Related Experiment Video
Updated: Oct 1, 2025
Identification and Quantification of Deranged Metabolites in Critically Ill Patients Using NMR-Based Metabolomics
Published on: November 29, 2024
Longitudinal Serum Metabolomics in Extremely Premature Infants: Relationships With Gestational Age, Nutrition, and
Anders K Nilsson1, Abdellah Tebani2,3, Daniel Malmodin4
1Section for Ophthalmology, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Insights
The serum metabolome of extremely premature infants changes significantly after birth, influenced by nutrition. Key metabolites correlate with gestational age and feeding methods, but not directly with major morbidities like ROP or BPD.
Area of Science:
- Biochemistry
- Neonatology
- Metabolomics
Background:
- Extremely premature infants are surviving neonatal care at increasing rates.
- Understanding the maturation of the preterm infant metabolome and its link to morbidities is crucial.
Purpose of the Study:
- To investigate the serum metabolic profile of extremely premature infants.
- To analyze how the metabolome changes from birth to term equivalent age.
- To explore relationships between the metabolome, gestational age, nutrition, and morbidities.
Main Methods:
- Utilized 1H-NMR spectroscopy to analyze serum metabolic profiles.
- Collected longitudinal samples from 87 infants with gestational age <28 weeks.
- Correlated metabolite levels with gestational age, postnatal age, nutrition, and morbidities.
Main Results:
- Low gestational age correlated with elevated levels of specific metabolites (e.g., 3-hydroxyisobutyrate, glucose, valine) at postnatal day 1.
- Most metabolites showed significant concentration changes postnatally, with phospholipid-related metabolites declining.
- Nutritional intake (enteral vs. parenteral) strongly correlated with 52% of metabolites; low enteral intake linked to higher levels of numerous metabolites.
Conclusions:
- The serum metabolome of extremely premature infants undergoes substantial changes in the neonatal period.
- Metabolomic shifts are primarily driven by the transition from parenteral to enteral nutrition.
- No significant associations were found between neonatal metabolite levels and retinopathy of prematurity or bronchopulmonary dysplasia after correction for multiple testing.
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.
