A Review of Adrenomedullin in Pediatric Patients: A Useful Biomarker
Abstract
:1. Introduction
2. Methods
3. Results
3.1. Adrenomedullin and Infection
3.1.1. Critically Ill Children and Septic Patients
3.1.2. Acute Appendicitis
3.1.3. Pneumonia
3.1.4. Pyelonephritis
3.1.5. Febrile Neutropenia
3.2. Cardiovascular Disease
3.2.1. Congenital Heart Disease
3.2.2. Cardiac Surgery
3.2.3. Fontan Procedure
3.2.4. Heart Failure and Dilated Cardiomyopathy
3.2.5. Postural Orthostatic Tachycardia Syndrome
3.3. Pulmonary Hypertension
3.4. Nephro-Urological Disease
3.5. Endocrine Pathology
3.6. Rheumatic Diseases
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
- Kitamura, K.; Kangawa, K.; Kawamoto, M.; Ichiki, Y.; Nakamura, S.; Matsuo, H.; Eto, T. Adrenomedullin: A novel hypotensive peptide isolated from human pheochromocytoma. Biochem. Biophys. Res. Commun. 1993, 192, 553–560. [Google Scholar] [CrossRef]
- Meeran, K.; O’Shea, D.; Upton, P.D.; Small, C.J.; Ghatei, M.A.; Byfield, P.H.; Bloom, S.R. Circulating Adrenomedullin Does Not Regulate Systemic Blood Pressure but Increases Plasma Prolactin after Intravenous Infusion in Humans: A Pharmacokinetic Study. J. Clin. Endocrinol. Metab. 1997, 82, 95–100. [Google Scholar] [CrossRef]
- Nishikimi, T.; Nakagawa, Y. Adrenomedullin as a Biomarker of Heart Failure. Heart Fail. Clin. 2018, 14, 49–55. [Google Scholar] [CrossRef]
- Struck, J.; Tao, C.; Morgenthaler, N.G.; Bergmann, A. Identification of an Adrenomedullin precursor fragment in plasma of sepsis patients. Peptides 2004, 25, 1369–1372. [Google Scholar] [CrossRef]
- Becker, K.L.; Nylen, E.S.; White, J.C.; Muller, B.; Snider, R.H., Jr. Procalcitonin and the Calcitonin Gene Family of Peptides in Inflammation, Infection, and Sepsis: A Journey from Calcitonin Back to Its Precursors. J. Clin. Endocrinol. Metab. 2004, 89, 1512–1525. [Google Scholar] [CrossRef] [Green Version]
- Linscheid, P.; Seboek, D.; Zulewski, H.; Keller, U.; Muller, B. Autocrine/paracrine role of inflammation-mediated calcitonin gene-related peptide and adrenomedullin expression in human adipose tissue. Endocrinology 2005, 146, 2699–2708. [Google Scholar] [CrossRef]
- Ichiki, Y.; Kitamura, K.; Kangawa, K.; Kawamoto, M.; Matsuo, H.; Eto, T. Distribution and characterization of immunoreactive adrenomedullin in human tissue and plasma. FEBS Lett. 1994, 338, 6–10. [Google Scholar] [CrossRef] [Green Version]
- Hinson, J.P.; Kapas, S.; Smith, D.M. Adrenomedullin, a Multifunctional Regulatory Peptide. Endocr. Rev. 2014, 21, 138–167. [Google Scholar]
- Eto, T. A review of the biological properties and clinical implications of adrenomedullin and proadrenomedullin N-terminal 20 peptide (PAMP), hypotensive and vasodilating peptides. Peptides 2001, 22, 1693–1711. [Google Scholar] [CrossRef]
- Samson, W.K. Adrenomedullin and the control of fluid and electrolyte homeostasis. Annu. Rev. Physiol. 1999, 61, 363–389. [Google Scholar] [CrossRef]
- Hirata, Y.; Mitaka, C.; Sato, K.; Nagura, T.; Tsunoda, Y.; Amaha, K.; Marumo, F. Increased circulating adrenomedullin, a novel vasodilatory peptide, in sepsis. J. Clin. Endocrinol. Metab. 1996, 81, 1449–1453. [Google Scholar]
- Pıo, R.; Martínez, A.; Unsworth, E.J.; Kowalak, J.A.; Bengoechea, J.A.; Zipfel, P.F.; Elsasser, T.H.; Cuttitta, F. Complement Factor H Is a Serum-binding Protein for Adrenomedullin, and the Resulting Complex Modulates the Bioactivities of Both Partners Complement Factor H Is a Serum-binding Protein for Adrenomedullin, and the Resultin. J. Biol. Chem. 2001, 276, 12292–12300. [Google Scholar] [CrossRef] [Green Version]
- Rey, C.; García-Hernández, I.; Concha, A.; Martínez-Camblor, P.; Botrán, M.; Medina, A.; Prieto, B.; López-Herce, J. Pro-adrenomedullin, pro-endothelin-1, procalcitonin, C-reactive protein and mortality risk in critically ill children: A prospective study. Crit. Care 2013, 17, R240. [Google Scholar] [CrossRef] [Green Version]
