Dottorato in TECNOLOGIE BIOMEDICHE INNOVATIVE IN MEDICINA CLINICA

Titolo della tesi: Activation of the gut-brain axis as a key strategy to improve neurodevelopmental outcomes in preterm-born children

Background Preterm-born babies are at high risk of brain damage and neurodevelopmental impairment. Several factors have been shown to impact the occurrence of neurological injury in these patients, including nutritional strategy. If in the past it has already been demonstrated that undernutrition exacerbates neurological damage, it still remains to assess whether timing of introduction of enteral nutrition (EN) could play a role in this phenomenon. Aim To verify the effects of early EN (< postnatal day [PND] 7) vs. late EN (≥ PND 7) on brain damage and neurodevelopment in preterm newborns, and mechanisms underlying the observed results. Methods Controlled study including patients with gestational age < 30 weeks and/or birth weight < 1500 g, which were divided into late-feeding (born January 2015-December 2017, group A) and early-feeding (born January 2020-June 2021, group B). All patients had serum Neurofilament Light chain (NfL) levels measured at birth and PND 28, and neurodevelopmental assessment performed at 12 and 24 months’ corrected age (CA) by means of Bayley scale – III Edition and Developmental Profile-3, respectively. Data about metabolic complications of parenteral nutrition (PN) were also collected. Results As regards characteristics of the study population, no statistically significant differences were detected between late-feeding (n=51) and early-feeding (n=29) patients. NfL serum levels at birth were similar between both groups; however, concentrations of this biomarker were lower in early-feeding babies at PND 28 (p=0.002). Infants belonging to group A had a significantly higher rate of motor impairment at 24 months’ CA than their early-feeding counterpart (p=0.016). Rates of metabolic complications following parenteral administration of nutrients were higher in late-feeding newborns, notably hyperglycemia (HG, p=0.020), hypertriglyceridemia (p=0.031), and metabolic acidosis (p=0.028). We demonstrated that HG related to administration of PN (particularly to parenteral energy intake in the first week ≥ 50th percentile of the study population, or 432 kcal/kg/first week) was a risk factor for motor impairment at 12 months’ CA. Sensitivity analysis considering newborns in total PN during the first postnatal week confirmed these findings. Conclusion Early EN prevents or reduces brain damage and improves long-term motor outcome in preterm patients. The higher incidence of metabolic complications following parenteral administration of nutrients could explain higher levels of NfL at PND 28 and brain injury in late-feeding patients, whereas HG related to PN is associated with motor delay.