Oral propranolol for retinopathy of prematurity: risks, safety concerns, and perspectives.

OBJECTIVE: To evaluate safety and efficacy of oral propranolol administration in preterm newborns affected by an early phase of retinopathy of prematurity (ROP). STUDY DESIGN: Fifty-two preterm newborns with Stage 2 ROP were randomized to receive oral propranolol (0.25 or 0.5 mg/kg/6 hours) added to standard treatment or standard treatment alone. To evaluate safety of the treatment, hemodynamic and respiratory variables were continuously monitored, and blood samples were collected weekly to check for renal, liver, and metabolic balance. To evaluate efficacy of the treatment, the progression of the disease (number of laser treatments, number of bevacizumab treatments, and incidence of retinal detachment) was evaluated by serial ophthalmologic examinations, and plasma soluble E-selectin levels were measured weekly. RESULTS: Newborns treated with propranolol showed less progression to Stage 3 (risk ratio 0.52; 95% CI 0.47-0.58, relative reduction of risk 48%) or Stage 3 plus (relative risk 0.42 95% CI 0.31-0.58, relative reduction of risk 58%). The infants required fewer laser treatments and less need for rescue treatment with intravitreal bevacizumab (relative risk 0.48; 95% CI 0.29-0.79, relative reduction of risk 52 %), a 100% relative reduction of risk for progression to Stage 4. They also had significantly lower plasma soluble E-selectin levels. However, 5 of the 26 newborns treated with propranolol had serious adverse effects (hypotension, bradycardia), in conjunction with episodes of sepsis, anesthesia induction, or tracheal stimulation. CONCLUSION: This pilot study suggests that the administration of oral propranolol is effective in counteracting the progression of ROP but that safety is a concern.

Oral topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia: a safety study.

OBJECTIVE: To investigate whether topiramate associated with mild or deep hypothermia in asphyxiated term infants is safe in relation to the short-term outcome. STUDY DESIGN: We report on 27 consecutive asphyxiated newborns who were treated with whole body hypothermia and 27 additional consecutive newborns with hypothermia who were co-treated with oral topiramate, once a day for 3 consecutive days, at 2 different doses. RESULTS: Newborns were divided in 6 groups according to the depth of hypothermia and the association with higher or lower topiramate dosage. A statistical comparison of the groups identified some differences in biochemical and hemodynamic variables, but no adverse effects attributable to topiramate were detected. There were no statistically significant differences in the groups in short-term outcomes, survival rate at discharge, or incidence of pathologic brain magnetic resonance imaging. CONCLUSION: Although the number of newborns in this study was limited, the short-term outcome and the safety data appear to support the evaluation of topiramate in clinical trials to explore its possible additive neuroprotective action.

Fluconazole prophylaxis prevents invasive fungal infection in high-risk, very low birth weight infants.

OBJECTIVES: To evaluate the benefit of fluconazole prophylaxis in preventing invasive fungal infection in very low birth weight (VLBW) infants with central vascular access. STUDY DESIGN: A 3-year baseline period (1998 to 2000) was compared with a subsequent 3-year period (2001 to 2003) during which a different protocol for preventing invasive fungal infection was used. All infants with a birth weight < 1500 g and with central vascular access were eligible for the study. Fluconazole (Diflucan R) was administered for 28 days at a dose of 6 mg/kg every third day during the first week and daily after the first week. RESULTS: There were no significant differences between the baseline and the fluconazole groups in demographic characteristics or risk factors for fungal infection. Fungal infection developed in 9 of the infants in the baseline group and in none of those in the fluconazole group (P=.003). A trend of decreasing mortality rate between the 2 groups (12.6% vs 8.1%; P=.32) was observed but was not statistically significant. No adverse effects of fluconazole therapy were documented. CONCLUSIONS: Fluconazole prophylaxis appeared to be beneficial in preventing invasive fungal infection in VLBW infants.