Clinical and Molecular Findings in Early Infant Death Associated with Genetic Diseases: A Multicenter Cohort Study in China

Abstract Background To investigate the impact of exome sequencing in critically ill infants and find out high-risk patients with genetic diseases for the 180-day mortality rate. Results A molecular diagnosis rate achieved in 203 of 439 (46.2%) sequenced infants. 60 of 203 (29.5%) diagnosed patients died before 180 days of life. Compared to the undiagnosed-cases, patients with genetic findings in metabolic-endocrine disorders (OR=2.89, 95% CI: 1.51-5.52), primary immunodeficiencies (OR=3.79, 95% CI: 1.25-11.53), and early-onset muscle disease (OR=6.49, 95% CI: 2.28-18.48) had high odds ratios of 180-day mortality. Based on the functions of the defective genes, infants with catalytic activity deficiency (OR=3.07, 95% CI: 1.51-6.25) and transporter activity deficiency (OR=4.15, 95% CI: 1.80-9.56) also had a high risk of 180-day mortality. Furthermore, the proportion of medical management correspondence to genetic findings increased from 22.4% to 40.3% (p=0.06), and the 180-day mortality rate decreased from 35.9% to 29.6% showing a moderate decreased trend (p trend =0.08) over 4 years.Conclusions Our study shows that patients with genetic findings in metabolic-endocrine disorders, primary immunodeficiencies and early-onset muscle disease are related to 180-day mortality, which are of great significance for improve the prognosis.