The Use of Hydroxyurea During Pregnancy in Sickle Cell Anemia Women: A Case Series and Literature Review
DOI:
https://doi.org/10.12974/2312-5411.2021.08.2Keywords:
Sickle cell disease, Pregnancy, Sickle cell anemia, Congenital anomalies, Hydroxyurea.Abstract
Hydroxyurea (HU) has been an effective treatment for sickle cell anemia (SCA) by inducing fetal hemoglobin production as well as reducing the rate of painful crisis. The use of HU during pregnancy still has been a concerned situation due to the risk of malformation, but there is already a proposal for the possibility of the use, even during pregnancy, depending on the situation of the disease. On the other side, the potential of HU for mutagenesis and teratogenesis in humans has not been confirmed yet. This case series describe the perinatal outcomes on women at a Women's Care Center in Recife, Brazil. Women used HU early in their pregnancies and no record of malformation was report. Our sample was composed of 13 SCA women using HU just before or during pregnancy. Of these women, 4 had gotten pregnant twice by using HU and for this we have analyzed a total of 17 cases. There were no reports on malformation in any of these cases. In the literature review, we found seven studies on the use of HU in pregnancy and only one of these studies reported malformation in a fetus. We concluded that HU usage and teratogenic effects has not been confirmed in humans yet and suggested to await results of well-controlled studies to define the use of HU as a treatment for vasooculsive crises during pregnancy. Thus, we consider that this publication could be added to other cases in which have been already published where fetal malformation has not been registered yet.
References
Habara AH, Shaikho EM, Steinberg MH. Fetal Hemoglobin in Sickle Cell Anemia: The Arab-Indian Haplotype and New Therapeutic Agents. Am J Hematol. 2017; 25(5): 1032-1057. https://doi.org/10.1002/ajh.24872
Charache S, Dover GJ, Moyer MA, Moore JW. Hydroxyureainduced augmentation of fetal hemoglobin production in patients with sickle cell anemia. Blood. 1987; 69(1): 109 - 116. https://doi.org/10.1182/blood.V69.1.109.109
Pule GD, Mowla S, Novitzky N, Wiysonge CS, Wonkam A. A systematic review of known mechanisms of hydroxyureainduced fetal hemoglobin for tratment of sickle cell disease. Expert Rev Hematol 2015; 8(5): 669-679. https://doi.org/10.1586/17474086.2015.1078235
Thein SL, Howard J. How I treat older adult with sickle cell disease. Blood 2018; 132(17): 1750-1960. https://doi.org/10.1182/blood-2018-03-818161
Brasil. Ministério da Saúde. Secretaria de Atenção à Saúde. Departamento de Atenção Hospitalar e de Urgência. Doença falciforme: Hidroxiureia: uso e acesso / 1ed., 1. reimpr. - Brasília: Ministério da Saúde, 2014. 56 p.: il. Available from: http://bvsms.saude.gov.br/bvs/publicacoes/doenca_falciform e_hidroxiureia_uso_acesso.pdf
Montironi R, Cupaiolo R, Kadji C, Badr DA, Deleers M, Charles V. at al. Management od sickle cell during pregnacy: experience in a third-level hospital and future recommendations. The Journal of Maternal-Fetal & Neonatal Medicine. 2020.
Santos JL, Bosquesi PL, Almeida AE, Chin CM, Varanda EA. Mutagenic and genotoxic effect of hydroxyurea. Int J Biomed Sci 2011; 7(4): 263-267.
Oliveira EAM, Boy KA, Santos APP, Machado CS, Velloso- Rodrigues C, Gerheim PSAS et al. Evaluation of hydroxyurea genotoxicity in patients with sickle cell disease. Einstein (São Paulo). 2019; 17(4): eAO4742.
