The importance of biomarkers in neonatology

Seminars in Fetal and Neonatal Medicine

Volumn 18, Issue 1, 2013, Pages 56-64

  Mussap, M ^a   Noto, A ^b   Cibecchini, F ^a   Fanos, V ^b  

^a UNIVERSITY OF GENOA   (Italy)

^b UNIVERSITY OF CAGLIARI   (Italy)

Author keywords

Acute phase reactants; Biomarker; Metabolomics; Necrotizing enterocolitis; Neonatal sepsis; Sepsis biomarkers; Surrogate endpoint; Translational medicine

Indexed keywords

ANGIOPOIETIN 1; ANGIOPOIETIN 2; BIOLOGICAL MARKER; C REACTIVE PROTEIN; CALGRANULIN; CD14 SUBTYPE PRESEPSIN; CLAUDIN 3; GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 6; INTERLEUKIN 8; LIPOPOLYSACCHARIDE BINDING PROTEIN; MANNOSE BINDING LECTIN; PROCALCITONIN; SERUM AMYLOID A; THROMBOCYTE ACTIVATING FACTOR; TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS 1; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UROKINASE RECEPTOR;

DIAGNOSTIC TEST; HUMAN; METABOLOMICS; NECROTIZING ENTEROCOLITIS; NEONATOLOGY; NEWBORN MORTALITY; NEWBORN SEPSIS; REVIEW;

BIOLOGICAL MARKERS; HUMANS; INFANT; INFANT, NEWBORN; INFANT, NEWBORN, DISEASES; SEPSIS;

EID: 84871932673     PISSN: 1744165X     EISSN: 18780946     Source Type: Journal    
DOI: 10.1016/j.siny.2012.10.006     Document Type: Review

References (130)

