Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Etiology and outcome of non-immune hydrops fetalis in relation to gestational age at diagnosis and intrauterine treatment

Journal of Perinatology volume 41, pages 2544–2548 (2021)Cite this article

Subjects

Abstract

Objective

To determine the etiology and outcome of non-immune hydrops fetalis (NIHF) according to gestational age at diagnosis and intrauterine treatment.

Study design

A total of 122 NIHF cases were included. Medical records and ultrasonographic images were reviewed. The etiology, outcome, and intrauterine treatment were assessed.

Results

The etiology was determined in 100 cases, and Hb Bart’s disease was the most common. Two cases each of homozygous Southeast Asian ovalocytosis (SAO) and hemoglobin Constant Spring (Hb CS) were found. NIHF diagnosed in early gestation (<24 weeks) had a higher rate of chromosomal abnormalities and fetal demise. Intrauterine treatment was given in 18 cases, and 50% had successful live births.

Conclusion

Hb Bart’s disease was the most common cause of NIHF. SAO and Hb CS were associated with hydrops. NIHF in gestational age <24 weeks was associated with chromosomal abnormalities and fetal demise. Intrauterine treatment should be offered in selected cases.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Norton ME, Chauhan SP, Dashe JS. Society for maternal-fetal medicine (SMFM) clinical guideline #7: nonimmune hydrops fetalis. Am J Obstet Gynecol 2015;212:127–39.

    Article  Google Scholar 

  2. Bellini C, Hennekam RC. Non-immune hydrops fetalis: a short review of etiology and pathophysiology. Am J Med Genet A 2012;158:597–605.

    Article  CAS  Google Scholar 

  3. Bellini C, Hennekam RC, Fulcheri E, Rutigliani M, Morcaldi G, Boccardo F, et al. Etiology of nonimmune hydrops fetalis: a systematic review. Am J Med Genet A 2009;149:844–51.

    Article  Google Scholar 

  4. 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.

    Article  Google Scholar 

  5. Liao C, Wei J, Li Q, Li J, Li L, Li D. Nonimmune hydrops fetalis diagnosed during the second half of pregnancy in Southern China. Fetal Diagn Ther 2007;22:302–5.

    Article  Google Scholar 

  6. 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.

    PubMed  Google Scholar 

  7. 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;7:111–5.

    Article  Google Scholar 

  8. Bellini C, Donarini G, Paladini D, Calevo MG, Bellini T, Ramenghi LA, et al. Etiology of non-immune hydrops fetalis: an update. Am J Med Genet A 2015;167:1082–8.

    Article  Google Scholar 

  9. Moreno CA, Kanazawa T, Barini R, Nomura ML, Andrade KC, Gomes CP, et al. Non-immune hydrops fetalis: a prospective study of 53 cases. Am J Med Genet A 2013;161:3078–86.

    Article  Google Scholar 

  10. Santo S, Mansour S, Thilaganathan B, Homfray T, Papageorghiou A, Calvert S, et al. Prenatal diagnosis of non-immune hydrops fetalis: what do we tell the parents? Prenat Diagn 2011;31:186–95.

    Article  Google Scholar 

  11. Jatavan P, Chattipakorn N, Tongsong T. Fetal hemoglobin Bart’s hydrops fetalis: pathophysiology, prenatal diagnosis and possibility of intrauterine treatment. J Matern Fetal Neonatal Med 2018;31:946–57.

    Article  Google Scholar 

  12. Laosombat V, Dissaneevate S, Wongchanchailert M, Satayasevanaa B. Neonatal anemia associated with Southeast Asian ovalocytosis. Int J Hematol 2005;82:201–5.

    Article  Google Scholar 

  13. Ngouprommin L, Sae-Ung N, Fucharoen S, Fucharoen G, Sanchaisuriya K, Jetsrisuparb A. Genetic compound heterozygosity for Southeast Asian ovalocytosis and thalassemia in Thailand: prevalence and phenotypic analysis. Clin Genet 2014;85:198–200.

    Article  CAS  Google Scholar 

  14. 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 2006;28:827–30.

