In addition to reviewing the risks of untreated ADHD in pregnancy, it is important to discuss the potential risks of treatment on the developing fetus. For treatment of ADHD, the FDA has approved stimulant therapy, which is the mainstay of treatment, as well as a nonstimulant medication called atomoxetine. The two most common types of stimulants used in the treatment of ADHD are dextroamphetamine and methylphenidate. Most data on dextroamphetamine exposure in pregnancy come from illicit rather than therapeutic use. Illicit stimulant use during pregnancy has been associated with decreased infant birth weight, prematurity, and increased maternal and fetal morbidity.
A 10-year follow-up study of children exposed in utero to illicit stimulants has shown significant effects on development. Although they had normal intellectual capacity, they were found to a have increased aggressive behaviors, a greater likelihood of being one grade below what was normal for their biologic age, and have decreased weight and height. However, it has been difficult to determine if adverse effects were the result of amphetamine exposure or confounding factors, such as exposure to other drugs of abuse, including alcohol, exposure to contaminants in nonpharmaceutical preparations, or other lifestyle choices.10,11
A recent chart review of 276 pregnant women with positive urine drug screen results for methamphetamine or statement of use during pregnancy showed they had greater rates of preterm delivery, cesarean delivery, and neonatal mortality, and their infants had lower Apgar scores at birth.12 Although there are a number of case reports of prescribed amphetamine exposure during human pregnancies associated with various fetal malformations, a prospective study of women prescribed anorectics failed to confirm any risk of congenital malformations. However, this report did suggest that maternal amphetamine use increased the risk of cleft palate.13
A large cohort study that monitored 50,282 women with medication exposures during pregnancy reported on 367 women taking dextroamphetamine and 215 women taking unspecified amphetamines during the first trimester; results indicated that there was no increased risk of fetal malformations.14
Data on exposure to methylphenidate are limited. There are several case reports in the literature, from which it is difficult to draw conclusions. The large cohort study that monitored 50,282 women with medication exposures during pregnancy included 11 mother-child pairs with first trimester methylphenidate exposures and found no significant increase in malformations.14 A second group of 13 newborns with early pregnancy methylphenidate exposure was examined as part of a surveillance study of Michigan Medicaid recipients. One major malformation and one cardiac defect were found within this group.15,16 A retrospective chart review examined the effects of intravenous methylphenidate and pentazocine abuse among 38 pregnant women; of the 39 exposed infants, 21% were born prematurely, 31% had growth retardation, and 28% had symptoms of withdrawal. Unfortunately, there was no control group and concurrent substance may have confounded the results.17
Data about the effects of atomoxetine (Strattera) exposure during pregnancy are also limited. There were three pregnancies studied during premarketing clinical trials, the details of which have not been published. These pregnancies resulted in two healthy newborns and one loss to follow-up.18
The lack of data on the impact of ADHD on pregnancy makes assessing the risk of untreated ADHD difficult. However, the literature from studies in the general population suggests that there could be a real impact of untreated ADHD on pregnancy. There are also limited data on the risks of psychopharmacologic treatment on the developing fetus. Available data suggest that dextroamphetamine does not have teratogenic effects, but may confer lower infant birth weights. Minimal data on methylphenidate and atomoxetine do not suggest teratogenicity, but conclusions cannot be definitively drawn. At this time, preconception counseling for women with ADHD is limited to presenting the minimal data available and allowing women to make informed decisions.