- Jordan, I.; Corniero, P.; Balaguer, M.; Ortiz, J.; Vila, D.; Velasco, J.; Cambra, F.J.; Esteban, E. Adrenomedullin is a useful biomarker for the prognosis of critically ill septic children. Biomark. Med. 2014, 8, 1065–1072. [Google Scholar] [CrossRef]
- Lan, J.; Zhang, Y.; Sun, Z.; Liu, W.; Zhang, C.; Lan, J.; Qian, L. ROC curve analysis of the significance of PCT combined with MR-proADM in the early diagnosis of childhood sepsis. Int. J. Clin. Exp. Med. 2019, 12, 9005–9010. [Google Scholar]
- Solé-Ribalta, A.; Bobillo-Pérez, S.; Valls, A.; Girona-Alarcón, M.; Launes, C.; Cambra, F.J.; Jordan, I.; Esteban, E. Diagnostic and prognostic value of procalcitonin and mid-regional pro-adrenomedullin in septic paediatric patients. Eur. J. Pediatr. 2020, 179, 1089–1096. [Google Scholar] [CrossRef]
- Míguez, C.; Souverbielle, C.T.; Haro, A.; Guerrero, G.; Pérez-Egido, L.; García-Gamiz, M.; Marañon, R. Evaluation of proadrenomedullin as a diagnostic or prognostic biomarker of acute appendicitis in children. Am. J. Emerg. Med. 2016, 34, 2298–2305. [Google Scholar] [CrossRef]
- Oikonomopoulou, N.; Míguez-Navarro, C.; Rivas-García, A.; Gamiz, M.G.; López-López, R.; Oliver-Sáez, P.; Riaño-Méndez, B.; Farfan-Orte, T.; Lobato-Salinas, Z.; Rúbies-Olives, J.; et al. Assessment of proadrenomedullin as diagnostic or prognostic biomarker of acute appendicitis in children with acute abdominal pain. Am. J. Emerg. Med. 2019, 37, 1289–1294. [Google Scholar] [CrossRef]
- Sánchez, M.S.; Hernández, J.C.; Hernández-Bou, S.; Teruel, G.C.; Rodríguez, J.V.; Cubells, C.L. Pro-adrenomedullin usefulness in the management of children with community- acquired pneumonia, a preliminar prospective observational study. BMC Res. Notes 2012, 5, 363. [Google Scholar] [CrossRef] [Green Version]
- Alcoba, G.; Manzano, S.; Lacroix, L.E.; Galetto-Lacour, A.; Gervaix, A. Proadrenomedullin and copeptin in pediatric pneumonia: A prospective diagnostic accuracy study. BMC Infect. Dis. 2015, 15, 347. [Google Scholar] [CrossRef] [Green Version]
- Esposito, S.; Di Gangi, M.; Cardinale, F.; Baraldi, E.; Corsini, I.; Da Dalt, L.; Tovo, P.A.; Correra, A.; Villani, A.; Sacco, O.; et al. Sensitivity and Specificity of Soluble Triggering Receptor Expressed on Myeloid Cells-1, Midregional Proatrial Natriuretic Peptide and Midregional Proadrenomedullin for Distinguishing Etiology and to Assess Severity in Community-Acquired Pneumonia. PLoS ONE 2016, 11, e0163262. [Google Scholar] [CrossRef]
- Korkmaz, M.F.; Güzel, A.; Açıkgöz, M.; Okuyucu, A.; Alaçam, H. Reliability of Pro-adrenomedullin and Interleukin 1β in Predicting Severity of Community-Acquired Pneumonia in Pediatric Patients. Ann. Clin. Lab. Sci. 2018, 48, 81–89. [Google Scholar]
- Dötsch, J.; Hänze, J.; Knüfer, V.; Steiss, J.O.; Dittrich, K.; Seidel, A.; Rascher, W. Increased urinary adrenomedullin excretion in children with urinary-tract infection. Nephrol. Dial. Transplant. 1998, 13, 1686–1689. [Google Scholar] [CrossRef] [Green Version]
- Kalman, S.; Buyan, N.; Yurekli, M.; Ozkaya, O.; Bakkaloglu, S.; Soylemezoglu, O. Plasma and urinary adrenomedullin levels in children with acute pyelonephritis. Nephrology 2005, 10, 487–490. [Google Scholar] [CrossRef]
- Sharifian, M.; Zand, R.E.; Ahmadi, M.; Ziaee, S.A.; Mohkam, M.; Dalirani, R.D.R.; Esfandiar, N. Urinary adrenomedullin level in children with acute pyelonephritis before and after treatment. Iran. J. Kidney Dis. 2013, 7, 277. [Google Scholar]
- Cetin, N.; Kiraz, Z.K.; Gencler, A. Serum Presepsin, Proadrenomedullin andTriggering Receptor Expressed on Myeloid Cells-1 (TREM-1) as Biomarkers for the Diagnosis of Acute Pyelonephritis. Indian Pediatr. 2020, 57, 715–718. [Google Scholar] [CrossRef]
- Penedo, R.P.; Lucas, M.R.; Walther, L.A.A.-S.; Benavent, A.T.; Losada, M.L.C.; Andrio, L.B.; Poves, A.B.R.; Campaña, M.B. MR-Proadrenomedullin as biomarker of renal damage in urinary tract infection in children. BMC Pediatr. 2021, 21, 292. [Google Scholar] [CrossRef]
