Prescription Stimulant Continuation in Pregnancy and Birth Outcomes

Although studies examining utero exposure to prescription stimulants have suggested an association with maternal and fetal adverse events, results have been inconsistent. Therefore, clinicians may not have clear guidance about stimulant use during pregnancy. The objective of this study was to evaluate maternal and fetal risks of prescription stimulant exposure among women of reproductive age throughout the continuum of pregnancy in a large, commercially insured United States population.

We used a large administrative claims database from 2013 to 2021 to compare stimulant exposed pregnancies to a matched cohort of non-exposed pregnancies. Stimulant exposed pregnancies included early stimulant use, defined as one or more stimulant prescription fills at any point during the first trimester and continued exposure, defined as continuation into the second or third trimesters. Relative risk regression models were used to compare the risk of each outcome between exposure and duration of exposure cohorts matched on clinical conditions and medication used by 1:1 greedy neighbor propensity score matching.

Among a sample of 10,265 matched patients, early stimulant exposure (first trimester only) was associated with a higher likelihood of live birth (RR = 1.08, 95% CI [1.06, 1.10]) and lower risks of spontaneous abortion (RR = 0.69, 95% CI [0.64, 0.76]) and preterm birth (RR = 0.75, 95% CI [0.62, 0.90]) compared with no stimulant exposure. Stillbirth and ectopic pregnancy did not differ. When exposure continued into the second or third trimesters, risks increased for placental abruption (RR = 1.63, 95% CI [1.03, 2.57]), pre-eclampsia (RR = 1.42, 95% CI [1.19, 1.69]), gestational hypertension (RR = 1.37, 95% CI [1.16, 1.61]), and preterm birth (RR = 1.34, 95% CI [1.12, 1.62]) compared with non-exposed pregnancies. Stillbirth was not significantly different in this comparison (RR = 1.42, 95% CI [0.76, 2.67]). Direct comparison of continued versus early exposure highlighted more pronounced risks with continuation: higher stillbirth (RR = 3.54, 95% CI [1.48, 8.44]), spontaneous abortion (RR = 1.53, 95% CI [1.38, 1.68]), preterm birth (RR = 1.86, 95% CI [1.51, 2.28]), placental abruption (RR = 1.78, 95% CI [1.11, 2.84]), and pre-eclampsia (RR = 1.33, 95% CI [1.12, 1.59]). Small-for-gestational-age infants were also more frequent in the continuation group (RR = 1.47, 95% CI [1.12, 1.92]). Analyses stratified by stimulant class (amphetamine vs methylphenidate containing) were directionally consistent with the overall findings.

Although early stimulant exposure was not associated with increases in maternal or fetal risk, our study suggests that continuation of stimulants into trimesters 2 and/or 3 may increase some pregnancy complications including stillbirth, preterm birth, hypertensive disorders of pregnancy, and placental abruption. Clinicians should consider these risks when making the decision to continue stimulants during pregnancy, especially in treating ADHD.