USE OF THERAPEUTIC AMFETAMINES IN PREGNANCY

Therapeutic amfetamines, including lisdexamfetamine and dexamfetamine, are licensed to treat attention deficit hyperactivity disorder (ADHD).

Untreated ADHD in the general population can increase the likelihood of risk-taking behaviour, including smoking and alcohol or recreational drug use. In addition, ADHD often manifests as anxiety-type behaviours in females; therefore, the continued treatment of ADHD in pregnancy may be beneficial for some patients. An individualised discussion of the risks and benefits of continued treatment is highly recommended.

Five studies describe approximately 6,200 unique therapeutic amfetamine-exposed pregnancies. Where details were provided, most of the exposures were documented to have occurred in early pregnancy only; as such, data regarding exposure to therapeutic amfetamines in the later stages of pregnancy are lacking.

The available safety data, although somewhat limited, have not associated use of therapeutic amfetamines in early pregnancy with an increased risk of congenital major malformation overall, cardiac malformation overall or any specific cardiac malformation. Use in the first half of pregnancy has not been associated with increased risks of perinatal death, impacts on birth weight outcomes (such as low birth weight, high birth weight or small for gestational age). However, the risk of growth impairment with use of therapeutic amfetamines in the later stages of pregnancy is unknown. Given that amfetamines can cause vasoconstriction, there is a theoretical risk of impaired placental perfusion, with possible impacts on fetal growth.

A large population-based and methodologically robust study has suggested a small increased risk of preterm delivery following maternal therapeutic amfetamine use in the first half of pregnancy. The findings from this study suggest an absolute risk of approximately 10%, relative to a background risk of 7.5%. There are methodologically limited data which suggest that the absolute risk may be further raised with continued exposure in the later stages of pregnancy (up to approximately 12%).

As therapeutic amfetamines are centrally acting stimulants, a possibility of neonatal withdrawal and associated complications may exist. Possible associations with placental abruption, pre-eclampsia, low 1-minute Apgar scores, and the requirement for neonatal resuscitation and neonatal admission have been described following maternal use in pregnancy. Pregnancies with exposure to CNS-acting medication in the later stages of gestation should ideally be delivered in a unit with adequate neonatal facilities to monitor for neonatal complications.

No studies investigating the risk of miscarriage, neurodevelopmental impairment or childhood cancer have been located in the literature. Animal studies of intrauterine amfetamine exposure have described learning and memory deficits and altered locomotor activity in the offspring. However, it is unclear how accurately these studies predict risks for human pregnancy exposures.

Exposure to therapeutic amfetamines at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy. Owing to a lack of sufficient safety data, additional fetal monitoring, particularly of fetal growth, may be warranted on a case-by-case basis. Other risk factors may be present in individual cases which could independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of considering such factors when performing case-specific risk assessments.