1. You D., Wardlaw T., Salama P., et al. Levels and trends in under-5 mortality, 1990-2008. Lancet 2011, 375(9709):100-103.
2. Countdown to 2015 decade report (2000-2010): taking stock of maternal, newborn and child survival 2010, World Health Organization, WHO, Geneva.
3. You D., Jones G., Wardlaw T. Levels and trends in child mortality: report 2011 2011, on behalf of the United Nations Inter-agency Group for Child Mortality Estimation, UNICEF.
4. Lawn J.E., Blencowe H., Pattinson R., et al. Stillbirths: Where? When? Why? How to make the data count?. Lancet 2011, 377(9775):1448-1463. Lancet's Stillbirths Series steering committee.
5. The global burden of disease: 2004 update 2008, World Health Organization, WHO, Geneva.
6. Biomarker and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001, 69:89-95. Biomarker Definitions Working Group.
7. World Health Organization (WHO). International programme on chemical safety. Biomarkers in risk assessment: validity and validation. 2001. Retrieved from http://www.inchem.org/documents/ehc/ehc/ehc222.htm.
8. Katz R. Biomarkers and surrogate markers: an FDA perspective. NeuroRx 2004, 1:189-195.
9. Wagner J.A. Strategic approach to fit-for-purpose biomarkers in drug development. Annu Rev Pharmacol Toxicol 2008, 48:631-651.
10. Strimbu K., Tavel J.A. What are biomarkers?. Curr Opin HIV AIDS 2010, 5:463-466.
11. Frakking F.N.J., Brouwer N., van Eijkelenburg N.K.A., et al. Low mannose-binding lectin (MBL) levels in neonates with pneumonia and sepsis. Clin Exp Immunol 2007, 150:255-262.
12. Zakynthinos S.G., Papanikolaou S., Theodoridis T., et al. Sepsis severity is the major determinant of circulating thrombopoietin levels in septic patients. Crit Care Med 2004, 32:1004-1010.
13. Food and Drug Administration Biomarker Qualification Review Team. Review of qualification data for biomarkers of nephrotoxicity submitted by the predictive safety testing consortium (FDA CDER, 21 February 2008). Rockville, MD: US FDA; 2008.
14. Warnock D.G., Peck C.C. A roadmap for biomarker qualification. Nat Biotechnol 2010, 28:444-445.
15. Pepe M.S., Feng Z., Janes H., et al. Pivotal evaluation of the accuracy of a biomarker used for classification or prediction: standards for study design. J Natl Cancer Inst 2008, 100:1432-1438.
16. Pepe M.S., Feng Z., Longton G., et al. Conditional estimation of sensitivity and specificity from a phase 2 biomarker study allowing early termination for futility. Stat Med 2009, 28:762-779.
17. Kesselheim A.S., Karlawish J. Biomarkers unbound - the Supreme Court's ruling on diagnostic-test patents. N Engl J Med 2012, 366:1-3.
18. Ransohoff D.F. How to improve reliability and efficiency of research about molecular markers: roles of phases, guidelines, and study design. J Clin Epidemiol 2007, 60:1205-1219.
19. Janes H., Pepe M.S., Bossuyt P.M., et al. Measuring the performance of markers for guiding treatment decisions. Ann Intern Med 2011, 154:253-259.
20. Olson S, Robinson S, Giffin R. Rapporteurs. Accelerating the development of biomarkers for drug safety: workshop summary. Institute of Medicine of the National Academies. Washington, DC: National Academies Press; 2009.
21. Zweig M.H., Campbell G. Receiver operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 1993, 39:561-577.
22. Obuchowski N.A., Lieber M.L., Wians F.H. ROC curves in clinical chemistry: uses, misuses, and possible solutions. Clin Chem 2004, 50:1118-1125.
23. Kattan M.W. Evaluating a new marker's predictive contribution. Clin Cancer Res 2004, 10:822-824.
24. Pepe M.S., Thompson M.L. Combining diagnostic test results to increase accuracy. Biostatistics 2000, 1:123-140.
25. Puntmann V.O. How-to guide on biomarkers: biomarker definitions, validation and applications with examples from cardiovascular disease. Postgrad Med J 2009, 85:538-545.
26. Avorn J., Kesselheim A.S. The NIH translational research center might trade public risk for private reward. Nat Med 2011, 17:1176.
27. Anonymous Translational research and experimental medicine in 2012. Editorial. Lancet 2012, 379(9810):1.
28. Price C.P. Evidence-based laboratory medicine: is it working in practice?. Clin Biochem Rev 2012, 33:13-19.
29. Furness P., Zimmern R., Wright C., et al. The evaluation of diagnostic laboratory tests and complex biomarkers: summary of a diagnostic summit 2008, Royal College of Pathologists, PHG Foundation, London.
