Genetic disorders and mortality in infancy and early childhood: delayed diagnoses and missed opportunities

Infants admitted to a level IV neonatal intensive care unit (NICU) who do not survive early childhood are a population that is probably enriched for rare genetic disease; we therefore characterized their genetic diagnostic evaluation. This is a retrospective analysis of infants admitted to our NICU between 1 January 2011 and 31 December 2015 who were deceased at the time of records review, with age at death less than 5 years. A total of 2,670 infants were admitted; 170 later died. One hundred six of 170 (62%) had an evaluation for a genetic or metabolic disorder. Forty-seven of 170 (28%) had laboratory-confirmed genetic diagnoses, although 14/47 (30%) diagnoses were made postmortem. Infants evaluated for a genetic disorder spent more time in the NICU (median 13.5 vs. 5.0 days; p = 0.003), were older at death (median 92.0 vs. 17.5 days; p < 0.001), and had similarly high rates of redirection of care (86% vs. 79%; p = 0.28). Genetic disorders were suspected in many infants but found in a minority. Approximately one-third of diagnosed infants died before a laboratory-confirmed genetic diagnosis was made. This highlights the need to improve genetic diagnostic evaluation in the NICU, particularly to support end-of-life decision making

Infant mortality: the contribution of genetic disorders

To determine the proportion of infant deaths occurring in the setting of a confirmed genetic disorder. A retrospective analysis of the electronic medical records of infants born from 1 January, 2011 to 1 June, 2017, who died prior to 1 year of age. Five hundred and seventy three deceased infants were identified. One hundred and seventeen were confirmed to have a molecular or cytogenetic diagnosis in a clinical diagnostic laboratory and an additional seven were diagnosed by research testing for a total of 124/573 (22%) diagnosed infants. A total of 67/124 (54%) had chromosomal disorders and 58/124 (47%) had single gene disorders (one infant had both). The proportion of diagnoses made by sequencing technologies, such as exome sequencing, increased over the years. The prevalence of confirmed genetic disorders within our cohort of infant deaths is higher than that previously reported. Increased efforts are needed to further understand the mortality burden of genetic disorders in infancy