Skin and Serum Carotenoids in Preterm Infants Fed on a Formula Supplemented With Carotenoids

Infants that are born prior to 37 weeks gestation often face complications resulting from their prematurity. Preterm infants are susceptible to morbidities that are not common in healthy term infants. Underdeveloped organs such as the lungs, eye, intestine, and brain can reveal conditions unique to prematurity: chronic lung disease, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis, intraventricular hemorrhage (IVH), etc. Infants in the Newborn Intensive Care Unit (NICU) have increased inflammation and oxidative stress in association with common diseases of prematurity and as well as the treatments used to combat their illnesses (Gitto et al 2004; Ochoa et al 2003; Saugstad 2003).

According to the National Eye Institute (U.S. National Institutes of Health), retinopathy of prematurity affects approximately 50% of preterm infants that are born weighing 1250 g or less. While 90% of infants with retinopathy of prematurity (ROP) experience the milder form of the disease, which requires little or no medical treatment, severe ROP can lead to serious visual impairments or even blindness. This condition is of particular interest since Hylander et al. (Hylander et al 2001) have reported that human milk feeding of preterm infants (<1500 g birth weight) has been associated with a lower incidence of ROP and this association was proposed to be driven by the antioxidant content of human milk. Human milk provides a variety of antioxidants to the breastfed infant, including the carotenoids lutein, zeaxanthin, lycopene, and beta-carotene. As discussed earlier, lutein and zeaxanthin are concentrated to the eye and are thought to provide protection against both light-induced and metabolic oxidative damage.

The retina and retinal vasculature are the last eye structures to develop in the human fetus/neonate. Eyes of children with a history of ROP are reported to have retinal thinning with diffuse hypopigmentation, mild linearization, or mild tortuosity of the major vessel branch, mottled pigmentation of the macula, and other peripheral retinal anomalies (Minicucci et al 1999). The lack of pigmentation in the retinal structure might be explained by the deficit of lutein acquired by the fetus (by placental transfer during late gestation) or by the neonate through the diet (by preterm infant formulas devoid of these carotenoids). Preterm infants are at a nutritional disadvantage at birth as they have been deprived of the period of maximal transfer of nutrients during the last few weeks of pregnancy. Blood levels of beta-carotene have been associated with gestational age (Ostrea et al 1986) and cord blood levels of beta-carotene (Herrera et al 2004; Kiely et al 1999; Yeum et al 1998), lutein (Kiely et al 1999), and lycopene (Herrera et al 2004; Kiely et al 1999) were reported to be significantly lower than maternal levels. Stores of fat-soluble antioxidant vitamins also could be compromised due to the minimal fat deposition in the preterm infant.

It is therefore reasonable to suggest that providing preterm infants with a milk-based ready-to-feed (RTF) preterm infant formula with DHA and ARA supplemented with carotenoids, which are found in human milk, would result in serum carotenoid levels more like the breastfed infant. Further, increased dietary carotenoid intake by preterm infants might decrease the prevalence of morbidities that are associated with prematurity, such as ROP, bronchopulmonary dysplasia (BPD), and intraventricular hemorrhage (IVH).