Associations Between ADHD Medication Use in Pregnancy and Severe Malformations Based on Prenatal and Postnatal Diagnoses: A Danish Registry-Based Study

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Overview

Do you have patients who take ADHD medication and are planning a pregnancy? How do you respond to questions of safety? This journal CME activity offers evidence.

Abstract

Objective: Attention-deficit/hyperactivity disorder (ADHD) medications are increasingly used in pregnancy. Studies on the pregnancy safety of these medications that are restricted to live births may underestimate severe teratogenic effects that cause fetal demise or termination of pregnancy. The present study addresses this limitation by including data from both prenatal and postnatal diagnoses of major malformations.

Methods: A nationwide registry-based study was conducted of 364,012 singleton pregnancies in Denmark from November 1, 2007, to February 1, 2014. Exposures to ADHD medication were obtained from redeemed prescriptions from the Danish Health Services Prescription Database. Outcome data included prenatally diagnosed malformations from the Danish Fetal Medicine Database and postnatally diagnosed malformations from the Danish National Patient Registry. The primary outcome was major malformations overall, and secondary outcomes were malformations of the central nervous system and cardiac malformations. The comparison group was pregnancies with no redeemed prescriptions for ADHD medication. We defined severe cardiac malformations (SCM) as concurrent diagnoses of a cardiac malformation with miscarriage, termination, stillbirth, postnatal death, or cardiac surgery within 1 year of birth.

Results: The prevalence of first-trimester exposure to ADHD medication increased during the study period from 0.05% in 2008 to 0.27% in 2013, with the majority (473/569) of the exposures being to methylphenidate. There were 5.1% malformations overall and 2.1% cardiac malformations among the exposed compared to 4.6% and 1.0%, respectively, among the unexposed. For methylphenidate, the adjusted prevalence ratios (PRs) were 1.04 (95% confidence interval [CI], 0.70–1.55) for malformations overall and 1.65 (95% CI, 0.89–3.05) for any cardiac malformations (number needed to harm [NNH] = 92), with septum defects in 10 out of 12 cases. The PR for ventricular septal defect was 2.74 (95% CI, 1.03–7.28) and for SCM, 2.59 (95% CI, 0.98–6.90).

Conclusions: Exposure to methylphenidate was not associated with an increased risk of malformations overall in data that included information from both prenatal and postnatal diagnoses of major malformations. There was an increased risk of cardiac malformations with NNH of 92 based on 12 cases among the exposed. More data are needed on other types of ADHD medication.

To cite: Kolding L, Ehrenstein V, Pedersen L, et al. Associations between ADHD medication use in pregnancy and severe malformations based on prenatal and postnatal diagnoses: a Danish registry-based study. J Clin Psychiatry. 2021;82(1):20m13458.

https://doi.org/10.4088/JCP.20m13458


Read the whole article at psychiatrist.com here: 
Associations Between ADHD Medication Use in Pregnancy and Severe Malformations Based on Prenatal and Postnatal Diagnoses: A Danish Registry-Based Study

© Copyright 2021 Physicians Postgraduate Press, Inc.

Target Audience

Psychiatrists

Learning Objectives

After studying this article, you should be able to:

  • Provide current data on potential pregnancy risks to patients taking medication for attention-deficit/hyperactivity disorder
Activity summary
Available credit: 
  • 1.00 AMA PRA Category 1 Credit™
  • 1.00 Participation
Activity opens: 
01/05/2021
Activity expires: 
02/28/2023
Cost:
$10.00
Rating: 
0

CME Background

Articles are selected for credit designation based on an assessment of the educational needs of CME participants, with the purpose of providing readers with a curriculum of CME articles on a variety of topics throughout each volume. Activities are planned using a process that links identified needs with desired results.

CME Objective

After studying this article, you should be able to:

  • Provide current data on potential pregnancy risks to patients taking medication for attention-deficit/hyperactivity disorder

Statement of Need and Purpose

Although past research assessing the association of ADHD medication use during pregnancy with fetal malformations has found the risk to be low, the majority of these studies were limited to live births and did not include outcomes such as pregnancy termination or miscarriage. This may have led to an underestimation of risk, since the studies could not detect associations for severe malformations that ended in pregnancy loss. Especially in the absence of guidelines, physicians need education on the rates of outcomes such as severe cardiac malformations with methylphenidate use so that they can conduct informed risk-benefit analyses and provide patients with accurate data.

