetamines and atomoxetine and offspring neurodevelopmental disorders - a population-based cohort study and meta-analysis

TY - JOUR

T1 - In utero exposure to methylphenidate, amphetamines and atomoxetine and offspring neurodevelopmental disorders - a population-based cohort study and meta-analysis

AU - Bang Madsen, Kathrine

AU - Larsson, Henrik

AU - Skoglund, Charlotte

AU - Liu, Xiaoqin

AU - Munk-Olsen, Trine

AU - Bergink, Veerle

AU - Newcorn, Jeffrey H

AU - Cortese, Samuele

AU - Lichtenstein, Paul

AU - Kuja-Halkola, Ralf

AU - Chang, Zheng

AU - D'Onofrio, Brian

AU - Hove Thomsen, Per

AU - Klungsøyr, Kari

AU - Brikell, Isabell

AU - Garcia-Argibay, Miguel

N1 - © 2025. The Author(s).

PY - 2025/3/27

Y1 - 2025/3/27

N2 - The use of Attention-Deficit/Hyperactivity Disorder (ADHD) medications during pregnancy is increasing, raising concerns about potential long-term effects on offspring. This study investigates in utero exposure to methylphenidate, amphetamines and atomoxetine and risk of offspring neurodevelopmental disorders (NDDs). The population-based cohort study identified from Swedish registers included 861,650 children born by 572,731 mothers from 2008-2017. We categorized exposure based on redeemed medication during pregnancy and compared exposed children to those whose mothers discontinued medication before conception. Main outcomes were any NDD, including ADHD and autism spectrum disorder (ASD). Cox proportional hazards regression estimated hazard ratios (HRs), adjusting for maternal psychiatric and sociodemographic factors. Sensitivity analyses included stratifications by medication type, timing, and duration of exposure, and sibling comparisons. We also performed a meta-analysis combining data from the present study with those from a previous Danish study. Results showed no increased risk for any NDD (HRadjusted 0.95, 95% CI 0.82-1.11), ADHD (HRadjusted 0.92, 95% CI 0.78-1.08), or ASD (HRadjusted 0.86, 95% CI 0.63-1.18). Sensitivity analyses showed consistent patterns of no increased risks across different exposure durations, medication types and between siblings. Meta-analyses further supported the findings (pooled HR for any NDD 1.00, 95% CI 0.83;1.20). Our study provides evidence that in utero exposure to ADHD medications does not increase the risk of long-term NDDs in offspring. This study replicates safety data for methylphenidate and extends it with new safety data on amphetamines and atomoxetine. These findings are crucial for informing clinical guidelines and helping healthcare providers and expectant mothers make informed decisions.

AB - The use of Attention-Deficit/Hyperactivity Disorder (ADHD) medications during pregnancy is increasing, raising concerns about potential long-term effects on offspring. This study investigates in utero exposure to methylphenidate, amphetamines and atomoxetine and risk of offspring neurodevelopmental disorders (NDDs). The population-based cohort study identified from Swedish registers included 861,650 children born by 572,731 mothers from 2008-2017. We categorized exposure based on redeemed medication during pregnancy and compared exposed children to those whose mothers discontinued medication before conception. Main outcomes were any NDD, including ADHD and autism spectrum disorder (ASD). Cox proportional hazards regression estimated hazard ratios (HRs), adjusting for maternal psychiatric and sociodemographic factors. Sensitivity analyses included stratifications by medication type, timing, and duration of exposure, and sibling comparisons. We also performed a meta-analysis combining data from the present study with those from a previous Danish study. Results showed no increased risk for any NDD (HRadjusted 0.95, 95% CI 0.82-1.11), ADHD (HRadjusted 0.92, 95% CI 0.78-1.08), or ASD (HRadjusted 0.86, 95% CI 0.63-1.18). Sensitivity analyses showed consistent patterns of no increased risks across different exposure durations, medication types and between siblings. Meta-analyses further supported the findings (pooled HR for any NDD 1.00, 95% CI 0.83;1.20). Our study provides evidence that in utero exposure to ADHD medications does not increase the risk of long-term NDDs in offspring. This study replicates safety data for methylphenidate and extends it with new safety data on amphetamines and atomoxetine. These findings are crucial for informing clinical guidelines and helping healthcare providers and expectant mothers make informed decisions.

UR - http://www.scopus.com/inward/record.url?scp=105001130351&partnerID=8YFLogxK

U2 - 10.1038/s41380-025-02968-4

DO - 10.1038/s41380-025-02968-4

M3 - Journal article

C2 - 40148550

SN - 1359-4184

JO - Molecular Psychiatry

JF - Molecular Psychiatry

M1 - 450

ER -