Does candidemia predict threshold retinopathy of prematurity in extremely low birth weight (<= 1000 g) neonates?

Background. Extreme prematurity is a risk factor for both candidemia and th reshold retinopathy of prematurity (ROP) and may confound the reported asso ciation between these conditions. Objective. To determine if candidemia is an independent risk factor for thr eshold ROP. Methods. A cohort study was conducted of infants weighing less than or equa l to 1000 g at birth using a prospectively maintained neonatal database. Th e study included infants admitted to the neonatal intensive care unit at le ss than or equal to 3 days of age between January 1, 1993 and December 31, 1997. We excluded infants not screened for ROP because they died, were disc harged, or transferred. Threshold ROP (ie, requiring ablative therapy withi n 72 hours of diagnosis) was defined by the criteria of the American Academ y of Pediatrics Section on Ophthalmology ROP subcommittee. Candidemia was d efined as Candida species growth from at least 1 blood culture. Cox proport ional hazards regression was used to determine independent risk factors for threshold ROP. Results. Six hundred fourteen infants weighing less than or equal to 1000 g at birth, of which 165 were excluded: 120 died before ROP screening, 40 we re admitted >3 days of age, and 5 were discharged or transferred before ROP screening. A total of 449 infants were included in the study; 58 (13%) dev eloped threshold ROP. Candidemia occurred in 58 (13%) infants before develo ping the worst stage of ROP. Candidemia occurred in 27 of 73 (37%) at 23 to 24 weeks' gestational age (GA), 25 of 197 (13%) at 25 to 26 weeks' GA, and 6 of 129 (5%) at 27 to 28 weeks' GA, 0 of 50 >28 weeks' GA. Similarly, thr eshold ROP occurred in 25 of 73 (34%) at 23 to 24 weeks' GA, 26 of 197 (13% ) at 25 to 26 weeks' GA, and 6 of 129 (5%) at 27 to 28 weeks' GA, and 1 of 50 (2%) >28 weeks' GA. Threshold ROP developed in 19 of 58 (33%) infants wi th a history of candidemia and 39 of 391 (10%) without candidemia. Proporti onal hazards analysis indicated that GA in weeks (hazard ratio = .75; 95% c onfidence interval [CI]: .61,.93) and non-black ethnicity (hazard ratio = 1 .8; 95% CI: 1.05, 3.08) were significantly associated with threshold ROP. A fter controlling for GA and other factors, candidemia did not remain signif icantly associated with threshold ROP (hazard ratio 5 1.6; 95% CI: .89, 2.8 9). Conclusion. Candidemia may not be an independent risk factor for threshold ROP in extremely low birth weight infants. The magnitude of the previously reported association between candidemia and threshold ROP (more than fivefo ld) is unlikely and much of the clinically observed association appears to be mediated by gestational age.