INTRODUCTION
Abnormal fetal growth is associated with adverse short and long-term outcomes1,2. Neonates born at the lower end of the birth weight continuum have a high risk of morbidity and mortality3,4 including poor neurobehavioral outcomes5-7. Yet, a non-linear association between birth weight and adverse outcomes has been reported8-11, disclosing a reverse J-shaped/U relationship. As worldwide obesity ratios are rising12-17, research focusing on the upper birth weight end, typically defined as large-for-gestational-age (LGA, >90th percentile), is increasing.
Neonates born LGA are at increased risk of mortality, obesity, type 2 diabetes, cardiovascular diseases, and metabolic syndrome18-22. However, evidence regarding neurodevelopmental outcomes is limited and inconsistent. In addition, the lack of consensus on terminology and criteria, with different cutoff values and the use of absolute birth weight or its normalization by gestational age hampers generalization. Elevated birth weight was associated, from childhood to adulthood with impaired cognitive function10,23,24, poor educational attainments8,25,26, and with cerebral palsy27, autism28, attention difficulties29, social disorder symptoms30 and externalizing behaviors11. However, other studies found no association31,32, or even a positive relationship33,34, with better development and higher educational outcomes for LGA compared to adequate-for-gestational-age (AGA).
A further limitation is that previous studies focused on children to adults, leaving unexplored the early years of life –a crucial period for neurodevelopment–. Biologically plausible models suggest a higher risk for poor cognitive outcomes in LGA compared to the general population11,35. Fetal growth is influenced by complex interactions between fetal genes and intrauterine environment, so that several studies have suggested that an adverse fetal environment translates into being LGA36-38. But perinatal central nervous system (CNS) dysfunctionality in LGA neonates remains unexplored. One approach, recently used to disclose functional CNS affections at birth in FGR neonates39, is through recordings of the frequency-following response (FFR), a variant of the auditory brainstem response (ABR) elicited to speech sounds.
FFRs provide a snapshot into the neurophysiological encoding of the periodic sound features of the human language across the auditory system40-42. FFR is disrupted in children affected by dyslexia, reading impairment and autism43-47, and predicts literacy skills one year ahead48, supporting its sensitivity to neurodevelopmental outcomes. Recordings of the neonatal FFR have been successfully carried out in the general population49-53 and under several pathological conditions such as hyperbilirubinemia54 and FGR39. Here we tested in a case-control sample of 50 neonates, whether being born LGA would lead to an altered neural processing of speech sounds.