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Lipidomics Reveals Circulating Lipid Biomarkers for Retinopathy of Prematurity in Preterm Infants
Kajetan Trošt1, Qian Gao1, Jasmin Pernille Hjerresen1
1Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Insights
Lipid profiles in preterm infants change significantly during the neonatal period. Altered lipid metabolism, particularly involving phosphatidylcholines, is associated with retinopathy of prematurity (ROP) severity.
Area of Science:
- Neonatal Medicine
- Ophthalmology
- Metabolomics
Background:
- Retinopathy of prematurity (ROP) is a leading cause of blindness in preterm infants.
- While high oxygen is a known factor, metabolic influences like lipids are increasingly implicated in ROP pathophysiology.
Purpose of the Study:
- To explore the association between lipid profiles and ROP development in preterm infants.
- To investigate how lipid species change during the neonatal period in relation to ROP severity.
Main Methods:
- An exploratory study involving 110 preterm infants (born before 32 weeks gestation).
- ROP screening and bi-weekly blood sample collection.
- Lipidomics analysis of 485 lipid species and statistical modeling.
Main Results:
- All major lipid classes (310 species) showed significant changes during the neonatal period.
- Early lipid profiles, especially phosphatidylcholines, correlated with ROP severity.
- Glycerophospholipids and sphingolipids changed slower in infants with severe ROP (stage 2-3).
Conclusions:
- Significant changes in lipid profiles occur in preterm infants throughout the neonatal period.
- Lipid metabolism alterations are associated with ROP pathogenesis.
- Further research into dyslipidemia in ROP is warranted.
Objective:
Retinopathy of prematurity (ROP) is a multifactorial eye disease affecting children born premature and is a leading cause of blindness in preterm infants worldwide. Although it has primarily been associated with high oxygen supplementation from respiratory support, there are indications that additional metabolic factors, like circulating lipids, may play a role in the disease's pathophysiology.
Design:
An exploratory study on the development of ROP in preterm infants was conducted in Denmark during 2018 and 2019. Infants who developed a maximum of stage 1 ROP were classified as having mild retinopathy, whereas those who developed stage 2 or 3 were classified as having severe retinopathy.
Participants:
The study involved 110 preterm infants born before 32 weeks of gestational age.
Methods:
During hospitalization in the neonatal wards, the infants were screened for ROP, and blood samples were collected every 2 weeks. A total of 485 lipid species were analyzed using lipidomics methodology, and mixed linear models were applied.
Main Outcome Measures:
The association of lipids in early life (postnatal weeks 3-4) and their change throughout the study period was investigated.
Results:
All lipid classes, involving 310 lipid species, changed significantly during the neonatal period. In early postnatal life, the lipid profiles of some classes (especially phosphatidylcholines and ether-linked phosphatidylcholines) were associated with the severity of ROP. In infants with stage 2 or 3 ROP, glycerophospholipids and sphingolipids changed more slowly compared with infants with no ROP. Similarly, glycerophospholipid pathways were enriched in infants with ROP.
Conclusions:
The lipidomic plasma profile in preterm infants shows significant change across the neonatal period, involving all lipid classes. The association with ROP suggests that lipid metabolism may also play a role in ROP pathogenesis. Dyslipidemia associated with ROP should be addressed in further studies.
Financial Disclosures:
The authors have no proprietary or commercial interest in any materials discussed in this article.
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