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Exposure to hydroxyurea during pregnancy: a case series

Leukemia volume 15, pages 1309–1311 (2001)Cite this article

Hydroxyurea (HU) is an antineoplastic drug currently used in the management of many myeloproliferative disorders and especially in essential thombocythemia (ET). The management of pregnancy in women with a myeloproliferative disorder is a real dilemna. Being faced directly with the problem of information and counselling about HU exposure in pregnancy, we decided to collect and evaluate data on the outcome of pregnancy following exposure to hydroxyurea because of essential thrombocythemia (ET), chronic myeloid leukaemia (CML), chromic myeloid splenomegaly (CMSM) and sickle cell disease (SCD).

We collected and evaluated pregnancy outcomes of 31 women with HU exposure. Data were collected in two distinct situations, both with prospective ascertainment of exposure. First, haematologists referred patients for advice to those of us who are geneticists (CTR and ANC). We were faced directly with the problem of information and counselling about HU exposure in pregnancy. We followed these patients and their children after birth. Second, data were collected from two teratogen information services in Paris and Lyon. Telephone calls were made by clinicians seeking information about HU-related risk, then follow-up forms were sent and returned after the pregnancies ended. Overall we collected 31 cases (Table 1). Indications of HU use were ET in 22/31 cases, CML in 6/31 cases, chronic myeloid splenomegaly (CMSM) in 2/31 cases, and SCD in 1/31 cases. HU exposure occurred during the first trimester of pregnancy (weeks 1–14 after last menstruation period) in 22/31 cases, during the first and second trimester in 2/31 cases, throughout pregnancy in 3/31 cases, and in the third trimester in 2/31 cases. Precise HU exposure duration was unknown in 2/31 cases. Doses varied from 0.5 g/day to 6 g/day orally. Other drugs were associated, mostly antibiotics and aspirin. Two cases received interferon-alpha but were lost to follow-up. One woman received misulban and melphalan; she gave birth to a healthy liveborn male infant. The 31 pregnancies with HU exposure ended in 24 liveborn infants (one pregnancy was twice), five induced abortions, one spontaneous abortion and two in utero fetal deaths (IUFD). Intrauterine growth retardation (IUGR) was found in 2/31 cases by ultrasound. Among the 24 liveborn infants, nine were premature and three had minor abnormalities, namely hip dysplasia, unilateral renal dilatation and pilonidal sinus. Five presented neonatal respiratory distress after gravidis toxaemia or pre-eclampsia, likely to be as a result of prematurity and not pulmonary malformation. No baby had major malformations. Fetal examination did not find any malformation in the two IUFD either. Prenatal or post-natal chromosomal analysis was normal in 6/7 studied cases and 1/7 cases showed inherited inversion of chromosome 9. Alpha fetoprotein was normal in the three amniotic fluids tested.

Table 1 Our cases of HU exposure during pregnancy
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Acknowledgements

We would like to thank Dr T Vialle, Dr Orfeuvre and Dr P Carlier for their collaboration.

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Authors and Affiliations

  1. Centre de Génétique, Dijon, France

    C Thauvin-Robinet & A Nivelon-Chevallier

  2. Service de Pédiatrie 1, Hôpital d'Enfants, Dijon, France

    C Maingueneau

  3. Institut Européen des Génomutations, Lyon, France

    E Robert

  4. Centre de Renseignements sur les Agents Tératogènes, CHU Saint Antoine, Paris, France

    E Elefant

  5. Hématologie Clinique, Hôpital Le Bocage, Dijon, France

    H Guy, D Caillot & RO Casasnovas

  6. Clinique Gynécologique et Obstétrique, Hôpital Le Bocage, Dijon, France

    S Douvier

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Thauvin-Robinet, C., Maingueneau, C., Robert, E. et al. Exposure to hydroxyurea during pregnancy: a case series. Leukemia 15, 1309–1311 (2001). https://doi.org/10.1038/sj.leu.2402168

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