The Roles of Maternal Depression, Serotonin Reuptake Inhibitor Treatment, and Concomitant Benzodiazepine Use on Infant Neurobehavioral Functioning Over the First Postnatal Month

Abstract

Objective: The purpose of this article was to systematically compare the developmental trajectory of neurobehavior over the first postnatal month for infants with prenatal exposure to pharmacologically untreated maternal depression, selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors (collectively: SSRIs), SSRIs with concomitant benzodiazepines (SSRI plus benzodiazepine), and no maternal depression or drug treatment (no exposure).

Method: Women (N=184) were assessed at two prenatal time points to determine psychiatric diagnoses, symptom severity, and prenatal medication usage. Infants were examined with a structured neurobehavioral assessment (Neonatal Intensive Care Unit Network Neurobehavioral Scale) at multiple time points across the first postnatal month. SSRI exposure was confirmed in a subset of participants with plasma SSRI levels. General linear-mixed models were used to examine group differences in neurobehavioral scores over time with adjustment for demographic variables and depression severity.

Results: Infants in the SSRI and SSRI plus benzodiazepine groups had lower motor scores and more CNS stress signs across the first postnatal month, as well as lower self-regulation and higher arousal at day 14. Infants in the depression group had low arousal throughout the newborn period. Infants in all three clinical groups had a widening gap in scores from the no-exposure group at day 30 in their response to visual and auditory stimuli while asleep and awake. Infants in the SSRI plus benzodiazepine group had the least favorable scores on the Neonatal Intensive Care Unit Network Neurobehavioral Scale.

Conclusions: Neonatal adaptation syndrome was not limited to the first 2 weeks postbirth. The profile of neurobehavioral development was different for SSRI exposure than depression alone. Concomitant benzodiazepine use may exacerbate adverse behavioral effects.

FIGURE 1

Model 3 Model-Estimated Means of the Significant Neonatal Intensive Care Unit Network Neurobehavioral Scale Summary Scores Over Days From Birth for Each of the Four Groups^{a a} The graphs represent the model adjusted for covariates of gestational age at birth, infant sex, socioeconomic status, and depression severity. For A) arousal, the results are: day 7, no exposure. depression; day 14, selective serotonin reuptake inhibitor (SSRI).depression, SSRI plus benzodiazepine. depression, SSRI, and no exposure; the trajectory is a significant cubic trend for all groups (χ²=9.59, p<0.002); a quadratic trend is within the no-exposure group (estimate=0.30, SE=0.12, t=2.6, p<0.011) and SSRI plus benzodiazepine group (estimate=−0.75, SE=0.32, t=−2.32, p<0.021); simple slope of the Inventory of Depressive Symptomatology score within group is significant for the depression group (estimate=0.02, SE=0.01, t=2.5, p<0.013) and SSRI group (estimate=−0.02, SE=0.01, t=−2.4, p<0.027). For B) attention, the results are: the trajectory has a significant linear (χ²=5.6, p<0.02) and quadratic (χ²=4.5, p<0.04) trend. For C) CNS stress signs, the results are: the trajectory has a significant cubic trend (χ²=3.8, p<0.05). For D) excitability, the results are: the trajectory has a significant cubic trend for all groups (χ²=7.9, p<0.005); within the no-exposure group, the trajectory has a significant linear (estimate=−0.19, SE=0.41, t=−2.9, p<0.005) and quadratic (estimate=1.6, SE=0.42, t=2.8, p<0.006) trend. For E) habituation, the results are: the trajectory over time is not statistically significant; however, mean scores at day 30 for the depression, SSRI, and SSRI plus benzodiazepine groups are all lower than the 5th percentile for normative scores at this age, while the no-exposure group is greater than the 50th percentile. For F) lethargy, the results are: the trajectory has a significant linear (χ²=5.2, p<0.02), cubic (χ²=5.4, p<0.021), and quartic (χ²=5.15, p<0.023) trend. For G) quality of movement, the results are: the trajectory has a significant linear (χ²=8.3, p<0.004) and cubic (χ²=10.2, p<0.002) trend. For H) self-regulation, the results are: day 2, no exposure, depression; day 14, SSRI, no exposure and depression, SSRI plus benzodiazepine, depression and SSRI; the trajectory has a significant cubic trend for all groups (χ²=9.0, p<0.003) and within the no-exposure group, a linear (estimate=6.9, SE=0.14, t=4.9, p<0.0001) and quadratic (estimate=−0.6, SE=0.14, t=−4.2, p<0.0001) trend. *p<0.05; **p<0.01, ***p<0.001.