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Mother-Infant Antidepressant Concentrations, Maternal Depression, and Perinatal Events

Dorothy Sit, MD; James M. Perel, PhD; Stephen R. Wisniewski, PhD; Joseph C. Helsel, BS; James F. Luther, MA; and Katherine L. Wisner, MD, MS

Published: July 15, 2011

Article Abstract

Objective: The authors explored the relationship of cord-maternal antidepressant concentration ratios and maternal depression with perinatal events and preterm birth.

Method: The investigators examined 21 mother-infant pairs that had antidepressant exposure during pregnancy. The antidepressants included serotonin reuptake inhibitors (SRIs) and nortriptyline (a norepinephrine inhibitor and mild SRI). The mothers were evaluated with the Structured Clinical Interview for DSM-IV. Depression ratings were repeated at 20, 30, and 36 weeks’ pregnancy. At delivery, investigators assessed cord and maternal antidepressant concentrations, neonatal outcomes on the Peripartum Events Scale (PES), and gestational weeks at birth. The investigators performed this study at the Women’s Behavioral HealthCARE Program, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pennsylvania, from April 2003 until September 2006.

Results: Mean ± SD cord-to-maternal concentration ratios were 0.52 ± 0.35 (range, 0.00-1.64) for the parent drug and 0.54 ± 0.17 (range, 0.28-0.79) for the metabolite. Nine of 21 mothers (43%) had a major depressive episode. From examining the maximum depression ratings, the mean ± SD Structured Interview Guide for the Hamilton Depression Rating Scale, Atypical Depression Symptoms Version score was 16.0 ± 7.6. One third (7/21) of infants had at least 1 perinatal event (PES ≥ 1). The frequency of deliveries complicated by any perinatal event was similar in depressed and nondepressed mothers. There was no significant association between perinatal events and cord-to-maternal antidepressant concentration ratios or maternal depression levels. Exposure to short half-life antidepressants compared to fluoxetine resulted in more perinatal events (7/16 = 44% vs 0/5 = 0%; P = .06). Fourteen percent (3/21) of infants were preterm. Preterm birth was not associated with cord-to-maternal metabolite concentration ratios, depression levels, or exposure to fluoxetine.

Conclusions: Antidepressant-exposed infants experienced a limited number of transient perinatal events. No association between cord-maternal concentration ratios or maternal depression and perinatal events could be identified. Contrary to other reports, we detected no increased risk for perinatal events with fluoxetine therapy compared to the short half-life antidepressants.

Trial Registration: Identifier: NCT00279370

J Clin Psychiatry 2011;72(7):994-1001

Submitted: August 3, 2010; accepted October 26, 2010 (doi:10.4088/JCP.10m06461).

Corresponding author: Dorothy Sit, MD, Women’s Behavioral HealthCARE, Western Psychiatric Institute and Clinic, University of Pittsburgh, 3811 O’ Hara St, Oxford 410, Pittsburgh, PA 15213 (

Volume: 72

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