Table 1. Summary of metabolic risk factors for ROP.

Risk factors	Comparison	Outcomes	References
DHA	no ROP, mild or moderate ROP (stage 1–2), or severe ROP (stage 3 and type 1).	High serum DHA correlated with less severe ROP, only in infants with sufficiently high ARA levels	Hellström et al., 2021b
	Enteral DHA vs. placebo	No difference in any stage of ROP, but DHA lowered the relative risk for severe ROP.	Bernabe-García et al., 2019
ARA	ROP vs. no ROP	Low serum ARA correlated with ROP development	Löfqvist et al., 2018
DHA +ARA	Enteral DHA +ARA vs. no supplementation	DHA:ARA at 1:2 ratio lowered severe ROP (stage 3 and/or type 1).	Hellström et al., 2021a
Metabolites	ROP vs. no ROP	Higher levels of glycolytic intermediates (pyruvate, lactate), lower levels of TCA metabolites (citrate, aconitate, succinyl carnitine), higher malonyl carnitine (C3DC), glycine in ROP	Yang et al., 2022; Yang et al., 2020
Insulin	No or mild ROP (1–2) vs. severe ROP (3-4)	Insulin exposure was a stronger predictor for severe ROP than hyperglycemia per se	Kaempf et al., 2011
	No or mild ROP vs severe ROP (needing treatment)	Blood glucose >150 mg/ml and insulin exposure associated with severe ROP	Lee et al., 2016
IGF-1	No ROP, ROP (1,2, 3-4)	Low plasma IGF-1 correlated with high glucose levels and increased ROP severity	Cakir et al., 2020
APN	No ROP stage vs. any ROP	Low serum APN correlated with ROP; serum APN positively correlated with serum DHA	Fu et al., 2015a
	Plasma glucose tertiles and retinal vascular coverage in preterm infants	Low serum APN correlated with high glucose levels and delayed retinal vascularization	Fu et al., 2018a