Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 1;81(5):477-488.
doi: 10.1001/jamapsychiatry.2023.5073.

Prescription Stimulant Use During Pregnancy and Risk of Neurodevelopmental Disorders in Children

Elizabeth A Suarez  1   2   3 , Brian T Bateman  4 , Sonia Hernandez-Diaz  5 , Loreen Straub  1 , Christopher J McDougle  6   7 , Katherine L Wisner  8   9 , Kathryn J Gray  10 , Page B Pennell  11 , Barry Lester  12   13   14 , Yanmin Zhu  1 , Helen Mogun  1 , Krista F Huybrechts  1
Affiliations

Prescription Stimulant Use During Pregnancy and Risk of Neurodevelopmental Disorders in Children

Elizabeth A Suarez et al. JAMA Psychiatry. .

Abstract

Importance: Use of medications for attention-deficit/hyperactivity disorder (ADHD) during pregnancy is increasing in the US. Whether exposure to these medications in utero impacts the risk of neurodevelopmental disorders in children is uncertain.

Objective: To evaluate the association of childhood neurodevelopmental disorders with in utero exposure to stimulant medications for ADHD.

Design, setting, and participants: This cohort study included health care utilization data from publicly insured (Medicaid data from 2000 to 2018) and commercially insured (MarketScan Commercial Claims Database data from 2003 to 2020) pregnant individuals aged 12 to 55 years in the US with enrollment from 3 months prior to pregnancy through 1 month after delivery, linked to children. Children were monitored from birth until outcome diagnosis, disenrollment, death, or end of the study (December 2018 for Medicaid and December 2020 for MarketScan).

Exposures: Dispensing of amphetamine/dextroamphetamine or methylphenidate in the second half of pregnancy.

Main outcomes and measures: Autism spectrum disorder, ADHD, and a composite of any neurodevelopmental disorder were defined using validated algorithms. Hazard ratios were estimated comparing amphetamine/dextroamphetamine and methylphenidate to no exposure.

Results: The publicly insured cohort included 2 496 771 stimulant-unexposed, 4693 amphetamine/dextroamphetamine-exposed, and 786 methylphenidate-exposed pregnancies with a mean (SD) age of 25.2 (6.0) years. The commercially insured cohort included 1 773 501 stimulant-unexposed, 2372 amphetamine/dextroamphetamine-exposed, and 337 methylphenidate-exposed pregnancies with a mean (SD) age of 31.6 (4.6) years. In unadjusted analyses, amphetamine/dextroamphetamine and methylphenidate exposure were associated with a 2- to 3-fold increased risk of the neurodevelopmental outcomes considered. After adjustment for measured confounders, amphetamine/dextroamphetamine exposure was not associated with any outcome (autism spectrum disorder: hazard ratio [HR], 0.80; 95% CI, 0.56-1.14]; ADHD: HR, 1.07; 95% CI, 0.89-1.28; any neurodevelopmental disorder: HR, 0.91; 95% CI, 0.81-1.28). Methylphenidate exposure was associated with an increased risk of ADHD (HR, 1.43; 95% CI, 1.12-1.82]) but not other outcomes after adjustment (autism spectrum disorder: HR, 1.06; 95% CI, 0.62-1.81; any neurodevelopmental disorder: HR, 1.15; 95% CI, 0.97-1.36). The association between methylphenidate and ADHD did not persist in sensitivity analyses with stricter control for confounding by maternal ADHD.

