Adverse pregnancy outcomes after exposure to methylphenidate or atomoxetine during pregnancy

Abstract

ObjectiveTo determine if prenatal exposure to methylphenidate (MPH) or atomoxetine (ATX) increases the risk of adverse pregnancy outcomes in women with attention deficit/hyperactivity disorder (ADHD).Materials and methodsThis was a population-based cohort study of all pregnancies in Denmark from 1997 to 2008. Information on use of ADHD medication, ADHD diagnosis, and pregnancy outcomes was obtained from nationwide registers.ResultsWe identified 989,932 pregnancies, in which 186 (0.02%) women used MPH/ATX and 275 (0.03%) women had been diagnosed with ADHD but who did not take MPH/ATX. Our reference pregnancies had no exposure to MPH/ATX and no ADHD diagnosis. Exposure to MPH/ATX was associated with an increased risk of spontaneous abortion (SA; ie, death of an embryo or fetus in the first 22 weeks of gestation) (adjusted relative risk [aRR] 1.55, 95% confidence interval [CI] 1.03–2.36). The risk of SA was also increased in pregnancies where the mother had ADHD but did not use MPH/ATX (aRR 1.56, 95% CI 1.11–2.20). The aRR of Apgar scores <10 was increased among exposed women (aRR 2.06, 95% CI 1.11–3.82) but not among unexposed women with ADHD (aRR 0.99, 95% CI 0.48–2.05).ConclusionMPH/ATX was associated with a higher risk of SA, but our study indicated that it may at least partly be explained by confounding by indication. Treatment with MPH/ATX was however associated with low Apgar scores <10, an association not found among women with ADHD who did not use MPH/ATX.

Placental Complications Associated With Psychostimulant Use in Pregnancy

“…24 A recent cohort study compared women who used ADHD medication and women with ADHD diagnosis without medication to women with no ADHD diagnosis or medication in the general population of pregnancies in Denmark from 1997–2008. 25 They reported that methylphenidate or atomoxetine use in pregnancy (n=186) was not associated with reduced birthweight or gestational age at birth. However, they reported that women with a hospital-based diagnosis of ADHD who did not use medication (n=275) were at an approximately 2-fold increased risk of preterm birth.…”

Maternal and neonatal outcomes after exposure to ADHD medication during pregnancy: A systematic review and meta‐analysis

“…Finally, eight cohort studies were eligible for inclusion in this review. We included three studies that used the Danish National Patient Registry because they reported different maternal and neonatal outcomes, although there was some overlap in the study periods.…”

Management of psychotropic drugs during pregnancy

“…150 The 2014 systematic review did not include the results of three population based Danish cohort studies (n=186 methylphenidate or atomoxetine; n=480 methylphenidate, modafinil, and atomoxetine; n=222 methylphenidate alone). [151][152][153] The first study found that prenatal exposure was associated with an increased risk of spontaneous abortion (adjusted relative risk 1.55, 1.03 to 2.36) and lower Apgar scores (2.06, 1.11 to 3.82). 151 The second found that prenatal exposure was associated with increased risk of elective terminations of pregnancy by maternal request (odds ratio 4.70, 3.77 to 5.85) and by special indication (2.99, 1.34 to 6.67) and of miscarriage (2.07, 1.03 to 2.36).…”

“…[151][152][153] The first study found that prenatal exposure was associated with an increased risk of spontaneous abortion (adjusted relative risk 1.55, 1.03 to 2.36) and lower Apgar scores (2.06, 1.11 to 3.82). 151 The second found that prenatal exposure was associated with increased risk of elective terminations of pregnancy by maternal request (odds ratio 4.70, 3.77 to 5.85) and by special indication (2.99, 1.34 to 6.67) and of miscarriage (2.07, 1.03 to 2.36). 152 However, the women using stimulants were more likely to be young, single, less well educated, receiving social security, and taking other psychotropics.…”