Efficacy of Intravenous Fluconazole Prophylaxis on Outcomes of Very-Low-Birth-Weight Infants Admitted to the Neonatal Intensive Care Unit: A Randomized Clinical Trial | ||
| Journal of Integrated Maternal and Pediatric Care | ||
| Articles in Press, Accepted Manuscript, Available Online from 16 September 2026 | ||
| Document Type: Original Article | ||
| Authors | ||
| Farzaneh Shakeri1; Seyed Reza Mirjalili* 2; Naeimeh Naserzadeh3; Mahmood Noorishadkam2; Mohamad Hosein Lookzadeh2; Arefeh Dehghani Tafti4; Mohammadtaha Nourishadkam5 | ||
| 1Student Research Committee, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran | ||
| 2Mother and Newborn Health Research Center, Comprehensive Research institute for Maternal and Child Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran | ||
| 3Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran | ||
| 4Department of Biostatistics and Epidemiology, Center for Healthcare Data Modeling, Shahid Sadoughi University of Medical Sciences, Yazd | ||
| 5University of Medicine and Pharmacy "Grigore T. Popa", Lasi, Romania | ||
| Abstract | ||
| Background: Invasive fungal infections (IFIs) cause significant morbidity and mortality in very-low-birth-weight (VLBW) infants, but the benefit of routine fluconazole prophylaxis in units with low baseline IFI rates is unclear. We evaluated the efficacy and safety of intravenous fluconazole prophylaxis on clinical outcomes of VLBW infants. Methods: In this randomized, open-label, controlled trial, 80 infants with birth weight <1500 g and gestational age ≥25 weeks admitted to a NICU in Yazd, Iran, were randomly assigned to intravenous fluconazole (3 mg/kg twice weekly for 4 weeks; n=40) or standard care (n=40). The primary outcome was IFI (positive blood culture at week 4). Secondary outcomes included respiratory, gastrointestinal, neurological, hematological, and mortality outcomes. Results: IFI occurred in one infant (2.5%) in the fluconazole group versus none in controls (P=1.000); the overall prevalence was 1.25%. In unadjusted comparisons, fluconazole was associated with higher bronchopulmonary dysplasia (40% vs. 17.5%, P=0.047), apnea (45% vs. 20%, P=0.031), necrotizing enterocolitis (40% vs. 17.5%, P=0.047), longer respiratory support (28.18 vs. 19.72 days, P=0.047), and third-week neutropenia (15% vs. 0%, P=0.026). However, fluconazole infants had lower gestational age (29.1 vs. 30.6 weeks; P=0.0036) and birth weight (1082 vs. 1222 g; P=0.0035). Mortality, intraventricular hemorrhage, retinopathy of prematurity, and length of stay did not differ. No hepatotoxicity occurred. Conclusion: In a NICU with low IFI prevalence (≤2%), routine fluconazole prophylaxis did not reduce infection. The unadjusted excess morbidity was confounded by baseline differences in gestational age and birth weight. These findings do not support routine prophylaxis in similar low-endemicity settings. | ||
| Keywords | ||
| Fluconazole; Antifungal Agents; Very Low Birth Weight Infant; Invasive Candidiasis; Intensive Care Units | ||
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