- Demirkaya, M.; Tugcu, D.; Akcay, A.; Aydogan, G.; Akıcı, F.; Salcioglu, Z.; Ekmekci, H.; Sevinir, B.; Ekmekci, O.B. Adrenomedullin—A new marker in febrile neutropenia: Comparison with CRP and procalcitonin. Pediatr. Hematol. Oncol. 2015, 32, 482–489. [Google Scholar] [CrossRef]
- Kesik, V.; Ataş, E.; Kurt, Y.G.; Aydın, F.N.; Babacan, O.; Gülgün, M.; Korkmazer, N. Adrenomedullin predicts high risk and culture positivity in children with solid tumors suffering from neutropenic fever. J. Infect. Chemother. 2016, 22, 617–621. [Google Scholar] [CrossRef]
- Agnello, L.; Bivona, G.; Parisi, E.; Lucido, G.D.; Iacona, A.; Ciaccio, A.M.; Giglio, R.V.; Ziino, O.; Ciaccio, M. Presepsin and Midregional Proadrenomedullin in Pediatric Oncologic Patients with Febrile Neutropenia. Lab. Med. 2020, 51, 585–591. [Google Scholar] [CrossRef]
- Fawzi, M.; Omran, A.; Masood, B. Serum level of midregional fragment of proadrenomedullin as an early sepsis marker in severely neutropenic patients with hematologic malignancies. Egypt. J. Haematol. 2019, 44, 118–123. [Google Scholar] [CrossRef]
- Michels, M.; Djamiatun, K.; Faradz, S.M.; Koenders, M.M.; de Mast, Q.; van der Ven, A.J. High plasma mid-regional pro-adrenomedullin levels in children with severe dengue virus infections. J. Clin. Virol. 2011, 50, 8–12. [Google Scholar] [CrossRef] [PubMed]
- Benito, J.; Luaces-Cubells, C.; Mintegi, S.; Astobiza, E.; Martinez-Indart, L.; Valls-Lafont, A.; Garcia-Garcia, J.J. Lack of value of midregional pro-adrenomedullin and C-terminal pro-endothelin-1 for prediction of severe bacterial infections in infants with fever without a source. Eur. J. Pediatr. 2013, 172, 1441–1449. [Google Scholar] [CrossRef] [PubMed]
- Campaña, M.B.; Lucas, M.R.; Rincon, A.F.; Calvo, C.; Roldan, L.M.; Martinez, R.D.L.M. Mid-regional pro-adrenomedullin could be a biomarker of severity in bronchiolitis. Acta Paediatr. 2018, 107, 1467–1468. [Google Scholar] [CrossRef]
- Girona-Alarcon, M.; on behalf of the KIDS-Corona Study Group; Bobillo-Perez, S.; Sole-Ribalta, A.; Hernandez, L.; Guitart, C.; Suarez, R.; Balaguer, M.; Cambra, F.-J.; Jordan, I.; et al. The different manifestations of COVID-19 in adults and children: A cohort study in an intensive care unit. BMC Infect. Dis. 2021, 21, 87. [Google Scholar] [CrossRef]
- Yoshibayashi, M.; Kamiya, T.; Nishikimi, T.; Saito, Y.; Matsuo, H.; Kangawa, K. Elevated plasma levels of adrenomedullin in congenital cyanotic heart disease. Clin. Sci. 1999, 96, 543–547. [Google Scholar] [CrossRef]
- Watanabe, K.; Nishikimi, T.; Takamuro, M.; Yasuda, K.; Ishikawa, Y.; Tanabe, S.; Yamada, O.; Nagaya, N.; Matsuoka, H.; Kangawa, K.; et al. Two Molecular Forms of Adrenomedullin in Congenital Heart Disease. Pediatr. Cardiol. 2003, 24, 559–565. [Google Scholar] [CrossRef]
- Zhu, X.-B.; Wang, Y.-B.; Hao, F.-Z.; Zhang, Z.-H.; Chen, S.-J. Plasma levels of adrenomedullin in children with congenital heart disease. Zhongguo Dang Dai Er Ke Za Zhi 2006, 8, 90–92. [Google Scholar]
- Komai, H.; Naito, Y.; Fujiwara, K.; Noguchi, Y.; Nishimura, Y. Plasma adrenomedullin level after cardiopulmonary bypass. Perfusion 1998, 13, 334–337. [Google Scholar] [CrossRef]
- Szekely, L.; Vijay, P.; Sharp, T.; Bando, K.; Brown, J. Correlation of Plasma Adrenomedullin to Myocardial Preservation During Open-Heart Surgery. Pediatr. Cardiol. 2000, 21, 228–233. [Google Scholar] [CrossRef]
- Takeuchi, M.; Morita, K.; Iwasaki, T.; Toda, Y.; Oe, K.; Taga, N.; Hirakawa, M. Significance of adrenomedullin under cardiopulmonary bypass in children during surgery for congenital heart disease. Acta Med. Okayama 2001, 55, 245–252. [Google Scholar] [PubMed]
- Florio, P.; Abella, R.; Marinoni, E.; Di Iorio, R.; Letizia, C.; Meli, M.; De La Torre, T.; Petraglia, F.; Cazzaniga, A.; Giamberti, A.; et al. Adrenomedullin Blood Concentrations in Infants Subjected to Cardiopulmonary Bypass: Correlation with Monitoring Parameters and Prediction of Poor Neurological Outcome. Clin. Chem. 2008, 54, 202–206. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abella, R.; Satriano, A.; Frigiola, A.; Varrica, A.; Gavilanes, A.D.; Zimmermann, L.J.; Vles, H.J.; Florio, P.; Calevo, M.G.; Gazzolo, D. Adrenomedullin alterations related to cardiopulmonary bypass in infants with low cardiac output syndrome. J. Matern. Neonatal Med. 2012, 25, 2756–2761. [Google Scholar] [CrossRef] [PubMed]
