Cardiac Arrhythmia in a Newborn Infant Associated with Fluoxetine Use during Pregnancy

TO THE EDITOR: Fluoxetine is a selective serotonin-reuptake inhibitor widely used for the treatment of depression as well as for obsessive–compulsive disorders and eating disorders.1 The few existing studies2,3 of maternal fluoxetine treatment in the second half of pregnancy reported some toxic effects (neurologic, hematologic) and a withdrawal syndrome in a small number of the infants. We report a cardiac arrhythmia detected preand postnatally in an infant of a mother treated with fluoxetine during the third trimester of pregnancy. Case Report. A 38-week-gestational-age male infant was born by spontaneous vaginal delivery to healthy nonconsanguineous parents. There was no family history of cardiac disturbances. The mother was treated for depression with fluoxetine ≤30 mg/d from week 28 of pregnancy. The drug was tapered and discontinued 5 days prior to delivery. The mother denied taking any other drugs, and there was no history of smoking, alcohol or caffeine intake, or infections during pregnancy. Alpha fetoprotein concentration and targeted fetal ultrasound study (at 22-wk gestation) were normal. On admission for labor, a fetal cardiac arrhythmia with irregular heart sounds was heard on auscultation. Fetal heart monitoring revealed irregular baseline rhythm. The infant was born spontaneously in the vertex position; Apgar scores were 9 and 10 at 1 and 5 minutes, respectively. Birth weight was 2700 g. Physical examination of the newborn, including tonus and reflexes, was normal except for irregular pulse with premature beats and wandering movements with sucking motions. The infant was placed in an incubator with cardiomonitoring. Blood cell count, blood gases, urea, creatinine, electrolytes, calcium, and glucose concentrations were normal. Electrocardiography showed sinus rhythm with multiple atrial and ventricular premature contractions (Figure 1). Echocardiography revealed a normal heart. The mother did not restart fluoxetine after delivery and did not breast-feed the infant. On the infant’s discharge at age 5 days, the arrhythmia persisted, but the premature contractions were much rarer than during the previous days. At follow-up at age 1 month, an electrocardiogram showed normal rhythm without any premature contractions. Discussion. Fluoxetine is thought to have minimal cardiovascular effects. However, several case reports4 in previously healthy adults describe cardiac disturbances such as atrial fibrillation, supraventricular tachycardia, and bradycardia with syncope after fluoxetine use. These arrhythmias appeared with minimal doses of fluoxetine (20 mg/d) and after, in general, 3–6 weeks of use (in 1 patient, after only 24 h). This is the first report describing a newborn infant with atrial and ventricular premature contractions possibly secondary to maternal fluoxetine treatment during the last trimester of pregnancy. The discontinuation of treatment 5 days before delivery does not rule out the possibility that fluoxetine induced the arrhythmia, because of the long half-life of the drug and its metabolite (norfluoxetine), and because of its well-known associated withdrawal syndrome, which typically appears after drug discontinuation. The use of the Naranjo probability scale5 indicated a possible relationship between the atrial and ventricular premature contractions and maternal fluoxetine therapy in our patient. Review of the literature6 indicates up to 1–2% baseline incidence of atrial premature contractions in utero. Therefore, another possible explanation is that the maternal fluoxetine use in this case was just coincidental. The significance of irregular fetal heart rhythm in atrial premature contractions is usually hemodynamically benign. However, fetal and neonatal echocardiography is mandated to exclude structural heart disease. Although fluoxetine-mediated arrhythmias in newborn infants seem to be very rare and not absolutely proven, we report the present case to increase the awareness of clinicians to this potentially important adverse effect.