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Is Prenatal Exposure to Triptans Linked to ADHD in Children?

  • Authors: News Author: Pauline Anderson; CME Author: Charles P. Vega, MD
  • CME / ABIM MOC / CE Released: 7/22/2022
  • Valid for credit through: 7/22/2023, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for primary care physicians, obstetrician gynecologists, neurologists, nurses, pharmacists, physician assistants, and other members of the healthcare team who treat and manage women with migraine.

The goal of this activity is for learners to be better able to assess whether maternal use of triptans during pregnancy might promote a higher risk for attention-deficit/hyperactivity disorder among their offspring.

Upon completion of this activity, participants will:

  • Evaluate the outcomes of pregnancy associated with the maternal use of triptans
  • Assess whether maternal triptan use affects the risk for attention-deficit/hyperactivity disorder among children
  • Outline implications for the healthcare team


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News Author

  • Pauline Anderson

    Freelance writer, Medscape


    Pauline Anderson has no relevant financial relationships.

CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine


    Charles P. Vega, MD, has the following relevant financial relationships:
    Consultant or advisor for: GlaxoSmithKline; Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Editor/Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC


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Compliance Reviewer

  • Yaisanet Oyola, MD

    Associate Director, Accreditation and Compliance, Medscape, LLC


    Yaisanet Oyola, MD, has no relevant financial relationships.

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This activity has been peer reviewed and the reviewer has no relevant financial relationships.

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Is Prenatal Exposure to Triptans Linked to ADHD in Children?

Authors: News Author: Pauline Anderson; CME Author: Charles P. Vega, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 7/22/2022

Valid for credit through: 7/22/2023, 11:59 PM EST


Clinical Context

Triptans are one of the most common medications used among women of childbearing age. The authors of the current study state that from 9% to 25% of women use triptans during pregnancy. What are the potential consequences of using triptans during pregnancy? Alexander Marchenko, MD, and colleagues evaluated this issue in a meta-analysis of 6 studies assessing the safety of triptans during pregnancy. Their results were published in the February 3, 2015, issue of Headache: The Journal of Face and Head Pain.[1]

Comparing children who were born to women with migraine who were and were not treated with triptans, there was no difference between groups in terms of rates of major congenital malformations, prematurity, or spontaneous abortions. Triptans were also not associated with higher rates of major congenital malformations or prematurity compared with children born to mothers without migraine. However, triptans were associated with a 3-fold increase in the risk for spontaneous abortion compared with the healthy control group. In contrast, children born to women with migraine who did not receive triptans experienced a higher rate of major congenital malformations compared with children delivered by women without migraine.

Previous research has found that triptan use during pregnancy might be associated with a higher risk for externalizing behaviors during early childhood. The current study evaluates whether maternal use of triptans might affect the risk for attention-deficit/hyperactivity disorder (ADHD) among children.

Study Synopsis and Perspective

Triptan use during pregnancy does not increase the risk for ADHD in offspring, new research suggests.

"The findings should reassure women who need to take this class of drugs during pregnancy," study author Hedvig Nordeng, PhD, professor and head of the Pharmacoepidemiology and Drug Safety Research Group at the University of Oslo, Norway.

She stressed the need to discuss with patients not only the risks of medication use during pregnancy but also "the risks of not treating severe and debilitating migraine for both the women and her child."

The study was published online June 3 in JAMA Network Open.[2]

Limited Safety Data

Experts estimate that from 9% to 25% of women with migraine use triptans during pregnancy. However, information on the safety of these drugs in pregnancy is limited, particularly for long-term outcomes, including their effect on neurodevelopmental outcomes in children, such as ADHD, which is common and has an estimated worldwide prevalence of 5%.

The study used data from the Norwegian Mother, Father and Child Cohort Study (MoBa), a population-based pregnancy cohort study, which Dr Nordeng said is one of the largest such studies in the world. MoBa is linked to the Medical Birth Registry of Norway, the Norwegian Patient Registry, and the Norwegian Prescription Database.

Study participants completed questionnaires at various stages of pregnancy and when their child was 5 years old. The sample included women who reported migraine or triptan use before or during pregnancy or who filled a triptan prescription in the 6 months before pregnancy.

Researchers defined 2 analytic groups: an ADHD diagnosis sample determined using registry information on diagnosis and dispensed medications and an ADHD symptoms sample, using items related to inattention and hyperactivity or impulsivity in offspring at age 5 years from the parent-reported Conners Parent Rating Scale–Revised, Short Form (CPRS-R[S]).

The authors believed that it was important to identify children with "more subtle problems that can actually be extremely challenging to a child" but may not meet "the threshold" for a diagnosis, said Dr Nordeng.

The ADHD diagnosis sample included 10,167 children born to 8412 mothers with migraine (mean age, 30.2 years). The ADHD symptoms sample had 4367 children born to 3855 mothers with migraine (mean age, 30.6 years).

The mean age of the children at the time of an ADHD diagnosis was 8.6 years, and these children were followed for a mean of 10.6 years.

About 8.2% of the ADHD diagnosis sample and 9.2% of the ADHD symptom sample were exposed to triptans during pregnancy. Researchers compared triptan-exposed children with two groups of unexposed children: those whose mothers reported migraine during pregnancy and those whose mothers had migraine only before pregnancy.

