Limited Evidence for Teratogenicity of Allopurinol Use During Pregnancy

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The association between allopurinol and teratogenicity appears to be weak and limited.
The association between allopurinol and teratogenicity appears to be weak and limited.

A review of animal and human studies found insufficient evidence of teratogenicity for allopurinol taken prior to or during pregnancy, according to a report published in Reproductive Toxicology.

Despite its longevity as a therapeutic mainstay in the treatment of gout, kidney stones, and inflammatory bowel disease, the teratogenic risk of allopurinol is still undetermined. Unfortunately, information from pregnancy exposure registries is lacking for allopurinol. Investigators sought to review the literature on its potential toxicity to more definitively establish a pregnancy safety profile.

An examination of human studies revealed a total of 53 reports of allopurinol exposure in infants, with only 2 cases describing major congenital malformations (both with similar patterns of multiple abnormalities of uncertain causality, but that appeared to resemble anomalies seen with mycophenolate administration), and 5 additional cases involving minor deformities. Evidence of its effect on male or female fertility is limited, and while placental transfer does occur, it has proven helpful in cases of birth asphyxia. Reports have both implicated and excluded allopurinol as a potential teratogen, with some researchers recommending cautious use during the first trimester. Lactation information is very sparse, consisting of only 1 report describing safe breastfeeding of a single infant.

In the face of limited and uncertain evidence for or against the safety and toxicity of allopurinol perinatally, the authors were unable to come to a solid conclusion regarding its use during this period, suggesting that a complex collection of determinants may be responsible for increasing the risk for adverse outcomes in some cases. However, they advised that physicians and patients need to weigh the benefits of therapy with possible fetal exposure against the potential dangers of enduring pregnancy with an untreated disease. Going forward, they concluded, “As allopurinol treatment evolves, prospective follow-up of exposed offspring and report of all exposed infants (ie, deviant and normal cases), should be encouraged.”

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Reference

Simsek M, Opperman RCM, Mulder CJJ, Lambalk CB, de Boer NKH. The teratogenicity of allopurinol: a comprehensive review of animal and human studies. Reprod Toxicol. 2018;81:180-187.

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