Effects of amiodarone administration during pregnancy on neonatal thyroid function and subsequent neurodevelopment
Abstract
Amiodarone, a benzofuranic derivative, iodine-rich drug, has been used in pregnancy for either maternal or fetal tachyarrhythmias. Amiodarone, its main metabolite (desethylamiodarone) and iodine are transferred, albeit incompletely, through the placenta, resulting in a relevant fetal exposure to the drug and iodine overload. Since the fetus acquires the capacity to escape from the acute Wolff-Chaikoff effect only late in gestation, the iodine overload may cause fetal/neonatal hypothyroidism and goiter. Among the reported 64 pregnancies in which amiodarone was given to the mother, 11 cases (17%) of hypothyroidism in the progeny (10 detected at birth, 1 in utero) were reported, 9 non-goitrous (82%) and 2 (18%) associated with goiter. Hypothyroidism was transient in all cases, and only 5 infants were treated short-term with thyroid hormones. Only 2 newborns had transient hyperthyroxinemia, associated with low serum TSH concentrations in one. Neurodevelopment assessment of the hypothyroid infants, when carried out, showed in some instances mild abnormalities, most often reminiscent of the Non-verbal Learning Disability Syndrome; however, these features were also reported in some amiodarone-exposed euthyroid infants, suggesting that there might be a direct neurotoxic effect of amiodarone during fetal life. Breast-feeding was associated with a substantial ingestion of amiodarone by the infant, but in the few cases followed it did not cause changes in the newborn's thyroid function. In conclusion, amiodarone therapy during pregnancy may cause fetal/neonatal hypothyroidism and, less frequently, goiter. Thus, the use of amiodarone in pregnancy should be limited to maternal/fetal tachyarrhythmias which are resistant to other drugs or life-threatening. If amiodarone is used during gestation, a careful fetal/neonatal evaluation of thyroid function and morphology is warranted. It seems prudent to advise that fetal/neonatal hypothyroidism be treated, as soon as the diagnosis is made, even in utero, to avoid neurodevelopment abnormalities, although the latter may occur independently of hypothyroidism. If breast-feeding is allowed, careful evaluation of the infant's thyroid function and morphology is required because of the continuing exposure of the infant to the drug.
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Amiodarone is associated with severe adverse foetal side-effects.
“Amiodarone is associated with severe adverse foetal side-effects and should only be considered for emergency situations.919”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [919]
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- Authors
- Bartalena, L., Bogazzi, F., Braverman, L. E., & Martino, E.
- Affiliations
- University of Insubria (IT)
- University of Pisa (IT)
- Boston Medical Center (US)
- Corresponding author
- Martino, E.
- Venue
- Journal of Endocrinological Investigation
- Published
- 2001-02
- Volume
- 24
- Issue
- 2
- Pages
- 116-130
- ISSN
- 0391-4097 (ISSN-L)
- 1720-8386
- OpenAlex
- W1964636323
- Cited by
- 199
- References
- 123
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 6 · 2023: 6 · 2022: 4 · 2021: 10 · 2020: 10 · 2019: 11 · 2018: 11 · 2017: 4 · 2016: 7 · 2015: 14 · 2014: 9 · 2013: 9 · 2012: 8
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Endocrinological Investigation (publishedVersion)
- PubMed (publishedVersion)
- IrInSubria (University of Insubria) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- amiodarone, pregnancy, neonatal hypothyroidism, fetal hypothyroidism, goiter, iodine excess, Wolff-Chaikoff effect, desethylamiodarone, maternal-fetal drug transfer, fetal tachyarrhythmia, brain development, breastfeeding, thyroid function
- MeSH terms
- Amiodarone, Female, Humans, Hypothyroidism, Infant, Newborn, Lactation, Maternal-Fetal Exchange, Nervous System, Pregnancy, Psychomotor Disorders
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