Allopurinol Use during Pregnancy - Outcome of 31 Prospectively Ascertained Cases and a Phenotype Possibly Indicative for Teratogenicity

PLoS One. 2013 Jun 19;8(6):e66637. doi: 10.1371/journal.pone.0066637. Print 2013.

Abstract

Allopurinol is a purine analogue that inhibits xanthine oxidase. It is mainly used for the treatment of hyperuricemia in patients with gout or tumor lysis syndrome. Experience with allopurinol in pregnancy is scarce. In 2011, Kozenko et al. reported on a child with multiple malformations after maternal treatment with allopurinol throughout pregnancy. Possible teratogenicity of allopurinol was proposed due to the similarity of the pattern of malformations in children with mycophenolate embryopathy. A possible common mechanism of both drugs, i.e. disruption of purine synthesis, was discussed. We report on the outcome of 31 prospectively ascertained pregnancies with allopurinol exposure at least during first trimester. Pregnancy outcomes were 2 spontaneous abortions, 2 elective terminations of pregnancy and 27 live born children. The overall rate of major malformations (3.7%) and of spontaneous abortions (cumulative incidence 11%, 95%-CI 3-40) were both within the normal range. However, there was one child with severe malformations including microphthalmia, cleft lip and palate, renal hypoplasia, low-set ears, hearing deficit, bilateral cryptorchidism, and micropenis. The striking similarity of the anomalies in this child and the case described by Kozenko et al. might be considered as a signal for teratogenicity. Thus, we would recommend caution with allopurinol treatment in the first trimester, until further data are available.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Therapeutic
  • Allopurinol / adverse effects*
  • Allopurinol / therapeutic use
  • Female
  • Gout / drug therapy
  • Humans
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Pregnancy Outcome*
  • Prospective Studies
  • Teratogens*
  • Tumor Lysis Syndrome / drug therapy

Substances

  • Teratogens
  • Allopurinol

Grants and funding

The study has been performed with financial support from the German Federal Institute for Drugs and Medical Devices. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.