- Arkader, R.; Malbouisson, L.M.; Del Negro, G.M.B.; Yamamoto, L.; Okay, T.S. Factors associated with hyperglycemia and low insulin levels in children undergoing cardiac surgery with cardiopulmonary bypass who received a single high dose of methylprednisolone. Clinics 2013, 68, 85–92. [Google Scholar] [CrossRef]
- Pérez-Navero, J.L.; de la Torre-Aguilar, M.J.; de la Rosa, I.I.; Gil-Campos, M.; Gómez-Guzmán, E.; Merino-Cejas, C.; Muñoz-Villanueva, M.C.; Llorente-Cantarero, F.J. Cardiac Biomarkers of Low Cardiac Output Syndrome in the Postoperative Period After Congenital Heart Disease Surgery in Children. Rev. Española Cardiol. 2017, 70, 267–274. [Google Scholar] [CrossRef]
- Pérez-Navero, J.L.; Merino-Cejas, C.; de la Rosa, I.I.; Jaraba-Caballero, S.; Frias-Perez, M.; Gómez-Guzmán, E.; Gil-Campos, M.; de la Torre-Aguilar, M.J. Evaluation of the vasoactive-inotropic score, mid-regional pro-adrenomedullin and cardiac troponin I as predictors of low cardiac output syndrome in children after congenital heart disease surgery. Med. Intensive 2018, 43, 329–336. [Google Scholar] [CrossRef]
- Bobillo-Perez, S.; Jordan, I.; Corniero, P.; Balaguer, M.; Sole-Ribalta, A.; Esteban, M.E.; Esteban, E.; Cambra, F.J. Prognostic value of biomarkers after cardiopulmonary bypass in pediatrics: The prospective PANCAP study. PLoS ONE 2019, 14, e0215690. [Google Scholar] [CrossRef]
- Bobillo-Perez, S.; Girona-Alarcon, M.; Corniero, P.; Sole-Ribalta, A.; Balaguer, M.; Esteban, E.; Valls, A.; Jordan, I.; Cambra, F.J. Pro-atrial natriuretic peptide and pro- adrenomedullin before cardiac surgery in children. Can we predict the future? PLoS ONE 2020, 15, e0236377. [Google Scholar]
- Hiramatsu, T.; Imai, Y.; Takanashi, Y.; Seo, K.; Terada, M.; Aoki, M.; Nakazawa, M. Time course of endothelin-1 and adrenomedullin after the Fontan procedure. Ann. Thorac. Surg. 1999, 68, 169–172. [Google Scholar] [CrossRef]
- Watanabe, K.; Nishikimi, T.; Takamuro, M.; Yasuda, K.; Ishikawa, Y.; Tanabe, S.; Yamada, O.; Yagihara, T.; Suga, S.; Kangawa, K.; et al. Possible role of adrenomedullin in the regulation of Fontan circulation: Mature form of plasma adrenomedullin is extracted in the lung in patients with Fontan procedure. Regul. Pept. 2007, 141, 129–134. [Google Scholar] [CrossRef]
- Kaiser, R.; Abdul-Khaliq, H.; Wilkens, H.; Herrmann, E.; Raedle-Hurst, T.M. Mid-regional pro-adrenomedullin: An indicator of the failing Fontan circuit in patients with univentricular hearts? Eur. J. Heart Fail. 2014, 16, 1082–1088. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kader, M.R.A.; Grace, B.D.M.; Badawi, N.E.S. Plasma levels of adrenomedullin and atrial natriuretic peptide in patients with congestive heart failure of various etiologies. Ital. J. Biochem. 2007, 56, 18–27. [Google Scholar]
- Hauser, J.; Demyanets, S.; Rusai, K.; Goritschan, C.; Weber, M.; Panesar, D.; Rindler, L.; Taylor, A.M.; Marculescu, R.; Burch, M.; et al. Diagnostic performance and reference values of novel biomarkers of paediatric heart failure. Heart 2016, 102, 1633–1639. [Google Scholar] [CrossRef]
- Balat, A.; Kılınç, M.; Cekmen, M.B.; Güler, E.; Yürekli, M.; Şahinöz, S.; Coşkun, Y. Adrenomedullin and total nitrite levels in children with acute rheumatic fever. Clin. Biochem. 2005, 38, 526–530. [Google Scholar] [CrossRef] [PubMed]
- Zhang, F.; Li, X.; Ochs, T.; Chen, L.; Liao, Y.; Tang, C.; Jin, H.; Du, J. Midregional Pro-Adrenomedullin as a Predictor for Therapeutic Response to Midodrine Hydrochloride in Children With Postural Orthostatic Tachycardia Syndrome. J. Am. Coll. Cardiol. 2012, 60, 315–320. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, H.; Zhang, F.; Wang, Y.; Liu, P.; Zhang, C.; Feng, X.; Du, J.; Jin, H. Predictive value of baseline plasma midregional fragment of pro-adrenomedullin level on long-term outcome of postural tachycardia syndrome children treated with midodrine hydrochloride. Zhonghua Xin Xue Guan Bing Za Zhi 2015, 43, 507–510. [Google Scholar]
