Hyperglycemia (HG) is an independent risk factor of mortality and morbidity in very low birth weight newborns (VLBW). Achievement of high nutritional intakes in the first days of life (DoL) by parenteral nutrition (PN) increases the risk of HG. We aim to assess if a delayed achievement of the PN macronutrient target dose could reduce the occurrence of HG in VLBW. We enrolled 353 VLBW neonates in a randomized controlled clinical trial comparing two PN protocols that differed in the timing of energy and amino acid target dose achievement: (1) early target dose achievement (energy within 4–5 DoL; amino acids within 3–4 DoL) vs. (2) late target dose achievement (energy within 10–12 DoL; amino acids within 5–7 DoL). The primary outcome was the occurrence of HG during the first week of life. An additional endpoint was long-term body growth. We observed a significant difference in the rate of HG between the two groups (30.7% vs. 12.2%, p = 0.003). Significant differences were observed in terms of body growth at 12 months of life between the two groups (weight Z-Score: −0.86 vs. 0.22, p = 0.025; length: −1.29 vs. 0.55, p < 0.001). Delayed achievement of energy and amino acid intake may be useful to reduce the risk of HG along with an increase of growth parameters in VLBW neonates.

Background/Objectives: Preterm neonates receiving parenteral nutrition (PN) are at risk of developing refeeding syndrome (RS). Risk factors and the related consequences remain largely undefined. In particular, the reason why only some preterm neonates out of a group receiving the same nutritional protocol will develop RS is yet to be fully understood. The aims of this study were to explore the clinical and nutritional factors contributing to RS and to assess the clinical consequences of this condition. Methods: A retrospective study was conducted, including all newborns with gestational age ≤ 34 weeks and/or body birth weight ≤ 1500 g who were consecutively admitted to the neonatal intensive care unit (NICU) of “Umberto I” Hospital, Sapienza University of Rome, from 2015 to 2022. The population was divided into two groups comprising newborns who developed RS (cases) and infants who did not develop the condition (controls) up to the first 2 weeks of life. The enrolled newborns were compared for clinical and nutritional factors and main morbidities. Results: A total of 412 neonates were enrolled, consisting of 53 cases and 359 controls. The main prenatal risk factor for RS was found to be fetal distress (p = 0.028). The occurrence of RS was identified as statistically significantly associated (p = 0.010; p = 0.007) with the development of extrauterine growth restriction (EUGR) and retinopathy of prematurity (ROP). Conclusions: Fetal distress is the predominant perinatal risk factor associated with the development of RS in preterm neonates managed with early currently recommended PN. These findings suggest an increased risk of ROP and EUGR in preterm neonates with RS.

Background/Objectives: Preterm infants are particularly vulnerable to nutritional deficiencies and electrolyte imbalances during the early stages of extrauterine life. To ensure optimal metabolic support, they often require the early initiation of “aggressive” parenteral nutrition (PN), which is a known risk factor for Refeeding Syndrome (RS), a potentially serious metabolic condition characterized by fluid and electrolyte disturbances, the most significant of which is hypophosphatemia. Hypophosphatemia can impair the metabolism, survival, and function of red blood cells, leading to a reduction in key intracellular metabolites and the development of a metabolic block that alters their quality and decreases their stability. It is therefore hypothesized that RS may contribute to the development of anemia of prematurity (AOP). At the same time, early enteral nutrition (EN) may promote metabolic adaptation and reduce exposure to the complications of prolonged parenteral support, potentially protecting against AOP. The primary aim of this study was to determine whether preterm infants who develop RS are at increased risk of AOP. A secondary aim was to evaluate whether early EN may act as a protective factor against the development of AOP. Methods: This retrospective observational study was conducted on infants with a gestational age ≤ 34 weeks and/or birth weight ≤ 1500 g, admitted to the Neonatal Intensive Care Unit of Policlinico Umberto I—Sapienza University of Rome, between January 2015 and November 2022. Infants diagnosed with AOP were classified as cases, while those without AOP served as the control group. Results: A total of 412 preterm infants were enrolled (110 cases, 302 controls). Refeeding Syndrome was significantly more frequent in infants with AOP (30.9% vs. 11.6%, p < 0.001). In the logistic regression model adjusted for gestational age, RS was independently associated with AOP (OR = 2.81; 95% CI: 1.55–5.10; p < 0.001), along with gestational age ≤ 34 weeks (OR = 7.10; 95% CI: 2.13–24.0; p = 0.001). Early enteral nutrition during the first week of life was associated with a significantly lower risk of AOP (OR = 0.12; 95% CI: 0.029–0.52; p = 0.005). The association between RS and AOP was confirmed in the model adjusted for birth weight (OR = 2.06; 95% CI: 1.16–3.79; p = 0.021). Infants with AOP showed significantly higher parenteral nutrition intake, delayed initiation of enteral feeding, and later achievement of full enteral nutrition compared with controls (all p < 0.001). Conclusions: RS is significantly associated with AOP in preterm infants, likely through pathophysiological mechanisms related to hypophosphatemia. Importantly, early EN may be a protective factor against AOP, suggesting that timely initiation and advancement in enteral feeding may counteract the metabolic derangements associated with intensive parenteral support. These findings support a nutritional approach that prioritizes early and progressive enteral nutrition as a strategy to reduce the risk of both RS and AOP. Further prospective studies are needed to confirm these associations and to define optimal EN protocols for this population.