30. Waikar S.S., Betensky R.A., Bonventre J.V. Creatinine as the gold standard for kidney injury biomarker studies?. Nephrol Dial Transplant 2009, 24:3263-3265.
31. Davis D., Evans M., Jadad A., et al. The case for knowledge translation: shortening the journey from evidence to effect. BMJ 2003, 327:33-35.
32. Zaidi A.K., Ganatra H.A., Syed S., et al. Effect of case management on neonatal mortality due to sepsis and pneumonia. BMC Public Health 2011, 11(Suppl. 3):s13.
33. Weston E.J., Pondo T., Lewis M.M., et al. The burden of invasive early-onset neonatal sepsis in the United States, 2005-2008. Pediatr Infect Dis J 2011, 30:937-941.
34. Russell J.A. Management of sepsis. N Engl J Med 2006, 355:1699-1713.
35. Ng P.C., Li K., Leung T.F., et al. Early prediction of sepsis-induced disseminated intravascular coagulation with interleukin-10, interleukin-6, and RANTES in preterm infants. Clin Chem 2006, 52:1181-1189.
36. Stoll B.J., Hansen N., Fanaroff A.A., et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002, 110:285-291.
37. Fanaroff A.A., Stoll B.J., Wright L.L., et al. Trends in neonatal morbidity and mortality for very low birthweight infants. Am J Obstet Gynecol 2007, 196:147.e1-147.e8.
38. Stoll B.J., Hansen N.I., Adams-Chapman I., et al. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA 2004, 292:2357-2365.
39. Mussap M., Molinari M.P., Senno E., et al. New diagnostic tools for neonatal sepsis: the role of a real-time polymerase chain reaction for the early detection and identification of bacterial and fungal species in blood samples. J Chemother 2007, 19:31-34.
40. Mussap M., Degrandi R., Cataldi L., et al. Biochemical markers for the early assessment of neonatal sepsis: the role of procalcitonin. J Chemother 2007, 19:35-38.
41. Standage S.W., Wong H.R. Biomarkers for pediatric sepsis and septic shock. Expert Rev Anti Infect Ther 2011, 9:71-79.
42. Hofer N., Zacharias E., Müller W., et al. An update on the use of C-reactive protein in early-onset neonatal sepsis: current insights and new tasks. Neonatology 2012, 102:25-36.
43. Vouloumanou E.K., Plessa E., Karageorgopoulos D.E., et al. Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis. Intensive Care Med 2011, 37:747-762.
44. Chiesa C., Natale F., Pascone R., et al. C reactive protein and procalcitonin: reference intervals for preterm and term newborns during the early neonatal period. Clin Chim Acta 2011, 412:1053-1059.
45. Spada S., Cuccu A., Mussap M., et al. Reliability of procalcitonin in neonatology. Experience in 59 preterm newborns. J Matern Fetal Neonatal Med 2009, 22(Suppl. 3):96-101.
46. Pizzini C., Mussap M., Plebani M., et al. C-Reactive protein and serum amyloid A protein in neonatal infections. Scand J Infect Dis 2000, 32:229-235.
47. Ng P.C., Li K., Wong R.P., et al. Proinflammatory and anti-inflammatory cytokine responses in preterm infants with systemic infections. Arch Dis Child Fetal Neonatal Ed 2003, 88:F209-F213.
48. Procianoy R.S., Silveira R.C. The role of sample collection timing on interleukin-6 levels in early-onset neonatal sepsis. J Pediatr (Rio J) 2004, 80:407-410.
49. Shirakawa K., Naitou K., Hirose J., et al. Presepsin (sCD14-ST): development and evaluation of one-step ELISA with a new standard that is similar to the form of presepsin in septic patients. Clin Chem Lab Med 2011, 49:937-939.
50. Shozushima T., Takahashi G., Matsumoto N., et al. Usefulness of presepsin (sCD14-ST) measurements as a marker for the diagnosis and severity of sepsis that satisfied diagnostic criteria of systemic inflammatory response syndrome. J Infect Chemother 2011, 17:764-769.
51. Ubenauf K.M., Krueger M., Henneke P., et al. Lipopolysaccharide binding protein is a potential marker for invasive bacterial infections in children. Pediatr Infect Dis J 2007, 26:159-162.
52. Zweigner J., Gramm H.J., Singer O.C., et al. High concentrations of lipopolysaccharide-binding protein in serum of patients with severe sepsis or septic shock inhibit the lipopolysaccharide response in human monocytes. Blood 2001, 98:3800-3808.
53. Opal S.M., Scannon P.J., Vincent J.L., et al. Relationship between plasma levels of lipopolysaccharide (LPS) and LPS-binding protein in patients with severe sepsis and septic shock. J Infect Dis 1999, 180:1584-1589.