- Wu, R.-Z.; Rong, X.; Ren, Y.; He, X.-X.; Xiang, R.-L. Heart rate variability, adrenomedullin and B-type natriuretic peptide before and after transcatheter closure in children with patent ductus arteriosus. Zhonghua Xin Xue Guan Bing Za Zhi 2010, 38, 334–336. [Google Scholar]
- Yoshibayashi, M.; Kamiya, T.; Kitamura, K.; Saito, Y.; Kangawa, K.; Nishikimi, T.; Matsuoka, H.; Eto, T.; Matsuo, H. Plasma Levels of Adrenomedullin in Primary and Secondary Pulmonary Hypertension in Patients <20 Years of Age. Am. J. Cardiol. 1997, 79, 1556–1558. [Google Scholar] [CrossRef]
- Vijay, P.; Szekely, L.; Sharp, T.G.; Miller, A.; Bando, K.; Brown, J.W. Adrenomedullin in patients at high risk for pulmonary hypertension. Ann. Thorac. Surg. 1998, 66, 500–504. [Google Scholar] [CrossRef]
- Nakayama, T.; Ishikita, T.; Matsuura, H.; Saji, T. Effects of long-term treatment with prostacyclin on plasma adrenomedullin in patients with primary pulmonary hypertension. J. Cardiol. 2001, 38, 263–271. [Google Scholar]
- Lu, H.; Chen, S.; Wang, H.; Cheng, P. Role of Adrenomedullin in Congenital Heart Disease Associated with Pulmonary Hypertension. FEBS Lett. 1994, 338, 6–10. [Google Scholar]
- Wang, T.; Li, S.-X.; Zhang, X.-Q.; Gu, X.-H.; Song, Y.; Zhang, G.; Wu, S.-M. Study on the effect of adrenomedulin and urotensin-II on pulmonary hypertension of patients with congenital heart disease. Zhonghua Yi Xue Za Zhi 2005, 85, 2691–2695. [Google Scholar] [PubMed]
- Balat, A.; Çekmen, M.; Yürekli, M.; Kutlu, O.; Islek, I.; Sönmezgöz, E.; Çakir, M.; Türköz, Y.; Yologlu, S. Adrenomedullin and nitrite levels in children with Bartter syndrome. Pediatr. Nephrol. 2000, 15, 266–270. [Google Scholar] [CrossRef] [PubMed]
- Balat, A.; Çekmen, M.; Yürekli, M.; Gülcan, H.; Kutlu, O.; Türköz, Y.; Yoloğlu, S. Adrenomedullin and nitrite levels in children with minimal change nephrotic syndrome. Pediatr. Nephrol. 2000, 15, 70–73. [Google Scholar] [CrossRef] [PubMed]
- Balat, A.; Çekmen, M.; Yürekli, M.; Gül, K.A.; Ozbek, E.; Korkut, M.; Tarakçioglu, M.; Şahinöz, S.; Anarat, A.; Tarakçıoğlu, M. Adrenomedullin and nitrite levels in children with primary nocturnal enuresis. Pediatr. Nephrol. 2002, 17, 620–624. [Google Scholar] [CrossRef]
- Balat, A.; Sarıca, K.; Çekmen, M.; Yürekli, M.; Yağcı, F.; Erbağcı, A. Adrenomedullin and nitric oxide in children with detrusor instability. Pediatr. Nephrol. 2003, 18, 422–425. [Google Scholar] [CrossRef]
- Kalman, S.; Buyan, N.; Yürekli, M.; Özkaya, O.; Bakkaloglu, S.; Söylemezoğlu, O. Plasma and urinary adrenomedullin levels in children with renal parenchymal scar and vesicoureteral reflux. Pediatr. Nephrol. 2005, 20, 1111–1115. [Google Scholar] [CrossRef]
- Del Ry, S.; Cabiati, M.; Bianchi, V.; Caponi, L.; Di Cecco, P.; Marchi, B.; Randazzo, E.; Caselli, C.; Prescimone, T.; Clerico, A. Mid-regional-pro-adrenomedullin plasma levels are increased in obese adolescents. Eur. J. Nutr. 2016, 55, 1255–1260. [Google Scholar] [CrossRef]
- Metwalley, K.A.; Farghaly, H.S.; Sherief, T. Plasma adrenomedullin level in children with obesity: Relationship to left ventricular function. World J. Pediatr. 2018, 14, 84–91. [Google Scholar] [CrossRef]
- El-Habashy, S.A.; Matter, R.M.; El-Hadidi, E.S.; Afifi, H.R. Plasma Adrenomedullin level in Egyptian children and Adolescents with type 1 diabetes mellitus: Relationship to microvascular complications. Diabetol. Metab. Syndr. 2010, 2, 12. [Google Scholar] [CrossRef] [Green Version]
- Semeran, K.; Pawłowski, P.; Lisowski, Ł.; Szczepaniak, I.; Wójtowicz, J.; Ławicki, S.; Bossowski, A. Plasma Levels of IL-17, VEGF, and Adrenomedullin and S-Cone Dysfunction of the Retina in Children and Adolescents without Signs of Retinopathy and with Varied Duration of Diabetes. Mediat. Inflamm. 2013, 2013, 274726. [Google Scholar] [CrossRef] [PubMed]
