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.

Nutrition in early life has an impact on white matter (WM) development in preterm-born babies. Quantitative analysis of pixel brightness intensity (PBI) on cranial ultrasound (CUS) scans has shown a great potential in the evaluation of periventricular WM echogenicity in preterm newborns. We aimed to investigate the employment of this technique to objectively verify the effects of parenteral nutrition (PN) on periventricular WM damage in preterm infants. Prospective observational study including newborns with gestational age at birth ≤32 weeks and/or birth weight ≤1500 g who underwent CUS examination at term-equivalent age. The echogenicity of parieto–occipital periventricular WM relative to that of homolateral choroid plexus (RE_CP) was calculated on parasagittal scans by means of quantitative analysis of PBI. Its relationship with nutrient intake through enteral and parenteral routes in the first postnatal week was evaluated. The study included 42 neonates for analysis. We demonstrated that energy and protein intake administered through the parenteral route positively correlated with both right and left RE_CP values (parenteral energy intake vs. right RE_CP: r = 0.413, p = 0.007; parenteral energy intake vs. left RE_CP: r = 0.422, p = 0.005; parenteral amino acid intake vs. right RE_CP: r = 0.438, p = 0.004; parenteral amino acid intake vs. left RE_CP: r = 0.446, p = 0.003). Multivariate linear regression analysis confirmed these findings. Quantitative assessment of PBI could be considered a simple, risk-free, and repeatable method to investigate the effects of PN on WM development in preterm neonates.

Background/Objectives: The safety of specific parenteral glucose intake values within the range currently recommended by international guidelines for the early acute phase in preterm neonates has not been established. This study aimed to evaluate whether exceeding a data-driven parenteral dextrose intake threshold during the first week of life is independently associated with hyperglycemia, hypertriglyceridemia, metabolic acidosis, and extrauterine growth restriction (EUGR). Methods: This was a single-center retrospective study involving preterm neonates (gestational age ≤ 34 weeks and/or birth weight ≤ 1500 g) admitted to the Neonatal Intensive Care Unit of Policlinico Umberto I, Rome, between 2015 and 2022. The analysis followed two pre-specified steps: (1) data-driven identification of an exposure threshold by restricted cubic spline logistic regression; (2) multivariable analyses with the dichotomized exposure, adjusting for gestational age, birth weight, enteral nutrition timing, neonatal morbidity, and perinatal compromise. Results: 389 preterm neonates met eligibility. The data-driven inflection point of the spline-derived log-odds curve identified a threshold of 7 g/kg/day. Exceeding this threshold during the first week of life was independently associated with both hyperglycemia (adjusted odds ratio 5.55, 95% confidence interval 2.56 to 12.03; p < 0.001) and hypertriglyceridemia (adjusted odds ratio 4.36, 95% confidence interval 1.41 to 13.45; p = 0.010), but not with metabolic acidosis or with EUGR at 36 weeks postmenstrual age. The divergence in daily parenteral glucose intake between cases and controls was apparent from the second day of life. Conclusions: Exceeding 7 g/kg/day of parenteral dextrose was independently associated with early metabolic complications, but not with growth outcomes. A safety threshold for parenteral glucose may exist within the currently recommended intake range; prospective multicenter studies are needed before clinical recommendations can be drawn.

Objectives: The hospital organizational model can have an impact on people’s health. A critical lesson can be drawn from the pandemic. The possible negative sequelae of the practice of separation of maternal–infant dyads adopted during an infant’s first SARS-CoV-2 pandemic infection on infants have not been considered. Our purpose was to investigate the short- and long-term effects on neonates born to SARS-CoV-2 infected mothers of two different mother–infant dyad management strategies after birth (Separation vs. Rooming-In). Methods: This prospective cohort study enrolled 60 pregnant women who tested positive for SARS-CoV-2 infection and their newborns. We identified two cohorts of study based on mother–infant dyad management after delivery: Cohort A (Separation) and Cohort B (Rooming-In). Inclusion criteria were neonates born from mothers infected with SARS-CoV-2 during the pregnancy undergoing or not undergoing separation. Main Outcome: Rate of exclusive breastfeeding at 6 months of age was the primary outcome. The rate of mother–infant transmission of SARS-CoV-2 infection, growth, incidence of acute infections and neurodevelopment up to 12 months of life were also evaluated. Results: In total, 60 mother–infant dyads (maternal age 30.6 vs. 33.8 years, p = 0.335; gestational age 39.0 vs. 38.9 weeks, p = 0.451) were enrolled at delivery, and 53 dyads completed the study at the 6-month follow-up. Baseline clinical characteristics were similar between the two cohorts. At 6-month follow-up, the rate of breastfeeding was significantly decreased in Cohort A compared with Cohort B (4% vs. 46%, p < 0.001). The rate of SARS-CoV-2 infection was similar between the two cohorts of the study. Weight gain at 6 months of life was significantly higher in Cohort A compared to Cohort B (8129 g, 95% CI, 7562 to 8695; vs. 7393 g, 95% CI, 6912 to 7874; p = 0.005). No differences were detected in terms of rate of acute neonatal infections and neurodevelopment outcomes. Conclusions: The separation practice led to a reduction in the rate of breastfeeding after discharge and to a consequently increased implementation of formula milk, which might justify the alarming increased weight gain of newborns who did not undergo the Rooming-In practice. Given the potential of recurrent outbreaks of other viral pandemics, our results suggest more caution early in life towards the disruption of consolidated procedures that may have long-term consequences. However, the COVID-19 pandemic offered a unique context to observe the effects of temporary mother–infant separation; clinicians should be reassured that the temporary separation practice did not affect neurodevelopment and be aware that it could be considered an option, at least if Rooming-In cannot be carried out due to severe reasons such as lack of staff or adequate space.

