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]

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.

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 z score considered indicative of clinically relevant problems.

There were no differences in mean z 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.

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.

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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