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The short-term mortality and morbidity of very low birth weight infants with trisomy 18 or trisomy 13 in Japan

Journal of Human Genetics volume 66, pages 273–285 (2021)Cite this article

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Abstract

Trisomy 18 (T18) and trisomy 13 (T13) are major concerns in prenatal genetic testing due to their poor prognosis; very low birth weight (VLBW) is also a concern in neonatology. The aim of this study was to investigate the mortality and morbidity of VLBW infants diagnosed with T18/T13 in Japan, compared with those with no birth defects (BD−). Maternal and neonatal data were collected prospectively from infants weighing <1501 g and were admitted to centers of the Neonatal Research Network of Japan during 2003 to 2016. Among 60,136 infants, 563 and 60 was diagnosed with T18 and T13, respectively. Although the age of mothers of infants with T18/T13 was higher, the frequency of maternal complications was lower than those with BD−. With maternal and neonatal characteristic adjustments, T18/T13 had a higher incidence of each morbidity when compared with BD−. Mortality rates in the NICU were 70, 77, and 5.8% for T18, T13, and BD−, respectively, while the survival discharge rates of T18 and T13 were 29.5 and 23.3%, respectively, which was significantly higher than previous reports. This was the first nationwide survey for VLBW infants with T18/T13 in Japan; this novel data will be relevant and useful for prenatal genetic counseling and perinatal management. Although T18/T13 were considered to be fatal in the past, with proper epidemiological information, discussions with affected families, and compassionate patient care, the mortality rate of T18/T13 can be improved.

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References

  1. Edwards JH, Harnden DG, Cameron AH, Crosse VM, Wolff OH. A new trisomic syndrome. Lancet. 1960;1:787–90.

    Article  CAS  Google Scholar 

  2. Patau K, Smith DW, Therman E, Inhorn SL, Wagner HP. Multiple congenital anomaly caused by an extra autosome. Lancet. 1960;1:790–3.

    Article  CAS  Google Scholar 

  3. Smith DW, Patau K, Therman E, Inhorn SL. A new autosomal trisomy syndrome: multiple congenital anomalies caused by an extra chromosome. J Pediatr. 1960;57:338–45.

    Article  CAS  Google Scholar 

  4. Jones KL. Smith’s recognizable patterns of human malformation. 4th ed. Philadelphia: WB Saunders; 1988.

    Google Scholar 

  5. Baty BJ, Blackburn BL, Carey JC. Natural history of trisomy 18 and trisomy 13: I. Growth, physical assessment, medical histories, survival, and recurrence risk. Am J Med Genet. 1994;49:175–88.

    Article  CAS  Google Scholar 

  6. Baty BJ, Jorde LB, Blackburn BL, Carey JC. Natural history of trisomy 18 and trisomy 13: II. Psychomotor development. Am J Med Genet. 1994;49:189–94.

    Article  CAS  Google Scholar 

  7. Rasmussen SA, Wong LY, Yang Q, May KM, Friedman JM. Population-based analyses of mortality in trisomy 13 and trisomy 18. Pediatrics. 2003;111:777–84.

    Article  Google Scholar 

  8. Embleton ND, Wyllie JP, Wright MJ, Burn J, Hunter S. Natural history of trisomy 18. Arch Dis Child Fetal Neonatal Ed. 1996;75:F38.

    Article  CAS  Google Scholar 

  9. Graham EM, Bradley SM, Shirali GS, Hills CB, Atz AM. Effectiveness of cardiac surgery in trisomies 13 and 18 (from the Pediatric Cardiac Care Consortium). Am J Cardiol. 2004;93:801–3.

    Article  Google Scholar 

  10. Kaneko Y, Kobayashi J, Yamamoto Y, Yoda H, Kanetaka Y, Nakajima Y, et al. Intensive cardiac management in patients with trisomy 13 or trisomy 18. Am J Med Genet A. 2008;146A:1372–80.

    Article  Google Scholar 

  11. Kosho T, Nakamura T, Kawame H, Baba A, Tamura M, Fukushima Y. Neonatal management of trisomy 18: clinical details of 24 patients receiving intensive treatment. Am J Med Genet A. 2006;140:937–44.

    Article  Google Scholar 

  12. Nishi E, Takasugi M, Kawamura R, Shibuya S, Takamizawa S, Hiroma T, et al. Clinical courses of children with trisomy 13 receiving intensive neonatal and pediatric treatment. Am J Med Genet A. 2018;176:1941–9.

