title: Does candidemia predict threshold retinopathy of prematurity in extremely low birth weight (</=1000 g) neonates?
abstract: BACKGROUND
  Extreme prematurity is a risk factor for both candidemia and threshold retinopathy of prematurity (ROP) and may confound the reported association between these conditions.
  
  
  OBJECTIVE
  To determine if candidemia is an independent risk factor for threshold ROP.
  
  
  METHODS
  A cohort study was conducted of infants weighing </=1000 g at birth using a prospectively maintained neonatal database. The study included infants admitted to the neonatal intensive care unit at </=3 days of age between January 1, 1993 and December 31, 1997. We excluded infants not screened for ROP because they died, were discharged, or transferred. Threshold ROP (ie, 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 1 blood culture. Cox proportional hazards regression was used to determine independent risk factors for threshold ROP.
  
  
  RESULTS
  Six hundred fourteen infants weighing </=1000 g at birth, of which 165 were excluded: 120 died before ROP screening, 40 were 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%) developed threshold ROP. Candidemia occurred in 58 (13%) infants before developing 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, threshold 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 with a history of candidemia and 39 of 391 (10%) without candidemia. Proportional hazards analysis indicated that GA in weeks (hazard ratio =.75; 95% confidence interval [CI]:. 61,.93) and non-black ethnicity (hazard ratio = 1.8; 95% CI: 1.05, 3. 08) were significantly associated with threshold ROP. After controlling for GA and other factors, candidemia did not remain significantly associated with threshold ROP (hazard ratio = 1.6; 95% CI:.89, 2.89).
  
  
  CONCLUSIONS
  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 fivefold) is unlikely and much of the clinically observed association appears to be mediated by gestational age.
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Children's Hospital of The King's Daughters, Norfolk, Virginia, USA. gkarlowi@chkd.com
authors.forename: M G
authors.initials: MG
authors.lastname: Karlowicz
authors.forename: P J
authors.initials: PJ
authors.lastname: Giannone
authors.forename: J
authors.initials: J
authors.lastname: Pestian
authors.forename: A L
authors.initials: AL
authors.lastname: Morrow
authors.forename: J
authors.initials: J
authors.lastname: Shults
mesh_terms: D002177:Candidiasis / Q000150:complications*; D015331:Cohort Studies; D005260:Female; D016469:Fungemia / Q000150:complications*; D006801:Humans; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D008297:Male; D011237:Predictive Value of Tests; D012178:Retinopathy of Prematurity / Q000382:microbiology*; D012307:Risk Factors; D012720:Severity of Illness Index