A Positive Public Health Message

Children exposed to triptans in utero had no increased risk for ADHD compared with unexposed children. This was true when they were compared with children whose mothers had migraine during pregnancy (weighted hazard ratio [HR], 1.16; 95% confidence interval [CI], 0.78-1.74) and those whose mothers had migraine only before pregnancy (weighted HR, 1.28; 95% CI, 0.84-1.94).

Weighted estimates were adjusted for several factors, including maternal age, parity, marital status, education, income, body mass index, folic acid use, smoking, alcohol intake, symptoms of anxiety or depression, and satisfaction with life, which is a proxy for migraine severity.

In the group with ADHD symptoms the mean CPRS-R(S) score was 1.39 and 5.5% of the children had a score considered indicative of clinically relevant problems.

There were no differences in mean scores between triptan-exposed children and triptan-unexposed children whose mothers had migraines during pregnancy (weighted mean difference, −0.11; 95% CI, −0.25 to 0.04) or only before pregnancy (weighted mean difference, −0.09; 95% CI, −0.24 to 0.07).

The finding of no relationship between triptans in pregnancy and ADHD risk "is a positive public health message for women with migraine in need of their medication," said Dr Nordeng. "This is directly answering questions that not only mothers have but also fathers and members of the healthcare team."

Some previous studies conducted by Dr Nordeng and colleagues showed a signal of behavior issues in children with prenatal triptan exposure, but this new study, which included information on child diagnosis from a nationwide patient registry, has a stronger design and more robust results, said Dr Nordeng.

However, the study does have limitations. Misclassification of triptan exposure may have affected the results; for example, in the last part of pregnancy, exposure was reported retrospectively and may be subject to poor recall. In addition, the investigators had no information about dosage, so dose-dependent effects cannot be ruled out.

Another study limitation was possible selection bias. The authors note that participants in the MoBa birth cohort were more likely to be married or cohabiting and to have a higher educational level and healthier lifestyle compared with the general population.

The results may not be generalizable to other countries, said Dr Nordeng, noting that the prevalence of ADHD among children in Norway is about 4% vs about 9% in the US. "The threshold and likelihood of getting an ADHD diagnosis may differ in different societies and healthcare systems," she said.

Welcome Research

Lauren Doyle Strauss, DO, an associate professor of neurology at Wake Forest University School of Medicine, Winston-Salem, North Carolina, who has focused on management of migraine in pregnancy, said that the study is "welcome and exciting."

It is reassuring to see that triptans, a commonly used class of drugs, are "seemingly relatively safe" to treat migraine in pregnancy, said Dr Strauss.

She noted that pregnant women with migraine are "a difficult patient population to study, and it takes lot of time and effort to look at children and to follow them throughout life."

ADHD is becoming increasingly recognized, and although treatments for it are available, "It has a huge impact on the family and on the patients and their ability to navigate the school system."

She said that she hopes there will be additional studies that examine other childhood diagnoses "to provide further reassurance, because treating pain in pregnancy is really important."

The investigators and Dr Strauss have disclosed no relevant financial relationships.

Study Highlights

  • Study data were drawn from the Mother, Father, and Child Cohort Study in Norway. This study was open to all Norwegian-speaking women with a pregnancy between 1999 and 2008, and 41% of potential participants provided study data. The total cohort includes 114,500 children and 95,200 mothers.
  • Only women who reported migraine or receiving migraine treatment before or during pregnancy were included in the present analysis.
  • The main study outcome was ADHD during childhood, which was defined by diagnosis codes and the use of ADHD medications. In addition, researchers included symptoms consistent with ADHD on the CPRS-R(S) as an outcome.
  • The study analysis focused on the relationship between triptan use before or during pregnancy and the subsequent incidence of ADHD in offspring. This result was adjusted to account for demographic factors, health habits among parents, parental mental health disorders, other medication use during pregnancy, and parent quality of life as a proxy for maternal migraine severity.
  • 11.2% of mothers reported a history of migraine before or during pregnancy. The ADHD diagnosis cohort included 377 children (3.7% of sample; similar to the national prevalence of ADHD in Norway), whereas 4367 children had positive survey findings for ADHD.
  • The average maternal age at delivery in the ADHD sample was 30 years. Just more than 50% of children were boys. Women using triptans during pregnancy tended to be older and more highly educated, and they were less likely to smoke during pregnancy.
  • Slightly more than 8% of children in the ADHD cohort were exposed to triptans in utero.
  • Compared with children of mothers with migraine who did not use triptans during pregnancy, there was no increase in ADHD associated with maternal triptan use (HR, 1.16; 95% CI, 0.78-1.74). The respective HR focused only on women who had migraine before pregnancy was 1.28 (95% CI, 0.84-1.94).
  • 5.5% of children had a likely diagnosis of ADHD based on the parental survey results.
  • Similarly, the use of triptans before or during pregnancy did not correlate significantly with symptoms of ADHD.

Clinical Implications

  • In a previous study, there was no difference in the rates of major congenital malformations, prematurity, or spontaneous abortions when comparing children who were born to women with migraine who were and were not treated with triptans. Maternal triptan use was also not associated with higher rates of major congenital malformations or prematurity compared with children born to mothers without migraine. However, maternal triptan use was associated with a 3-fold increase in the risk for spontaneous abortion compared with the healthy control group.
  • The current study finds no association between maternal triptan use before or during pregnancy and the risk for ADHD in offspring.
  • Implications for the healthcare team: The healthcare team can reassure patients who need triptan therapy during pregnancy that use of these drugs is not associated with a higher risk for ADHD among offspring.


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