Fetal oxidative stress, micronutrient deficiency and risk of retinopathy of prematurity: a nested case-control study
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We hypothesized that fetal oxidative stress and micronutrient deficiencies contribute to higher incidence of retinopathy of prematurity (ROP) in developing countries. In a nested case-control study, preterm infants (< 37 weeks, < 1700 g) were included at birth and followed until 40 weeks post-menstrual age (PMA). Maternal, cord, and neonatal serum/plasma samples at 40 weeks PMA were frozen. Samples of "cases" with ROP and gestational age (GA) and birth weight-matched "controls" with no ROP (in 1:4 ratio) were thawed and analyzed. PRIMARY OUTCOME: MDA concentration in cord plasma. SECONDARY OUTCOMES: MDA in maternal and 40-week PMA plasma; copper, zinc, and vitamin A in maternal, cord, and 40-week PMA samples. Thirty-eight cases and 151 controls had a mean (SD) GA of 29.5 (1) and 29.9 (1) weeks respectively. Following were associated with ROP: higher MDA concentration in cord and 40-week PMA samples; lower copper and zinc in maternal serum; lower zinc and vitamin A in cord sample (all p < 0.05). MDA [adjusted OR (aOR) = 4.13 (95% CI 1.83-9.27)] and vitamin A [aOR = 0.09 (95% CI 0.02-0.4)] concentration in cord plasma and weight gain (g/kg/week) [aOR = 0.97 (0.95-0.99)] independently predicted ROP. CONCLUSION: Increased oxidative stress and deficiency of micronutrients from fetal life were associated with ROP. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry of India CTRI/REF/2014/12/008174. What is Known: • In developing countries, there is a higher incidence of retinopathy of prematurity (ROP), but micronutrient deficiencies have not been adequately investigated as risk factors. • Few observational studies have shown an association between ROP and postnatal increase in malondialdehyde (MDA) levels and deficiencies of antioxidant vitamins and minerals, but none in cord blood. What is New: • High MDA, low zinc, and low vitamin A levels in cord blood and low copper and zinc levels in maternal blood are associated with the development of ROP. • On multivariable analysis, high cord blood MDA and low cord blood vitamin A are independent predictors of ROP.