    Article  CAS  Google Scholar 

  15. Komvilaisak P, Komvilaisak R, Jetsrisuparb A, Wiangnon S, Jirapradittha J, Kiatchoosakun P, et al. Fetal anemia causing hydrops fetalis from an alpha-globin variant: homozygous hemoglobin constant spring. J Pediatr Hematol Oncol 2018;40:405–8.

    Article  Google Scholar 

  16. 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.

    Article  Google Scholar 

  17. Palek J. Introduction: red blood cell membrane proteins, their genes and mutations. Semin Hematol 1993;30:1–3.

    CAS  PubMed  Google Scholar 

  18. Maisonneuve E, Ben M’Barek I, Leblanc T, Da Costa L, Friszer S, Pernot F, et al. Managing the unusual causes of fetal anemia. Fetal Diagn Ther 2020;47:156–64.

    Article  Google Scholar 

  19. Sparks TN, Thao K, Lianoglou BR, Boe NM, Bruce KG, Datkhaeva I, et al. Nonimmune hydrops fetalis: identifying the underlying genetic etiology. Genet Med 2019;21:1339–44.

    Article  Google Scholar 

  20. Kosinski P, Krajewski P, Wielgos M, Jezela-Stanek. A nonimmune hydrops fetalis-prenatal diagnosis, genetic investigation, outcomes and literature review. J Clin Med. 2020;9:1789.

  21. Sileo FG, Kulkarni A, Branescu I, Homfray T, Dempsey E, Mansour S, et al. Non-immune fetal hydrops: etiology and outcome according to gestational age at diagnosis. Ultrasound Obstet Gynecol 2020;56:416–21.

    Article  CAS  Google Scholar 

  22. Sohan K, Carroll SG, De La Fuente S, Soothill P, Kyle P. Analysis of outcome in hydrops fetalis in relation to gestational age at diagnosis, cause and treatment. Acta Obstet Gynecol Scand 2001;80:726–30.

    Article  CAS  Google Scholar 

  23. Heinonen S, Ryynanen M, Kirkinen P. Etiology and outcome of second trimester non-immunologic fetal hydrops. Acta Obstet Gynecol Scand 2000;79:15–8.

    CAS  PubMed  Google Scholar 

  24. Yuan SM. Cardiac etiologies of hydrops fetalis. Z Geburtshilfe Neonatol 2017;221:67–72.

    Article  Google Scholar 

  25. Moodley S, Sanatani S, Potts JE, Sandor GG. Postnatal outcome in patients with fetal tachycardia. Pediatr Cardiol 2013;34:81–7.

    Article  Google Scholar 

  26. Kleinman CS, Copel JA. Electrophysiological principles and fetal antiarrhythmic therapy. Ultrasound Obstet Gynecol 1991;1:286–97.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The study was supported by the Prince of Songkla University, Songkhla, Thailand. The authors would like to thank Miss Jirawan Jayuphan from the Epidemiology Unit, Faculty of Medicine, Prince of Songkla University for her assistance in data analysis. We also would like to thank Mr. Dave Patterson from the International Affairs Office, Faculty of Medicine, Prince of Songkla University for English language editing.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand

    Natthicha Chainarong, Worachot Muangpaisarn & Chitkasaem Suwanrath

Authors
  1. Natthicha Chainarong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Worachot Muangpaisarn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chitkasaem Suwanrath
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

N.C. and W.M. designed, planned, and conducted the study. N.C., W.M., and C.S. contributed to the data analysis and to the first and final drafts of the manuscript.

Corresponding author

Correspondence to Natthicha Chainarong.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethical approval

This study was performed in accordance with the Declaration of Helsinki and approval was obtained from the Human Research Ethics Committee of the Faculty of Medicine, Prince of Songkla University before the study began.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chainarong, N., Muangpaisarn, W. & Suwanrath, C. Etiology and outcome of non-immune hydrops fetalis in relation to gestational age at diagnosis and intrauterine treatment. J Perinatol 41, 2544–2548 (2021). https://doi.org/10.1038/s41372-021-01202-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-021-01202-7

Search

Advanced search

Quick links