Over the last several years, a number of studies have indicated that exposure to antidepressants near the time of delivery may be associated with poor neonatal outcomes. A recent prospective study from Dubnov-Raz and colleagues published in the journal Pediatrics found an association between QTc interval prolongation in neonates and antenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants.  The QT interval is a measurement of the heart’s electrical cycle from ventricular depolarization to the end of ventricular polarization.  It is determined from an electrocardiogram (ECG) and is corrected for heart rate.

Given reports of SSRI-induced QT prolongation in adults (typically seen in cases of overdose), Dubnov-Raz and colleagues set out to investigate the effects of maternal SSRI use in pregnancy and to investigate the possibility of neonatal QT prolongation.  The sample was obtained from the Rabin Medical Center in Israel where all newborns of mothers exposed to psychoactive or cardiovascular medications in utero typically undergo a thorough physical exam, routine serum biochemistry, and 12-lead electrocardiography (ECG) within the first days of life.

Included in the study were healthy infants with a gestational age of at least 35 weeks and Apgar scores greater than 7, born to healthy mothers on no other chronic medications during pregnancy and with no family history of long QT syndrome.  Neonates with evidence of hypoxia or abnormal electrolytes, also common causes of QT prolongation, were excluded.  52 newborns exposed to SSRI antidepressants in the immediate antepartum period were compared to 52 matched control subjects.

In this study, a prolonged QTc was defined as an interval of greater than 460 milliseconds.  While the SSRI-exposed group had a mean QTc which was significantly longer compared to the control subjects, the mean QTc was not considered to be prolonged (409 +/- 42 vs. 392 +/-29 ms).  However, 10% of the SSRI-exposed neonates (5 newborns) did have a prolonged QTc interval (range: 462-543 ms) compared to none of the infants in the control group.  In follow-up ECGs all 5 newborns had normalization of their QTc intervals.

These data suggest that exposure to SSRIs may be associated with a transient increase in QTc interval in some neonates.  The clinical relevance of these findings, however, remains unclear.  Reassuringly, none of the infants with prolonged QTc experienced any adverse events.  While the authors do not suggest that this data should be used to restrict SSRI use during pregnancy, they do suggest that screening ECGs may be considered in newborns exposed to SSRI antidepressants.

April Hirschberg, MD

Dubnov-Raz, et al. Antenatal Use of Selective Serotonin-Reuptake Inhibitors and QT Interval Prolongation in Newborns. Pediatrics 2008; 122: e710-e715.

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