Preterm-born children are at risk for later neurodevelopmental problems and cardiometabolic diseases; early-life growth restriction and suboptimal neonatal nutrition have been recognized as risk factors. Prevention of these long-term sequelae has been the focus of intervention studies. High supplies of protein and energy during the first weeks of life (i.e., energy > 100 kcal kg⁻¹ day⁻¹ and a protein-to-energy ratio > 3 g/100 kcal) were found to improve both early growth and later neurodevelopmental outcome. Discontinuation of this high-energy diet is advised beyond 32–34 weeks postconceptional age to prevent excess fat mass and possible later cardiometabolic diseases. After discharge, nutrition with a higher protein-to-energy ratio (i.e., > 2.5–3.0 g/100 kcal) may improve growth and body composition in the short term.Conclusion: Preterm infants in their first weeks of life require a high-protein high-energy diet, starting shortly after birth. Subsequent adjustments in nutritional composition, aimed at achieving optimal body composition and minimizing the long-term cardiometabolic risks without jeopardizing the developing brain, should be guided by the growth pattern. The long-term impact of this strategy needs to be studied. What is Known:• Preterm infants are at risk for nutritional deficiencies and extrauterine growth restriction.• Extrauterine growth restriction and suboptimal nutrition are risk factors for neurodevelopmental problems and cardiometabolic disease in later life. What is New:• Postnatally, a shorter duration of high-energy nutrition may prevent excess fat mass accretion and its associated cardiometabolic risks and an early switch to a protein-enriched diet should be considered from 32-34 weeks postconceptional age.• In case of formula feeding, re-evaluate the need for the continuation of a protein-enriched diet, based on the infant’s growth pattern.

Infants born moderate-to-late preterm (i.e., 32 ⁰/₇-35 ⁶/₇ weeks' gestation) are, analogous to those born very preterm, at risk of later obesity, hypertension, and diabetes. Appropriate early life nutrition is key for ensuring optimal growth and body composition, thereby mitigating potential cardiometabolic risks. To compare growth and body composition between infants born moderate-to-late preterm fed isocaloric but protein- and mineral-enriched postdischarge formula (PDF) or standard term formula (STF) until 6 months corrected age (CA; i.e., after term equivalent age [TEA]). After enrolment (≤7 days postpartum), infants received PDF if (fortified) mother's own milk (MOM) was insufficient. At TEA, those receiving >25% of intake as formula were randomized to either continue the same PDF (n=47) or switch to STF (n=50); those receiving ≥75% of intake as MOM (n=60) served as references. At TEA and 6 months CA, we assessed anthropometry and body composition using both dual-energy x-ray absorptiometry and air displacement plethysmography. Feeding groups had similar gestational age (median [p25;p75]: 34.3 [33.5;35.1] weeks), birthweight (mean ± SD: 2175 ± 412 g), anthropometry and body composition at TEA. At 6 months CA, infants fed PDF had slightly, but significantly, higher length (67.6 ± 2.5 and 66.9 ± 2.6 cm, p<0.05) and larger head circumference (43.9 ± 1.3 and 43.4 ± 1.5 cm, p<0.05) compared to infants fed STF. Also, infants fed PDF had higher lean mass and bone mineral content estimated by dual-energy x-ray absorptiometry (4772 ± 675 and 4502 ± 741 g; 140 ± 20 and 131 ± 23 g, respectively; p<0.05). Air displacement plethysmography estimates, however, were not statistically different between feeding groups. Infants born moderate-to-late preterm demonstrated modest increases in length, head circumference, lean mass, and bone mineral content when fed PDF compared to STF for 6 months after TEA. International Clinical Trial Registry Platform (https://trialsearch.who.int) as: NTR5117 (old-NTR) and NTR NL4979 (new-NTR) .

Introduction: Neonatal propylene glycol (PG) clearance is low with long plasma half-life. We hypothesized that neonatal brain PG clearance is diminished and may be related to perinatal asphyxia, infection, or stroke, via different blood-brain barrier permeability. This study aimed to estimate cerebral PG half-life with a clearance model including PG measured with MR spectroscopy (MRS) in neonates that received phenobarbital as the only PG source and to evaluate whether PG clearance was related to intracerebral pathology, for example, perinatal asphyxia, infection, or stroke. Methods: In this retrospective cohort study, 45 neonates receiving any dose of phenobarbital underwent MRS (short echo time single-voxel MRS at 1.5 T). Cumulative phenobarbital/PG doses were calculated. MRS indications were perinatal asphyxia (n = 22), infection (n = 4), stroke (n = 10), metabolic disease (n = 4), and others (n = 5). Results: Medians (interquartile range) included gestational age 39.4 (3.1) weeks, birth weight 3,146 (1,340) g, and cumulative PG dose 700 (1,120) mg/kg. First-order kinetics with mono-exponential decay showed cerebral PG half-life of 40.7 h and volume of distribution of 1.6 L/kg. Zero-order kinetics showed a rate constant of 0.048 mM/h and a volume of distribution of 2.3 L/kg, but the fit had larger residuals than the first-order model. There were no differences in ΔPG (i.e., PG estimated with clearance model minus PG observed with MRS) in infants with perinatal asphyxia, infection, or stroke. Discussion/Conclusion: This study showed a long cerebral PG half-life of 40.7 h in neonates, unrelated to perinatal asphyxia, infection, or stroke. These findings should increase awareness of possible toxic PG concentrations in neonatal brain due to intravenous PG-containing drugs.