Objective: To explore the genetic etiologies of newborn deaths. Methods: A total of 98 newborns who were recruited to the Neonatal Genome Project of the Children's Hospital of Fudan University and died in the hospital from January 2018 to August 2020 were enrolled in this study. The genetic information and the interventions based on the genetic findings were retrospectively analyzed. T-test, Mann-Whitney U test, Chi square test and Fisher's exact probability test were used to compare the demographic features and clinical characteristics between the patients with or without a genetic finding. Results: Among 98 newborns (55 males and 43 females), there were 63 preterm and 35 term infants, with a gestational age of (33±5) weeks, a birth weight of (2 107±975) g and the age at death of 12 (2,34) days. Sixteen (16%)patients were identified with genetic variants, including 11 with single nucleotide variants, 4 with copy number variants and 1 with both single nucleotide variant and copy number variant. The detected single nucleotide variants were spanning 12 genes, among which 3 were multiple disorders-related, 2 metabolic disorder-related, 2 hematological disorder-related, 2 respiratory disorder-related, 2 cardiovascular disorder-related and 1 skeletal disorder-related. The patients with a positive genetic finding had significant differences in the birth weight ((2 605±940) vs. (2 009±957) g, t=2.283, P=0.025), the gestational age ((36±5) vs. (33±5) weeks, t=2.131, P=0.036), the age at death ((37 (5, 69) vs. 11 (2, 29) days, Ζ=-2.245, P=0.025) and the history of asphyxia at birth (1/16 vs. 46% (38/82), P=0.002)when compared to those without a genetic finding. In addition, the genetic etiology rates of patients who were born term or with a birth weight ≥ 2 000 g were significantly higher than those who were born preterm (29% (10/35) vs. 10% (6/63), P=0.022) or with a birth weight<2 000 g (25% (13/51) vs. 7% (3/46), χ2=5.016,P=0.025), respectively. Six cases were medically actionable based on the genetic findings and the treatments included special diet, applying specific medicine, hematopoietic stem cell transplantation and lung transplantation. Conclusions: Genetic etiologies are not rare in newborn deaths and mainly associated with metabolic disorder, multi-system disorders, hematological disorder, respiratory disorder, cardiovascular disorder and skeletal disorder. Some findings are medically actionable, based on which the specific treatments could be scheduled timely. A genetic etiology should be investigated in newborn deaths especially in those who are term birth or with a birth weight ≥2 000 g or without a history of asphyxia at birth.
目的： 探讨新生儿死亡病例的遗传学病因。 方法： 收集2018年1月至2020年8月参与复旦大学附属儿科医院“新生儿基因组计划”并在住院期间死亡的98例患儿的病例资料。回顾性分析其基因测序结果及其中可根据遗传学病因进行临床早期针对性干预的情况。并采用t检验、Mann-Whitney U检验、χ²检验或Fisher确切概率法对基因阳性与阴性患儿的人口学特征和临床特点进行比较。 结果： 98例患儿中男55例、女43例，出生胎龄为（33±5）周，出生体重为（2 107±975）g，死亡年龄12（2，34）日龄，早产儿63例，足月儿35例。二代测序检测到16例（16%）患儿存在基因阳性结果，其中11例携带单核苷酸变异，4例携带拷贝数变异，1例同时携带单核苷酸变异和拷贝数变异。检测到的单核苷酸变异分布于12个基因，其中与多系统异常相关的3个，与代谢性疾病、血液系统疾病、呼吸系统疾病、心血管疾病相关的各2个，与骨骼发育相关1个。基因阳性患儿的出生体重、出生胎龄及死亡年龄均大于基因阴性患儿［（2 605±940）比（2 009±957） g，（36±5）比（33±5）周，37（5，69）比11（2，29）日龄；t=2.283、2.131，Z=-2.245；P=0.025、0.036、0.025］；基因阳性患儿与基因阴性患儿在出生窒息抢救史方面差异有统计学意义［1/16比46%（38/82），P=0.002］。足月儿遗传学病因诊断率高于早产儿［29%（10/35）比10%（6/63），P=0.022］，出生体重≥2 000 g的患儿高于出生体重<2 000 g的患儿［25%（13/51）比7%（3/46），χ²=5.016，P=0.025］。6例患儿可根据遗传学病因进行早期临床干预，干预的方法主要包括特殊饮食、特殊药物、造血干细胞移植以及肺移植。 结论： 新生儿死亡病例中的遗传学病因并不少见，主要与多系统异常、代谢性疾病、血液系统疾病、呼吸系统疾病、心血管疾病以及骨骼发育异常相关。部分患儿可根据遗传学病因给予针对性干预。出生体重≥2 000 g、足月出生或无出生窒息抢救史的死亡患儿更需警惕其存在遗传学病因。.