Lutein and zeaxanthin for reducing morbidity and mortality in preterm infants

Lutein and zeaxanthin are nutrients with antioxidant properties found in the macula of the eye and brain tissue. They have been reported to play a role in reducing oxidative damage, especially in the eyes and possibly in other organ systems. Oxygen free radicals are one of the agents postulated to cause tissue damage in preterm infants, which leads to morbidities such as retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH), and necrotising enterocolitis (NEC). Supplementation with lutein and zeaxanthin may reduce oxidative damage, hence reducing morbidity and mortality in preterm infants.

To assess the effectiveness of lutein and zeaxanthin supplementation in reducing morbidity and mortality in preterm infants.

We conducted searches up to 17 December 2024 in CENTRAL, MEDLINE, Embase, and two trial registries. We also searched the reference lists of included studies, and related reviews and studies.

We included randomised controlled trials (RCTs), cluster-RCT, cross-over trials, and quasi-RCTs that compared lutein and zeaxanthin supplementation against placebo or no supplementation for preterm infants less than 37 completed weeks' postmenstrual age.

We used standard Cochrane methods. Our primary outcomes were the incidence of any stage of ROP, incidence of ROP stage 3 and above, incidence of visual impairment, and mortality assessed throughout the neonatal intensive care unit (NICU) stay. Secondary outcomes included the incidence of IVH, incidence of NEC, and any reported adverse effects. We used GRADE to assess the certainty of the evidence.

We included five studies (666 preterm infants) that compared lutein and zeaxanthin supplementation versus control (placebo or no supplementation). All five studies were conducted in high-income countries (Italy and the USA). We did not find any studies comparing lutein or zeaxanthin separately versus placebo or no supplementation. Most of the studies had a low risk of bias in most key domains, such as allocation concealment and blinding. The evidence suggests that lutein and zeaxanthin supplementation probably has little or no effect on ROP (any stage) when comparing infants who received lutein and zeaxanthin supplementation with those who did not (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.66 to 1.24; P = 0.53; I² = 0%; 4 studies, 532 infants; moderate-certainty evidence). Lutein and zeaxanthin supplementation probably reduces the incidence of ROP stage 3 and above (RR 0.49, 95% CI 0.29 to 0.81; P = 0.005; I² = 0%; 4 studies, 532 infants; moderate-certainty evidence). No studies assessed the incidence of visual impairment. Lutein and zeaxanthin supplementation may have little or no effect on mortality assessed throughout the NICU stay (RR 0.95, 95% CI 0.42 to 2.17; P = 0.91; I² = 0%; 4 studies, 470 infants; low-certainty evidence), incidence of IVH (all grades) (RR 0.87, 95% CI 0.44 to 1.75; P = 0.70; I² = 0%; 4 studies, 483 infants; low-certainty evidence), and incidence of NEC: Bell's stage II or greater (RR 0.87, 95% CI 0.43 to 1.76; P = 0.71; I² = 0%; 5 studies, 666 infants; low-certainty evidence). No adverse effects were reported in either group.

While supplementation with lutein and zeaxanthin from day one of life in preterm infants until discharge probably reduces the incidence of ROP stage 3 and above, it may have little or no effect on the incidence of ROP at any stage, IVH or NEC, or mortality assessed throughout the NICU stay. However, the pooled estimates for these outcomes may change with further rigorously conducted trials. There were no adverse effects reported.