Association of Prenatal Exposure to Triptans, Alone or Combined With Other Migraine Medications, and Neurodevelopmental Outcomes in Offspring

Abstract

Background and objectives: The long-term reproductive safety of migraine medications remains uncertain. This study sought to examine the effect of different intensities and durations of prenatal exposure to triptans, alone and combined with other preventive migraine medications, on neurodevelopmental disorders (NDDs) in children.

Methods: This nationwide health registry study in Norway included pregnancies of women with migraine before pregnancy and followed up their children up to 14 years of age. Single and multiple group-based trajectory models and group-based multitrajectory models were applied to cluster triptan exposure alone and combined with preventive antimigraine medications. Child outcomes, based on specialist outpatient and inpatient diagnoses, included autism spectrum and behavioral disorders, learning and intellectual disabilities, speech/language and developmental coordination disorders, and attention-deficit hyperactivity disorders (ADHDs). We fit adjusted and weighted pooled logistic regression models and standardized risk curves using propensity score-based overlap weighting.

Results: We included 26,210 pregnancies of women with migraine; 4,929 and 21,281 were, respectively, nonmedicated and medicated with triptans in the year of prepregnancy. In the latter group, we identified 4 group-based trajectories of triptans alone and combined with preventive medications: discontinuers before (low use) (41.5%, 47.0%), early discontinuers (short-term low use) (31.3%, 28.8%), late discontinuers (moderate use) (21.3%, 9.1%), and late discontinuers (high use) (5.9%, 15.2%). Overall, 1,140 children (4.3%) had a NDD (mean follow-up time: 8 years). Children born to women with any triptan trajectory had a slightly higher risk of NDD compared with children of nonmedicated women (magnitude range of the weighted hazard ratio [wHR]: 1.05-1.16). These risks decreased to the null when discontinuers before (low use) acted as a comparator (magnitude of wHR: 0.94-1.01) or when analyzing speech/language disorders or ADHD (magnitude of wHR: 0.82-1.14). There was a slightly elevated risk of autism disorders with both triptan late discontinuation trajectories (wHR 1.24, 95% CI [0.78-1.97]; wHR 1.30, 95% CI [0.66-2.56]), but the 95% CI crossed the null and the weighted risk difference remained low.

Discussion: Our findings indicate that prenatal exposure to triptans, alone or combined with other migraine medications, does not substantially increase the risk of a broad range of neurodevelopmental outcomes in children up to adolescence.