Published online January 4, 2006
PEDIATRICS Vol. 117 No. 1 January 2006, pp. 84-92 (doi:10.1542/peds.2004-2292)
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Candidiasis (Moniliasis, Thrush)

Neonatal Candidiasis Among Extremely Low Birth Weight Infants: Risk Factors, Mortality Rates, and Neurodevelopmental Outcomes at 18 to 22 Months

Daniel K. Benjamin, Jr, MD, MPH, PhDa, Barbara J. Stoll, MDb, Avory A. Fanaroff, MB, BChc, Scott A. McDonald, MSd, William Oh, MDe, Rosemary D. Higgins, MDf, Shahnaz Duara, MDg, Kenneth Poole, PhDd, Abbot Laptook, MDe, Ronald Goldberg, MDa on behalf of the National Institute of Child Health and Human Development Neonatal Research Network

a Department of Pediatrics, Duke Clinical Research Institute, Duke University, Durham, North Carolina
b Department of Pediatrics, Emory University, Atlanta, Georgia
c Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland, Ohio
d Research Triangle Institute, Research Triangle Park, North Carolina
e Brown University, Rhode Island Hospital, Providence, Rhode Island
f National Institute of Child Health and Human Development, Bethesda, Maryland
g University of Miami, Jackson Memorial Hospital, Miami, Florida

BACKGROUND. Neonatal candidiasis is associated with substantial morbidity and mortality rates. Neurodevelopmental follow-up data for a large multicenter cohort have not been reported.

METHODS. Data were collected prospectively for neonates born at <1000 g at National Institute of Child Health and Human Development-sponsored Neonatal Research Network sites between September 1, 1998, and December 31, 2001. Uniform follow-up evaluations, including assessments of mental and motor development with the Bayley Scales of Infant Development II, were completed for all survivors at corrected ages of 18 to 22 months. We evaluated risk factors for the development of neonatal candidiasis, responses to antifungal therapy, and the association between candidiasis and subsequent morbidity and death.

RESULTS. The cohort consisted of 4579 infants; 320 of 4579 (7%) developed candidiasis; 307 of 320 had Candida isolated from blood, 27 of 320 had Candida isolated from cerebrospinal fluid, and 13 (48%) of 27 of those with meningitis had negative blood cultures. In multivariate analysis of risk factors on day of life 3, birth weight, cephalosporins, gender, and lack of enteral feeding were associated with development of candidiasis. After diagnosis, most neonates had multiple positive cultures despite antifungal therapy, and 10% of neonates had candidemia for ≥14 days. Death or neurodevelopmental impairment (NDI) was observed for 73% of extremely low birth weight infants who developed candidiasis. Death and NDI rates were greater for infants who had delayed removal or replacement of central catheters (>1 day after initiation of antifungal therapy), compared with infants whose catheters were removed or replaced promptly.

CONCLUSIONS. Blood cultures were negative for approximately one half of the infants with Candida meningitis. Persistent candidiasis was common. Delayed catheter removal was associated with increased death and NDI rates.

Key Words: candidiasis • meningitis • sensitivity • specificity • culture • premature infant

Abbreviations: CSF—cerebrospinal fluid • CI—confidence interval • DOL—day of life • EGA—estimated gestational age • ELBW—extremely low birth weight • IVH—intraventricular hemorrhage • NDI— neurodevelopmental impairment • MDI—Mental Developmental Index • OR—odds ratio • PDA—patent ductus arteriosus • PDI—Psychomotor Developmental Index

Accepted Mar 29, 2005.




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