- Nishida, K.; Watanabe, K.; Echigo, S.; Mayumi, M.; Nishikimi, T. Increased plasma adrenomedullin levels in kawasaki disease with coronary artery involvement. Am. J. Med. 2001, 111, 165–166. [Google Scholar] [CrossRef]
- Islek, I.; Balat, A.; Muslu, A.; Sivasli, E. Adrenomedullin and total nitrite levels in children with Henoch-Schönlein purpura. Pediatr. Nephrol. 2003, 18, 1132–1137. [Google Scholar] [CrossRef] [PubMed]
- Balat, A.; Işlek, I.; Çekmen, M.; Yürekli, M.; Tekin, D.; Muslu, A.; Şahinöz, S. Adrenomedullin and total nitrite levels in children with familial Mediterranean fever. J. Paediatr. Child Health 2006, 42, 240–243. [Google Scholar] [CrossRef] [PubMed]
- Kalman, S.; Sakallioglu, O.; Dogru, I.; Gul, D.; Gok, F. Effect of Genotype on Plasma and Urinary Adrenomedullin Levels in Children with Familial Mediterranean Fever. Turk. Klin. J. Med. Sci. 2012, 32, 453–458. [Google Scholar] [CrossRef]
- Polat, A.; Saglam, C.; Kurt, Y.G.; Başbozkurt, G.; Sözeri, B.; Dursun, I.; Kasapçopur, O.; Peru, H.; Şimşek, D.; Gündüz, Z.; et al. Adrenomedullin levels in patients with Familial Mediterranean Fever: A long term follow-up. Pediatr. Rheumatol. 2014, 12, P242. [Google Scholar] [CrossRef] [Green Version]
- Özgür, B.G.; Aksu, H.; Yılmaz, M.; Demirkaya, S.K. The probable role of adrenomedullin and nitric oxide in childhood attention deficit hyperactivity disorder. Nord. J. Psychiatry 2017, 71, 521–524. [Google Scholar] [CrossRef]
- Zoroğlu, S.S.; Yürekli, M.; Meram, İ.; Söğüt, S.; Tutkun, H.; Yetkn, Ö.; Sivasli, E.; Savaş, H.A.; Yanik, M.; Herken, H.; et al. Pathophysiological role of nitric oxide and adrenomedullin in autism. Cell Biochem. Funct. 2002, 21, 55–60. [Google Scholar] [CrossRef]
- Kucukosmanoglu, E.; Keskin, O.; Karcin, M.; Cekmen, M.; Balat, A. Plasma adrenomedullin levels in children with asthma: Any relation with atopic dermatitis ? Allergol. Immunopathol. 2012, 40, 215–219. [Google Scholar] [CrossRef]
- Piccin, A.; Murphy, C.; Eakins, E.; Kunde, J.; Corvetta, D.; Di Pierro, A.; Negri, G.; Sainati, L.; Mahon, C.M.; Smith, O.P.; et al. Circulating microparticles, protein C, free protein S and endothelial vascular markers in children with sickle cell anaemia. J. Extracell. Vesicles 2015, 4, 28414. [Google Scholar] [CrossRef]
- Robertson, C.L.; Minamino, N.; Ruppel, R.A.; Kangawa, K.; Wisniewski, S.R.; Tsuji, T.; Janesko, K.L.; Ohta, H.; Adelson, P.D.; Marion, D.W.; et al. Increased Adrenomedullin in Cerebrospinal Fluid after Traumatic Brain Injury in Infants and Children. J. Neurotrauma 2001, 18, 861–868. [Google Scholar] [CrossRef] [PubMed]
- Pollack, M.M.; Patel, K.M.; Ruttimann, U.E. PRISM III An updated Pediatric Risk of Mortality score. Crit. Care Med. 2011, 26, 123–127. [Google Scholar]
- Graciano, A.L.; Balko, J.A.; Rahn, D.S.; Ahmad, N.; Giroir, B.P. The Pediatric Multiple Organ Dysfunction Score (P-MODS): Development and validation of an objective scale to measure the severity of multiple organ dysfunction in critically ill children*. Crit. Care Med. 2005, 33, 1484–1491. [Google Scholar] [CrossRef] [PubMed]
- Schlapbach, L.J.; Straney, L.; Bellomo, R.; MacLaren, G.; Pilcher, D. Prognostic accuracy of age-adapted SOFA, SIRS, PELOD-2, and qSOFA for in-hospital mortality among children with suspected infection admitted to the intensive care unit. Intensiv. Care Med. 2017, 44, 179–188. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Leteurtre, S.; Duhamel, A.; Salleron, J.; Grandbastien, B.; Lacroix, J.; Leclerc, F.; Groupe Francophone de Réanimation et d’Urgences Pédiatriques. PELOD-2: An update of the PEdiatric logistic organ dysfunction score. Crit. Care Med. 2013, 41, 1761–1773. [Google Scholar] [CrossRef]
- Christ-Crain, M.; Morgenthaler, N.G.; Struck, J.; Harbarth, S.; Bergmann, A.; Müller, B. Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: An observational study. Crit. Care 2005, 9, R816–R824. [Google Scholar] [CrossRef] [Green Version]
