Rapid genomic sequencing in the NICU: who to test and why.

Rapid genomic sequencing, whether exome or genome, shortens time to diagnosis in the neonatal intensive care unit, but its benefit depends on the criteria used to decide which newborns should be tested.

The accessibility of rapid genomic sequencing, both exome and genome, is transforming care in neonatal intensive care units by enabling timely and precise diagnoses with high yield and substantial impact on clinical management; deciding which infants to sequence nevertheless remains a major challenge, particularly where genetic expertise and access to genomic resources are limited. The authors conducted a structured literature review of patient selection approaches for genomic sequencing in the NICU. Across 39 included studies, all but one relied on phenotype-driven inclusion criteria — congenital anomalies, neurological manifestations, multisystem disease, unexplained critical illness — with only one study using a predominantly exclusion-based, genotype-first strategy. Studies were conducted mainly in tertiary or well-resourced NICUs, highlighting persistent disparities in access to genomic testing and specialist expertise. The authors conclude that no single strategy optimises diagnostic yield, equity, feasibility and cost simultaneously, and call for prospective comparisons of selection frameworks and for scalable implementation models.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The review deserves credit for naming what everyone observes: selection criteria owe less to demonstration than to local practice, and the fact that 38 of 39 studies start from the phenotype mostly shows that the genotype-first strategy has almost never been evaluated. No new data are produced here and the literature search strategy is not detailed in what is reported, which limits the weight of the count. The genuinely useful point lies elsewhere: the almost exclusively tertiary recruitment of published studies means that the reported diagnostic yields are not transferable to a general neonatal intensive care unit.

Analysis by Dr Thibaut Benquey