Multiple studies have demonstrated an increased risk of poor neonatal adaptation associated with exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants in late pregnancy.  Results in the literature consistently indicate that about 25%-30% of infants exposed to SSRIs late in pregnancy manifest symptoms of poor neonatal adaptation.  The most commonly observed symptoms include jitteriness, restlessness, increased muscle tone, and rapid breathing.  These symptoms are transient, resolving spontaneously with no specific medical intervention.

What causes poor neonatal adaptation in these infants is not fully understood.  While these symptoms may represent SSRI withdrawal similar to that seen in adults after abruptly discontinuing SSRIs, these symptoms may also signal excess serotonergic activity in the infant’s CNS.  

Further complicating the picture is the fact that few studies have attempted to parse out the relative contributions of different factors on neonatal outcomes. In most studies, it is difficult to differentiate between the effects of medication exposure and the effects of the underlying disorder.  We know from older studies that depressive symptoms and anxiety, even in the absence of medication exposure, increases the risk of adverse outcomes, such as preterm birth, lower birth weight, and lower Apgar scores.  Depression in pregnancy may also be associated with other factors that may negatively affect outcomes, including smoking, substance abuse, insufficient prenatal care, and increased levels of psychosocial stressors.

In a recent study published in the American Journal of Psychiatry, researchers observed the outcomes in infants born to 184 women and attempted to tease apart the effects of medication exposure from exposure to depressive illness.  The women were assessed at two time points during pregnancy to determine psychiatric diagnoses, symptom severity, and prenatal medication usage. Infants were examined using a structured neurobehavioral assessment (Neonatal Intensive Care Unit Network Neurobehavioral Scale) at several time points during the first month of life: at days 2, 4, and 7 when levels of SSRIs in exposed infants are likely to be changing rapidly and at days 14 and 30.

The researchers compared outcomes in the following groups of women:

Group A: No depression, no SSRI exposure (n=66)

Group B: Depression during pregnancy, but no SSRI exposure (n=56)

Group C: Exposure to SSRI (n=52)

Group D: Exposure to SSRI and benzodiazepines (n=10)

There were no significant differences between the groups in terms of birth weight, gestational age at birth, 5-minute Apgar scores, neonatal intensive care unit admission, respiratory distress, or breastfeeding.

Infants in both the SSRI and SSRI plus benzodiazepine exposure groups had lower quality of movement than those in the no-exposure group and those in the depression group. Infants in the SSRI and SSRI plus benzodiazepine groups had more CNS stress-abstinence signs than those in the no-exposure group and those in the depression group. In addition, SSRI-exposed newborns also had poorer self-regulation and higher arousal levels at day 14 than those in the no-exposure and depression groups.

The Bottom Line

Few studies have observed the trajectory of poor neonatal adaptation in SSRI-exposed children.  Other studies have demonstrated that SSRI-exposed infants have lower scores on tests of motor functioning.  However, this is the first study to observe that these symptoms persist beyond the first week.  But there are inconsistencies across the various studies.  In another study, Suri and colleagues did not observe differences between SSRI-exposed and non-exposed infants at either the first week after delivery or at 6 to 8 weeks of age using the Brazelton Neonatal Behavioral Assessment Scale (BNBAS).

Do these findings change what we would recommend clinically? Probably not.  Women who make the decision to use antidepressants during pregnancy do so because they are at high risk for recurrent illness during pregnancy and the postpartum period.  While SSRIs may carry some risks, discontinuing treatment proximate to delivery may place the woman at increased risk for relapse as she enters into the postpartum period, a time of very high risk in women with histories of depression.  Furthermore, there is at least one study suggesting that discontinuing antidepressants during the third trimester does not decrease the risk of poor neonatal adaptation.

Ruta Nonacs, MD PhD

Salisbury AL, O’Grady KE, Battle CL, Wisner KL, et al.  The Roles of Maternal Depression, Serotonin Reuptake Inhibitor Treatment, and Concomitant Benzodiazepine Use on Infant Neurobehavioral Functioning Over the First Postnatal Month.  Am J Psychiatry. 2015 Oct 30.

Suri R, Hellemann G, Stowe ZN, et al: A prospective, naturalistic, blinded study of early neurobehavioral outcomes for infants following prenatal antidepressant exposure. J Clin Psychiatry 2011; 72:1002–1007.

Warburton W, Hertzman C, Oberlander TF: A register study of the impact of stopping third trimester selective serotonin reuptake inhibitor exposure on neonatal health. Acta Psychiatr Scand 2010; 121:471–479.