- Suberviola, B.; Castellanos-Ortega, A.; Ruiz, A.R.; Lopez-Hoyos, M.; Santibañez, M. Hospital mortality prognostication in sepsis using the new biomarkers suPAR and proADM in a single determination on ICU admission. Intensiv. Care Med. 2013, 39, 1945–1952. [Google Scholar] [CrossRef]
- Cavallazzi, R.; El-Kersh, K.; Abu-Atherah, E.; Singh, S.; Loke, Y.K.; Wiemken, T.; Ramirez, J. Midregional proadrenomedullin for prognosis in community-acquired pneumonia: A systematic review. Respir. Med. 2014, 108, 1569–1580. [Google Scholar] [CrossRef] [Green Version]
- Pereira, J.M.; Azevedo, A.; Basilio, C.; Sousa-Dias, C.; Mergulhao, P.; Paiva, J.A. Mid-regional proadrenomedullin: An early marker of response in critically ill patients with severe community-acquired pneumonia? Rev. Port. Pneumol. 2016, 22, 308–314. [Google Scholar] [CrossRef] [Green Version]
- Akpinar, S.; Rollas, K.; Alagoz, A.; Seğmen, F.; Sipit, T. Performance evaluation of MR-proadrenomedullin and other scoring systems in severe sepsis with pneumonia. J. Thorac. Dis. 2014, 6, 921–929. [Google Scholar]
- Ishimitsu, T.; Ono, H.; Minami, J.; Matsuoka, H. Pathophysiologic and therapeutic implications of adrenomedullin in cardiovascular disorders. Pharmacol. Ther. 2006, 111, 909–927. [Google Scholar] [CrossRef] [PubMed]
- Yanagawa, B.; Nagaya, N. Adrenomedullin: Molecular mechanisms and its role in cardiac disease Review Article. Amino Acids 2007, 32, 157–164. [Google Scholar] [CrossRef] [PubMed]
- Nishikimi, T.; Yoshihara, F.; Mori, Y.; Kangawa, K.; Matsuoka, H. Cardioprotective Effect of Adrenomedullin in Heart Failure. Hypertens. Res. 2003, 26, S121–S127. [Google Scholar] [CrossRef] [Green Version]
- Maisel, A.; Mueller, C.; Nowak, R.; Peacock, W.F.; Landsberg, J.W.; Ponikowski, P.; Mockel, M.; Hogan, C.; Wu, A.H.B.; Richards, M.; et al. Mid-Region Pro-Hormone Markers for Diagnosis and Prognosis in Acute Dyspnea Results From the BACH (Biomarkers in Acute Heart Failure) Trial. J. Am. Coll. Cardiol. 2010, 55, 2062–2076. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gegenhuber, A.; Struck, J.; Dieplinger, B.; Poelz, W.; Pacher, R.; Morgenthaler, N.G.; Bergmann, A.; Haltmayer, M.; Mueller, T. Comparative Evaluation of B-Type Natriuretic Peptide, Mid-Regional Pro-A-type Natriuretic Peptide, Mid-Regional Pro-Adrenomedullin, and Copeptin to Predict 1-Year Mortality in Patients With Acute Destabilized Heart Failure. J. Card. Fail. 2007, 13, 42–49. [Google Scholar] [CrossRef]
- Balat, A.; Yilmaz, K.; Kılınç, M.; Çekmen, M.; Yurekli, M.; Sahinoz, S. Adrenomedullin and Nitrite Levels in Children with Dilated Cardiomyopathy. Pediatr. Cardiol. 2003, 24, 381–385. [Google Scholar]
Study | Type of Study | Setting | Biomarkers Studied | Aim | Gold Standard | AUC | Cut-Off | Se | Sp | PPV/ NPV | Conclusion |
---|---|---|---|---|---|---|---|---|---|---|---|
Critically Ill Children | |||||||||||
Rey C. et al. (2013) [13] | P, O, MC (2PICU) | <18 yr n = 254 PICU patients | MR-proADM CT-proET-1 PCT CRP | To identify biomarkers that can be used as predictors of mortality risk. | PRISM III and PIM mortality risk scores, no. of organ failures | 0.866 0.922 | 0.79 nmol/L (scores) 0.77 nmol/L (organ failure) | 93 91 | 76 85 | 33.7/98.2 69.3/95.6 | MR-proADM appears to improve diagnostic accuracy for detecting patients with higher risk of mortality scores and more than one organ failure. |
Sepsis | |||||||||||
Jordan I. et al. (2014) [14] | P, O, SC | 9 d–13 yr n = 95 Septic PICU patients | MR-proADM PCT CRP | To determine MR-proADM’s prognostic usefulness. | Organ failure, PRISM III, and in-hospital mortality | 0.77 | 2.2 nmol/L (mortality risk) | 72.7 | 81 | 31/96.2 | MR-pro-ADM levels are good indicators of disease severity and show better reliability than PCT and CRP for predicting in-hospital mortality. |
