The neurodevelopmental impact of
fentanyl given to preterm newborns for
pain control is still unknown. The aim of this study was to assess the neurodevelopmental impact of 2 regimens of
fentanyl administration by a prospective follow-up evaluation. In our previous multicenter, double-blind, randomized controlled trial, 131 mechanically ventilated newborns (gestational age ≤32 weeks) were randomized to
fentanyl (continuous infusion of
fentanyl + open label boluses of
fentanyl) or placebo (continuous infusion of placebo + open label boluses of
fentanyl). Infant development was evaluated using Griffiths Mental Developmental Scales (Griffiths, 1996) until 24 months of corrected age by trained psychologists who were not aware of the group allocation. 106/131 infants survived at discharge; 3 died after discharge, 25 were lost to follow-up (12 in the
fentanyl and 13 in the placebo group). Seventy-eight patients were evaluated at 2 years of corrected age. Children in the
fentanyl group, compared with those in the placebo group, obtained significantly lower Griffiths general developmental quotient (mean [SD]: 89.95 [13.64] vs 97.18 [12.72], P = 0.024) together with the scores on the eye-hand coordination (mean [SD]: 89.09 [12.13] vs 99.19 [13.19], P = 0.002) and performance skills (mean [SD]: 79.71 [15.80] vs 90.09 [15.28], P = 0.009) scales. After adjustment for clinical confounders (gestational age,
CRIB score, and sex) only eye-hand co-ordination was associated with
fentanyl infusion. This study demonstrates that continuous infusion of
fentanyl in very preterm infants, given at 1 mcg·kg·h during
mechanical ventilation, is associated with a significant decrease in eye and hand co-ordination skills. Longer follow-up is needed to evaluate the impact on future motor, cognitive, and behavioral functions.