    Article  Google Scholar 

  13. Tamura M, Nishida H, Funato M, Tamai M, Ikeda K, Nakamura T, et al. Guidelines for healthcare providers and parents to follow in determining the medical care of newborns with severe disease [in Japanese]. Comprehensive research group on guidelines for medical care of severely handicapped newborns and diagnostic systems for high-risk newborns; 2004/4. Report No.: 03866289. 2004. http://plaza.umin.ac.jp/~jspn/guideline.pdf.

  14. Goel N, Morris JK, Tucker D, de Walle HEK, Bakker MK, Kancherla V, et al. Trisomy 13 and 18-prevalence and mortality-a multi-registry population based analysis. Am J Med Genet A. 2019;179:2382–92.

    Article  CAS  Google Scholar 

  15. Meyer RE, Liu G, Gilboa SM, Ethen MK, Aylsworth AS, Powell CM, et al. Survival of children with trisomy 13 and trisomy 18: a multi-state population-based study. Am J Med Genet A. 2016;170a:825–37.

    Article  Google Scholar 

  16. Nelson KE, Rosella LC, Mahant S, Guttmann A. Survival and surgical interventions for children with trisomy 13 and 18. JAMA. 2016;316:420–8.

    Article  Google Scholar 

  17. Kato E, Kitase Y, Tachibana T, Hattori T, Saito A, Muramatsu Y, et al. Factors related to survival discharge in trisomy 18: a retrospective multicenter study. Am J Med Genet A. 2019;179:1253–9.

    PubMed  Google Scholar 

  18. Special Report of the Neonatal Research Network of Japan - summary of the first 10 years of the network database. Neonatal Research Network of Japan, The Japan Society for Neonatal Health and Development; 2018.

  19. Neonatal Research Network Database Japan. Available from http://plaza.umin.ac.jp/nrndata/indexe.htm.

  20. Shim JW, Jin HS, Bae CW. Changes in survival rate for very-low-birth-weight infants in Korea: comparison with other countries. J Korean Med Sci. 2015;30(Suppl 1):S25–34.

    Article  Google Scholar 

  21. Helenius K, Sjors G, Shah PS, Modi N, Reichman B, Morisaki N, et al. Survival in very preterm infants: an international comparison of 10 National Neonatal Networks. Pediatrics. 2017;140:e20171264.

  22. Shah PS, Lui K, Sjors G, Mirea L, Reichman B, Adams M, et al. Neonatal outcomes of very low birth weight and very preterm neonates: an international comparison. J Pediatr. 2016;177:144–52.e6.

    Article  Google Scholar 

  23. Boghossian NS, Hansen NI, Bell EF, Stoll BJ, Murray JC, Carey JC, et al. Mortality and morbidity of VLBW infants with trisomy 13 or trisomy 18. Pediatrics. 2014;133:226–35.

    Article  Google Scholar 

  24. Yamada T, Majima H, Nakamura Y, Togawa Y, Suginmoto M, Kouwaki M, et al. Prognosis of very low birth weight infants with trisomy 18 [in Japanese]. J Jpn Soc Perinat Neonatal Med. 2015;51:954–9.

    Google Scholar 

  25. WHO. International Statistical Classification of Diseases and Related Health Problems: World Health Organization [10th revision]. 2003. http://apps.who.int/classifications/apps/icd/icd10online2003/fr-icd.htm.

  26. Ministry of Health, Labour and Welfare. Vital statistics, the portal site of Official Statistics of Japan (e-Stat). 2019. https://www.e-stat.go.jp/en/stat-search/files?page=1&toukei=00450011&tstat=000001028897.

  27. Ministry of Health, Labour and Welfare. List of perinatal medical centers [in Japanese]. 2019. [updated Apr 2019]. https://www.mhlw.go.jp/content/10800000/000507227.pdf.

  28. Acharya K, Leuthner S, Clark R, Nghiem-Rao TH, Spitzer A, Lagatta J. Major anomalies and birth-weight influence NICU interventions and mortality in infants with trisomy 13 or 18. J Perinatol. 2017;37:420–6.

    Article  CAS  Google Scholar 

  29. Imataka G, Suzumura H, Arisaka O. Clinical features and survival in individuals with trisomy 18: a retrospective one-center study of 44 patients who received intensive care treatments. Mol Med Rep. 2016;13:2457–66.

    Article  CAS  Google Scholar 

  30. Imai K, Uchiyama A, Okamura T, Ago M, Suenaga H, Sugita E, et al. Differences in mortality and morbidity according to gestational ages and birth weights in infants with trisomy 18. Am J Med Genet A. 2015;167a:2610–7.

