Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, California.
Department of Pediatrics, University of California, San Diego, La Jolla.
JAMA Netw Open. 2023 Feb 1;6(2):e2254069. doi: 10.1001/jamanetworkopen.2022.54069.
Understanding the causes of infant mortality shapes public health, surveillance, and research investments. However, the association of single-locus (mendelian) genetic diseases with infant mortality is poorly understood.
To determine the association of genetic diseases with infant mortality.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted at a large pediatric hospital system in San Diego County (California) and included 546 infants (112 infant deaths [20.5%] and 434 infants [79.5%] with acute illness who survived; age, 0 to 1 year) who underwent diagnostic whole-genome sequencing (WGS) between January 2015 and December 2020. Data analysis was conducted between 2015 and 2022.
Infants underwent WGS either premortem or postmortem with semiautomated phenotyping and diagnostic interpretation.
Proportion of infant deaths associated with single-locus genetic diseases.
Among 112 infant deaths (54 girls [48.2%]; 8 [7.1%] African American or Black, 1 [0.9%] American Indian or Alaska Native, 8 [7.1%] Asian, 48 [42.9%] Hispanic, 1 [0.9%] Native Hawaiian or Pacific Islander, and 34 [30.4%] White infants) in San Diego County between 2015 and 2020, single-locus genetic diseases were the most common identifiable cause of infant mortality, with 47 genetic diseases identified in 46 infants (41%). Thirty-nine (83%) of these diseases had been previously reported to be associated with childhood mortality. Twenty-eight death certificates (62%) for 45 of the 46 infants did not mention a genetic etiology. Treatments that can improve outcomes were available for 14 (30%) of the genetic diseases. In 5 of 7 infants in whom genetic diseases were identified postmortem, death might have been avoided had rapid, diagnostic WGS been performed at time of symptom onset or regional intensive care unit admission.
In this cohort study of 112 infant deaths, the association of genetic diseases with infant mortality was higher than previously recognized. Strategies to increase neonatal diagnosis of genetic diseases and immediately implement treatment may decrease infant mortality. Additional study is required to explore the generalizability of these findings and measure reduction in infant mortality.
了解婴儿死亡率的原因有助于公共卫生、监测和研究投资。然而，单基因（孟德尔）遗传疾病与婴儿死亡率之间的关联尚未被充分了解。
确定遗传疾病与婴儿死亡率之间的关联。
设计、地点和参与者：这项队列研究在加利福尼亚州圣地亚哥县的一家大型儿科医院系统中进行，共纳入 546 名婴儿（112 名婴儿死亡[20.5%]和 434 名急性疾病存活的婴儿[79.5%]；年龄 0 至 1 岁），他们在 2015 年 1 月至 2020 年 12 月期间接受了全基因组测序（WGS）诊断。数据分析于 2015 年至 2022 年进行。
婴儿在生前或死后进行 WGS，同时进行半自动表型分析和诊断解释。
与单基因遗传疾病相关的婴儿死亡比例。
在圣地亚哥县 2015 年至 2020 年期间的 112 名婴儿死亡中（54 名女婴[48.2%]；8 名非裔美国人或黑人[7.1%]，1 名美洲原住民或阿拉斯加原住民[0.9%]，8 名亚洲人[7.1%]，48 名西班牙裔或拉丁裔[42.9%]，1 名夏威夷原住民或太平洋岛民[0.9%]，34 名白人婴儿[30.4%]），单基因遗传疾病是最常见的可识别的婴儿死亡原因，46 名婴儿中有 47 种遗传疾病（41%）被确定。其中 39 种（83%）先前已报告与儿童死亡率相关。在 46 名婴儿中的 28 份死亡证明（62%）中，没有提到遗传病因。对于 14 种（30%）遗传疾病，可以提供改善预后的治疗方法。在 7 名死后发现遗传疾病的婴儿中，有 5 名如果在症状发作或区域重症监护病房入院时进行快速诊断性 WGS，死亡可能可以避免。
在这项对 112 名婴儿死亡的队列研究中，遗传疾病与婴儿死亡率的关联高于先前的认识。增加新生儿遗传疾病诊断并立即实施治疗的策略可能会降低婴儿死亡率。需要进一步的研究来探索这些发现的普遍性，并衡量婴儿死亡率的降低。
