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In pediatric age and particularly in newborn infants the drug efficacy and safety are influenced by the growth and development on drug Absorption, Distribution, Metabolism and Excretion (ADME). Thanks to the fast development of pharmacogenomics and pharmacogenetics, the drug therapy promises to be adapted to the genetic profile of the individual, reducing considerably the side effects of drugs and increasing their efficacy. Interindividual variability in drug response is well known in both adults and children. Such a variability is multifactorial considering both intrinsic and extrinsic factors. Drug distribution in the neonate is influenced by a variety of age-dependent factors as a total body water content and distribution variations, role of drug transporters, blood/tissue protein binding, blood and tissue pH and perfusion. The development of enzymes involved in human metabolism were classified in 3 categories: 1) those expressed during the whole or part of the fetal period, but silenced or expressed at low levels within 1-2 years after birth; 2) those expressed at relatively constant levels throughout fetal development, but increased to some extent postnatally; and 3) those whose onset of expression can occur in the third trimester, but substantial increase is noted in the first 1-2 years after birth. Besides this intrinsic aspects influencing pharmacokinetics during the neonatal period there are other important events such as inborn or acquired diseases, environment and finally pharmacogenetics and pharmacogenomics. Thousands of deaths every years are caused by fatal drug reactions; among the potential causes there are not only the severity of the disease being treated, drug interactions, nutritional status, renal and liver functions, but also the inherited differences in drug metabolism and genetic polymorphism. Adverse drug reactions (ADRs) among pediatric patients have been shown to be three times more frequent than in adults. On August 2010 The National Institute of Child Health and Human Development (NICHD) addressed patient safety issues in the NICU, recognizing that to understand and prevent adverse events, systematic research and education in safety issues needed. From all these concepts in terms of ADME, pharmacogenetics (relative to a single gene) and pharmacogenomics (relative to many genes) it is becoming more evident the perspective of the new concept of individualized medicine. The goal of this should be to identify which group of patients responds positively, which patients are nonresponders and who experiences adverse reaction for the same drug and dose. The interindividual variability in response to any drug is mostly dependent on DNA sequence variations across the human genome, the haplotype map (HAPMAP). At present there is still a big distance beween the knowledge in genetic and the practical application to model the drug profile to the genetic/genomic profile of the single patient. In the neonatal period the effects of growth in the pharmacodynamic, processes can help optimizing the dosa...

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Background Perinatal asphyxia is a major cause of mortality and morbidity in neonates: The aim of the present study was to investigate, by means of longitudinal assessment of urinary S100B, the effectiveness of hypothermia, in infants complicated by perinatal asphyxia and hypoxic-ischemic encephalopathy. Methods We performed a retrospective case-control study in 108 asphyxiated infants, admitted to nine tertiary departments for neonatal intensive care from January 2004 to July 2017, of whom 54 underwent hypothermia treatment and 54 did not. The concentrations of S100B protein in urine were measured using an immunoluminometric assay at first urination and 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120 h after birth. The results were correlated with the achievement of S100B levels within normal ranges at 72 h from hypothermia treatment. Routine laboratory parameters, longitudinal cerebral function monitoring, cerebral ultrasound and neurologic patterns were assessed according to standard protocols. Results Higher S100B concentrations were found in hypothermia-treated infants in both moderate (up to 12 h) and severe (up to 24 h) hypoxic-ischemic encephalopathy. S100B levels returned to normal ranges starting from 20 h of hypothermia treatment in moderate and from 36 h in severe hypoxic-ischemic encephalopathy. Conclusions The present results offer additional support to the usefulness of longitudinal neuro-biomarkers monitoring in asphyxiated infants treated by hypothermia. The pattern of S100B concentrations during hypothermia supports the need for further investigations aimed at reconsidering the time-window for patient recruitment and treatment, and the optimal duration of the cooling and rewarming phases of the hypothermia procedure.

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