Ocular Effects of Prenatal Carotenoid Supplementation in the Mother and Her Child: The Lutein and Zeaxanthin in Pregnancy (L-ZIP) Randomized Trial - Report Number 2

Abstract

Purpose: Lutein (L) and zeaxanthin (Z) are xanthophyll carotenoids that have been promoted to enhance maternal health and infant visual and neurodevelopment. In this study, we determined the effects of prenatal L and Z supplementation on systemic and ocular carotenoid status in the mother and her newborn infant (NCT03750968). This report focuses on the ocular effects of prenatal carotenoid supplementation.

Design: A prospective randomized clinical trial with 47 subjects randomly assigned by 1:1 allocation to receive standard-of-care prenatal vitamins along with 10 mg L and 2 mg Z softgel (Carotenoid Group) or standard-of-care prenatal vitamins with a placebo softgel (Control Group) starting in the first trimester.

Subjects: We enrolled low-risk pregnancy subjects aged ≥18 years from the obstetrics and gynecology clinic of the University of Utah Hospital.

Methods: Maternal macular, skin, and serum carotenoid concentrations were measured using autofluorescence imaging, resonance Raman spectroscopy, and high-performance liquid chromatography, respectively. Infants' ocular carotenoids and retinal architecture were measured by blue light reflectance imaging and spectral-domain OCT, respectively.

Main outcome measures: Changes in maternal and infant macular pigment, skin, and serum carotenoid status over the study period. Differences in infants' retinal maturity indicators between the 2 study groups.

Results: Following supplementation, there was a statistically significant increase in maternal macular pigment optical volume (P < 0.001) in the Carotenoid Group relative to the Control Group at all study time points, and there was no detectable maternal ocular carotenoid depletion. Infant skin and serum carotenoids increased significantly in the Carotenoid Group compared with the Control Group. As exploratory endpoints, infants in the Carotenoid Group had a 20% increase in macular pigment optical density (P = 0.242) and more mature foveal parameters compared with those in the Control Group.

Conclusion: Prenatal carotenoid supplementation significantly increased maternal and infant systemic carotenoids and caused a pattern of increased infant ocular carotenoid status, which may benefit both mothers and their infants' ocular development and function. This study provides important data to design and power a future multicenter study of prenatal carotenoid supplementation in higher-risk pregnancies.

Financial disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Keywords: Infant foveal architecture; Infant ocular carotenoid status; Lutein and zeaxanthin in pregnancy; Ocular effects; Prenatal carotenoid supplementation.

Figure 2

Changes in maternal MPOV between the Carotenoid (n = 21) and the Control (n = 20) Groups over the study duration. There was a statistically significant difference between the Carotenoid and the Control Group at all study time points following study intervention initiation (∗, P < 0.001). Also, MPOV was significantly increased relative to T1 at the T2, T3, and PP visits (†, P < 0.001) in the Carotenoid Group, whereas within the Control Group, MPOV did not change significantly throughout pregnancy. Error bars represent 95% confidence interval. MPOV = macular pigment optical volume; PP = postpartum; T1 = first trimester/baseline; T2 = second trimester; T3 = third trimester.

Figure 6

Systemic and ocular carotenoid status in infants whose mothers were in the Carotenoid and the Control Group. Infant serum lutein + zeaxanthin and skin carotenoid status increased significantly in the Carotenoid Group relative to the Control Group (P < 0.0001). Infants in the Carotenoid Group had a 20% increase in MPOD (P = 0.242). For A, Control (n = 18) and Carotenoid (n = 19); B, Control (n = 20) and Carotenoid (n = 20); C, Control (n = 11) and Carotenoid (n = 12). MPOD = macular pigment optical density; RRU = resonance Raman units.

Figure 7

Infant’s retinal parameters (A) and the EZ grading (B). B, A retina with a complete EZ with a grade of 4 evidenced by the merging of nasal and temporal EZs at the center of the fovea. CFT = central foveal thickness; ELM = external limiting membrane; EZ = ellipsoid zone; FWHM = full width at half maximum; GCL = ganglion cell layer; ILM = inner limiting membrane; INL = inner nuclear layer; IPL = inner plexiform layer; ONL = outer nuclear layer; OPL = outer plexiform layer; NFL = nerve fiber layer; RPE = retinal pigment epithelium; SD-OCT = spectral-domain OCT.