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: Fentanyl is widely used in ventilated preterm neonates, but respiratory safety evidence is limited. We assessed the association between fentanyl exposure during mechanical ventilation and respiratory outcomes in preterm neonates <34 weeks and explored a candidate exposure-duration threshold, defined as the duration of continuous fentanyl infusion beyond which the risk of adverse respiratory outcomes rises sharply. Methods: Single-centre retrospective cohort study at Policlinico Umberto I, Sapienza University, Rome (2015–2022). Fentanyl-exposed neonates were 1:2 matched to unexposed neonates on gestational age and birth-weight z-score. Primary outcome: bronchopulmonary dysplasia at 36 weeks postmenstrual age (multivariable logistic regression); secondary outcome: duration of invasive ventilation. A composite outcome (bronchopulmonary dysplasia or invasive ventilation ≥ 7 days) was used for threshold analysis with restricted cubic splines, maximally selected Wald χ², and segmented logistic regression. Results: Of 315 eligible neonates, 50 fentanyl-exposed neonates were matched with 92 unexposed neonates (n = 142). Fentanyl exposure was associated, after adjustment for gestational age and fetal distress, with bronchopulmonary dysplasia (adjusted odds ratio 5.49, 95% CI 1.72–17.54) and longer invasive ventilation (adjusted exp(β) 2.25, 95% CI 1.54–3.29). Three complementary threshold methods were consistent with an exploratory signal around 3 days of continuous infusion, beyond which composite-outcome odds rose, although the breakpoint estimate was imprecise. Conclusions: Fentanyl exposure during mechanical ventilation was associated, after adjustment for gestational age and fetal distress, with bronchopulmonary dysplasia and longer invasive ventilation in preterm neonates <34 weeks. A possible signal around 3 days of continuous infusion is proposed as a hypothesis-generating stewardship prompt, not as a decision rule.