This study contributes to the small but expanding literature that suggests that prenatal antidepressant use does not appear to have major adverse effects on infant neurobehavioral development.6–9,12,13,16
Our prospective study with comparable numbers of subjects to previously published studies found no significant differences in blinded neurobehavioral assessments shortly after delivery and within 2 months of age among infants of mothers with a history of major depressive disorder and prenatal antidepressant treatment, infants of mothers with a history of major depressive disorder with minimal to no prenatal antidepressant exposure, and infants of healthy control mothers. The scale used, the BNBAS, is sensitive to medication effects, and our results can be contrasted with those of studies of other prenatal exposures, particularly cocaine, that utilize the BNBAS to assess neurobehavioral outcome. Morrow et al,25
for example, found consistent but subtle deficits associated with prenatal cocaine exposure on almost all clusters of the BNBAS, partly mediated by effects on fetal growth, with effects being most pronounced in infants with exposure in all 3 trimesters. Our results, from a well-characterized and prospective sample, comport with the majority of studies of infant outcome of antidepressant exposure in pregnancy, and they add to the small but important body of literature.6–8,12,13,16
In contrast to our study, some earlier studies10,11,14
have reported neurobehavioral effects of antidepressant exposure in utero. Differences in outcome between some of these positive studies and our study may be related to design (cross-sectional versus prospective, blinded versus nonblinded), the age at which infants were assessed, the method of infant or child assessment, a potential confound with other psychotropic medications, and a potential confound with substance abuse (which the mothers in our study were screened out for early in pregnancy if positive).
Our study did find differences in 3 of the individual items from the major clusters of the BNBAS (rapidity of buildup under the range of state cluster at Time 1, inanimate auditory under the orientation cluster at Time 2, and defense under the motor cluster at Time 2); however, these were no longer significant after Bonferroni correction. While the BNBAS assesses the physiologic, motor, slate, and attentional/interactional dimensions of infant neurobehavior, it is possible that SSRIs may influence an aspect of development that this scale does not measure. Although this study conducted 2 serial BNBAS assessments, it is also possible that additional later assessments would have captured a change in neurobehavioral development that becomes apparent in infants at an older age.
The current study attempted to isolate the effects of antidepressant exposure on neurobehavioral development by using a detailed prospective design with serial blinded assessments. Our study has several limitations, including a small sample size, a maternal population with homogenous demographic characteristics (educated, married, early prenatal care, and lack of substance use), lack of control for the setting of the BNBAS (home versus hospital), and grouping of multiple individual antidepressants. While the difference in size between our 3 groups is a limitation that may have reduced the power of our within-group comparisons, the larger sample size of our main group of interest (history of MDD, taking antidepressants) provided more precise parameter estimates within that group. To ensure that nonsignificant findings were not due to small sample size, these results should be replicated in future large-scale studies with larger sample sizes. Future studies should also look at medication class (eg, SSRI, serotonin-norepinephrine reuptake inhibitor, TCA) and individual medications within an antidepressant class (eg, SSRIs) and also conduct repeated assessments over a longer period of follow-up, to support more specific information on neurobehavioral outcome to guide clinical recommendations. Other factors to consider include the limited normative base of the BNBAS, with results that can be influenced by numerous subtle factors, and the inability of our study to examine the effects of duration of exposure on neurobehavioral outcome, since most of the women who took antidepressants did so for the duration of pregnancy.
While our study attempted to control for history of major depressive disorder, women were not required to have active symptoms of depression at study entry. Most of our subjects were not severely depressed during pregnancy, and thus we cannot address the impact of depression per se on neurobehavioral outcomes. It is interesting to note that both treated and untreated depressed groups in this study had similar, relatively low depression scores across pregnancy. Scores may have been comparable for a variety of reasons. One possibility is that women in the treated group attempted to decrease or wean their medication and became symptomatic. Women who became symptomatic may have been advised by their treating psychiatrist to start medication. A third possibility is that women who were severely depressed and untreated may not have met inclusion criteria or been able or willing to participate in this study.
Overall, our study found that antidepressant use in pregnancy was not associated with significant neurobehavioral effects in infants, as assessed by the major clusters of the Brazelton Neonatal Behavioral Assessment Scale. Our study contributes to the small body of literature suggesting a lack of adverse neurobehavioral outcomes for infants exposed in utero to antidepressants. However, given the limited literature on infant neurobehavioral outcome with prenatal antidepressant exposure, future larger-scale studies are warranted. Any decision regarding treatment of depression during pregnancy must be made carefully, individually weighing the risks and benefits of treatment versus lack of treatment for both mother and developing infant.