In a recent retrospective cohort study, data collected from linked records from the Women’s and Children’s Health Network in South Australia were used to investigate neonatal outcomes in children exposed prenatally to selective serotonin reuptake inhibitors (SSRIs).  Women were included in this study if they gave birth to a singleton, live-born infant between September 2000 and December 2008 (n = 33,965).

221 women filled a prescription for an SSRI during pregnancy, 1566 had a psychiatric illness during pregnancy but did not receive an SSRI.  The control group consisted of 32,004 women who did not have a psychiatric illness and did not receive an SSRI. The presence of a psychiatric illness during pregnancy was recorded by midwives if the woman was receiving a psychotropic medication or if it was recorded that the woman was receiving psychological/psychiatric support during her pregnancy.

As seen in other similar studies, women with psychiatric illness differed considerably from those without.  Compared to women with no psychiatric illness, women exposed to SSRIs were more likely to be older; of higher parity; white; smokers; substance users; alcohol abusers; have preexisting medical conditions such as epilepsy, thyroid disorders, diabetes, and asthma; and to have also received a prescription for an anxiolytic medication during pregnancy.

The authors attempted to control for the various confounding factors (e.g., age, smoking, use of alcohol and other substances) which may affect neonatal outcomes.  Outcomes in SSRI-exposed infants were compared to outcomes in infants born to mothers with a psychiatric illness but who did not take an SSRI.  Infants exposed to SSRIs had an increased risk of preterm delivery (adjusted odds ratio [OR] , 2.68; 95% CI, 1.83-3.93), low birth weight (adjusted OR, 2.26; 95% CI, 1.31-3.91), admission to hospital (adjusted OR, 1.92; 95% CI, 1.39-2.65), and length of hospital stay longer than 3 days (adjusted OR, 1.93; 95% CI, 1.11-3.36) but were not more likely to be  small-for-gestational age (adjusted OR, 1.13; 95% CI, 0.65-1.94).

Infants born to mothers with a psychiatric illness but no SSRI use did not differ substantially from mothers with no psychiatric illness and no SSRI exposure.  The only difference was a small increase in the likelihood of neonatal hospital admission (adjusted OR, 1.21; 95% CI, 1.07-1.38).

Based on these findings, the authors conclude that SSRI exposure in pregnancy increases the risk of certain complications, including preterm delivery, low birth weight, and neonatal admission to the hospital.  In previous studies investigating the impact of SSRIs on neonatal outcomes, it has been difficult to separate the effects of the medication from the effects of the underlying disease. This is one of the few studies that have directly compared neonatal outcomes in infants of women taking SSRIs during pregnancy to infants born to women with depression (or other psychiatric illnesses) but who were not taking any antidepressants during pregnancy.  One of the shortcomings here is that we have no information on the severity of the depression, and there might be some very important differences between the women who decide to take antidepressants versus those who have elected to avoid them.  It is likely that the women in the SSRI exposure group have more severe illness than in the group without SSRI exposure.

While there have been many recent database-driven studies investigating the impact of SSRIs on neonatal outcomes, there is tremendous variation in the quality of data analyzed in these studies (read more about this).  The data used in this study was relatively good, although all of the administrative database studies lack rigor in terms of making an accurate psychiatric diagnosis.   This study was careful about considering various confounding factors and choosing appropriate control groups.   This is about as good as it gets given this type of study design.

We are still left to deal with conflicting results.  Other well-done studies (such as the one from Nordeng and colleagues) demonstrate that exposure to SSRIs does not increase risk of preterm delivery or low birth weight.  Given the large number of variables that may affect neonatal outcomes, it is not surprising that there is such variability among studies carried out using different methodologies in different populations. What we can say at this point is that while SSRIs may affect certain neonatal outcomes, including risk of preterm delivery and low birth weight, they do not appear to dramatically increase the risk of these adverse outcomes.

Ruta Nonacs, MD PhD

Grzeskowiak LE, Gilbert AL, Morrison JL.  Neonatal Outcomes After Late-Gestation Exposure to Selective Serotonin Reuptake Inhibitors.   J Clin Psychopharmacol. 2012 Oct;32(5):615-21.

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