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Poor Neonatal Adaptation After in Utero Exposure to Duloxetine

To The Editor: Risk-benefit analysis is central when forming a treatment plan for pregnant women with mental illness. This task is further complicated by limited data pertaining to the effects of antidepressants on the fetus, neonate, and child. To our knowledge, this is the first case report of in utero exposure to duloxetine.

"Ms. A" was a 36-year-old Caucasian female with a history of recurrent major depression, anorexia, and chronic neck pain. When she sought psychiatric consultation at 34 weeks’ gestation, she was 1) in complete remission, 2) being treated by an anesthesiologist, 3) and receiving monotherapy duloxetine (90 mg/day). She was educated about neonatal behavioral syndrome, and duloxetine was subsequently decreased to 60 mg/day.

The child was delivered without complication at 38 weeks. Upon delivery, she was blue, with minimal respiratory effort and oxygen saturations in the 80s. Her Apgar scores were 7 and 9. After birth, she was transferred to the neonatal intensive care unit because she continued to require oxygen. The child was started on antibiotics while possible causes of transient tachypnea were assessed. Basic laboratory examination, blood gas, echocardiogram, and chest and abdominal x-rays were all normal on day 1. Breast feeding was discouraged because of concerns of exposure to duloxetine, and the mother was advised to switch to sertraline. Antibiotic treatment was discontinued after blood cultures remained negative.

On day 3, the child was weaned to room air but developed "jerky rhythmic movements," or "twitchiness." An electroencephalogram (EEG) showed nonspecific encephalopathic findings. The child did have episodes of shaking, and the EEG revealed no correlated changes. Phenobarbital was started, and despite a high blood level the following day, the child continued to experience occasional twitching. Head computed tomography, magnetic resonance imaging, and lumbar puncture were all normal. A repeat EEG conducted at 7 days was suggestive of subclinical seizures. A follow-up EEG at 7 weeks was normal. Phenobarbital was discontinued, and the child was diagnosed with tremors and neonatal seizures associated with neonatal behavior syndrome. At age 2, the child is healthy with consistently normal neurobehavioral development.

This case demonstrates the syndrome referred to as poor neonatal adaptation or neonatal behavioral syndrome, characterized by jitteriness, poor muscle tone, weak cry, respiratory distress, hypoglycemia, low Apgar score, and seizure (1). These symptoms start within hours, generally require only supportive care, and end within 1 to 2 weeks. The syndrome may occur in up to 30% of infants with selective serotonin reuptake inhibitor exposure (2), with a risk ratio of approximately 3.0 (3)or higher for premature infants (4). The mechanism underlying the syndrome is unclear. A dose of fluoxetine or nursing may decrease symptoms assuming they stem from withdrawal. Reports indicate a higher risk with exposure to paroxetine and venlafaxine, agents with the shortest half-lives, but data are very limited pertaining to newer antidepressants such as duloxetine, mirtazapine, and bupropion. Better characterization of poor neonatal adaptation and its etiology could reduce invasive procedures and inform the difficult decisions in treating mental illness during pregnancy.

Footnotes

The authors report no competing interests.

This letter (doi: 10.1176/appi.ajp.2008.07071194) was accepted for publication in January 2008.

References

1. Koren G, Matsui D, Einarson A, Knoppert D, Steiner M: Is maternal use of selective serotonin reuptake inhibitors in the third trimester of pregnancy harmful to neonates? CMAJ 2005; 172:1457–1459[Free Full Text]
2. Levinson-Castiel R, Merlob P, Linder N, Sirota L, Klinger G: Neonatal abstinence syndrome after in utero exposure to selective serotonin reuptake inhibitors in term infants. Arch Pediatr Adolesc Med 2006; 160:173–176[Abstract/Free Full Text]
3. Moses-Kolko EL, Bogen D, Perel J, Bregar A, Uhl K, Levin B, Wisner KL: Neonatal signs after late in utero exposure to serotonin reuptake inhibitors. JAMA 2005; 293:2372–2382[Abstract/Free Full Text]
4. Ferreira E, Carceller AM, Agogué C, Martin BZ, St-André M, Francoeur D, Bérard A: Effects of selective serotonin reuptake inhibitors and venlafaxine during pregnancy in term and preterm neonates. Pediatrics 2007; 119:52–59[Abstract/Free Full Text]

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