Lipidomics Reveals Circulating Lipid Biomarkers for Retinopathy of Prematurity in Preterm Infants

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.