Risk of Major Congenital Malformations Associated With the Use of Methylphenidate or Amphetamines in Pregnancy.

The use of prescription psychostimulants during pregnancy has been increasing in recent years. One large and 3 small studies have recently examined the risk of major congenital malformations following the use of methylphenidate and amphetamines during the first trimester of pregnancy. The broad findings of these studies are that first trimester gestational exposure to methylphenidate or amphetamines is associated with an increased risk of major congenital malformations but the associations are no longer statistically significant after adjusting analyses for confounding variables; that first trimester exposure to amphetamines is not associated with an increased risk of cardiovascular malformations; and that first trimester exposure to methylphenidate may increase the risk of cardiovascular malformations. A closer look at the data on the last-mentioned finding, however, suggests that the statistical significance of the finding is in doubt and that even if the finding is statistically significant, it is probably not clinically significant. Furthermore, all the findings emerged from observational studies that cannot exclude confounding by indication and other sources of confounding. A reasonable conclusion, therefore, is that there is no evidence, at present, to suggest that methylphenidate and amphetamines are teratogenic. Nevertheless, because absence of evidence of risk is not evidence of absence of risk, the benefits of continuing psychostimulant medication during pregnancy should be weighed against potential risks in an individualized and shared decision-making process.