The follow-up of the critical infant and benchmarking: the improvement of morbidity through the critical analysis of perinatal data

The improvement of peri-neonatal care has allowed a progressive drastic increase in the survival of high-risk preterm infants, i.e., very preterm or very low birth weight (VLBW) and extremely preterm or extremely low birth weight (ELBW) infants. However, the increased survival correlates with an almost stable incidence of disability as a result of the same prematurity, in particular for the lower gestational age (GA) groups. Furthermore, even infants born moderate and late preterm (32-36 weeks GA), although at a lower risk, are not exempt from clinical problems which also result in significant economic and social costs, considering the large number of these patients. In order to improve the short and long-term outcomes of these infants at risk, increasing attention in neonatology is focused on understanding the pathophysiological mechanisms underlying the prematurity-related diseases, and -at the same time- on the study of the individual diversification of these mechanisms. The concepts of fetal programming and developmental reprogramming represent the biological substrates that explain the importance of the mother-placenta-fetus/newborn triad in the realization of the long-term global health status and justify the interest in the development of a “precision neonatology”, that is, of personalized care solutions according to a tailored approach. The identification of the newborn at risk and its potential problems therefore represents a fundamental step for the implementation of follow-up programs for these newborns, and vice versa an adequate follow-up path allows, over time, the critical analysis of the pathophysiological mechanisms and the perinatal data feedback: both of them represent essential steps in the benchmarking process, which in turn contributes to the definition of individualized strategies for improving clinical and care performance. Throughout the diagnostic-care process that includes the identification of the newborn at risk, the individual risk stratification, the early diagnosis of pathology and the effects of any therapeutic intervention, biomarkers represent essential tools, such as those of oxidative stress (OS, that is critical for fetal programming and common denominator of many prematurity-related pathologies, called in fact “free radical related diseases of prematurity”) and the potential biomarkers identifiable through the modern approaches of metabolomics, “the new clinical chemistry” [Antonucci R. 2010]. With these objectives, the Ph.D. research project has therefore been articulated on various preliminary work fronts, which can open the way to research aimed at developing a precision neonatology in a continuous evolution. The present thesis aims to summarize and unify the evidence-based scientific knowledge extrapolated from the literature and that obtained through the personal studies carried out, especially in the more recent field of metabolomics. The following topics are therefore addressed and illustrated: a brief introduction on the evolution in neonatology and the role and importance of biomarkers between research and clinical practice (Chapter 1); the conditions that define neonatal risk, even those less known and in which the long-term risk is less striking but significantly impacts on social and health costs (Chapter 2); the critical review of the literature regarding biomarkers of oxidative stress, potential clinical biomarkers of diagnostic-prognostic utility in the preterm infant (Chapter 3); the possible preventive and antioxidant defense strategies in the newborn and the potential role of melatonin in preterm infants (Chapter 4); the application of metabolomics in neonatology between physiology and pathophysiology in the long-term follow-up of both full-term and preterm newborns (Chapter 5); finally, the conclusions and future perspectives of the research theme are briefly discussed, for a possible extension of the preliminary works presented through the project of the Ph.D. (Chapter 6).