Timing and Duration of ADHD Medication Use in Pregnancy and Risk of Preterm Birth

Background: Attention-deficit hyperactivity disorder (ADHD) medication use in pregnancy is increasing and might be associated with adverse perinatal outcomes. While previous research on ADHD medication use in pregnancy has suggested a small increased risk of preterm birth, there has been limited focus on timing and duration of medication use in pregnancy.

Objectives: To determine the effect of timing and duration of ADHD medication use in pregnancy on the risk of preterm birth.

Methods: This was a population-based cohort study. Data on births, filled prescriptions, and potential confounders were obtained from the medical birth registers linked with the prescribed drug registers and national patient registers of Norway (2009-2020) and Sweden (2007-2019). Singleton pregnancies delivered at 22-44 weeks were included and the population was restricted to women filling prescriptions for ADHD medication from 3 months before conception until 22 gestational weeks. ADHD medication (amphetamine, dexamphetamine, methylphenidate, atomoxetine, lisdexamfetamine, or guanfacine) use was defined as 1 or more prescription fills during pregnancy. Treatment episodes were constructed to quantify medication use in a time-dependent manner. Exposure was defined as follows: 1) Time-fixed exposure to ADHD medication defined as exposed or unexposed during late pregnancy i.e., between last menstrual period (LMP)+154 to LMP+258 days based on falling within or outside a treatment episode; 2) For each day of pregnancy at risk of preterm birth, cumulative medication exposure to ADHD medication corresponding to the total number of days of use since conception was calculated. Preterm birth was defined as live births < 37 weeks. We used propensity scores-based inverse probability of treatment weights to control for confounding. Flexible parametric survival modeling was used to estimate hazard ratios (HR).

Results: Among women who filled prescriptions for ADHD medication (N=7,856), time-fixed exposure in late pregnancy was associated with increased (unadjusted) risk of preterm birth (HR 1.46, 95% CI 1.21-1.75). After confounder adjustment, the increased risk was attenuated (HR 1.19, 95% CI 0.98-1.45). For every 30 days of cumulative exposure to ADHD medication during pregnancy, increasing duration of exposure was not associated with increased risk of preterm birth (unadjusted HR 1.04, 95% CI 1.01-1.07; adjusted HR 1.02, 95% CI 0.98-1.05).

Conclusions: In this study, exposure to ADHD medication in late pregnancy as well as greater cumulative exposure to ADHD medication during pregnancy were not associated with a meaningfully increased risk of preterm birth.