Recent advances in understanding pathophysiology of non-nutritional stunting in very preterm infants

Very preterm infants (VPIs) often experience extrauterine growth failure. Therefore, aggressive nutritional management of VPIs is recommended with the goal of achieving the postnatal growth of an equivalent fetus. However, VPIs frequently present postnatal length growth restriction at term-corrected age that remains lower than the standard weight and have greater fat mass and lower lean and bone mass than term-born infants. This condition differs from the classic pattern of infant undernutrition defined as a significantly lower weight for a given length. Moreover, it suggests that nonnutritional factors play a key role in length growth restriction. While weight faltering has been extensively studied, the significance of length growth failure in VPIs has only recently emerged. The nonnutritional factors underlying poor length growth in VPIs are currently not fully understood. In this review, we address recent advances in our understanding of the pathophysiology of length growth restriction, which has been identified as a major predictor of adverse neurodevelopmental and cognitive outcomes in VPIs. First, we review the shortand long-term consequences of poor length growth in VPIs; next, we highlight the effects of nonnutritional factors on postnatal length growth with focus on sustained neonatal inflammation; and finally, we discuss hypothesis and future lines of research attempting to understand the complex inflammatory-endocrine interactions and pathophysiological changes during early postnatal life, appropriately guide and apply clinical strategies aimed at optimizing length growth of VPIs, and identify evidence of the associations between sustained neonatal inflammation, stunting, and long-term health risks and the potential implications thereof.