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Antidepressant Impact on Neonatal and Long-Term Outcomes Vivien Burt, MD, PhD The Women’s Life Center Resnick Neuropsychiatric Hospital at UCLA

Issues Needing Consideration and Review SSRIs No increased risk for: Miscarriage Stillbirth Neonatal mortality Postneonatal mortality No clinically significant lower birth weight SSRIs and untreated maternal depression Small statistically significant reduction in the length of gestation ~ 3 days (Probably not clinically significant) Ross, L. E., Grigoriadis, S., Mamisashvili, L., VonderPorten, E. H., Roerecke, M., Rehm, J., ... & Cheung, A. (2013). Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis. JAMA psychiatry, 70(4), 436-443. Stephansson, O., Kieler, H., Haglund, B., Artama, M., Engeland, A., Furu, K., ... & Valdimarsdóttir, U. (2013). Selective serotonin reuptake inhibitors during pregnancy and risk of stillbirth and infant mortality. Jama, 309(1), 48-54.

Neonatal Adaptive Difficulties Usually mild 15% to 30% of cases  Transient perinatal adverse events, for example: Temporary Exposure to antidepressants in the third trimester Jitteriness Dissipates within 2 weeks  Poor muscle tone Weak cry (generally hours) Respiratory distress Hypoglycemia Difficulty feeding Seizure (rare) Chambers, C. D., Johnson, K. A., Dick, L. M., Felix, R. J., & Jones, K. L. (1996). Birth outcomes in pregnant women taking fluoxetine. New England Journal of Medicine, 335(14), 1010-1015. Källén, B. (2004). Neonate characteristics after maternal use of antidepressants in late pregnancy. Archives of pediatrics & adolescent medicine, 158(4), 312-316. Laine, K., Heikkinen, T., Ekblad, U., & Kero, P. (2003). Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in.

Neonatal Adaptive Difficulties Exposed infants to be monitored after birth for 48 hours Prospective follow-up of infants who have had transient perinatal adverse events No difference from controls on Intelligence Aberrant behaviors Up to 4 to 5 years old Depression Anxiety Misri, S., Reebye, P., Kendrick, K., Carter, D., Ryan, D., Grunau, R. E., & Oberlander, T. F. (2006). Internalizing behaviors in 4-year-old children exposed in utero to psychotropic medications. American Journal of Psychiatry, 163(6), 1026-1032.

Persistent Pulmonary Hypertension of the Newborn (PPHN) Possibly associated with SSRI use in the last trimester “It is premature to reach any conclusion about a possible link between SSRI use in pregnancy and PPHN.” 2011 http: www.fda.gov/Safety/MedWatch/Safety Information/Safety Alerts for Human Medical Products/ucm283696.htm

Large Medicaid Cohort Study Possible increased risk of PPHN The absolute risk with SSRIs is very small.  Adjusted risk: 1.28 Confidence interval: 1.01-1.64 Non-SSRIs The adjusted risk was not significant. Huybrechts, K. F., Bateman, B. T., Palmsten, K., Desai, R. J., Patorno, E., Gopalakrishnan, C., ... & Hernandez-Diaz, S. (2015). Antidepressant use late in pregnancy and risk of persistent pulmonary hypertension of the newborn. Jama, 313(21), 2142-2151.

Long-Term Neurobehavioral Studies No effect of antidepressants on IQ or behavioral outcomes Untreated depression: increased risk for postpartum depression Prenatal and postnatal depression Associated with behavioral problems in the offspring Possible increased risk for long-term psychopathology Nulman, I., Koren, G., Rovet, J., Barrera, M., Pulver, A., Streiner, D., & Feldman, B. (2012). Neurodevelopment of children following prenatal exposure to venlafaxine, selective serotonin reuptake inhibitors, or untreated maternal depression. American Journal of Psychiatry, 169(11), 1165-1174. Viktorin, A., Uher, R., Kolevzon, A., Reichenberg, A., Levine, S. Z., & Sandin, S. (2017). Association of antidepressant medication use during pregnancy with intellectual disability in offspring. JAMA psychiatry, 74(10), 1031-1038.

Key Points Prenatal exposure to SSRIs does not cause clinically significant lower birth weight. Prenatal exposure to antidepressants is not associated with a clinically significant reduction in the length of gestation. The risk for PPHN with prenatal exposure to serotonergic antidepressants is small and should not be a reason to avoid use in pregnancy if needed to address serious maternal depression and/or anxiety. Prenatal exposure to antidepressants does not appear to have negative effects on offspring cognition.

Next Presentation Reviewing the Literature: SSRIs in Pregnancy and Association with Autism