54. Mussap M., Noto A., Fravega M., et al. Soluble CD14 subtype presepsin (sCD14-ST) and lipopolysaccharide binding protein (LBP) in neonatal sepsis: new clinical and analytical perspectives for two old biomarkers. J Matern Fetal Neonatal Med 2011, (Suppl. 2):12-14.
55. Maisonpierre P.C., Suri C., Jones P.F., et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 1997, 277(5322):55-60.
56. Spronk P.E., Zandstra D.F., Ince C. Bench-to-bedside review: sepsis is a disease of the microcirculation. Crit Care 2004, 8:462-468.
57. Shapiro N.I., Schuetz P., Yano K., et al. The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis. Crit Care 2010, 14:R182.
58. Thurston G., Rudge J.S., Ioffe E., et al. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 2000, 6:460-463.
59. Fiedler U., Reiss Y., Scharpfenecker M., et al. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med 2006, 12:235-239.
60. Tsigos S., Koutsilieris M., Papapetropoulos A. Angiopoietins in angiogenesis and beyond. Expert Opin Investig Drugs 2003, 12:933-941.
61. Roviezzo F., Tsigos S., Kotanidou A., et al. Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage. J Pharmacol Exp Ther 2005, 314:738-744.
62. Young Koh G., Kim I., Kwak H., et al. Biomedical significance of endothelial cell specific growth factor, angiopoietin. Exp Mol Med 2002, 34:1-11.
63. Alves B.E., Montalvao S.A., Aranha F.J., et al. Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia. BMC Infect Dis 2010, 10:143.
64. Mankhambo L.A., Banda D.L., Jeffers G., et al. The role of angiogenic factors in predicting clinical outcome in severe bacterial infection in Malawian children. Crit Care 2010, 14:R91.
65. Giuliano J.S., Lahni P.M., Harmon K., et al. Admission angiopoietin levels in children with septic shock. Shock 2007, 28:650-654.
66. Kranidioti H., Orfanos S.E., Vaki I., et al. Angiopoietin-2 is increased in septic shock: evidence for the existence of a circulating factor stimulating its release from human monocytes. Immunol Lett 2009, 125:65-71.
67. Colonna M. TREMs in the immune system and beyond. Nat Rev Immunol 2003, 3:1-9.
68. Gómez-Piña V., Martínez E., Fernández-Ruíz I., et al. Role of MMPs in orchestrating inflammatory response in human monocytes via a TREM-1-PI3K-NF-κB pathway. J Leukoc Biol 2012, 91:933-945.
69. Bouchon A., Facchetti F., Weigand M.A., et al. TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature 2001, 410:1103-1107.
70. Gibot S., Kolopp-Sarda M.N., Béné M.C., et al. Plasma level of a triggering receptor expressed on myeloid cells-1: its diagnostic accuracy in patients with suspected sepsis. Ann Intern Med 2004, 141:9-15.
71. Collins C.E., La D.T., Yang H.T., et al. Elevated synovial expression of triggering receptor expressed on myeloid cells 1 in patients with septic arthritis or rheumatoid arthritis. Ann Rheum Dis 2009, 68:1768-1774.
72. Determann R.M., Weisfelt M., de Gans J., et al. Soluble triggering receptor expressed on myeloid cells 1: a biomarker for bacterial meningitis. Intensive Care Med 2006, 32:1243-1247.
73. Miedema K.G., de Bont E.S., Elferink R.F., et al. The diagnostic value of CRP, IL-8, PCT, and sTREM-1 in the detection of bacterial infections in pediatric oncology patients with febrile neutropenia. Support Care Cancer 2011, 19:1593-1600.
74. Gibot S., Cravoisy A., Levy B., et al. Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia. N Engl J Med 2004, 350:451-458.
75. Derive M., Gibot S. Urine sTREM-1 assessment in diagnosing sepsis and sepsis-related acute kidney injury. Crit Care 2011, 15:1013.
76. Dimopoulou I., Orfanos S.E., Pelekanou A., et al. Serum of patients with septic shock stimulates the expression of Trem-1 on U937 monocytes. Inflamm Res 2009, 58:127-132.
77. Zhang J., She D., Feng D., et al. Dynamic changes of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) reflect sepsis severity and can predict prognosis: a prospective study. BMC Infect Dis 2011, 11:53.
78. May A.E., Kanse S.M., Lund L.R., et al. Urokinase receptor (CD87) regulates leukocyte recruitment via beta 2 integrins in vivo. J Exp Med 1998, 188:1029-1037.
79. Tarui T., Mazar A.P., Cines D.B., et al. Urokinase-type plasminogen activator receptor (CD87) is a ligand for integrins and mediates cell-cell interaction. J Biol Chem 2001, 276:3983-3990.
80. Huai Q., Mazar A.P., Kuo A., et al. Structure of human urokinase plasminogen activator in complex with its receptor. Science 2006, 311(5761):656-659.
81. Ragno P. The urokinase receptor: a ligand or a receptor? Story of a sociable molecule. Cell Mol Life Sci 2006, 63:1028-1037.
