Bilirubin is a known antioxidant. We hypothesized that the degree of bilirubinemia is inversely associated with oxidative stress-mediated retinopathy of prematurity (ROP). A prospective study was performed to determine if bilirubinemia is associated with ROP in infants ≤ 29 wks' gestational age and birth weights ≤ 1000 g. Total serum bilirubin (TSB) levels were measured at least twice daily during the first week and at least daily during the second week to determine peak and mean TSB levels. The outcomes were the incidence and severity of ROP. Of 193 infants studied, 110 developed ROP: 53 had mild (stage 1 in zone 2 or 3); 31 had moderate (stage 2 in zone 2 or 3); and 26 had severe ROP ( ≥ stage 3 in any zone or any stage in zone 1). Mean TSB levels were associated with the severity (adjusted odds ratio [AOR] 0.68, 95% confidence interval [CI]:0.47-0.98, p = 0.04), but not with the incidence of ROP (AOR 0.81, 95% CI:0.52-1.27, p = 0.3). Peak TSB levels were also associated with the severity (AOR 0.71, 95% CI:0.52-0.96, p = 0.02), but not with the incidence of ROP (AOR 0.71, 95% CI:0.48-1.01, p = 0.07). Bilirubinemia may be protective against severity of ROP. Retinopathy of prematurity (ROP) is a disease mediated by oxidative stress. Increasing antioxidant status may decrease the incidence and severity of ROP. Bilirubin is a known antioxidant; however, findings from observational studies evaluating the role of bilirubinemia against the incidence and/or severity of ROP in premature infants are conflicting. Our findings from this prospective study suggests that bilirubinemia may be protective against the severity of ROP.
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