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Fetal oxidative stress, micronutrient deficiency and risk of retinopathy of prematurity: a nested case-control study
Gopal Agrawal1, Sourabh Dutta2, Rajendra Prasad3
1Newborn Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.
Insights
Fetal oxidative stress and micronutrient deficiencies, including low vitamin A and zinc, are linked to retinopathy of prematurity (ROP) in preterm infants. High cord blood malondialdehyde (MDA) and low vitamin A independently predict ROP development.
Area of Science:
- Neonatology
- Ophthalmology
- Nutritional Science
Background:
- Retinopathy of prematurity (ROP) incidence is higher in developing nations.
- Micronutrient deficiencies are under-investigated risk factors for ROP.
- Previous studies linked ROP to postnatal oxidative stress and nutrient deficiencies, but not cord blood levels.
Purpose of the Study:
- To investigate the association between fetal oxidative stress and micronutrient status and the incidence of ROP.
- To identify specific biomarkers in maternal and cord blood that predict ROP development in preterm infants.
Main Methods:
- A nested case-control study included preterm infants (<37 weeks gestation).
- Maternal, cord, and neonatal serum/plasma samples were analyzed for malondialdehyde (MDA), copper, zinc, and vitamin A.
- Cases with ROP were matched with controls without ROP (1:4 ratio).
Main Results:
- Higher cord plasma MDA and lower cord plasma vitamin A were associated with ROP.
- Lower maternal serum copper and zinc, and lower cord serum zinc were observed in ROP cases.
- High cord blood MDA and low cord blood vitamin A were independent predictors of ROP.
Conclusions:
- Increased fetal oxidative stress and specific micronutrient deficiencies are associated with ROP.
- Cord blood MDA and vitamin A levels are significant predictors of ROP in preterm infants.
Abstract:
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.
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