Fetal Anemia in Northern Thailand: Etiologies and Outcomes
Keywords:
fetal anemia, Hb Bart’s disease, Hb Constant Spring, hydrops fetalis, red cell membrane disordersAbstract
OBJECTIVE In Southeast Asia, hemoglobin (Hb) Bart’s disease is the primary cause of fetal anemia, although other causes are increasingly being identified. This study aimed to characterize the etiologies and outcomes of fetal anemia in northern Thailand.
METHODS A retrospective chart review was conducted, involving pregnant women who attended antenatal care at Chiang Mai University Hospital between 2014 and 2021 and had a diagnosis by ultrasound findings of fetal anemia, or a fetal diagnosis of Hb Bart’s disease or other known hereditary anemias.
RESULTS Among 71 fetuses from 64 pregnancies, 45 (63.4%) had Hb Bart’s disease. Twelve cases (16.9%) of fetal anemia were from other causes, including three cases of homozygous Hb Constant Spring, three cases of hereditary pyropoikilocytosis, one case of suspected red cell membrane disorder, one case each of Rh(D) alloimmunization, Hb H/Hb Pakse disease, transient abnormal myelopoiesis, syphilis infection, and one of unknown cause. All of the seven sets of twins (19.7%) had twin-to-twin transfusion syndrome (TTTS). Intrauterine transfusion was given in four cases of fetal hemolytic anemia which rendered good outcomes. Overall, 12 cases (16.9%) survived beyond the neonatal period.
CONCLUSIONS Hb Bart’s disease remains the leading cause of fetal anemia in northern Thailand. Increasingly, frequently diagnosed causes include hemoglobinopathies and red cell membrane disorders.
References
Takci S, Gharibzadeh M, Yurdakok M, Ozyuncu O, Korkmaz A, Akcoren Z, et al. Etiology and outcome of
hydrops fetalis: report of 62 cases. Pediatr Neonatol.2014;55:108-13.
He S, Wang L, Pan P, Wei H, Meng D, Du J, et al. Etiology and Perinatal Outcome of Nonimmune Hydrops Fetalis in Southern China. AJP Rep. 2017;7:e111-5. PubMed PMID: 28611934
McEwan A. Fetal anaemia. Obstet Gynaecol Reprod Med. 2015;25:22-8.
Mari G, Norton ME, Stone J, Berghella V, Sciscione AC, Tate D, Schenone MH, Society for Maternal-Fetal
Medicine (SMFM) Society for Maternal-Fetal Medicine (SMFM) Clinical Guideline# 8: the fetus at risk
for anemia–diagnosis and management. Am J Obstet Gynecol. 2015;212:697-710.
Garratty G, Glynn SA, McEntire R, Retrovirus Epidemiology Donor S. ABO and Rh(D) phenotype frequencies of different racial/ ethnic groups in the United States. Transfusion. 2004;44:703-6.
Ng ZM, Seet MJ, Erng MN, Buendia F, Chang AS, Sriram B. Nonimmune hydrops fetalis in a children’s hospital: a six-year series. Singapore Med J. 2013;54:487-90.
Ratanasiri T, Komwilaisak R, Sittivech A, Kleebkeaw P, Seejorn K. Incidence, causes and pregnancy outcomes of hydrops fetalis at Srinagarind Hospital, 1996-2005: a 10-year review. J Med Assoc Thai. 2009;92:594-9.
Thong XY, Lee LY, Chia DA, Wong YC, Biswas A. Management and Outcomes of Fetal Hydrops in a Tertiary Care Centre in Singapore. Ann Acad Med Singapore. 2017;46:4-10.
Taweevisit M, Thorner PS. Hydrops fetalis in the stillborn: a series from the central region of Thailand.
Pediatr Dev Pathol. 2010;13:369-74.
Hockham C, Ekwattanakit S, Bhatt S, Penman BS, Gupta S, Viprakasit V, et al. Estimating the burden
of α-thalassaemia in Thailand using a comprehensive prevalence database for Southeast Asia. eLife.
;8:e40580. PubMed PMID: 31120421
Ittiwut C, Natesirinilkul R, Tongprasert F, Sathitsamitphong L, Choed-Amphai C, Fanhchaksai K, et al. Novel mutations in SPTA1 and SPTB identified by whole exome sequencing in eight Thai families with hereditary pyropoikilocytosis presenting with severe fetal and neonatal anaemia. Br J Haematol. 2019;185:578-82.
