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The Pediatric Forum |

Selective Serotonin Reuptake Inhibitor Exposure in Pregnancy and Neonatal Adverse Events

Gal Dubnov-Raz, MD, MSc; Gideon Koren, MD, FRCPC; Yaron Finkelstein, MD
[+] Author Affiliations

Author Affiliations: Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel (Dr Dubnov-Raz); Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada (Drs Koren and Finkelstein); and Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts (Dr Finkelstein).


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Arch Pediatr Adolesc Med. 2010;164(4):394-395. doi:10.1001/archpediatrics.2010.34
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We read with great interest the article by Lund et al1 on selective serotonin reuptake inhibitor (SSRI) exposure in utero and pregnancy outcomes. This study, and several previous ones, demonstrated the effects of SSRI use during pregnancy on duration, birth weight, neonatal adaptation, and respiratory effects. Lund et al identified an elevated risk for low Apgar scores and neonatal intensive care unit admissions among SSRI-exposed neonates, which were not explained by the underlying psychiatric condition.

We wish to suggest a possible mechanism for such early adverse outcomes in these infants. In a review of prospectively collected electrocardiograms from SSRI-exposed newborns in late pregnancy, we identified a long mean QT interval and a 10% rate of a prolonged QTc interval.2 This prevalence was much higher compared with a matched control group and about 1000-fold higher than expected in the general population. Recently, a possible link between serotonin action and cardiac development and function was identified, using a serotonin transporter-knockout mouse as a model for sudden infant death syndrome.3 This transporter is responsible for the reuptake of serotonin from the synaptic cleft back into the presynaptic neuron and is the site of action of SSRIs. Knockout mice lacking a serotonin transporter, thus mimicking the a state of SSRI use, developed cardiac fibrosis, and 75% experienced sudden death in the first week of life.

Collectively, these animal and human data suggest there is a role of serotonin in cardiac development and action and potential negative effects of maternal SSRI use on the fetal and neonatal heart. Given the widespread use of SSRIs during pregnancy, we wish to draw clinicians' attention to these possible transient but life-threatening effects and suggest that screening electrocardiography be performed in newborns exposed to SSRI antidepressants soon after delivery. Whether the SSRI-induced prolonged QT interval could potentially lead to malignant arrhythmias remains to be determined.

AUTHOR INFORMATION

Correspondence: Dr Dubnov-Raz, Safra Children's Hospital, Sheba Medical Center, Ramat Gan 52621, Israel (gal-d@bezeqint.net).

Author Contributions:Study concept and design: Dubnov-Raz and Finkelstein. Acquisition of data: Dubnov-Raz. Analysis and interpretation of data: Dubnov-Raz, Koren, and Finkelstein. Drafting of the manuscript: Dubnov-Raz, Koren, and Finkelstein. Critical revision of the manuscript for important intellectual content: Finkelstein. Statistical analysis: Finkelstein. Administrative, technical, and material support: Dubnov-Raz. Study supervision: Dubnov-Raz.

Financial Disclosure: None reported.

Lund  N, Pedersen  LH, Henriksen  TB. Selective serotonin reuptake inhibitor exposure in utero and pregnancy outcomes. Arch Pediatr Adolesc Med 2009;163 (10) 949- 954
PubMed
Dubnov-Raz  G, Juurlink  DN, Fogelman  R.  et al.  Antenatal use of selective serotonin-reuptake inhibitors and QT interval prolongation in newborns. Pediatrics 2008;122 (3) e710- e715
PubMed
Pavone  LM, Spina  A, Rea  S.  et al.  Serotonin transporter gene deficiency is associated with sudden death of newborn mice through activation of TGF-β1 signaling. J Mol Cell Cardiol 2009;47 (5) 691- 697
PubMed

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Lund  N, Pedersen  LH, Henriksen  TB. Selective serotonin reuptake inhibitor exposure in utero and pregnancy outcomes. Arch Pediatr Adolesc Med 2009;163 (10) 949- 954
PubMed
Dubnov-Raz  G, Juurlink  DN, Fogelman  R.  et al.  Antenatal use of selective serotonin-reuptake inhibitors and QT interval prolongation in newborns. Pediatrics 2008;122 (3) e710- e715
PubMed
Pavone  LM, Spina  A, Rea  S.  et al.  Serotonin transporter gene deficiency is associated with sudden death of newborn mice through activation of TGF-β1 signaling. J Mol Cell Cardiol 2009;47 (5) 691- 697
PubMed

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