Fritz H, Hess R. Effects of hydroxyurea on postnatal growth and behaviour of rats. Agents Actions. 1980; 10(4): 389-393. https://doi.org/10.1007/BF01971445
Byrd DC, Pitts SR, Alexander CK. Hydroxyurea in two pregnant women with sickle cell anemia. Phamacotherapy. 1999; 19(12): 1459-1462. https://doi.org/10.1592/phco.19.18.1459.30901
Diav-Citrin O, Hunnisett L, Sher GD, Koren G. Hydroxyurea use during pregnancy: A case report in sickle cell disease and review of the literature. Am J Hematol. 1999; 60(2): 148- 150. https://doi.org/10.1002/(SICI)1096- 8652(199902)60:2<148::AID-AJH12>3.0.CO;2-I
Montalembert M, Begue P, Bernaudin F, Thuret I, Bachir D, Micheau M. Preliminary report of a toxicity study of hydroxyurea in sickle cell disease. Arch Dis Child. 1999; 81(5): 437-439. https://doi.org/10.1136/adc.81.5.437
Italia KY, Jijina FF, Chandrakala S, Nadkarni AH, Sawant P, Ghosh K, et al. Exposure to hydroxyurea during pregnancy in sickle-β Thalassemia: A report of 2 cases. J Clin Pharmacol. 2010; 50(2): 231-234. https://doi.org/10.1177/0091270009343933
Daigavane MM, Jena RK, Kar TJ. Perinatal outcome in sickle cell anemia: a prospective study from India. Hemoglobin. 2013; 37(6): 507-515. https://doi.org/10.3109/03630269.2013.828301
Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert S V, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med. 1995; 332(20): 1317-1322. https://doi.org/10.1056/NEJM199505183322001
Ballas SK, McCarthy WF, Guo N, DeCastro L, Bellevue R, Barton BA, et al. Exposure to hydroxyurea and pregnancy outcomes in patients with sickle cell anemia. J Natl Med Assoc. 2009; 101(10): 1046-1051. https://doi.org/10.1016/S0027-9684(15)31072-5
Poli PA, Jesani JK, Kosgey W, Bett K CN, Mishra P, Beatrice J, et al. Exposure to hydroxyurea during pregnancy: a case report of congenital malformation, update on the current evidence and management od sikle cell disese during pregnancy. Gynecol Obstet Case Rep. 2020; 6(5): 28.
Fescina RH, De Mucio B, Díaz Rossello JL, Martínez G, Granzotto JA. Saúde sexual e reprodutiva: guias para a atenção continuada de mulher e do recém-nascido focalizadas na APS. Montevideu. CLAP/SMR; 2010. (CLAP/SMR. Publicacao Cientifica; 1562.3).
Hanft VN, Fruchtman SR, Pickens CV, Rosse WF, Howard TA, Ware RE. Acquired DNA mutations associated with in vivo hydroxyurea exposure. Blood. 2000; 95(11): 3589-3593. https://doi.org/10.1182/blood.V95.11.3589
Ware RE. Optimizing hydroxyurea therapy for sickle cell anemia. Hematology. 2015; 2015(1): 436-443. https://doi.org/10.1182/asheducation.V2015.1.436.3917688
Silva FAC, Ferreira ALCG, Hazin-Costa MF, Dias MLG, Araújo AS, Souza AI. Adverse clinical and obstetric outcomes among pregnant women with different sickle cell disease genotypes. Int J Gynecol Obstet 2018; 143(1): 89- 93. https://doi.org/10.1002/ijgo.12626
Oteng-Ntim E, Meeks D, Seed PT, Webster L, Howard J, Doyle P, et al. Adverse maternal and perinatal outcomes in pregnant women with sickle cell disease: systematic review and meta-analysis. Blood. 2015; 125(21): 3316-3325. https://doi.org/10.1182/blood-2014-11-607317
Oteng-Ntim E, Ayensah B, Knight M, Howard J. Pregnancy outcome in patients with sickle cell disease in the UK - a national cohort study comparing sickle cell anaemia (HbSS) with HbSC disease. Br J Haematol. 2015; 169(1): 129-137. https://doi.org/10.1111/bjh.13270
Kuo K, Caughey AB. Contemporary outcomes of sickle cell disease in pregnancy. Am J Obstet Gynecol 2016; 215(4): 505e1-505e5.