Attention-Deficit/Hyperactivity Disorder Medication Use in Pregnancy and Risk of Preterm Birth: A Population-Based Cohort Study.

Background: Medication use during pregnancy for attention-deficit/hyperactivity disorder (ADHD) is increasing, but evidence on its safety in pregnancy for foetal health is limited, with little attention to time-related biases in observational research.

Objective: To determine the association between ADHD medication use in early and late pregnancy and the risk of preterm birth.

Methods: This population-based cohort study utilised data from national registers, including records on births, prescription medications, specialist healthcare visits, hospitalisations and educational attainment, to account for relevant potential confounders. We included singleton births delivered between 22 and 44 gestational weeks among pregnant individuals with ADHD medication use in the year before conception from Norway (2009-2020) and Sweden (2007-2019). ADHD medications (amphetamine, dexamphetamine, methylphenidate, atomoxetine, lisdexamfetamine and guanfacine) were assessed during early (conception to 21 gestational weeks) and late pregnancy (22-36 gestational weeks). The main outcome was preterm birth, defined as a live birth before 37 completed weeks of pregnancy. Risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using log-binomial regression and flexible parametric survival modelling to determine the risk of preterm birth in early and late pregnancy, respectively.

Results: Among 11,075 pregnancies, early pregnancy ADHD medication use was associated with higher preterm birth risk with ≥ 2 filled prescriptions (aRR 1.29, 95% CI 1.08, 1.53), but not as ≥ 1 prescription (aRR 1.08, 95% CI 0.93, 1.25). Any medication use in late pregnancy increased preterm birth risk (aHR 1.15, 95% CI 0.95, 1.39). For every 30 days of cumulative exposure to ADHD medication, the risk of preterm birth increased in late pregnancy (aHR 1.07, 95% CI 1.02, 1.12), but not in early pregnancy (aHR 1.01, 95% CI 0.97, 1.05).

Conclusions: ADHD medication may modestly increase the risk of preterm birth, especially with atomoxetine early and methylphenidate late in pregnancy, and with longer durations of use.