Sirilert S, Charoenkwan P, Sirichotiyakul S, Tongprasert F, Srisupundit K, Luewan S, et al. Prenatal diagnosis and management of homozygous hemoglobin constant spring disease. J Perinatol. 2019;39:927-33.
Suwanrath-Kengpol C, Kor-anantakul O, Suntharasaj T, Leetanaporn R. Etiology and outcome of non-immune hydrops fetalis in southern Thailand. Gynecol Obstet Invest. 2005;59:134-7.
Tongsong T, Charoenkwan P, Sirivatanapa P, Wanapirak C, Piyamongkol W, Sirichotiyakul S, et al. Effectiveness of the model for prenatal control of severe thalassemia. Prenat Diagn. 2013;33:477-83.
Meng D, Li Q, Hu X, Wang L, Tan S, Su J, et al. Etiology and Outcome of non-immune Hydrops Fetalis
in Southern China: report of 1004 cases. Sci Rep. 2019;9:10726. PubMed PMID: 31341179
Laig M, Pape M, Hundrieser J, Flatz G, Sanguansermsri T, Das BM, et al. The distribution of the Hb Constant Spring gene in Southeast Asian populations. Hum Genet. 1990;84:188-90.
Clegg JB, Weatherall DJ, Milner PF. Haemoglobin Constant Spring—A Chain Termination Mutant ? Nature.1971;234:337-40.
Charoenkwan P, Sirichotiyakul S, Chanprapaph P, Tongprasert F, Taweephol R, Sae-Tung R, et al. Anemia and hydrops in a fetus with homozygous hemoglobin Constant Spring. J Pediatr Hematol Oncol.
;28:827-30.
He Y, Zhao Y, Lou J-W, Liu Y-H, Li D-Z. Fetal anemia and hydrops fetalis associated with homozygous
Hb constant spring (HBA2: c.427T > C). Hemoglobin.2016;40:97-101.
Lorey F, Charoenkwan P, Witkowska HE, Lafferty J, Patterson M, Eng B, et al. Hb H hydrops foetalis syndrome: a case report and review of literature. Br J Haematol. 2001;115:72-8.
Henderson S, Pitman M, McCarthy J, Molyneux A, Old J. Molecular prenatal diagnosis of Hb H Hydrops Fetalis caused by haemoglobin Adana and the implications to antenatal screening for α-thalassaemia. Prenat Diagn. 2008;28:859-61.
Luewan S, Charoenkwan P, Sirichotiyakul S, Tongsong T. Fetal haemoglobin H-Constant Spring disease: a role for intrauterine management. Br J Haematol. 2020;190:e233-6. PubMed PMID: 32488867.
Luewan S, Sirichotiyakul S, Charoenkwan P, Phirom K, Tongsong T. Hydrops Fetalis Associated with Fetal Hemoglobin H-Pakse Disease. Fetal Diagn Ther. 2022;49:528-35.
Songdej D, Kadegasem P, Tangbubpha N, Sasanakul W, Deelertthaweesap B, Chuansumrit A, et al. Whole-exome sequencing uncovered genetic diagnosis of severe inherited haemolytic anaemia: Correlation with clinical phenotypes. Br J Haematol. 2022;198:1051-64.
Hecher K, Gardiner HM, Diemert A, Bartmann P. Long-term outcomes for monochorionic twins after
laser therapy in twin-to-twin transfusion syndrome. Lancet Child Adolesc Health. 2018;2:525-35.
Bliss JM, Carr SR, De Paepe ME, Luks FI. What—and Why—the Neonatologist Should Know About Twin-To-Twin Transfusion Syndrome. NeoReviews. 2017;18: e22-32.
Yoda H. Fetal and neonatal circulatory disorders in twin to twin transfusion syndrome (The secondary
publication). J Nippon Med Sch. 2019;86:192-200.
Quintero RA, Morales WJ, Allen MH, Bornick PW, Johnson PK, Kruger M. Staging of twin-twin transfusion syndrome. J Perinatol. 1999;19:550-5.
Khalil A, Rodgers M, Baschat A, Bhide A, Gratacos E, Hecher K, et al. ISUOG Practice Guidelines: role of
ultrasound in twin pregnancy. Ultrasound Obstet Gynecol2016;47:247-63.
Bamberg C, Hecher K. Twin-to-twin transfusion syndrome: Controversies in the diagnosis and management. Best Pract Res Clin Obstet Gynaecol. 2022;84:143-54.
