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Mortality and morbidity of infants with trisomy 21, weighing 1500 grams or less, in Japan

Journal of Human Genetics volume 67, pages 623–628 (2022)Cite this article

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Abstract

Although very low birth weight (VLBW) is well studied in neonatology and the perinatal prognosis of VLBW infants has improved over time, little is known about the prognosis of VLBW infants with trisomy 21 (T21). We aimed to investigate the mortality and morbidity of VLBW infants with T21 during NICU admission in Japan, in comparison to those of infants without birth defects (BD−). Maternal and neonatal data of infants weighing 1500 grams or less admitted to the centers of the Neonatal Research Network of Japan from 2003 to 2016 were collected prospectively. Of 60,136 infants, 328 (0.55%) had T21. Although maternal age in the case of T21 infants was higher, maternal complications tended to be less frequent than in those with BD−. Multivariable analysis revealed that morbidities were higher in infants with T21 than in those with BD− but respiratory distress syndrome and retinopathy of prematurity were less frequent in those with T21 (p < 0.001, and p = 0.014, respectively), and no significant difference was observed between the two groups in the proportion of late-onset circulatory collapse of prematurity as well as cystic periventricular leukomalacia (p = 0.739 and p = 0.733, respectively). The survival rate at discharge from the NICU was 77% and 94% for T21 and BD−, respectively. This was the first nationwide survey of VLBW infants with T21 in Japan. Although there were no data regarding the timing of diagnosis, these data will aid prenatal genetic counseling and perinatal management of T21 infants.

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References

  1. Neoonatal Mortality: UNICEF; 2021. Available from: https://data.unicef.org/topic/child-survival/neonatal-mortality/.

  2. Lawn JE, Blencowe H, Oza S, You D, Lee AC, Waiswa P, et al. Every newborn: progress, priorities, and potential beyond survival. Lancet. 2014;384:189–205.

    Article  Google Scholar 

  3. Gleason CA, Juul SE. Avery’s Diseases of the Newborn, 10th ed. Elsevier; 2018.

  4. 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:S25–34.

    Article  Google Scholar 

  5. 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.

    Article  Google Scholar 

  6. 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 

  7. 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.

  8. Alldred MJ, Martini AC, Patterson D, Hendrix J, Granholm A-C. Aging with down syndrome—Where are we now and where are we going? J Clin Med. 2021;10:4687.

    Article  CAS  Google Scholar 

  9. Takeuchi C. Involvement in children with Down Syndrome with an eye on adulthood [in Japanese]. Pediatr Health Res. 2020;79:2–9.

    Google Scholar 

  10. Boghossian NS, Hansen NI, Bell EF, Stoll BJ, Murray JC, Laptook AR, et al. Survival and morbidity outcomes for very low birth weight infants with Down syndrome. Pediatrics. 2010;126:1132–40.

    Article  Google Scholar 

  11. Kumasaka S, Yoda H, Ishida F, Mizogami M, Kodama H, Saito K, et al. Clinical characteristics of very low birth weight infants with trisomy 21 [in Japanese]. J Jpn Soc Premature Newborn Med. 2011;23:83–7.

    Google Scholar 

  12. Kawasaki H, Yamada T, Takahashi Y, Nakayama T, Wada T, Kosugi S. The short-term mortality and morbidity of very low birth weight infants with trisomy 18 or trisomy 13 in Japan. J Hum Genet. 2021;66:273–85.

    Article  Google Scholar 

  13. International statistical classification of diseases and related health problems: World Health Organization; 2003. 10th revision: Available from: http://apps.who.int/classifications/apps/icd/icd10online2003/fr-icd.htm.

  14. Vital statistics, the Portal Site of Official Statistics of Japan (e-Stat): the Ministry of Health, Labour and Welfare; Available from: https://www.e-stat.go.jp/en/stat-search/files?page=1&toukei=00450011&tstat=000001028897.

  15. Kucik JE, Shin M, Siffel C, Marengo L, Correa A. Trends in survival among children with Down syndrome in 10 regions of the United States. Pediatrics. 2013;131:e27–36.

