We congratulate Balada et al.1 for pursuing important transcriptomic research in neonatal encephalopathy (NE). They examined the messenger RNA (mRNA) expression of 23 candidate genes in whole blood using real-time polymerase chain reaction from 24 babies with NE and 34 control babies (1 healthy; 33 with mild polycythaemia), and also at ages <6 h (n = 15 NE vs. 2 controls), 12 h (n = 17 NE vs. 1 control), 24 h (n = 18 NE vs. 2 controls), 48 h (n = 14 NE vs. 13 controls), 72 h (n = 13 NE vs. 9 controls), and 96 h (n = 4 NE vs. 7 controls). Six genes (MMP9, PPARG, IL8, HSPA1A, TLR8, and CCR5) had a discriminant graphical pattern between babies with NE and control infants, and hence were selected for subsequent statistical modeling.

While this is useful information, we would like to highlight some limitations of these observations and methodology. First, the use of a preselected panel of just 23 genes may lead to erroneous conclusions, particularly in preliminary studies. Often, the results of microarray-based gene expression studies are not reproducible, and when the analysis is limited to a small set of preselected genes, the significance of the observed differences is even more difficult to interpret.2 Second, two controls were recruited within 6 h and only one within 12 h, which limited the contribution of the first two time points to the identification of the differentially expressed genes to be used for the analysis. While we acknowledge that recruitment of control infants represents a significant challenge for neonatal studies, the identification of a gene expression profile within 6 h of birth is pivotal since the therapeutic window for neonatal neuroprotective interventions is narrow, and treatments need to be initiated within hours after birth to have a chance of success. Finally, this is not the first report on use of gene expression in NE, as authors have claimed. We had previously reported differences in gene expression profiles of babies with NE, healthy control, and those with sepsis, using next-generation sequencing approach.3,4

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD