Strength and limitations
The present study utilizes a novel technique –recordings of the so-called frequency-following response– to assess CNS functionality in LGA neonates during the first days of life. The neonatal sample was selected from non-diabetic mothers, a well-known risk factor for poor infant neurodevelopment68,69, making it possible to assess specifically the effect of neonatal high birth weight on CNS functionality, free of maternal disease influences. Yet, the present results should be interpreted with caution, as key limitations include sample size, potential confounds, single-center origin, and the lack of postnatal follow-up. Our sample was indeed small but yet similar to that of previous electrophysiological studies on other clinical conditions43-47. Also, we acknowledge that our results were obtained on a sample recruited from one single maternity unit. Future multi-centric studies should increase external validity. Furthermore, the inclusion of a much larger number of cases would allow us conduct multiple regression analysis to control for potential confounds, such as maternal smoking. Follow-up studies should aim at determining whether the CNS alterations observed at birth are only transient to normalize with development or, otherwise have a potential predictive value. In the next stage of our project, we pursue assessing neurodevelopment at the age of 2 years. The existence of previous studies demonstrating that the FFR can predict literacy scores one year ahead48 makes us confident that it will be possible to corroborate a relationship between the neonatal FFR and neurodevelopmental test scores.