Main Article Content
Therapeutic advances, including the availability of oral iron chelators and new non-invasive methods for early detection and treatment of iron overload, have significantly improved the life expectancy and quality of life of patients with thalassemia, with a consequent increase in their reproductive potential and desire to have children. Hundreds of pregnancies have been reported so far, highlighting that women carefully managed during preconception usually carry out a successful gestation and labour, both in case of spontaneous conception and use of assisted reproductive techniques. A multidisciplinary team including a cardiologist, an endocrinologist and a gynaecologist, with the supervision of an expert in beta-thalassemia should be involved.
During pregnancy, a close follow-up of maternal disorders and of the baby's status is recommended. Haemoglobin should be maintained over 10 g/dL to to allow normal foetal growth. Chelators are not recommended during pregnancy; nevertheless, it may reasonable to consider restarting chelation therapy with desferrioxamine towards the end of the second trimester when the potential benefit outweighs the potential foetal risk.
Women with non-transfusion-dependent thalassemia who have never previously been transfused or who have received only minimal transfusion therapy are at risk of severe alloimmune anaemia if blood transfusions are required during pregnancy. Since pregnancy increases the risk of thrombosis three-fold to four-fold and thalassemia is also a hypercoagulable state, the recommendation is to keep women who are at higher risk -such as those who are not regularly transfused and those splenectomised- on prophylaxis during pregnancy and during the postpartum period.
Keywords:Pregnancy, Thalassemia major, Thalassemia intermedia, Haemoglobin H disease, Counselling
Downloads month by month
2. Origa R, Sollaino MC, Giagu N, Barella S, Campus S, Mandas C, Bina P, Perseu L, Galanello R. Clinical and molecular analysis of haemoglobin H disease in Sardinia: haematological, obstetric and cardiac aspects in patients with different genotypes. Br J Haematol. 2007 Jan;136(2):326-332.
3. Borgna-Pignatti C1, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC, Romeo MA, Forni GL, Gamberini MR, Ghilardi R, Piga A, Cnaan A. Survival and complications in patients with β major treated with transfusion and deferoxamine. Haematologica. 2004 Oct;89(10):1187-93.
4. Cunningham MJ, Macklin EA, Neufeld EJ, Cohen AR; Thalassemia Clinical Research Network.Complications of beta-thalassemia major in North America. Blood. 2004 Jul 1;104(1):34-39.
5. Floris F, Comitini F, Leoni G, Moi P, Morittu M, Orecchia V, Perra M, Pilia MP, Zappu A, Casini MR, Origa R. Quality of life in Sardinian patients with transfusion-dependent Thalassemia: a cross-sectional study. Qual Life Res. 2018 Jun 19. doi: 10.1007/s11136-018-1911-7. [Epub ahead of print]
6. Walker EH, Whelton MJ, Beaven GH. Successful pregnancy in a patient with thalassaemia major. J Obstet Gynaecol Br Commonw. 1969 Jun;76(6):549-553.
7. Thompson AA, Kim HY, Singer ST, Vichinsky E, Eile J, Yamashita R, Giardina PJ, Olivieri N, Parmar N, Trachtenberg F, Neufeld EJ, Kwiatkowski JL; Thalassemia Clinical Research Network. Pregnancy outcomes in women with thalassemia in North America and the United Kingdom. Am J Hematol. 2013 Sep;88(9):771-773.
8. Origa R, Piga A, Quarta G, Forni GL, Longo F, Melpignano A, Galanello R. Pregnancy and beta-thalassemia: an Italian multicenter experience. Haematologica. 2010 Mar;95(3):376-381.
9. Origa R. β-Thalassemia. Genet Med. 2017 Jun;19(6):609-619.
10. Noetzli LJ1, Panigrahy A, Mittelman SD, Hyderi A, Dongelyan A, Coates TD, Wood JC. Pituitary iron and volume predict hypogonadism in transfusional iron overload. Am J Hematol. 2012 Feb;87(2):167-171.
11. Carlberg KT, Singer ST, Vichinsky EP. Fertility and Pregnancy in Women with Transfusion-Dependent Thalassemia. Hematol Oncol Clin North Am. 2018 Apr;32(2):297-315.
12. Tuck SM. Fertility and pregnancy in thalassemia major. Ann N Y Acad Sci. 2005;1054:300-307
13. Singer ST, Vichinsky EP, Gildengorin G, van Disseldorp J, Rosen M, Cedars MI. Reproductive capacity in iron overloaded women with thalassemia major. Blood. 2011 Sep 8;118(10):2878-2881.
14. Chang HH, Chen MJ, Lu MY, Chern JP, Lu CY, Yang YL, Jou ST, Lin DT, Yang YS, Lin KH. Iron overload is associated with low anti-müllerian hormone in women with transfusion-dependent β-thalassaemia. BJOG. 2011 Jun;118(7):825-831.
15. Danesi L, Scacchi M, Miragoli AM, Pincelli AI, Dubini A, Maiolo AT, Cavagnini F, Polli EE. Induction of follicle maturation and ovulation by gonadotropin administration in women with beta-thalassemia. Eur J Endocrinol. 1994 Dec;131(6):602-606.
16. Cassinerio E, Baldini IM, Alameddine RS, Marcon A, Borroni R, Ossola W, Taher A, Cappellini MD. Pregnancy in patients with thalassemia major: a cohort study and conclusions for an adequate care management approach. Ann Hematol. 2017 Jun;96(6):1015-1021..
17. Smith V, Osianlis T, Vollenhoven B. Prevention of Ovarian Hyperstimulation Syndrome: A Review. Obstet Gynecol Int. 2015;2015:514159
18. Ansari S, Azarkeivan A, Tabaroki A. Pregnancy in patients treated for beta thalassemia major in two centers (Ali Asghar Children's Hospital and Thalassemia Clinic): outcome for mothers and newborn infants. Pediatr Hematol Oncol. 2006 Jan-Feb;23(1):33-37.
19. Toumba M, Kanaris C, Simamonian K, Skordis N. Outcome and management of pregnancy in women with thalassaemia in Cyprus. East Mediterr Health J. 2008 May-Jun;14(3):628-635.
20. Skordis N, Petrikkos L, Toumba M, Hadjigavriel M, Sitarou M, Kolnakou A, Skordos G, Pangalou E, Christou S. Update on fertility in thalassaemia major. Pediatr Endocrinol Rev. 2004 Dec;2 Suppl 2:296-302.
21. Gamberini MR, De Sanctis V, Gilli G. Hypogonadism, diabetes mellitus, hypothyroidism, hypoparathyroidism: incidence and prevalence related to iron overload and chelation therapy in patients with thalassaemia major followed from 1980 to 2007 in the Ferrara Centre. Pediatr Endocrinol Rev. 2008 Oct;6 Suppl 1:158-169.
22. Origa R, Danjou F, Orecchia V, Zappu A, Dessì C, Foschini ML, Leoni GB, Moi P,, Morittu M, Demurtas A, Loche S. Current growth patterns in children and adolescents with thalassemia major. Blood. 2016 Nov 24;128(21):2580-2582.
23. Supramaniam PR, Mittal M, McVeigh E, Lim LN. The correlation between raised body mass index and assisted reproductive treatment outcomes: a systematic review and meta-analysis of the evidence. Reprod Health. 2018 Feb 27;15(1):34.
24. Monni G, Peddes C, Iuculano A, Ibba RM. From Prenatal to Preimplantation Genetic Diagnosis of β-Thalassemia. Prevention Model in 8748 Cases: 40 Years of Single Center Experience. J Clin Med. 2018 Feb 20;7(2).
