The effect of early prophylactic L-carnitine supplementation on retinopathy of prematurity: a retrospective cohort study

Retinopathy of prematurity (ROP) is a common blinding eye disease in preterm infants. Energy-metabolism disturbance and oxidative stress represent key pathogenic mechanisms of ROP. L‑carnitine participates in fatty acid β‑oxidation and may improve energy metabolism and mitigate oxidative damage; nevertheless, its influence on ROP onset and progression remains unclear. This study aimed to explore the association between early prophylactic L-carnitine supplementation and ROP incidence among preterm infants, to provide real-world clinical evidence for ROP prevention. A retrospective cohort study was performed. Preterm infants meeting ROP screening criteria were enrolled and stratified into L-carnitine-exposed group ( n = 63) and non-exposed control group ( n = 204) according to whether early prophylactic L-carnitine supplementation was administered. Baseline demographic, clinical treatment and outcome data were collected. The primary outcomes were overall ROP incidence, Type 1 ROP and Type 2 ROP. Secondary neonatal complications were also compared. Subgroup and interaction analyses were conducted stratified by sex, gestational age and birth weight. Multivariate logistic regression was applied to evaluate factors associated with Type 2 ROP. Baseline characteristics were comparable between the two groups (all P > 0.05). Compared with the non-exposed group, the L-carnitine-exposed group showed lower overall ROP incidence (17.5% vs. 38.2%, P = 0.002), lower Type 2 ROP incidence (6.3% vs. 20.6%, P = 0.009), and lower blood-transfusion rate (49.2% vs. 66.2%, P = 0.015). No significant inter-group differences were observed for Type 1 ROP, sepsis, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage or periventricular leukomalacia (all P > 0.05). Subgroup interaction tests demonstrated significant interactions of gestational age and birth weight with the effect of L-carnitine on ROP (all P < 0.05); the potential protective association was more evident in infants with gestational age 30–32 weeks and birth weight ≥ 1500 g, while no significant interaction was found for sex ( P > 0.05). Multivariate logistic regression indicated that early L‑carnitine supplementation was independently associated with lower odds of Type 2 ROP (OR = 0.253, 95%CI = 0.085‑0.756, P = 0.014). Early prophylactic L-carnitine supplementation is associated with reduced risks of overall ROP and Type 2 ROP in preterm infants who meet ROP screening criteria, with no detectable association for Type 1 ROP. This observational association is modified by gestational age and birth weight. Causal inference cannot be drawn from this retrospective cohort. Large-scale prospective randomized controlled trials are warranted to confirm whether L-carnitine exerts genuine protective effects against ROP.