Publication Date

2015-04-24

Document Type

Doctoral Dissertation

Academic Program

Clinical and Population Health Research

Department

Psychiatry

First Thesis Advisor

Jean A. Frazier, MD

Keywords

Tryptamines, Migraine Disorders, Mothers, Prenatal Exposure Delayed Effects, Pregnancy, Child Behavior, Child Behavior Disorders

Subjects

Dissertations, UMMS; Tryptamines; Migraine Disorders; Mothers; Prenatal Exposure Delayed Effects; Pregnancy; Child Behavior; Child Behavior Disorders

Abstract

Background: Migraine headache is a chronic pain condition that affects 20% of women of reproductive age, and is often treated with triptans. Triptans are serotonin 1B, 1D, and 1F receptor agonists that act as vasoconstrictors and inhibitors of the trigeminal cervical complex as well as peripheral neurons; they cross the blood brain barrier and placenta, and as such are plausible neurodevelopmental teratogens. No studies have examined risk of neurodevelopmental problems in children with prenatal triptan exposure. This dissertation had three aims: (1) to examine risk of behavioral problems in children using in the presence of time-varying confounding by concomitant medication use; (2) to examine risk of temperamental, motor, and communication disturbances associated with prenatal triptans exposure, adjusting for unmeasured confounding by migraine type and severity; and (3) to examine changes in neurodevelopment over time associated with prenatal triptan exposure.

Methods: This dissertation used data from the Norwegian Mother and Child Cohort Study, a prospective birth cohort including more than 100,000 women recruited during their first prenatal ultrasound visit. Aims 1 and 3 used marginal structural models to assess the risk of (1) neurodevelopmental problems at age 36 months (Aim 1), or (2) change in risk of neurodevelopmental problems from 18 to 36 months (Aim 3) associated with prenatal triptan exposure. Aim 2 used propensity matching and calibration to adjust for unmeasured confounding by migraine type, severity, and attitudes towards medication use in pregnancy. Neurodevelopmental outcome measures included the Child Behavior Checklist (CBCL), the Emotionality, Activity, and Temperament Scale (EAS), and the Ages and Stages Questionnaire (ASQ). Exposure to triptans was ascertained by self-report.

Results: Prenatal triptan exposure was associated with greater externalizing behavior problems at 18 and 36 months, as well as greater increases in emotionality and activity from 18 to 36 months. We observed no association between triptan exposure and motor skills or communication problems; triptan use during pregnancy was associated with migraine severity but not migraine type, and adjustment for unmeasured migraine characteristics moved effect estimates towards the null.

Conclusions: Prenatal triptan exposure is associated with externalizing-type behaviors and temperament in children, while migraine itself is associated with internalizing-type behaviors and temperament. The use of concomitant medications and the severity of the underlying condition both exerted substantial influence on observed effect estimates, and should be considered in any future studies of triptan medication use in pregnancy.

DOI

10.13028/M2K59J

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