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Genetic architecture in neonatal intensive care unit patients with congenital heart defects: a retrospective study from the China Neonatal Genomes Project
  1. Huijun Wang1,
  2. Feifan Xiao1,2,
  3. Yanyan Qian1,
  4. Bingbing Wu1,
  5. Xinran Dong1,
  6. Yulan Lu1,
  7. Guoqiang Cheng2,
  8. Laishuan Wang2,
  9. Kai Yan2,
  10. Lin Yang3,
  11. Liping Chen4,
  12. Wenqing Kang5,
  13. Long Li6,
  14. Xinnian Pan7,
  15. Qiufen Wei7,
  16. Deyi Zhuang8,
  17. Dongmei Chen9,
  18. Zhaoqing Yin10,
  19. Ling Yang11,
  20. Qi Ni1,
  21. Renchao Liu1,
  22. Gang Li1,
  23. Ping Zhang1,
  24. Xu Li1,
  25. Xiaomin Peng1,
  26. Yao Wang1,
  27. Huiyao Chen1,
  28. Xiaojing Ma12,
  29. Fang Liu12,
  30. Yun Cao2,
  31. Guoying Huang12,13,
  32. Wenhao Zhou1,2,13
  1. 1Center for Molecular Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
  2. 2Division of Neonatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
  3. 3Department of Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
  4. 4Department of Neonatology, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi, China
  5. 5Department of Neonatology, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China
  6. 6Department of Neonatology, The People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China
  7. 7Department of Neonatology, Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China
  8. 8Department of Pediatrics, Xiamen Children's Hospital, Xiamen, Fujian, China
  9. 9Department of Neonatal Intensive Care Unit, Quanzhou Women's and Children's Hospital, Quanzhou, Fujian, China
  10. 10Department of Neonatology, The People's Hospital of Dehong, Dehong, Yunnan, China
  11. 11Department of Neonatology, Hainan Women and Children's Medical Center, Haikou, Hainan, China
  12. 12Cardiovascular Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
  13. 13Shanghai Key Laboratory of Birth Defects, Shanghai, China
  1. Correspondence to Professor Wenhao Zhou, Center for Molecular Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China; zhouwenhao{at}fudan.edu.cn; Professor Guoying Huang, Cardiovascular Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China; gyhuang{at}shmu.edu.cn

Abstract

Background Congenital heart defects (CHDs) are the most common type of birth defects. The genetic aetiology of CHD is complex and incompletely understood. The overall distribution of genetic causes in patients with CHD from neonatal intensive care units (NICUs) needs to be studied.

Methods CHD cases were extracted from the China Neonatal Genomes Project (2016–2021). Next-generation sequencing results and medical records were retrospectively evaluated to note the frequency of genetic diagnosis and the respective patient outcomes.

Results In total, 1795 patients were included. The human phenotype ontology term of atrial septal defect, patent ductus arteriosus and ventricular septal defect account for a large portion of the CHD subtype. Co-occurring extracardiac anomalies were observed in 35.1% of patients. 269 of the cases received genetic diagnoses that could explain the phenotype of CHDs, including 172 copy number variations and 97 pathogenic variants. The detection rate of trio-whole-exome sequencing was higher than clinical exome sequencing (21.8% vs 14.5%, p<0.05). Further follow-up analysis showed the genetic diagnostic rate was higher in the deceased group than in the surviving group (29.0% vs 11.9%, p<0.05).

Conclusion This is the largest cohort study to explore the genetic spectrum of patients with CHD in the NICU in China. Our findings may benefit future work on improving genetic screening and counselling for NICU patients with CHD.

  • Genetics
  • Pediatrics

Data availability statement

Data are available upon reasonable request. WZ, Children’s Hospital of Fudan University, Shanghai, China, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Data availability statement

Data are available upon reasonable request. WZ, Children’s Hospital of Fudan University, Shanghai, China, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Footnotes

  • HW and FX are joint first authors.

  • Contributors HW and FX collected the data and wrote the manuscript. YQ, BW, XD, YL, LY, QN, RL, GL, PZ, XL, XP, YW and HC interpreted medical exome results and conducted analysis on the aggregated large cohort data. GC, LW, KY, LC, WK, LL, XP, QW, DZ, DC, ZY, LY, FL, XM and YC collected, supervised and reviewed the clinical data. WZ and GH supervised the study, critically examined and revised the manuscript. WZ is responsible for the overall content as guarantor

  • Funding This study was supported by National Key Research and Development Program (2021YFC2701000, Professor Huang), Chinese Academy of Medical Sciences Research Unit (2018RU002, Professor Huang), Shen Kang Hospital Development Centre Clinical Science and Technology innovation project of Shanghai (SHDC2020CR6028-002, Professor Zhou), Shanghai Sailing Programme (18YF1402600, Dr Qian), Shanghai Municipal Science and Technology Major Project (Grant No. 20Z11900600, Professor Zhou), the project of Shanghai Key Laboratory of Birth Defects (13DZ2260600) and Shanghai Municipal Science and Technology Major Project (Grant No. 2017SHZDZX01, Professor Zhou).

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  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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