Background: Use of medication during pregnancy for treatment of attention-deficit/hyperactivity disorder (ADHD) is increasing. Evidence supporting ADHD medication safety in pregnancy for fetal health is limited.
Objectives: To determine if ADHD medication use in pregnancy is associated with an increased risk of preterm birth.
Methods: We conducted a population-based cohort study using data from the patient, birth, and prescribed drug registers of Norway (2009-2020) and Sweden (2006-2019). We included singleton births with a valid gestational age (22-44 weeks). ADHD was defined as having a diagnosis from specialist care (ICD-10 F90) at any time before delivery or a prescription fill for ADHD medication (amphetamine, dexamphetamine, methylphenidate, atomoxetine, lisdexamfetamine, or guanfacine) from a year before the last menstrual period (LMP) until delivery. We defined ADHD medication use as ≥1 prescription fill for ADHD medication from the estimated date of conception (LMP+14 days) to < 22 weeks (LMP+153 days). Unexposed pregnancies had no prescription fills for ADHD medication from 3 months before conception to < 22 weeks. Preterm birth was defined as birth before 37 completed weeks of gestation ( < 259 days). We described the risk of preterm birth in women with ADHD versus no ADHD, regardless of treatment use. We then restricted to births in women with ADHD and estimated the crude and adjusted risk ratios (RRs) for preterm birth according to ADHD medication use. We estimated propensity scores and inverse-probability of treatment weights to adjust for confounders including maternal sociodemographic variables, comorbidities and psychotropic comedication. We used weighted log-binomial regression to estimate adjusted RRs.
Results: We included 689 921 births from Norway, and 1 451 438 from Sweden. Those with ADHD (n=28 137) had an increased risk of preterm birth (7.4%) compared to those without ADHD (5.4%), regardless of their medication use during pregnancy (crude RR 1.4, 95% CI 1.3-1.4). Among women with ADHD, the risk of preterm birth was higher for those exposed to ADHD medication (n=4 270, 8.4%) in early pregnancy compared to unexposed (n=20 055, 7.1%; crude RR 1.2, 95% CI 1.1-1.3). However, the association was attenuated to the null when we adjusted for all confounders (adjusted RR 1.0, 95% CI 1.0-1.1).
Conclusions: There is a higher baseline risk of preterm birth among women with ADHD. In this study, ADHD medication use in early pregnancy was not associated with an increase in the risk of preterm birth. There remains a need to explore the risk associated with medication exposure in late pregnancy, accounting for differential length of exposure time.
