Phd in INNOVATIVE BIOMEDICAL TECHNOLOGIES IN CLINICAL MEDICINE

Thesis title: Effects of nutrition on neurodevelopment of preterm neonates

Background. Current guidelines for preterm newborns recommend high energy and protein intake soon after birth in order to limit growth restriction. The impact of this nutritional strategy on the brain is still debated. However, it has been recently suggested that parenteral nutrition (PN) may have detrimental effects on neurodevelopment (NDV) in preterm neonates. On the other hand, enteral nutrition (EN) seems to be protective. We aimed to study the different effects of enteral and parenteral route on the Nerve growth factor (NGF) and Brain-derived neurotrophic factor (BDNF) serum levels and secondly, with a translational approach, on the cerebral growth and maturation. We included preterm neonates with gestational age < 32 weeks or birth weight (BW) < 1500 g. Specimens of blood were obtained at 28 days of life (DOL) for NGF/BDNF serum determination. Measurement of cerebral structures was performed by cranial Ultrasonography (cUS) between 3 and 7 DOL and at 28 DOL. Electroencephalography (EEG) recording was obtained every 2 weeks up to discharge to quantify the Functional Brain Age (FBA). Results. We analysed the relation between protein and energy intake and neurotrophins’ levels at 28 DOL in 20 newborns enrolled. Serum NGF value at 28 DOL were positively correlated with enteral protein and energy intake (r= 0.767; r = 0.746 p<0.001), whereas, negatively related with parenteral protein and energy intake (r = −0.652, p<0.001; r = −0.466, p<0.05). Similar significant correlations were described for BDNF values. We also evaluated the relation between energy and protein intake and cerebral growth and maturation at 28 DOL and at discharge, respectively. We observed in 100 preterm neonates a significant (p< 0.05) negative correlation between energy intake received by PN and right caudate head growth (r= −0.243*) and a positive correlation between enteral protein intake and biparietal diameter (r 0.490**), occipital frontal diameter (r =0.608**) and transverse cerebellum diameter (r= 0.440**). No correlations were found between FBA delay at discharge and nutritional intake. Multivariate analysis showed that energy and protein intake in the first week of life, given by EN, was an independent risk factor influencing, positively, the cerebral growth of specific brain structures. Conclusion. Neurotrophins’ values varied according with nutrition route. Enteral intake seems to positively influence NGF production. The route of protein and energy administration in the first week of life may have different impact on cerebral measurements of preterm neonates, but not on brain maturation.