Antidepressant Prescription in Pregnancy: The Importance of Prenatal Maternal Anemia as a Potential Confound in Studies on Neurodevelopmental and Other Outcomes.

Many observational studies have found an association between antidepressant drug prescription during pregnancy and neurodevelopmental disorders such as autism spectrum disorder, attention-deficit/hyperactivity disorder, and intellectual disability. The results of such studies cannot be considered conclusive because of the possible presence of inadequately measured, unmeasured, and unknown confounds. In this context, maternal anemia before or at but not after 30 weeks of gestation was recently associated with an increased risk of all 3 of these neurodevelopmental disorders. Additionally, meta-analysis has shown that maternal anemia during pregnancy is associated with other adverse gestational outcomes, as well. Given that anemia is common during pregnancy, and that iron deficiency during pregnancy can compromise neurodevelopment in the offspring, it is clear that maternal anemia during pregnancy should be included as a confound that is adjusted for in analyses in studies of psychotropic drugs in pregnancy. However, many studies that significantly associated gestational exposure to antidepressants with adverse pregnancy outcomes did not adjust for maternal anemia during pregnancy. This issue is not merely academic because studies with such "significant" findings discourage depressed pregnant women from accepting antidepressants; therefore, women and their unborn children may risk experiencing the known harms associated with untreated depression during pregnancy. Additionally, such "significant" findings may provoke unjustified guilt in women who do use antidepressants during pregnancy, especially if the pregnancy is associated with an adverse outcome. Whereas this is not an endorsement of the unquestioning use of antidepressants during pregnancy, it does imply that those who argue against medication use during pregnancy should re-examine the science on which their views are based.