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

3. 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),
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),

4. 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),
Källén, B. (2004). Neonate characteristics after maternal use of antidepressants in late pregnancy. Archives of pediatrics & adolescent medicine, 158(4),
Laine, K., Heikkinen, T., Ekblad, U., & Kero, P. (2003). Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in.

5. 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),

6. 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: Information/Safety Alerts for Human Medical Products/ucm htm

7. Large Medicaid Cohort Study
Possible increased risk of PPHN
The absolute risk with SSRIs is very small. 
Adjusted risk: 1.28
Confidence interval:
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),

8. 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),
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),

9. 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.

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