    Article  Google Scholar 

  31. Nishida H, Sakamoto S. Ethical problems in neonatal intensive care unit — medical decision making on the neonate with poor prognosis. Early Hum Dev. 1992;29:403–6.

    Article  CAS  Google Scholar 

  32. Cheema IU, Ahluwalia JS. Feasibility of tidal volume-guided ventilation in newborn infants: a randomized, crossover trial using the volume guarantee modality. Pediatrics. 2001;107:1323–8.

    Article  CAS  Google Scholar 

  33. Toyoshima K, Kawataki M, Ohyama M, Shibasaki J, Yamaguchi N, Hoshino R, et al. Tailor-made circulatory management based on the stress-velocity relationship in preterm infants. J Formos Med Assoc. 2013;112:510–7.

    Article  Google Scholar 

  34. Thureen PJ, Hay WW Jr. Early aggressive nutrition in preterm infants. Semin Neonatol. 2001;6:403–15.

    Article  CAS  Google Scholar 

  35. Wilcock DM, Schmitt FA, Head E. Cerebrovascular contributions to aging and Alzheimer’s disease in Down syndrome. Biochim Biophys Acta. 2016;1862:909–14.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Two hundred and four institutions enrolled in the study of the Neonatal Research Network of Japan were as follows: Sapporo City General Hospital, Asahikawa Kosei General Hospital, Engaru-Kosei General Hospital, Kushiro Red Cross Hospital, Obihiro-Kosei General Hospital, Tenshi Hospital, NTT Higashinihon Sapporo Hospital, Nikko Memorial Hospital, Nayoro City General Hospital, Sapporo Medical University, Asahikawa Medical University, Aomori Prefectural Central Hospital, Iwate Medical University, Iwate Prefectural Ofunato Hospital, Iwate Prefectural Kuji Hospital, Iwate Prefectural Ninohe Hospital, Sendai Red Cross Hospital, Akita Red Cross Hospital, Tsuruoka Municipal Shonai Hospital, Yamagata University, Yamagata Prefectural Central Hospital, Fukushima Medical University, Takeda General Hospital, Fukushima National Hospital, Tsukuba University, Tsuchiura Kyodo Hospital, Ibaraki Children’s Hospital, Dokkyo Medical University, Jichi Medical University, Ashikaga Red Cross Hospital, Gunma Children’s Medical Center, Kiryu Kosei General Hospital, Fuji Heavy Industries Health Insurance Society Ota Memorial Hospital, Gunma University, Saitama Children’s Medical Center, Nishisaitama-chuo National Hospital, Saitama Medical University Saitama Medical Center, Kawaguchi Municipal Medical Center, Jichi Medical University Saitama Medical Center, Asahi General Hospital, Chiba Kaihin Municipal Hospital, Kameda Medical Center, Tokyo Women’s Medical University Yachiyo Medical Center, Juntendo University Urayasu Hospital, Tokyo Metropolitan Children’s Medical Center, Tokyo Women’s Medical University, Aiiku Hospital, Nihon University Itabashi Hospital, National Center for Global Health and Medicine, Tokyo Medical University, Teikyo University, Showa University, Japan Red Cross Medical Center, National Center for Child Health and Development, Tokyo Metropolitan Otsuka Hospital, Toho University, Tokyo Metropolitan Bokuto Hospital, Tokyo Jikei Medical University, Tokyo Medical and Dental University, Saint Luke’s International Hospital, Juntendo University, Sanikukai Hospital, Katsushika Red Cross Hospital, Yokohama Rosai Hospital, Yokohama City University Medical Center, St. Marianna University School of Medicine Hospital, Kanagawa Children’s Medical Center, Tokai University, Kitazato University, Odawara Municipal Hospital, Nippon Medical School Musashi Kosugi Hospital, Saiseikai Yokohamashi Tobu Hospital, National Hospital Organization Yokohama Medical Center, Yamanashi Prefectural Central Hospital, Nagano Children’s Hospital, Shinshu University, Iida Municipal Hospital, National Hospital Organization Shinshu Ueda Medical Center, Saku General Hospital, Niigata University, Niigata Prefectural Central Hospital, Niigata Municipal Hospital, Nagaoka Red Cross Hospital, Koseiren Takaoka Hospital, Toyama Prefectural Central Hospital, Toyama University, Ishikawa Medical Center for Maternal and Child Health, Kanazawa Medical University, Kanazawa Medical Center, Fukui Prefectural Hospital, Fukui University, Gifu Prefectural General Medical Center, National Hospital Organization Nagara Medical Center, Takayama Red Cross