25. Rosatelli MC, Saba L. Prenatal Diagnosis of β-Thalassemias and Haemoglobinopathies. Mediterr J Hematol Infect Dis. 2009 Nov 15;1(1):e2009011.
26. Vrettou C, Kakourou G, Mamas T, Traeger-Synodinos J. Prenatal and preimplantation diagnosis of haemoglobinopathies. Int J Lab Hematol. 2018 May;40 Suppl 1:74-82.
27. Petrakos G, Andriopoulos P, Tsironi M. Pregnancy in women with thalassemia: challenges and solutions. Int J Womens Health. 2016 Sep 8;8:441-451.
28. Fu Q. Hemodynamic and Electrocardiographic Aspects of Uncomplicated Singleton Pregnancy. Adv Exp Med Biol. 2018;1065:413-431.
29. Skordis N1, Petrikkos L, Toumba M, Hadjigavriel M, Sitarou M, Kolnakou A, Skordos G, Pangalou E, Christou S. Update on fertility in thalassaemia major. Pediatr Endocrinol Rev. 2004 Dec;2 Suppl 2:296-302.
30. Triunfo S, Lanzone A, Lindqvist PG. Low maternal circulating levels of vitamin D as potential determinant in the development of gestational diabetes mellitus. J Endocrinol Invest. 2017 Oct;40(10):1049-1059.
31. Stathopoulos IP, Liakou CG, Katsalira A, Trovas G, Lyritis GG, Papaioannou NA, Tournis S. The use of bisphosphonates in women prior to or during pregnancy and lactation. Hormones (Athens). 2011 Oct-Dec;10(4):280-91
32. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum.Thyroid. 2017 Mar;27(3):315-389.
33. American Diabetes Association. 13. Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018 Jan;41(Suppl 1):S137-S143.
34. Kanninen TT, Dieterich D, Asciutti S. HCV vertical transmission in pregnancy: New horizons in the era of DAAs. Hepatology. 2015 Dec;62(6):1656-1658.
35. Figueiredo ACMG, Gomes-Filho IS, Silva RB, Pereira PPS, Mata FAFD, Lyrio AO, Souza ES, Cruz SS, Pereira MG. Maternal Anaemia and Low Birth Weight: A Systematic Review and Meta-Analysis. Nutrients. 2018 May 12;10(5). pii: E601.
36. Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V, editors. Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT) [Internet]. 3rd edition. Nicosia (CY): Thalassaemia International Federation; 2014.
37. Galanello R, Campus S. Deferiprone chelation therapy for thalassemia major.Acta Haematol. 2009;122(2-3):155-164.
38. Berdoukas V, Bentley P, Frost H, Schnebli HP. Toxicity of oral iron chelator L1. Lancet. 1993 Apr 24;341(8852):1088.
39. Diamantidis MD, Neokleous N, Agapidou A, Vetsiou E, Manafas A, Fotiou P, Vlachaki E. Iron chelation therapy of transfusion-dependent β-thalassemia during pregnancy in the era of novel drugs: is deferasirox toxic? Int J Hematol. 2016 May;103(5):537-544.
40. Vini D, Servos P, Drosou M. Normal pregnancy in a patient with β-thalassaemia major receiving iron chelation therapy with deferasirox (Exjade®). Eur J Haematol. 2011 Mar;86(3):274-275.
41. Anastasi S1, Lisi R, Abbate G, Caruso V, Giovannini M, De Sanctis V. Absence of teratogenicity of deferasirox treatment during pregnancy in a thalassaemic patient. Pediatr Endocrinol Rev. 2011 Mar;8 Suppl 2:345-347.
42. Bruin GJ, Faller T, Wiegand H, Schweitzer A, Nick H, Schneider J, Boernsen KO, Waldmeier F. Pharmacokinetics, distribution, metabolism, and excretion of deferasirox and its iron complex in rats. Drug Metab Dispos. 2008 Dec;36(12):2523-2538.
