(BSPOT17) Trajectories for migraine medication in pregnancy and neurodevelopmental outcomes in offspring - a nationwide registry-based study

Background: The longer-term neurodevelopmental safety of migraine medications during pregnancy is unclear.

Objectives: This study aimed at evaluating the association between triptan exposure trajectories during pregnancy, alone and in combination with other preventive migraine medications, and risk for a broad and specific set of neurodevelopmental outcomes in children up to 14 years of age.

Methods: This a nationwide, health-registry linkage study in Norway. Based on the Medical Birth Registry data, we included 26,804 pregnancies with a delivery date between 2009-2019 with migraine within the 12 months before the last menstrual period (LMP) date. Single and multiple group-based trajectory models (GBTM and GBMTM) were applied to model longitudinal exposure (based on filled prescriptions) to triptans alone and combined with preventive antimigraine medications, respectively, from 12 months before LMP through delivery. Outcome measures were based on specialist outpatient and inpatient clinical diagnoses in offspring up to adolescence, for specific developmental outcomes and for a broad composite measure. We fit adjusted and weighted pooled logistic regression models, as well as standardized risk curves, using propensity score-based overlap weighting.

Results: 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%). Children born to women in any triptan trajectory group had consistently a small increased hazard for the composite developmental outcome (magnitude range of the hazard ratio (HR): 1.05-1.16) relative to non-medicated with migraine. Standardized risks curves showed a risk difference inferior to 2%, considering both single and multi-trajectories for this comparison. These risks decreased to the null when “Discontinuers before (low use)” acted as comparator, and results remained consistent in relation to speech/language or attention/deficit-hyperactivity disorders. There was a slightly elevated risk (24-30%) for autism disorders with both triptan late discontinuation trajectories, but the 95% CI crossed the null and the weighted risk difference remained low.

Conclusions: In this population of women with pre-pregnancy migraine, we found no increased risk for a broad set of neurodevelopmental outcomes in children up to adolescence following prenatal triptan exposure at different intensity, alone or combined with other preventive medications.