ADHD, Stimulants and Teratogenic Effects

Since 2003, stimulant medications such as methamphetamine, amphetamines and methylphenidate have been among the most commonly abused substances that precipitate admission of women to U.S. federally funded health centers for substance use disorder (SUD) treatment. Yet stimulant use among women of child-bearing age often occurs in combination with use of other substances such as opioids, marijuana, cigarettes and alcohol. The connection between alcohol use and teratogenic effects has been established, but there is a paucity of human studies that show clear conclusions regarding the effects of stimulants on a fetal development. However, from a handful of previous studies of various reliability, stimulant use (primarily methamphetamine) during pregnancy is associated with several adverse teratogenic outcomes, including:

  • Higher rates of preterm birth
  • Placental abruption
  • Cardiac anomalies
  • Smaller head circumference
  • Fetal distress
  • Fetal growth restriction (at rates similar to those for pregnant women who use cocaine)

Increasing Prevalence of Stimulant Use

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder diagnosed in children, teens and young adults in the U.S. There are three clinical manifestations: 1.) Inattention, lack of focus, 2.) Hyperactivity-impulsivity, and 3.) Mixed, whereas features of both types are present. Although originally defined as a childhood disorder, newer data suggests that ADHD can persist into adulthood. The estimated prevalence of ADHD in the U.S. is 3%. Methamphetamine Psychosis and Schizophrenia

Stimulant medication, including amphetamines and methylphenidate, are considered first-line treatment for managing ADHD. Given the rapidly increasing use of these medications among women of childbearing age, the risk of exposure to stimulant medication is an inherent developmental risk factor. This age cohort is at greater risk of SUDs and unprotected sexual behavior. As a result, there is a need to better understand both risk and protective factors of high-risk women of child bearing age. Yet there remains confusion regarding the differences between stimulants.

* Methamphetamine, which was not included in this study, is also FDA approved and prescribed for ADHD. But because of its abuse potential, it is rarely used for this reason. It is however, clandestinely manufactured and sold illicitly and abused by millions.

In this original JAMA research, Huybrechts and Bröms, et al., examine the risks associated with first-trimester intrauterine exposure to amphetamines used to treat ADHD and major congenital malformations, including the most common teratogenic malformation—cardiac defects. In the primary analysis, the investigative team culled and analyzed a cohort of pregnancies linked to offspring of Medicaid beneficiaries throughout the U.S. At follow-up from the primary analysis, the researchers replicated the analyses methodology using data from five Nordic nationwide health registries (Denmark, Finland, Iceland, Norway and Sweden). The findings from this cohort study included 1.8 million pregnancies in the U.S. Medicaid Analytic group between 2000-2013, which suggested a small increased risk of cardiac malformations associated with methylphenidate use (pooled relative risk, 1.28; 95% CI, 1.00-1.64); an increase in the risk of this malformation type was not found for amphetamines. Neither methylphenidate nor other amphetamines commonly prescribed for ADHD were associated with a substantial increased risk for malformations overall.

Why Does This Matter?

Abuse and addiction to stimulants is a major health concern. ADHD is a debilitating neurological disorder that can alter the life trajectory for children and adolescents. Balancing the risk and rewards is the line that clinicians who treat ADHD must walk each day. Not all stimulants are equal, and patient response varies considerably. Untreated ADHD is associated with increased risk of SUDs, depression and numerous social and psychological issues. Given the prevalence of ADHD, educating health providers and parents should remain a public health priority.

Krista F. Huybrechts, MS, PhD; Gabriella Bröms, MD, PhD, et al. Association Between Methylphenidate and Amphetamine Use in Pregnancy and Risk of Congenital Malformations
A Cohort Study from the International Pregnancy Safety Study Consortium. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.3644 Published online December 13, 2017.

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