43. Bosque MA1, Domingo JL, Corbella J. Assessment of the developmental toxicity of deferoxamine in mice. Arch Toxicol. 1995;69(7):467-471.
44. Tampakoudis P, Tsatalas C, Mamopoulos M, Tantanassis T, Christakis JI, Sinakos Z, Mantalenakis S. Transfusion-dependent homozygous beta-thalassaemia major: successful pregnancy in five cases. Eur J Obstet Gynecol Reprod Biol. 1997 Aug;74(2):127-131.
45. Tsironi M, Karagiorga M, Aessopos A. Iron overload, cardiac and other factors affecting pregnancy in thalassemia major. Haemoglobin. 2010 Jun;34(3):240-250.
46. Singer ST, Vichinsky EP. Deferoxamine treatment during pregnancy: is it harmful? Am J Hematol. 1999 Jan;60(1):24-26.
47. Tsironi M, Ladis V, Margellis Z, Deftereos S, Kattamis Ch, Aessopos A. Impairment of cardiac function in a successful full-term pregnancy in a homozygous beta-thalassemia major: does chelation have a positive role? Eur J Obstet Gynecol Reprod Biol. 2005 May 1;120(1):117-118.
48. Kumar RM, Rizk DE, Khuranna A. Beta-thalassemia major and successful pregnancy. J Reprod Med. 1997 May;42(5):294-298.
49. Al-Riyami N, Al-Khaduri M, Daar S. Pregnancy Outcomes in Women with Homozygous Beta Thalassaemia: A single-centre experience from Oman. Sultan Qaboos Univ Med J. 2014 Aug;14(3):e337-341.
50. Voskaridou E, Balassopoulou A, Boutou E, Komninaka V, Christoulas D, Dimopoulou M, Delaki EE, Loukopoulos D, Terpos E. Pregnancy in beta-thalassemia intermedia: 20-year experience of a Greek thalassemia center. Eur J Haematol. 2014 Dec;93(6):492-499.
51. Pepe A, Meloni A, Neri MG, Allò M, Facchini E, Casini T, Maggio A, Positano V, Valeri G, Chiodi E, Salvatori C, Gamberini MR. Changes of Cardiac Iron and Function during Pregnancy in Trasfusion-Dependent Thalassemia Patients. Blood 2015 126:3367;
52. Brenner B. Haemostatic changes in pregnancy. Thromb Res. 2004;114(5-6):409-414.
53. James AH. Thrombosis in pregnancy and maternal outcomes. Birth Defects Res C Embryo Today. 2015 Sep;105(3):159-166.
54. Cappellini MD, Motta I, Musallam KM, Taher AT.Redefining thalassemia as a hypercoagulable state. Ann N Y Acad Sci. 2010 Aug;1202:231-236.
55. Taher AT, Musallam KM, Karimi M, El-Beshlawy A, Belhoul K, Daar S, Saned M, Cesaretti C, Cappellini MD. Splenectomy and thrombosis: the case of thalassemia intermedia. J Thromb Haemost. 2010 Oct;8(10):2152-2158.
56. Nassar AH, Usta IM, Taher AM. Beta-thalassemia intermedia and pregnancy: should we anticoagulate? J Thromb Haemost. 2006 Jun;4(6):1413-1414.
57. Eldor A, Rachmilewitz EA. The hypercoagulable state in thalassemia. Blood. 2002 Jan 1;99(1):36-43.
58. Nassar AH, Naja M, Cesaretti C, Eprassi B, Cappellini MD, Taher A. Pregnancy outcome in patients with beta-thalassemia intermedia at two tertiary care centers, in Beirut and Milan. Haematologica. 2008 Oct;93(10):1586-1587.
59. Xu TT, Zhou F, Deng CY, Huang GQ, Li JK, Wang XD. Low-Dose Aspirin for Preventing Preeclampsia and Its Complications: A Meta-Analysis. J Clin Hypertens (Greenwich). 2015 Jul;17(7):567-573.
