The Lutein and Zeaxanthin in Pregnancy (L-ZIP) study—carotenoid supplementation during pregnancy: ocular and systemic effects—study protocol for a randomized controlled trial

Author:

Addo Emmanuel KofiORCID,Gorusupudi ArunaORCID,Allman Susan,Bernstein Paul S.ORCID

Abstract

Abstract Background Lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ), collectively called the macular pigment (MP), are dietary carotenoids that preferentially localize in the macula of the human eye. MP protects the macula from photo-oxidative damage and enhances visual function. Inadequate maternal intake of carotenoids, coupled with the placental transfer of maternal carotenoids to support fetal brain and retina development, potentially put mothers at risk of depletion systemically and in their ocular tissues. Presently, maternal carotenoid status throughout pregnancy remains poorly characterized, and no prospective randomized controlled trial of L and Z supplementation via prenatal vitamins has assessed maternal and infants’ systemic and ocular carotenoid status during pregnancy. We hypothesize that prenatal maternal carotenoid supplementation will counteract maternal carotenoid depletion during pregnancy and will improve biomarkers of carotenoid status of both mothers and infants. Methods Lutein and Zeaxanthin in Pregnancy (L-ZIP) is a phase 2, single-center, prospective, double-masked, randomized active-controlled clinical trial conducted at the John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA. Participants consume a daily standard prenatal multivitamin with no added carotenoids and are randomized (1:1 allocation) to receive either a capsule containing 10 mg L and 2 mg Z in safflower oil (Carotenoid group) or a capsule containing only safflower oil with no added carotenoids (Control group) for a period of 6 to 8 months. Skin, serum, and ocular carotenoids are measured at every study visit (i.e., within the first trimester [baseline], second trimester, third trimester, and 0–2 weeks postpartum). Skin carotenoid assessment is by resonance Raman spectroscopy (RRS); serum carotenoid status is quantified using high-performance liquid chromatography (HPLC); and MP is measured with the dual-wavelength autofluorescence. Infants’ MP and foveal anatomy are assessed using RetCam retinal camera and Bioptigen SD-OCT, respectively. The primary outcomes are changes in maternal systemic and ocular carotenoid status during pregnancy. Discussion L-ZIP is the first prospective RCT to investigate maternal carotenoid status throughout pregnancy and to determine whether prenatal maternal carotenoid supplementation will offset maternal carotenoid depletion and improve biomarkers of maternal and infant’s carotenoid status. Findings from L-ZIP will strengthen recommendations regarding prenatal carotenoid supplementation and consequently inform policy decisions. Trial registration ClinicalTrials.gov NCT03750968. Registered on November 23, 2018

Funder

National Eye Institute

Research to Prevent Blindness

Publisher

Springer Science and Business Media LLC

Subject

Pharmacology (medical),Medicine (miscellaneous)

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