Longitudinal Serum Metabolomics in Extremely Premature Infants: Relationships With Gestational Age, Nutrition, and Morbidities

Abstract

An increasing number of extremely premature infants survive the neonatal period and beyond. Little is known about the maturation of the preterm infant’s metabolome and its relation to the development of morbidities. Using 1H-NMR, we investigated the serum metabolic profile of 87 infants born at a gestational age (GA) <28 weeks [mean GA (SD) 25.4 (1.4) weeks] in samples longitudinally collected from birth to term equivalent age. The infant metabolome was analyzed in relation to GA, postnatal age, nutrition, and preterm morbidities. At postnatal day 1, low GA correlated with high levels of 3-hydroxyisobutyrate, acetate, acetoacetate, acetone, formate, glucose, and valine. Nearly all quantified metabolites displayed postnatal concentration changes. For example, the two phospholipid-related metabolites myo-inositol and ethanolamine displayed a similar decline from birth over the first weeks of life, irrespectively of GA. The proportion of enteral/parenteral energy intake in the first 28 days significantly correlated with mean levels of 52% of the analyzed metabolites. Low enteral energy intake was associated with high serum levels of 3-hydroxyisobutyrate, creatinine, glucose, glycerol, histidine, lactate, leucine, lysine, methionine, ornithine, phenylalanine, proline, threonine, and uridine. There were also significant correlations between high enteral intake and high serum levels of isoleucine and tyrosine. Retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) outcomes were not significantly associated with metabolite levels in the neonatal period after correcting for multiple testing. In conclusion, the serum metabolome of extremely premature infants changes substantially in the neonatal period, largely driven by the gradual transfer from total parenteral nutrition to full enteral feeding. Further studies are needed to disentangle the intricate relationships between the metabolome, nutritional management, GA, and the development of preterm morbidities.

Improved Macro- and Micronutrient Supply for Favorable Growth and Metabolomic Profile with Standardized Parenteral Nutrition Solutions for Very Preterm Infants

“…In contrast to other studies, postnatal complications or degree of immaturity did not alter the metabolomic profiles [ 51 ]. The only exception were differentially co-regulated levels of the amino acids alpha-aminobutyric acid and phenylalanine with macro- and micronutrient intake, in line with previous studies indicating negative correlations with energy supplementation [ 52 ] but indicating lower risk profiles for morbidity and mortality [ 53 , 54 , 55 ] in infants with optimized PN at the same time.…”

Integrated Omics Approach: Revealing the Mechanism of Auxenochlorella pyrenoidosa Protein Extract Replacing Fetal Bovine Serum for Fish Muscle Cell Culture

“…Transferrin could reduce the production of toxic free radicals and transport ferric-ions into cells . Sodium selenite could protect cells from oxidative damage and reduce free radicals, while selenium deficiency induced the apoptosis and necroptosis of smooth muscle cells through the ROS/MAPK pathway. , Ethanolamine was a precursor for the synthesis of phospholipids and could act as a growth factor to stimulate cell proliferation …”

“…56,57 Ethanolamine was a precursor for the synthesis of phospholipids and could act as a growth factor to stimulate cell proliferation. 58 The fluorescence intensity of the 0%FBS+APE+ITS-X+Lascorbic acid group was 1.75 times higher than that of the 10% FBS group and 1.57 times higher than that of the 0%FBS+APE group (Figure 3G,H), suggesting that L-ascorbic acid and ITS-X could be compounded with APE for the short-term culture of CAM cells under serum-free conditions. For the scale-up culture of CAM cells, the cell density of the 0%FBS+APE+ITS-X+L-ascorbic acid group was higher than that of the 0%FBS group for the first 2 days (Figure 3I).…”

Retinopathy of prematurity: Metabolic risk factors

“…This study found perturbed metabolism of lipids, arginine, glycine, serine and threonine, alanine and aspartate and glutamate. As parenteral versus enteral nutrition during the neonatal period has a profound impact on the serum metabolome ( Nilsson et al, 2022 ; Vanhaesebrouck et al, 2008 ), further validation of longitudinal nutritional management, serum metabolome and ROP risks is needed. In mice modeling hypoxia-induced severe ROP, retinal changes include increased metabolites associated with lipids, glycine and serine and threonine metabolism ( Tomita et al, 2021a ).…”