    Article  Google Scholar 

  16. McGoldrick E, Stewart F, Parker R, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2020;12:Cd004454.

    PubMed  Google Scholar 

  17. Doshi H, Moradiya Y, Roth P, Blau J. Variables associated with the decreased risk of intraventricular haemorrhage in a large sample of neonates with respiratory distress syndrome. Arch Dis Child Fetal Neonatal Ed. 2016;101:F223–9.

    Article  Google Scholar 

  18. Condò V, Cipriani S, Colnaghi M, Bellù R, Zanini R, Bulfoni C, et al. Neonatal respiratory distress syndrome: are risk factors the same in preterm and term infants? J Matern Fetal Neonatal Med. 2017;30:1267–72.

    Article  Google Scholar 

  19. Greene AK, Kim S, Rogers GF, Fishman SJ, Olsen BR, Mulliken JB. Risk of vascular anomalies with Down syndrome. Pediatrics. 2008;121:e135–40.

    Article  Google Scholar 

  20. Hasle H, Clemmensen IH, Mikkelsen M. Risks of leukaemia and solid tumours in individuals with Down’s syndrome. Lancet. 2000;355:165–9.

    Article  CAS  Google Scholar 

  21. Corsi MM, Dogliotti G, Pedroni F, Galliera E, Malavazos AE, Villa R, et al. Adipocytokines in Down’s syndrome, an atheroma-free model: role of adiponectin. Arch Gerontol Geriatr. 2009;48:106–9.

    Article  CAS  Google Scholar 

  22. Movsas TZ, Spitzer AR, Gewolb IH. Trisomy 21 and risk of retinopathy of prematurity. Pediatrics. 2015;136:e441–7.

    Article  Google Scholar 

  23. Cua CL, Blankenship A, North AL, Hayes J, Nelin LD. Increased incidence of idiopathic persistent pulmonary hypertension in Down syndrome neonates. Pediatr Cardiol. 2007;28:250–4.

    Article  CAS  Google Scholar 

  24. Cua CL, Haque U, Miao Y, Backes CH. Necrotizing enterocolitis incidence, characteristics, and outcomes in neonatal Down syndrome patients. Am J Perinatol. 2017;34:1368–74.

    Article  Google Scholar 

  25. Head E, Phelan MJ, Doran E, Kim RC, Poon WW, Schmitt FA, et al. Cerebrovascular pathology in Down syndrome and Alzheimer disease. Acta Neuropathol Commun. 2017;5:93.

    Article  Google Scholar 

  26. 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 

  27. Santoro SL, Steffensen EH. Congenital heart disease in Down syndrome – a review of temporal changes. J Congenit Cardiol. 2021;5:1.

    Article  CAS  Google Scholar 

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Acknowledgements

The 204 institutions enrolled in the study of the Neonatal Research Network of Japan are listed in the supplementary text.

Author information

Authors and Affiliations

  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

  3. Tokyo Healthcare University, Tokyo, Japan

    Satoshi Kusuda

  4. Osaka Women’s and Children’s Hospital, Izumi, Japan

    Masanori Fujimura & Shinya Hirano

  5. Kobe University, Kobe, Japan

    Hajime Nakamura

  6. Tokyo Woman’s Christian University, Tokyo, Japan

    Hiroshi Nishida

  7. Kitazato University, Sagamihara, Japan

    Hidehiko Nakanishi

  8. Sakai Takeo Babies & Children Clinic, Sendai, Japan

    Takeo Sakai

  9. Fukuzumi Hospital, Matsuyama, Japan

    Masato Kajiwara

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  1. Hidenori Kawasaki
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  2. Takahiro Yamada
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  3. Yoshimitsu Takahashi
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  4. Takeo Nakayama
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  5. Takahito Wada
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  6. Shinji Kosugi
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Consortia

on behalf of the Neonatal Research Network of Japan

  • Satoshi Kusuda
  • , Masanori Fujimura
  • , Hajime Nakamura
  • , Hiroshi Nishida
  • , Shinya Hirano
  • , Hidehiko Nakanishi
  • , Takeo Sakai
  •  & Masato Kajiwara

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Correspondence to Takahiro Yamada.

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Kawasaki, H., Yamada, T., Takahashi, Y. et al. Mortality and morbidity of infants with trisomy 21, weighing 1500 grams or less, in Japan. J Hum Genet 67, 623–628 (2022). https://doi.org/10.1038/s10038-022-01061-w

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