Some studies have shown an association between in utero exposure to antidepressants and various pregnancy outcomes, including preterm delivery, low birth weight, and lower Apgar scores; however, these outcomes have also been observed in infants born to depressed mothers who are not taking medication. Thus, it has been difficult to determine if there is a causal relationship between antidepressant exposure and these negative pregnancy outcomes or if untreated maternal depression is itself responsible for these negative outcomes.

A new study published in the American Journal of Psychiatry compares the growth of children born to women with major depressive disorder during pregnancy, either untreated or treated with selective serotonin reuptake inhibitor (SSRI) antidepressants, to outcomes in a group of infants born to non-depressed, non-medicated mothers.

In this prospective observational study, pregnant women were evaluated at weeks 20, 30, and 36 of gestation.  Pregnant women with psychosis, bipolar disorder, active substance use, or any antenatal exposure to benzodiazepines or drugs included by the FDA in class D or X were excluded.  Mother and infant pairs were assessed at 2, 12, 26, and 52 weeks postpartum. Three distinct groups of women were defined according to their pregnancy exposures:

  • Group 1: No SSRI and no depression (N=97)
  • Group 2: SSRI exposure (N=46)
  • Group 3: Major depression present without SSRI treatment (N=31)

Maternal demographic and clinical characteristics and newborn outcomes were compared across exposure groups. Infant weight, length, and head circumference were measured by a physician or physician’s assistant who was blinded to the mother’s depression and medication status.

Both adjusted and unadjusted analyses revealed neither antenatal major depression nor SSRI exposure was significantly associated with any changes in infant weight, length, or head circumference relative to no exposure.  This study has many strengths, most importantly the inclusion of a group of depressed women with no exposure to medication.  The authors also attempted to limit the contribution of other factors which may potentially affect outcomes by excluding women who were taking certain medications (including benzodiazepines) and women with psychosis, bipolar disorder, or substance abuse.

Given the relatively small sizes of the tree groups, it is possible that this study may not be able to identify small differences in the variables studied, but the findings here are reassuring, indicating that if there are any differences in infant growth, they are small and unlikely to be clinically meaningful.  This study parallels the meta-analysis we reviewed several weeks ago, where the authors failed to find statistically significant and/or clinically relevant differences between antidepressant-exposed and non-exposed infants across a number of variables, including birth weight, length of gestation, and Apgar scores.

So why have other studies suggested that antidepressants may affect infant growth?

This study highlights the importance of carefully collecting and analyzing high quality data and making an effort to minimize the contribution of various confounding factors (e.g., untreated maternal illness, other medications, and substance use).  Over the last few years we have seen multiple reports on the reproductive safety of various psychotropic medications which have emerged from the analysis of large databases.  While these databases have offered larger sample sizes and have more statistical power than smaller prospective studies, they often do not yield the type of data we need to rule out the effects of various confounding factors.  It is certainly possible that in these studies where it appears that SSRIs have had a negative impact on certain outcomes, we are actually observing the effects of other exposures – for example, exposure to untreated maternal depression or exposure to smoking or alcohol or illicit drugs.  The bottom line is that we need more studies like this one which attempt to disentangle the complex interplay between the multiple factors which may affect pregnancy outcomes in order to generate accurate and clinically useful data on the reproductive safety of these medications.

Ruta Nonacs, MD PhD

Wisner KL, Bogen DL, Sit D, et al. Does Fetal Exposure to SSRIs or Maternal Depression Impact Infant Growth? Am J Psychiatry. 2013 Mar 20.