In Session with Amy Salisbury, PhD: Newborn Infant Behaviors Following In Utero Exposure to SSRIs and Maternal Depression

Dr. Salisbury discusses research in which in utero exposure to maternal depression (with and without pharmacological treatment) was found to have some apparent influence on infants’ postnatal behavioral outcomes at one month following birth, reinforcing the importance of focusing on remission of maternal depression symptoms during pregnancy.

Amy L. Salisbury, PhD

Associate Professor, Departments of Pediatrics and Psychiatry & Human Behavior, Alpert Medical School at Brown University; Clinical Nurse Specialist, Child & Family Psychiatry, Brown Center for Children & Families at Women & Infants Hospital, Providence, RI

Interview by Lonnie Stoltzfoos


Q: What is generally understood about the risks or benefits posted to infants whose mothers received SSRI treatment during pregnancy?

A: Previous research has found that ~30% of infants whose mothers received antidepressant treatment during pregnancy may demonstrate an array of behavioral and physiological signs of distress (e.g., irritability, poor feeding, and tremulousness). Several studies reported that the signs were no longer observed after the first 7–10 days following birth. Some of these signs were similar to infants who show withdrawal behaviors after in utero opiate exposure, so it was suggested that these infants were experiencing withdrawal from the antidepressants medication. It was unclear, however, why some infants had these signs and others didn’t, nor was it clear whether any of these signs could be attributed to a mother’s underlying diagnosis of a depressive disorder.

We devised our own study, with a goal of measuring these infant behaviors with a standardized neurobehavioral exam over the first postnatal month. This would enable us to characterize the course of behaviors during the postnatal period and to see if that course differed between infants exposed to antidepressants in utero compared with those whose mothers were depressed during pregnancy but chose not to take medication.

We used a standardized neurobehavioral assessment (called the NNNS: NICU Network Neurobehavioral Assessment), in which a trained observer spends 30–60 minutes testing the infants’ reflexes, motor tone, and social and behavioral responses to various stimuli, and records behaviors that may indicate stress, such as hiccups, startles, tremors, or back arching. The exam was conducted on days 2, 4, 7, 14, and 30 following delivery. We also measured blood plasma levels of antidepressant medication in a subset of mothers at delivery.

Four groups of infants were included in the study: exposure to SSRI-only, exposure to SSRI+benzodiazepine, exposure to maternal depression with no pharmacological treatment, and no exposure to maternal depression or psychotropics. We expected infants in the SSRI and SSRI+benzodiazepine groups to have worse scores for motor quality and CNS stress signs on the exam than non-treated depressed and controls in the first 7 days, with improvement by day 14. We expected infants in the non-treated maternal depression group and in the two SSRI-exposed groups to have worse scores for arousal, attention, and lethargy compared to control group across all time points.

Q: How did postnatal behavioral outcomes vary in infants across the continuum of exposure in your study?

A: None of the full-term infants in the study appeared to have any serious adverse events that could be attributed to medication or depression exposure. Infants in the SSRI-exposed and SSRI+benzodiazepine groups had lower quality of movement and more CNS stress signs than infants in the non-exposed group and the non-treated depression group overall. Although the change over time was not statistically different between groups, the trajectories show that both quality of movement and CNS stress signs were highest at the 14-day assessment for SSRI-exposed infants, who also had higher amounts of arousal and excitability with lower self-regulation at day 14. This indicates that SSRI-exposed infants were more irritable than the other infants during the first several weeks following birth. Infants with SSRI+benzodiazepine exposure continued to have lower quality of movement and lower self-regulation than other infants at day 30, as well.

There was a trend for all three clinical groups to have a widening gap from the control infants by day 30 for attention and habituation. Attention is a measure of infants’ visual tracking and following stimuli while awake, while habituation is a measure of infants’ responses to stimuli while asleep with a decrease in response with repeated presentation. These measures were expected to show an increase over time in infants’ habituation and attention scores in the three clinical groups, as seen with the control infants. In fact, the infants in the three clinical groups showed a flattening in scores toward day 30 for attention scores, and a decline in habituation scores. Maternal depression was a common factor for these three groups, which suggests that depression, rather than medication exposure alone, may have contributed to these findings, and that the effects attributable to maternal depression may be more apparent later in the first month than effects attributable to medication exposure.

Q: What is the importance of measuring infant functioning during first postnatal month?

A: The first month tests the direct effects of medication exposure and maternal conditions in pregnancy on the young infant (with relatively little time for varying parenting, social, and environmental variables to influence observed behaviors), as well as any potential withdrawal effects that might occur as a result of the exposure in utero. If the difficulties are due solely to withdrawal symptoms, then clinical recommendations related to timing of maternal use of antidepressants might be helpful. In this study we found evidence that: these behaviors are not due solely to withdrawal; that early discontinuation of the medication (prior to the final month of pregnancy) did not change outcomes by day 30; and that the underlying maternal depressive disorder diagnosis, in agreement with other studies, does have an effect on newborn neurobehavior.

Q: How might these findings come to bear in the clinical setting?

A: With its more limited sample size, this study was not designed to test safety of the medications, but it does address the course of the behaviors often seen in infants after SSRI exposure. This information can be used to prepare women for what to expect after delivery, particularly that the infant may exhibit irritability and distress, which may actually get worse after the first two weeks, especially with SSRI+benzodiazepine exposure, but that most infants will show improvement in these behaviors by the end of the first month.

The number of infants with additional benzodiazepine exposure was small, so more studies are needed to examine those risks and behaviors more systematically.

Remission of maternal depressive symptoms during pregnancy should remain the focus of treatment for women with depression. Meanwhile, the next steps for our research include looking at other factors that might contribute to the course of these outcomes, such as cord blood serotonin levels and fetal behaviors in utero for these same infants, which will give us an idea of the behaviors during exposure rather than solely after removal.


Reference:

Salisbury AL, O’Grady KE, Battle CL, 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. [Epub ahead of print]