60. Bajoria R1, Chatterjee R. Current perspectives of fertility and pregnancy in thalassemia. Haemoglobin. 2009;33 Suppl 1:S131-135.
61. Daskalakis GJ, Papageorgiou IS, Antsaklis AJ, Michalas SK. Pregnancy and homozygous beta thalassaemia major. Br J Obstet Gynaecol. 1998 Sep;105(9):1028-1032.
62. Lekawanvijit S, Chattipakorn N. Iron overload thalassemic cardiomyopathy: iron status assessment and mechanisms of mechanical and electrical disturbance due to iron toxicity. Can J Cardiol. 2009 Apr;25(4):213-218.
63. Tovo PA, Calitri C, Scolfaro C, Gabiano C, Garazzino S. Vertically acquired hepatitis C virus infection: Correlates of transmission and disease progression. World J Gastroenterol. 2016 Jan 28;22(4):1382-1392.
64. Konstantopoulos K, Plataniotis G, Maris T, Voskaridou E, Rekoumi L, Stratigaki M, Loukopoulos D. Extramedullary haemopoiesis in thalassaemia intermedia: an unusual case of relapsing paraparesis in pregnancy. Haematologia (Budap). 1995;27(1):29-32.
65. Aessopos A, Karabatsos F, Farmakis D, Katsantoni A, Hatziliami A, Youssef J, Karagiorga M. Pregnancy in patients with well-treated beta-thalassemia: outcome for mothers and newborn infants. Am J Obstet Gynecol. 1999 Feb;180(2 Pt 1):360-365.
66. Tongsong T, Srisupundit K, Luewan S. Outcomes of pregnancies affected by haemoglobin H disease. Int J Gynaecol Obstet. 2009 Mar;104(3):206-208
67. Jaovisidha A, Ajjimarkorn S, Panburana P, Somboonsub O, Herabutya Y, Rungsiprakarn R. Prevention and control of thalassemia in Ramathibodi Hospital, Thailand. Southeast Asian J Trop Med Public Health. 2000 Sep;31(3):561-565.
68. Taweevisit M, Thorner PS. Hydrops foetalis in the stillborn: a series from the central region of Thailand. Pediatr Dev Pathol. 2010 Sep-Oct;13(5):369-374.
69. Ong HC, White JC, Sinnathuray TA. Haemoglobin H disease and pregnancy in a Malaysian woman. Acta Haematol. 1977;58(4):229-233.
70. Tantiweerawong N, Jaovisidha A, Israngura Na Ayudhya N. Pregnancy outcome of haemoglobin H disease. Int J Gynaecol Obstet. 2005 Sep;90(3):236-237.
71. Vaeusorn O, Fucharoen S, Wasi P.A study of thalassemia associated with pregnancy. Birth Defects Orig Artic Ser. 1988;23(5B):295-299.
72. Aiken L, Linpower L, Tsitsikas DA, Win N. Hyperhaemolysis in a pregnant patient with HbH disease. Transfus Med. 2018 Mar 1. doi: 10.1111/tme.12518. [Epub ahead of print]
73. Politou M, Dryllis G, Efstathopoulou M, Valsami S, Triantafyllou FE, Tsaroucha A, Kattamis A, Vlahos NF. Pregnancy Complications in a-Thalassemia (Haemoglobinopathy H): A Case Study. Case Rep Obstet Gynecol. 2018 May 27;2018:8532081.
74. Insiripong S, Prabriputaloong S, Wisanuyothin N. Thalassemic mothers and their babies. Southeast Asian J Trop Med Public Health. 2009 Mar;40(2):302-305.
75. Rabiee M1, Shams JA2, Zafargandie N1. The Adverse Effects of Pregnancies Complicated by Haemoglobin H (HBH) Disease. Iran J Pathol. 2015 Fall;10(4):318-321.