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

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

Maria Hoeltzenbein  1 , Katja Stieler, Mary Panse, Evelin Wacker, Christof Schaefer
Affiliations

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

Maria Hoeltzenbein et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Flow chart on cases of allopurinol exposure and pregnancy (FUP =  Follow-up).
Figure 2
Figure 2. Diagram summarizing pregnancy interval of allopurinol exposure, week at first contact and outcome of 31 prospectively ascertained pregnancies.
Figure 3
Figure 3. Estimation of cumulative incidences using survival analysis technique.
Probability of spontaneous abortion was 11% (95%-confidence interval (CI) 3–40), ETOP 9% (95%-CI 2–32), and live birth 80% (95%-CI 60–85).
Figure 4
Figure 4. Birth weight percentiles.
Bars in colors give the proportions of newborns by percentiles. Grey bars represent the proportion of newborn in the German Perinatal Project general population in each percentile category.
See this image and copyright information in PMC

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Publication types

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.