Comparing Newborn Outcomes After Prenatal Exposure to Individual Antidepressants: A Retrospective Cohort Study

Comparing Newborn Outcomes After Prenatal Exposure to Individual Antidepressants: A Retrospective Cohort Study
Yesenia Lopez-Mendoza, PharmD, Community-University Health Care Center

Background: A Centers of Disease Control and Prevention (CDC) study found that 1 in 10 women in the United States reported experiencing major depression symptoms in 2018 and 1 in 8 women experience symptoms of postpartum depression (PPD). PPD can cause lower rates of breastfeeding initiation, poorer maternal-infant bonding, and infant developmental delays. Untreated depression in pregnancy can cause preterm delivery, preeclampsia, behavioral disturbances in babies at birth, and maternal suicidal ideations or attempts. In addition to cognitive behavioral therapy, antidepressants may also reduce the complications associated with major depression during pregnancy and PPD; however, because pregnant women are often excluded from studies, there is a lack of evidence supporting the safety of antidepressants in this population. Current depression guidelines support the safety of selective serotonin reuptake inhibitors (SSRIs) and selective-norepinephrine reuptake inhibitors (SNRIs) over other antidepressant drug classes for the general population. This study explored the safety of using SSRI and/or SNRI agents during pregnancy to help guide clinical decisions in this population.

Purpose: To compare safety outcomes in newborns of different antidepressant agents during pregnancy and help guide recommendations in the ambulatory care practice. 

Study Design: Investigators pulled retrospective data from January 2010 to December 2019 from electronic medical records of several large health systems in Indiana to find patients that were prescribed an SSRI and/or SNRI starting from 100 days before the last menstrual period through the date of delivery. The study controlled for maternal age (average age was 29 + 5.8 years), race, insurance, estimated gestational age at delivery, and newborn weight, length, and head circumference between drug groups. SSRIs included citalopram, escitalopram, fluoxetine, paroxetine, and sertraline. SNRIs included bupropion, desvenlafaxine, duloxetine, and venlafaxine. Primary outcomes included neonatal intensive care unit (NICU) admission and any signs of adaptation syndrome (such as respiratory distress, feeding difficulty, jitteriness, or irritability). For this study, adaptation syndrome included diagnosis of neonatal abstinence syndrome (NAS) and pediatric adaptation syndrome (PAS). Women were categorized as either early exposure (within three months before pregnancy began or in the first trimester) or third trimester exposure (after 28 weeks of gestation).

Results: The study included 3694 women who were prescribed sertraline, escitalopram, fluoxetine, bupropion, citalopram, duloxetine, venlafaxine, paroxetine, and/or desvenlafaxine (n = 1653, 581, 579, 406, 385, 139, 132, 55, and 16, respectively). Bupropion had the lowest rate of adverse events of all agents, and was therefore used as the reference to compare the other agents (22.4% NICU admission and 4.7% any adaptation syndrome). Meanwhile, sertraline had the second lowest rate in adverse events after bupropion (23.3% NICU admission and 4.5% adaptation syndrome). In contrast, duloxetine had the highest rates of NICU admission (39.6%) and any adaptation syndrome (15.1%). Paroxetine also had higher rates of adaptation syndrome (12.7%) while venlafaxine had the highest rate of transient tachypnea of the newborn (TTN; 18.2%).  

Women with early pregnancy exposure to duloxetine and/or escitalopram had increased odds of any adaptation syndrome, adjusted odds ratio (aOR) 2.31 [95% CI 1.11 - 4.8] and aOR 1.72 [95% CI 1.09 - 2.71], respectively, compared to women that did not have exposure to any antidepressants during early pregnancy. Alternatively, in third trimester exposure versus no exposure to any antidepressant, citalopram, duloxetine, escitalopram, fluoxetine, sertraline, and venlafaxine had greater odds of adaptation syndrome and bupropion, citalopram, duloxetine, escitalopram and fluoxetine had higher odds for NICU admissions.

Conclusions: The safety of medications in pregnancy is challenging due to the ethical and logistical barriers to investigating therapies in this population. This retrospective study evaluated the rate of adaptation syndrome, NICU admission, and TTN to unveil the safety of SSRI and/or SNRI exposure during pregnancy. Results found that duloxetine and escitalopram had the greatest risk for any adaptation syndrome and NICU admission, while bupropion and sertraline tended to have the lowest risk for these outcomes and were the most used antidepressants during this study. These outcomes may be related to the agent's affinity for SERT (serotonin transporter) but further investigation should be done to draw this conclusion. The study was not able to account for under- or over-capturing outcomes due to inconsistencies with use of ICD9/10 codes, variability in dosing, and influence of other onboard therapies like opioids. Also, adherence was assumed but cannot be guaranteed as a retrospective study. 

Key Points: The findings from this study can help guide recommendations in ambulatory care practice when selecting safer antidepressant agents for individuals that are pregnant or planning on becoming pregnant.


  1. Marks C, Silvola R, Teal E, Quinney SK, Haas DM. Comparing newborn outcomes after prenatal exposure to individual antidepressants: a retrospective cohort study. Pharmacotherapy: official journal of the American College of Clinical Pharmacy. 2021;(0). doi:10.1002/phar.2628
  2. Bauman BL, Ko JY, Cox S, et al. Vital Signs: Postpartum depressive symptoms and provider discussions about perinatal depression - United States, 2018. MMWR Morbidity and mortality weekly report. 2020;69(19):575-581. doi:10.15585/MMWR.MM6919A2