Tamara van Donge

Ibuprofen-related maturational adverse events in ELBW neonates 159 8 Previous study showed that the half-life of amikacin in preterm neonates with a gestational age less than 31 weeks, who received either ibuprofen or placebo, was significantly higher in the patients who received ibuprofen (16.4 versus 14.2 h) in early neonatal life. 17 Similar results were also observed for amikacin clearance (0.36 versus 0.6 ml/kg/min), indicating that ibuprofen reduces the clearance of amikacin. Being aware of the fact that amikacin is eliminated completely by glomerular filtration, these findings can also be applied on the clearance of creatinine. 17 It has to be acknowledged that these data were generated in the first 3 days postnatal age (<72 hours after birth), and therefore the magnitude of this negative effect of ibuprofen exposure to the glomerular filtration cannot simply be extrapolated beyond this age. The current study confirmed that ibuprofen has a more pronounced effect on the serum creatinine concentrations (and glomerular filtration rate) when exposed during the first week of life as compared to later in neonatal life. Vieux et al. illustrated that among all drugs that are potentially nephrotoxic in very preterm infants, ibuprofen alone proved nephrotoxic (decrease in estimated glomerular filtration rate) for a one-month follow-up. 18 Besides the type of drug, the amount of administered drugs are as well of relevance, it has been shown that very low birth weight infants with acute kidney injury received more nephrotoxic drugs than those who did not, illustrated by Rhone et al. . 19 In contrast, long-term outcome data on renal function in young adolescence provided evidence that there is no persistent effect of ibuprofen exposure in former ELBW cases. 20 Observing a substantial increase of serum creatinine after birth for an ELBW neonate, could reflect a pathological condition associated with adverse drug reaction, rather than the immaturity of the kidney. Along the same line, the absence of a decline in serum creatinine concentrations during the postnatal period might reflect impaired glomerular filtration and thus diminished kidney function. Although this study is not focusing on acute kidney injury, it needs to be acknowledged that physiological maturational events (i.e. adaptation to extra-uterine life) early after birth result in changes in serum creatinine concentrations, irrespective of (acute) kidney injury. Therefore, we emphasize to incorporate annotations related to neonatal physiology in the definition of acute kidney injury. Furthermore, the recognition of drug toxicity signals in neonates, together with the extent of the adverse effect of ibuprofen also relates to the postnatal age. The small fluctuations that are being observed in creatinine concentrations and clearance can be identified as a limitation, albeit this study illustrates the impact of both maturational and non-maturational related effects, such as ibuprofen treatment on kidney function, which can help in recognizing an adverse drug reaction. In addition, the mechanism of