Does candidemia predict threshold retinopathy of prematurity in extremely low birth weight (≤ 1000G) neonates?

Background: Candidemia has been reported to be independently associated with threshold retinopathy of prematurity (ROP) in extremely low birth weight infants (Pediatrics 1998; 101:654). However, extreme prematurity is a risk factor for both candidemia and threshold ROP and may confound the apparent association between these conditions. Objective: To determine if candidemia is an independent risk factor for threshold ROP after controlling for extreme prematurity. Methods: A retrospective study was conducted of infants with birth weight ≤ 1000 g, who were admitted to the NICU ≤ 3 days of age between 1/1/93 and 12/31/97. Data on ROP, candidemia, gestational age (GA), and demographic factors were obtained from a neonatal registry that was maintained prospectively. We excluded infants who did not get ROP screening because they died, were discharged or transferred. Threshold ROP, i.e. requiring ablative therapy within 72 hours of diagnosis, was defined by the criteria of the American Academy of Pediatrics Section on Ophthalmology ROP subcommittee. Candidemia was defined as Candida species growth from at least one blood culture. Logistic regression was used to determine the impact on threshold ROP of GA, birth weight, ethnicity, chronic lung disease, 5 minute Apgar score, and history of candidemia. Results: Six hundred fourteen infants had birth weight ≤ 1000 g, of which 165 were excluded: 120 died before ROP screening, 40 were admitted >3 days of age, and 5 were discharged or transferred prior to ROP screening. A total of 449 infants were included in the study; 58 (13%) developed threshold ROP. Candidemia occurred in 58 (13%) infants prior to developing the worst stage of ROP. Candidemia occurred in 27 of 73 (37%) at 23-24 wk GA, 25 of 197 (13%) at 25-26 wk GA, and 6 of 129 (5%) at 27-28 wk GA, p<.0001. Threshold ROP developed in 19 of 58 (33%) infants with history of candidemia and 39 of 391 (10%) without candidemia (OR= 4.4; 95% CI: 2.3-8.3). Logistic regression analysis indicated that GA (OR= 0.6; 95% CI: 0.5-0.8, p<.005), non-black ethnicity (OR=1.9; 95%CI 1.1-3, p<.05), and candidemia (OR=2.3; 95% CI 1.1-4.7, p<.005) were significantly associated with threshold ROP. However, when the interaction of candidemia and GA was introduced into the model, GA and non-black ethnicity, only were significant. Conclusion: Our data suggest that the association between candidemia and threshold ROP is influenced by gestational age. More research is needed to determine if gestational age confounds or modifies the association between candidemia and threshold ROP.