Conclusions and relevance: The findings in this study suggest that amphetamine/dextroamphetamine and methylphenidate exposure in utero are not likely to meaningfully increase the risk of childhood neurodevelopmental disorders.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Bateman reported grants from the National Institutes of Health during the conduct of the study. Dr Hernandez-Diaz reported grants from Takeda and personal fees from Johnson & Johnson and Moderna outside the submitted work. Dr Straub reported grants from the National Institute of Child Health and Human Development outside the submitted work. Dr McDougle reported consulting fees from Acadia Pharmaceuticals and Sage Therapeutics, royalties from Oxford University Press and Springer Publishing, and a lecture honorarium from American Psychiatric Association outside the submitted work. Dr Gray reported personal fees from BillionToOne, Roche, and Aetion outside the submitted work. Dr Pennell reported personal fees from Harvard T. H. Chan School of Public Health for serving on the BRAINS scientific advisory board during the conduct of the study and grants from the National Institutes of Health outside the submitted work. Dr Zhu reported grants from Takeda outside the submitted work. Dr Huybrechts reported grants from Takeda (paid to institution) and UCB (paid to institution) outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Cumulative Incidence of Neurodevelopmental Disorders by Late Pregnancy Stimulant Exposure and Data Source
Crude cumulative incidence curves are presented for the composite of any neurodevelopmental disorder, stratified by stimulant exposure status (defined as having a stimulant dispensed between 127 days after last menstrual period to the day prior to delivery) and data source. The cumulative incidence at age 12 years in each stratum is noted in the figure.
Figure 2.
Figure 2.. Hazard Ratios (HRs) for Neurodevelopmental Disorders Among Children Exposed to Amphetamine/Dextroamphetamine in Pregnancy
The exposed cohort is defined by amphetamine/dextroamphetamine dispensing in late (127 days after the last menstrual period to the day prior to delivery) or early (last menstrual period to 126 days after last menstrual period) pregnancy. The reference group consists of all stimulant-unexposed pregnancies (A), all stimulant-unexposed pregnancies with a diagnosis of ADHD (B), or pregnancies with a dispensing of amphetamine/dextroamphetamine between 90 and 31 days prior to the last menstrual period but not from 30 days prior to the last menstrual period through delivery (C). ADHD indicates attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; NDD, neurodevelopmental disorder.
Figure 3.
Figure 3.. Hazard Ratios (HRs) for Neurodevelopmental Disorders Among Children Exposed to Methylphenidate in Pregnancy
The exposed cohort is defined by methylphenidate dispensing in late (127 days after the last menstrual period to the day prior to delivery) or early (last menstrual period to 126 days after the last menstrual period) pregnancy. The reference group consists of all stimulant-unexposed pregnancies (A), all stimulant-unexposed pregnancies with a diagnosis of ADHD (B), or pregnancies with a dispensing of methylphenidate between 90 and 31 days prior to the last menstrual period but not from 30 days prior to the last menstrual period through delivery (C). ADHD indicates attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; NDD, neurodevelopmental disorder.
Figure 4.
Figure 4.. Adjusted Hazard Ratios (HRs) for Neurodevelopmental Disorders in Sensitivity Analyses
The exposed cohort is defined by stimulant dispensing (A, amphetamine/dextroamphetamine and B, methylphenidate) in late (127 days after the last menstrual period to the day prior to delivery) or early (last menstrual period to 126 days after last menstrual period) pregnancy. The reference group consists of all stimulant-unexposed pregnancies. Sensitivity analysis results presented include requiring 2 or more instances of dispensing the exposure medication during the exposure window to be included in the exposed group (≥2 fills) and restricting the cohort to children with at least 2 years of continuous enrollment after delivery (>2 years of follow-up). ADHD indicates attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; NDD, neurodevelopmental disorder.
See this image and copyright information in PMC

References

    1. Fayyad J, Sampson NA, Hwang I, et al. ; WHO World Mental Health Survey Collaborators . The descriptive epidemiology of DSM-IV adult ADHD in the World Health Organization World Mental Health Surveys. Atten Defic Hyperact Disord. 2017;9(1):47-65. doi:10.1007/s12402-016-0208-3 - DOI - PMC - PubMed
    1. Song P, Zha M, Yang Q, Zhang Y, Li X, Rudan I. The prevalence of adult attention-deficit hyperactivity disorder: a global systematic review and meta-analysis. J Glob Health. 2021;11:04009. doi:10.7189/jogh.11.04009 - DOI - PMC - PubMed
    1. Zhu Y, Liu W, Li Y, Wang X, Winterstein AG. Prevalence of ADHD in publicly insured adults. J Atten Disord. 2018;22(2):182-190. doi:10.1177/1087054717698815 - DOI - PubMed
    1. Knight TK, Kawatkar A, Hodgkins P, et al. . Prevalence and incidence of adult attention deficit/hyperactivity disorder in a large managed care population. Curr Med Res Opin. 2014;30(7):1291-1299. doi:10.1185/03007995.2014.901940 - DOI - PubMed
    1. Montejano L, Sasané R, Hodgkins P, Russo L, Huse D.. Adult ADHD: prevalence of diagnosis in a US population with employer health insurance. Curr Med Res Opin. 2011;27(sup2):5-11. doi:10.1185/03007995.2011.603302 - DOI - PubMed

Publication types

MeSH terms