Release, Expiration, and Review Dates

This educational activity was published in January 2021 and is eligible for AMA PRA Category 1 Credit™ through February 28, 2023. The latest review of this material was December 2020.

Disclosure of Off-Label Usage

The authors have determined that, to the best of their knowledge, no investigational information about pharmaceutical agents or device therapies that is outside US Food and Drug Administration–approved labeling has been presented in this article.

Funding/Support

This study was funded by the University of Aarhus Denmark, Director Jacob Madsen and wife Olga Madsen’s Foundation, Ove William Buhl Olesen and Mrs Edith Buhl Olesen Memorial Foundation, Carl and Ellen Hertz’s scholarship, Professor Ann Tabor’s Foundation, the Solar Foundation of 1978, and Health Research Fund of Central Denmark Region. Dr Petersen holds a professorship funded by Novo Nordisk Foundation grant NNFSA170030576.

Role of the Sponsor

The funders had no role in the design, analysis, interpretation, or publication of this study.

Acknowledgments

The authors thank the Danish Fetal Medicine Study Group. The Danish Fetal Medicine Study Group reports data to the database and has approved the study.

Additional information

Ethical approval: this study received the required approvals from the Danish Data Protection Agency (Aarhus University J.nr. 2016-051-000001/KEA-2017-24), from the Research Committee of the Danish Fetal Medicine Database, and from the Board of the Danish Health Service Prescription Database.

Faculty Affiliation

Line Kolding, MD, PhD*
Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

Vera Ehrenstein, MPH, DSc
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus University, Aarhus, Denmark

Lars Pedersen, MSc, PhD
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus University, Aarhus, Denmark

Puk Sandager, MD, PhD
Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Centre for Fetal Diagnostics, Aarhus University Hospital, Aarhus University, Aarhus, Denmark

Olav B. Petersen, MD, PhD
Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Copenhagen, Denmark

Niels Uldbjerg, MD, DMSc
Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

Lars H. Pedersen, MD, PhD
Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark
Department of Biomedicine, Aarhus University, Aarhus, Denmark

*Corresponding author: Line Kolding, MD, PhD, Department of Obstetrics and Gynecology, Aarhus University Hospital, Palle Juul-Jensens Blvd 99, 8200 Aarhus N, Denmark (e-mail: lkolding@clin.au.dk).

Financial Disclosure

All individuals in a position to influence the content of this activity were asked to complete a statement regarding all relevant personal financial relationships between themselves or their spouse/partner and any commercial interest. The CME Institute has resolved any conflicts of interest that were identified. In the past year, Marlene P. Freeman, MD, Editor in Chief of The Journal of Clinical Psychiatry, has received research funding from JayMac and Sage; has been a member of the advisory boards for Otsuka, Alkermes, and Sunovion; has been a member of the Independent Data Safety and Monitoring Committee for Janssen; has been a member of the Steering Committee for Educational Activities for Medscape; and, as a Massachusetts General Hospital (MGH) employee, works with the MGH National Pregnancy Registry, which is sponsored by Teva, Alkermes, Otsuka, Actavis, and Sunovion, and works with the MGH Clinical Trials Network and Institute, which receives research funding from multiple pharmaceutical companies and the National Institute of Mental Health. No member of the CME Institute staff reported any relevant personal financial relationships.

Drs Kolding, Ehrenstein, L. Pedersen, Sandager, Petersen, Uldbjerg, and L. H. Pedersen have no personal affiliations or financial relationships with any commercial interest to disclose relative to the article.

Accreditation Statement

The CME Institute of Physicians Postgraduate Press, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Credit Designation

The CME Institute of Physicians Postgraduate Press, Inc., designates this journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Note: The American Nurses Credentialing Center (ANCC) and the American Academy of Physician Assistants (AAPA) accept certificates of participation for educational activities certified for AMA PRA Category 1 Credit™ from organizations accredited by the ACCME.

Available Credit

  • 1.00 AMA PRA Category 1 Credit™
  • 1.00 Participation

Price

Cost:
$10.00
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