The importance of biomarkers in neonatology M. Mussap a, * , A. Noto b , F. Cibecchini a , V. Fanos b a Department of Laboratory Medicine, IRCCS San Martino-IST, University Hospital, National Institute for Cancer Research, Genoa, Italy b Department of Pediatrics and Clinical Medicine, Section of Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, Azienda Mista and University of Cagliari, Cagliari, Italy Keywords: Acute-phase reactants Biomarker Metabolomics Necrotizing enterocolitis Neonatal sepsis Sepsis biomarkers Surrogate endpoint Translational medicine summary Despite a 35% decline in the mortality rate for infants aged <5 years over the past two decades, every year nearly 40% of all deaths in this age group occur in the neonatal period, defined as the first 28 days of life. New knowledge on molecular and biochemical pathways in neonatal diseases will lead to the discovery of new candidate biomarkers potentially useful in clinical practice. In the era of personalized medicine, biomarkers may play a strategic role in accelerating the decline in neonatal mortality by assessing the risk of developing neonatal diseases, by implementing tailored therapeutic treatment, and by predicting the clinical outcome. However, there is an urgent need to reduce the gap in translating newly acquired knowledge from bench to bedside. Traditional and candidate biomarkers for neonatal sepsis and necrotizing enterocolitis will be discussed in this review, such as C-reactive protein (CRP), procalcitonin (PCT), serum amyloid A (SAA), soluble form of CD14 subtype presepsin (sCD14-ST), lipolysaccharide binding protein (LBP), angiopoietins (Ang)-1 and -2, soluble form of triggering receptor expressed on myeloid cells (sTREM-1), soluble form of urokinase-type plasminogen activator receptor (suPAR), platelet-activating factor (PAF) and calprotectin. New frontiers in managing critically ill newborns may be opened by metabolomics, a diagnostic tool based on the recognition of metabolites contained in biological fluids. Metabolomics represents the passage from a descriptive science to a predictive science, having the potential to translate benchtop research to real clinical benefits. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction Neonatal mortality is increasingly important because the proportion of deaths of infants aged <5 years occurring during the neonatal period is increasing as the mortality for infants of this age group declines. 1 Despite a 35% decline in the mortality rate of infants aged <5 years over the past two decades, every year nearly 40% of all deaths of this age group occur in the first 28 days of life, 2 the neonatal period. In 2010, neonatal mortality was estimated to be 23 deaths per 1000 live births worldwide, equal to 3.06 million babies dying in the neonatal period. 3 Only 1% of neonatal deaths occur in high-income countries, corresponding to an average neonatal mortality rate of 4 per 1000 live births. Finally, 75% of all neonatal deaths occur within the first seven days of life and almost 33% of these babies die during the first 24 h of life. 4 Infections (pneumonia, diarrhea, and tetanus), asphyxia, and preterm birth, together account for nearly 80% of these deaths. 5 Deaths caused by preterm birth, asphyxia, and congenital defects occur predomi- nantly during the first week of life, whereas infections are the major cause of neonatal deaths thereafter. A relevant indirect cause of neonatal mortality is low- and very low birth weight (LBW and VLBW, respectively). Although globally only 16% of newborns have LBW, 60e80% of neonatal deaths occur in LBW infants. LBW is due to short gestation (preterm birth), intrauterine growth restriction (IUGR), or both. Globally, almost one-third of neonatal deaths are directly attributable to preterm birth. Consequently, a baby born with LBW, especially if preterm, is at much greater risk of dying or of becoming sick than other newborns. A great deal of effort in reducing neonatal mortality rate is focused on looking for new biochemical markers able to predict early the risk of developing neonatal acute diseases and to accu- rately monitor the course of the disease in acute critically ill newborns. Significant challenges arise in the discovery of clinically useful biomarkers: new knowledge on molecular and biochemical pathways in human diseases calls for renewed efforts in searching for biomarkers closely related to specific pathological processes or to a disease state with increasing sensitivity and specificity. In the era of personalized medicine, biomarkers are the essential tools for * Corresponding author. Department of Laboratory Medicine, IRCCS University Hospital San Martino-IST, National Institute for Cancer Research, Largo Rosanna Benzi 10, Genoa 16132, Italy. Tel.: þ39 (0) 105553191; fax: þ39 (0) 105556891. E-mail address: michele.mussap@hsanmartino.it (M. Mussap). Contents lists available at SciVerse ScienceDirect Seminars in Fetal & Neonatal Medicine journal homepage: www.elsevier.com/locate/siny 1744-165X/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.siny.2012.10.006 Seminars in Fetal & Neonatal Medicine xxx (2012) 1e9 Please cite this article in press as: Mussap M, et al., The importance of biomarkers in neonatology, Seminars in Fetal & Neonatal Medicine (2012), http://dx.doi.org/10.1016/j.siny.2012.10.006