Abstract:

Drug dosage in the perinatal period represents a continuous challenge for the neonatologist because of interindividual variability of drug metabolism. The human liver plays a central role in the uptake, transport, metabolism and excretion of the vast majority of xenobiotics and drugs. The protein products of human CYP3A account for the largest portion of CYP450 proteins in human liver. At least 50% of currently used drugs in neonatal intensive care units (NICUs) are substrates of CYP3A4 including antibiotics, antivirals, antifungals, immunomodulators, benzodiazepines, proton pump inhibitors, steroid hormones and acetaminophen. The variable CYP3A4 and CYP3A7 expression recently reported in neonatal liver suggests the existence of a marked interindividual variability in drug metabolism during the intrauterine and neonatal lives and, as a consequence, the need of an individualized tailored therapeutic approach in NICUs. The increased risk for adverse effects reported for some drugs in neonates could be related to pharmacokinetic peculiarities of the newborn liver. The fetal and neonatal liver in infants undergoing drug-induced liver injury (DILI) is always characterized by the overlapping between developmental and pathological changes, the differential diagnosis between these changes representing often a challenge for the pathologist. Data here reported clearly evidence the peculiarity of the histological examination of the newborn liver, as compared to the adult liver. In conclusion, the role of the pathologist in the interpretation of liver reactions to drugs may be relevant, only when supported by the dialogue with neonatologists. A deep knowledge of the events taking place during liver development at different gestational ages is necessary for a dedicated neonatal pathologist, in order to avoid misinterpretation of the histological changes related to liver development, giving them a pathological significance.

Keywords: