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Original research
Genetic aetiology of early infant deaths in a neonatal intensive care unit
  1. Lin Yang1,2,
  2. Xu Liu1,3,
  3. Zixiu Li2,
  4. Peng Zhang3,
  5. Bingbing Wu2,
  6. Huijun Wang2,
  7. Liyuan Hu3,
  8. Guoqiang Cheng3,
  9. Laishuan Wang3,
  10. Wenhao Zhou1,2,3,4
  1. 1 Clinical Genetic Center, Children's Hospital of Fudan University, Shanghai, China
  2. 2 Key Laboratory of Birth Defects, Children’s Hospital of Fudan University, Shanghai, China
  3. 3 Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China
  4. 4 Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University, Shanghai, China
  1. Correspondence to Professor Wenhao Zhou, Department of Neonatology, Children's Hospital of Fudan University, Shanghai 201102, China; zhouwenhao{at}


Background Congenital anomalies are the leading cause of early neonatal death in neonatal intensive care units (NICUs), but the genetic causes are unclear. This study aims to investigate the genetic causes of infant deaths in a NICU in China.

Methods Newborns who died in the hospital or died within 1 week of discharge were enrolled from Children’s Hospital of Fudan University between January 1, 2015 and December 31, 2017. Whole exome sequencing was performed in all patients after death.

Results There were 223 deceased newborns with a median age at death of 13 days. In total, 44 (19.7%) infants were identified with a genetic finding, including 40 with single nucleotide variants (SNVs), two with CNVs and two with both SNVs and CNVs. Thirteen (31%, 13/42) patients with SNVs had medically actionable disorders based on genetic diagnosis, which included 10 genes. Multiple congenital malformation was identified as the leading genetic cause of death in NICUs with 13 newborns identified with variants in genes related to multiple congenital malformations. For newborns who died on the first day, the most common genetic cause of death was major heart defects, while metabolic disorders and respiratory failure were more common for newborns who died in the first 2 weeks.

Conclusion Our study shows genetic findings among early infant deaths in NICUs and provides critical genetic information for precise genetic counselling for the families. Effective therapies enable the improvement of more than a quarter of newborns with molecular diagnoses if diagnosed in time.

  • early infant death
  • neonatal intensive care units
  • whole exome sequencing
  • genetic counseling
  • precise treatment

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  • LY and XL contributed equally.

  • Correction notice This article has been corrected since it was published Online First. Authors LY and XL have contributed equally.

  • Contributors WZ and LY designed the project. ZL, PZ, LH, GC and LW collected the data. LY, BW and HW did the data curation. XL and ZL analysed the data. XL, ZL, LY and WZ drafted the manuscript. All authors revised and approved the manuscript.

  • Funding This work was supported by grants from the National Key Research and Development Program of China (2016YFC0905100), the Shanghai Municipal Commission of Health and Family Planning (GDEK201701), the Shanghai Shen Kang Hospital Development Center (SHDC12017110), Science and Technology Commission of Shanghai Municipality (16ZR1446500), and Shanghai Sailing Program (16YF1401000).

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Ethics approval This study was approved by the ethics committees of Children’s Hospital of Fudan University (2015 (No. 169)).

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

  • Data availability statement Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.