82. Huttunen R., Syrjanen J., Vuento R., et al. Plasma level of soluble urokinase-type plasminogen activator receptor as a predictor of disease severity and case fatality in patients with bacteraemia: a prospective cohort study. J Intern Med 2011, 270:32-40.
83. Ostergaard C., Benfield T., Lundgren J.D., et al. Soluble urokinase receptor is elevated in cerebrospinal fluid from patients with purulent meningitis and is associated with fatal outcome. Scand J Infect Dis 2004, 36:14-19.
84. Dekkers P.E.P., ten Hove T., te Velde A.A., et al. Upregulation of monocyte urokinase plasminogen activator receptor during human endotoxemia. Infect Immun 2000, 68:2156-2160.
85. Kofoed K., Andersen O., Kronborg G., et al. Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study. Crit Care 2007, 11:R38.
86. Yilmaz G., Mentese A., Kaya S., et al. The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in Crimean-Congo hemorrhagic fever. J Clin Virol 2011, 50:209-211.
87. Donadello K., Scolletta S., Covajes C., et al. suPAR as a prognostic biomarker in sepsis. BMC Med 2012, 10:2.
88. Ostrowski S.R., Ravn P., Hoyer-Hansen G., et al. Elevated levels of soluble urokinase receptor in serum from mycobacteria infected patients: still looking for a marker of treatment efficacy. Scand J Infect Dis 2006, 38:1028-1032.
89. Koch A., Voigt S., Kruschinski C., et al. Circulating soluble urokinase plasminogen activator receptor is stably elevated during the first week of treatment in the intensive care unit and predicts mortality in critically ill patients. Crit Care 2011, 15:R63.
90. Mizukami I.F., Faulkner N.E., Gyetko M.R., et al. Enzyme-linked immunoabsorbent assay detection of a soluble form of urokinase plasminogen activator receptor in vivo. Blood 1995, 86:203-211.
91. Stephens R.W., Pedersen A.N., Nielsen H.J., et al. ELISA determination of soluble urokinase receptor in blood from healthy donors and cancer patients. Clin Chem 1997, 43:1868-1876.
92. Pedersen A.N., Brünner N., Høyer-Hansen G., et al. Determination of the complex between urokinase and its type-1 inhibitor in plasma from healthy donors and breast cancer patients. Clin Chem 1999, 45:1206-1213.
93. Neu J., Walker A. Necrotizing enterocolitis. N Engl J Med 2011, 364:255-264.
94. Dorling J., Kempley S., Leaf A. Feeding growth restricted preterm infants with abnormal antenatal Doppler results. Arch Dis Child Fetal Neonatal Ed 2005, 90:359-363.
95. Guillet R., Stoll B.J., Cotten C.M., et al. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics 2006, 117:e137-e142.
96. Fitzgibbons S.C., Ching Y., Yu D., et al. Mortality of necrotizing enterocolitis expressed by birth weight categories. J Pediatr Surg 2009, 44:1072-1075.
97. Hintz S.R., Kendrick D.E., Stoll B.J., et al. Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics 2005, 115:696-703.
98. Hallstrom M., Koivisto A.M., Janas M., et al. Laboratory parameters predictive of developing necrotizing enterocolitis in infants born before 33 weeks of gestation. J Pediatr Surg 2006, 41:792-798.
99. Pourcyrous M., Korones S.B., Yang W., et al. C-reactive protein in the diagnosis, management, and prognosis of neonatal necrotizing enterocolitis. Pediatrics 2005, 116:1064-1069.
100. Rabinowitz S.S., Dzakpasu P., Piecuch S., et al. Platelet-activating factor in infants at risk for necrotizing enterocolitis. J Pediatr 2001, 138:81-86.
101. Thuijls G., Derikx J.P., van Wijck K., et al. Non-invasive markers for early diagnosis and determination of the severity of necrotizing enterocolitis. Ann Surg 2010, 251:1174-1180.
102. Carroccio A., Iacono G., Cottone M., et al. Diagnostic accuracy of fecal calprotectin assay in distinguishing organic causes of chronic diarrhea from irritable bowel syndrome: a prospective study in adults and children. Clin Chem 2003, 49:861-867.
103. Dale I., Fagerhol M.K., Naesgaard I. Purification and partial characterization of a highly immunogenic human leukocyte protein, the L1 antigen. Eur J Biochem 1983, 134:1-6.
104. Dale I., Brandtzaeg P., Fagerhol M.K., et al. Distribution of a new myelomonocytic antigen (L1) in human peripheral blood leukocytes. Immunofluorescence and immunoperoxidase staining features in comparison with lysozyme and lactoferrin. Am J Clin Pathol 1985, 84:24-34.
105. Carroll D., Corfield A., Spicer R., et al. Fecal calprotectin concentrations and diagnosis of necrotizing enterocolitis. Lancet 2003, 361:310-311.