Hospital, Seirei Hamamatsu Hospital, Shizuoka Saiseikai Hospital, Shizuoka Children’s Hospital, Hamamatsu Medical University, Numazu Municipal Hospital, Yaizu City Hospital, Fujieda Municipal General Hospital, Nagoya Red Cross Daini Hospital, Nagoya University, Nagoya Red Cross Daiichi Hospital, Toyohashi Municipal Hospital, Nagoya City West Medical Center, Anjo kosei Hospital, Tosei General Hospital, Komaki Municipal Hospital, TOYOTA Memorial Hospital, Okazaki Municipal Hospital, Konan Kosei Hospital, National Mie Central Medical Center, Ise Red Cross Hospital, Yokkaichi Municipal Hospital, Otsu Red Cross Hospital, Shiga University of Medical Science Hospital, Nagahama Red Cross Hospital, Uji Tokushukai Hospital, The Japan Baptist Hospital, Kyoto University, Kyoto Red Cross Daiichi Hospital, National Maizuru Medical Center, Fukuchiyama City Hospital, Kyoto Prefectural University of Medicine Hospital, Kyoto City Hospital, Mitsubishi Kyoto Hospital, Yodogawa Christian Hospital, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka University, Takatsuki General Hospital, Kansai Medical University, Osaka City General Hospital, Osaka City Sumiyoshi Hospital, Aizenbashi Hospital, Toyonaka Municipal Hospital, National Cerebral and Cardiovascular Center, Kitano Hospital, Saiseikai Suita Hospital, Chifune Hospital, Bellland General Hospital, Rinku General Medical Center, Osaka Red Cross Hospital, Yao Municipal Hospital, Osaka General Medical Center, Osaka City University, Hyogo Prefectural Kobe Children’s Hospital, Kobe University, Kakogawa West City Hospital, Saiseikai Hyogoken Hospital, Kobe City Medical Center General Hospital, Hyogo College of Medicine Hospital, Himeji Red Cross Hospital, Toyooka Public Hospital, Hyogo Prefectural Awaji Medical Center, Nara Medical University, Wakayama Medical University, Tottori Prefectural Central Hospital, Tottori University, Shimane Prefectural Central Hospital, Matsue Red Cross Hospital, Kurashiki Central Hospital, Tsuyama Central Hospital, Kawasaki Medical School Hospital, National Hospital Organization Okayama Medical Center, Okayama Red Cross Hospital, Hiroshima City Hiroshima Citizens Hospital, Hiroshima Prefectural Hospital, Hiroshima University, Tsuchiya General Hospital, National Hospital Organization Kure Medical Center, Yamaguchi University, Yamaguchi Grand Medical Center, Tokushima University, Tokushima Municipal Hospital, Kagawa University, National Hospital Organization Kagawa Children’s Hospital, Matsuyama Red Cross Hospital, Ehime Prefectural Central Hospital, Kochi Health Science Center, St. Mary’s Hospital, National Kyushu Medical Center, Kurume University, Kitakyushu Municipal Medical Center, University of Occupational and Environmental Health, Fukuoka University, Kyushu University, Iizuka Hospital, National Hospital Organization Kokura Medical Center, National Hospital Organization Saga Hospital, National Hospital Organization Nagasaki Medical Center, Kumamoto City Hospital, Kumamoto University, Oita Prefectural Hospital, Almeida Memorial Hospital, Nakatsu Municipal Hospital, Miyazaki University, National Hospital Organization Miyakonojo Medical Center, Kagoshima City Hospital, Imakiire General Hospital, Okinawa Prefectural Nanbu Medical Center and Children’s Medical Center, Okinawa Prefectural Chubu Hospital, Naha City Hospital, and Okinawa Red Cross Hospital. Furthermore, we would like to thank Editage (www.editage.com) for English language editing.

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  1. Department of Medical Ethics and Medical Genetics, Kyoto University School of Public Health, Kyoto, Japan

    Hidenori Kawasaki, Takahiro Yamada, Takahito Wada & Shinji Kosugi

  2. Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan

    Yoshimitsu Takahashi & Takeo Nakayama

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  1. Hidenori Kawasaki
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Kawasaki, H., Yamada, T., Takahashi, Y. et al. The short-term mortality and morbidity of very low birth weight infants with trisomy 18 or trisomy 13 in Japan. J Hum Genet 66, 273–285 (2021). https://doi.org/10.1038/s10038-020-00825-6

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