Clinical Genetic Center, Children's Hospital of Fudan University, Shanghai, China.
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai, China.
J Med Genet. 2020 Mar;57(3):169-177. doi: 10.1136/jmedgenet-2019-106221. Epub 2019 Sep 9.
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.
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.
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.
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.
先天性异常是新生儿重症监护病房（NICU）中新生儿早期死亡的主要原因，但遗传原因尚不清楚。本研究旨在探讨中国 NICU 中婴儿死亡的遗传原因。
2015 年 1 月 1 日至 2017 年 12 月 31 日，复旦大学附属儿科医院收治了在院死亡或出院后 1 周内死亡的新生儿。所有患者死后均进行全外显子组测序。
共有 223 例死亡新生儿，中位死亡年龄为 13 天。共有 44 例（19.7%）患儿发现遗传发现，包括 40 例单核苷酸变异（SNVs）、2 例 CNVs 和 2 例 SNVs 和 CNVs 均有。根据遗传诊断，13 例（31%，13/42）SNVs 患儿存在有医学意义的疾病，包括 10 个基因。多种先天性畸形是 NICU 死亡的主要遗传原因，有 13 例新生儿的基因变异与多种先天性畸形有关。对于在出生后第 1 天死亡的新生儿，最常见的死亡遗传原因是主要心脏缺陷，而对于在出生后前 2 周死亡的新生儿，代谢紊乱和呼吸衰竭更为常见。
本研究显示了 NICU 中早期婴儿死亡的遗传发现，并为家庭提供了精确遗传咨询的关键遗传信息。如果及时诊断，有效的治疗方法可使超过四分之一的分子诊断新生儿受益。