Background: Hypertriglyceridemia (HiTG) is a frequent metabolic complication in preterm neonates receiving parenteral nutrition (PN), with potential implications for respiratory outcomes. However, predisposing factors and the clinical impact of HiTG in this population remain poorly defined. Objectives: To identify factors predisposing preterm neonates to HiTG development and to assess the association between HiTG and neonatal respiratory morbidity. Methods: A retrospective matched cohort study was conducted, nested within a single-center cohort of neonates receiving routine parenteral nutrition (PN) and on respiratory support, with gestational age ≤ 32 weeks and/or a birth weight ≤ 1500 g, consecutively admitted between January 2015 and May 2023 into the Neonatal Intensive Care Unit (NICU) of ‘Umberto I’ University Hospital, Sapienza University of Rome. HiTG was defined as at least one serum triglyceride (TG) value > 180 mg/dL during the first 7 days of life. TG levels were measured from morning samples collected alongside routine laboratory draws; for borderline values (180–200 mg/dL), a confirmatory sample was obtained after a 4 h lipid-free interval. Neonates with HiTG were classified as cases; newborns without HiTG served as controls, matched 1:1 for gestational age and birth weight. Results: A total of 110 neonates were enrolled (55 cases, 55 controls). HiTG was independently associated with bronchopulmonary dysplasia (BPD) (OR 29.46; 95% CI 5.82–149.07; p < 0.001) and prolonged invasive mechanical ventilation (pIMV) (OR 4.85; 95% CI 1.69–13.89; p = 0.003), after adjustment for surfactant administration and extremely low birth weight. Time to achieve full enteral feeding (FEF) was independently associated with HiTG development (β = +0.153; p < 0.001), whereas parenteral lipid intake during the first week of life was inversely associated (β = −0.081; p = 0.039). Conclusions: HiTG is independently associated with BPD and prolonged invasive mechanical ventilation in preterm neonates. Parenteral lipid intake during the first week was not higher in infants who developed HiTG. Delayed achievement of FEF was also associated with HiTG, but it occurred after the exposure window and cannot therefore be regarded as a predisposing factor. These findings are hypothesis-generating. Randomized trials are needed to assess whether closer monitoring of triglyceride levels and early advancement of enteral feeding in preterm neonates may help reduce BPD.

Background/Objectives: Survival of infants born very preterm or with very low birth weight has improved without a comparable reduction in neurodevelopmental morbidity, and the exposures acting during neonatal intensive care are usually studied in isolation. We aimed to identify which prenatal, perinatal and postnatal factors are independently associated, domain by domain, with neurodevelopment at 24 months’ corrected age (CA) and with the composite outcome of neurodevelopment and survival. Methods: Single-centre prospective cohort of 146 infants (135 assessed at 24 months’ CA and 11 who died between day 8 of life and the assessment) with gestational age ≤ 32 weeks and/or birth weight ≤ 1500 g admitted to a level III unit (2018–2022). Neurodevelopment was assessed with the Bayley-III; a score < 85, rather than the conventional <70 being taken as pathological, was used, with the third edition yielding systematically higher scores. Eighty-one candidate exposures were screened; for each domain a primary composite outcome (score < 85 or death) and a secondary survivors-only outcome were analysed by exploratory multivariable logistic regression. Results: Twenty-nine of 164 eligible survivors (17.68%) were lost to follow-up and did not differ appreciably from the analysed cohort (all standardised differences ≤ 0.10). Severe intraventricular haemorrhage was associated with language, sepsis and anaemia requiring transfusion with motor, and male sex and sepsis with socio-emotional development, whereas no covariate was associated with cognition. No nutritional, metabolic or postnatal-growth variable was independently associated with any domain, and no association survived Benjamini–Hochberg control of the false discovery rate (optimism-corrected c-statistics 0.598–0.739). Conclusions: These findings are associations rather than evidence of causality; they are hypothesis-generating and warrant multicentre external validation and longer follow-up.