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Neurodevelopment after in utero amiodarone exposure
L A Magee1, I Nulman, J F Rovet
1Motherisk Program, Division of Clinical Pharmacology/Toxicology, The Hospital for Sick Children, Toronto, ON, Canada. laura.magee@utoronto.ca
Insights
Transplacental amiodarone exposure may impact fetal neurodevelopment. While toddlers showed no IQ differences, older children exhibited learning difficulties, suggesting potential neurotoxicity.
Area of Science:
- Neuroscience
- Developmental Pediatrics
- Pharmacology
Background:
- Amiodarone is known to be neurotoxic in adults.
- The effects of fetal amiodarone exposure on neurodevelopment are not well-established.
Purpose of the Study:
- To evaluate the neurodevelopmental outcomes in children exposed transplacentally to amiodarone.
- To identify potential neurotoxic effects of prenatal amiodarone exposure.
Main Methods:
- A historical cohort study of 10 children with transplacental amiodarone exposure.
- Cognitive and language skills assessed using standardized tests.
- Comparison of toddlers with matched controls and older children with normative data.
Main Results:
- No significant difference in IQ scores between amiodarone-exposed toddlers and controls.
- Toddlers exposed to amiodarone showed poorer expressive language skills compared to receptive language skills (p=0.046).
- One toddler exhibited global developmental delay; older children had reading, writing, and arithmetic challenges.
Conclusions:
- Transplacental amiodarone exposure may be associated with neurodevelopmental deficits.
- Findings suggest potential neurotoxicity, possibly resembling Nonverbal Learning Disability Syndrome.
- Further follow-up is warranted to fully understand long-term effects.
Abstract:
It is not known whether amiodarone is neurotoxic to the fetus, as it is to adults. We evaluated neurodevelopment of a historical cohort (N = 10) of children exposed transplacentally to amiodarone. Scores on standardized tests of cognitive and language skills were compared (by Wilcoxon signed rank test) between eight toddlers and matched controls. It was not possible to obtain controls for older amiodarone-exposed children (aged 9.7 and 12.0 years), whose test results were compared descriptively with normative data. There was no difference in IQ scores between amiodarone-exposed toddlers and controls. All had favorable temperaments. However, amiodarone-exposed toddlers showed expressive language skills that were relatively poorer than verbal skills, when compared with controls (p = 0.046). One amiodarone-exposed toddler exhibited global developmental delay. The older amiodarone-exposed children had well-developed social competence, favorable global IQ scores, but problems with reading comprehension, written language, and arithmetic. This picture is reminiscent of the Nonverbal Learning Disability Syndrome. There may be neurotoxicity associated with transplacental exposure to amiodarone. Follow-up is warranted, although most mothers were happy with the development of their children.