106. Josefsson S., Bunn S.K., Domellöf M. Fecal calprotectin in very low birth weight infants. J Pediatr Gastroenterol Nutr 2007, 44:407-413.
107. Yang Q., Smith P.B., Goldberg R.N., et al. Dynamic change of fecal calprotectin in very low birth weight infants during the first month of life. Neonatology 2008, 94:267-271.
108. Zoppelli L., Güttel C., Bittrich H.J., et al. Fecal calprotectin concentrations in premature infants have a lower limit and show postnatal and gestational age dependence. Neonatology 2012, 102:68-74.
109. Nicholson J.K., Connelly J., Lindon J.C., et al. Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov 2002, 1:153-161.
110. Nicholson J.K., Lindon J.C. Systems biology: metabonomics. Nature 2008, 455(7216):1054-1056.
111. Atzori L., Xanthos T., Barberini L., et al. A metabolomic approach in an experimental model of hypoxia-reoxygenation in newborn piglets: urine predicts outcome. J Matern Fetal Neonatal Med 2010, 23(Suppl. 3):134-137.
112. Atzori L., Antonucci R., Barberini L., et al. Metabolomics: a new tool for the neonatologist. J Matern Fetal Neonatal Med 2009, 22(Suppl. 3):50-53.
113. Clayton T.A., Lindon J.C., Cloarec O., et al. Pharmaco-metabonomic phenotyping and personalized drug treatment. Nature 2006, 440(7087):1073-1077.
114. Lindon J.C., Holmes E., Nicholson J.K. Metabonomics techniques and applications to pharmaceutical research and development. Pharm Res 2006, 23:1075-1088.
115. Roberts R., Rodriguez W., Murphy D., et al. Pediatric drug labeling: improving the safety and efficacy of pediatric therapies. JAMA 2003, 290:905-911.
116. Mañalich R., Reyes L., Herrera M., et al. Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int 2000, 58:770-773.
117. Cuzzolin L., Fanos V., Pinna B., et al. Postnatal renal function in preterm newborns: a role of diseases, drugs and therapeutic interventions. Pediatr Nephrol 2006, 21:931-938.
118. Fanos V., Barberini L., Antonucci R., et al. Metabolomics in neonatology and pediatrics. Clin Biochem 2011, 44:452-454.
119. Antonucci R., Bassareo P., Zaffanello M., et al. Patent ductus arteriosus in the preterm infant: new insights into pathogenesis and clinical management. J Matern Fetal Neonatal Med 2010, 23(Suppl. 3):34-37.
120. Fanos V., Marcialis M.A., Bassareo P.P., et al. Renal safety of non steroidal anti inflammatory drugs (NSAIDs) in the pharmacologic treatment of patent ductus arteriosus. J Matern Fetal Neonatal Med 2011, 24(Suppl. 1):50-52.
121. Bassareo P.P., Fanos V., Crisafulli A., et al. Cardiovascular phenotype in extremely low birth weight infants: long-term consequences. J Matern Fetal Neonatal Med 2011, 24(Suppl. 2):4-6.
122. Diderholm B. Perinatal energy metabolism with reference to IUGR and SGA: studies in pregnant women and newborn infants. Indian J Med Res 2009, 130:612-617.
123. Pallotto E.K., Kilbride H.W. Perinatal outcome and later implications of intrauterine growth restriction. Clin Obstet Gynecol 2006, 49:257-269.
124. Rosso P., Winick M. Intrauterine growth retardation. A new systematic approach based on the clinical and biochemical characteristics of this condition. J Perinat Med 1974, 2:147-160.
125. Béringue F., Blondeau B., Castellotti M.C., et al. Endocrine pancreas development in growth-retarded human fetuses. Diabetes 2002, 51:385-391.
126. Laviola L., Perrini S., Belsanti G., et al. Intrauterine growth restriction in humans is associated with abnormalities in placental insulin-like growth factor signaling. Endocrinology 2005, 146:1498-1505.
127. Nissen P.M., Nebel C., Oksbjerg N., et al. Metabolomics reveals relationship between plasma inositols and birth weight: possible markers for fetal programming of type 2 diabetes. J Biomed Biotechnol 2011, pii:378268.
128. Regnault T.R.H., Teng C., de Vrijer B., et al. The tissue and plasma concentration of polyols and sugars in sheep intrauterine growth retardation. Exp Biol Med 2010, 235:999-1006.
129. Sanz-Cortés M., Figueras F., Bargalló N., et al. Abnormal brain microstructure and metabolism in small-for-gestational-age term fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 2010, 36:159-165.
130. Dessì A., Atzori L., Noto A., et al. Metabolomics in newborns with intrauterine growth retardation (IUGR): urine reveals markers of metabolic syndrome. J Matern Fetal Neonatal Med 2011, 24(Suppl. 2):35-39.