Lan J. et al. (2019) [15] | CC, SC | 6–12 yr n = 139 (94 septic, 25 SIRS, 20 controls) | PCT MR-proADM | To evaluate the role of MR-proADM and PCT in the early diagnosis of childhood sepsis. | - | 0.869 | 3.46 mmol/L (sepsis diagnosis) | 85.11 | 71.1 | - | PCT and MR-proADM concentrations significantly increase as severity of sepsis worsens. The diagnostic effect of MR-proADM in children with sepsis was better than that of PCT. Their combined detection effect was better than either by itself. |
Solé-Ribalta A. et al. (2020) [16] | P, O, SC | <16 yr n = 75 Febrile patients with suspected sepsis | PCT MR-proADM | To evaluate the diagnostic, prognostic, and stratification potential of MR-proADM at the onset of fever. | Goldstein 2005 diagnostic criteria | 0.729 | 1.37 nmol/L (severe sepsis) | 79.4 | 50 | 79.4/50 | PCT appears to be superior to MR-proADM in diagnosing sepsis; MR-proADM in the early stage of sepsis could be a useful tool for the stratification of sepsis and the prediction of morbidity. |
Acute Appendicitis | |||||||||||
Míguez et al. (2016) [17] | P, O, SC | 3–16 yr n = 136 ED patients with suspicion of AA | CRP WBC and neutrophil count MR-proADM PAS score | To evaluate the usefulness of MR-proADM in diagnosing AA in children presenting with acute abdominal pain. | Histological confirmation on surgeon’s report | 0.75 | 0.34 nmol/L (to rule out AA diagnosis) | 93 | 46 | 45/93 | The performance of MR-proADM alone, while statistically significant, is not optimal. MR-proADM levels of <0.35 nmol/L in combination with low CRP seems useful for the identification of children with a low risk of AA. |
Oikonomopoulou et al. (2019) [18] | P, O, MC (6 ED) | <18 yr n = 285 ED patients with suspicion of AA | MR-proADM CRP WBC and neutrophil count | To investigate the utility of pro-ADM for diagnosing AA. | Histological confirmation on surgeon’s report | 0.66 | 0.35 nmol/L (to rule out AA diagnosis) | 92 | 32 | 43/88 | MR-proADM alone is not enough to diagnose AA early. The combination of low values of MR-proADM and CRP can help select children with a low risk of AA. |
Pneumonia | |||||||||||
Sardà M. et al. (2012) [19] | P, O, SC | <18 yr n = 50 ED patients admitted with CAP | pro-ADM | To determine the levels of pro-ADM in children with CAP and analyse the relationship between these levels and the patients’ prognosis. | Radiological imaging | The median level of pro-ADM was 1.0065 nmol/L (IQR 0.3715–7.2840) The patients presenting complications had higher levels of pro-ADM (2.3190 vs. 1.1758 nmol/L, p = 0.013). Specifically, the presence of pleural effusion was associated with higher levels of pro-ADM (2.9440 vs. 1.1373 nmol/L, p < 0.001). | Higher levels of pro-ADM at admission were related to a greater likelihood of complications during the hospital stay, especially pleural effusion. | ||||
Alcoba G. et al. (2015) [20] | P, O, MC (3 ED) | <16 yr n = 88 Presenting at ED with CAP | pro-ADM CoPEP | To assess the diagnostic accuracy of pro-ADM and CoPEP for predicting CAP complications in children. | Culture, chest X-ray | 0.72 | 0.16 nmol/L (complications) | 72.7 | 71.4 | 26.7/94.8 | Proadrenomedullin seems to be a reliable and readily available predictor for CAP complications. |
Esposito S. et al. (2016) [21] | P, O, MC (N = 11) | 4 mo-14 yr n = 433 Children hospitalised with CAP | sTREM-1 MR-proANP MR-proADM | To evaluate the diagnostic accuracy of biomarkers to distinguish bacterial from viral CAP and to identify severe cases of CAP. | Blood and respiratory samples, real-time PCR, chest X-ray, BTS criteria | 0.58 0.55 | 0.32 nmol/L (bacterial infection) 0.39 nmol/L (severe disease) | 78.0 51.4 | 35.7 66.1 | 59.8/57.0 7.5/34.7 | MR-proADM blood levels cannot be used to differentiate bacterial from viral diseases or to identify severe cases. |
Korkmaz M.F. et al. (2018) [22] | P, O, SC | 3 mo-18 yr n = 66 Children hospitalised with CAP | pro-ADM IL-1β | To investigate the value of Pro-ADM and IL-1β for severity assessment and outcome prediction in children with CAP. | Chest imaging, culture, Respiratory Clinical Score | - 1.00 | 1.75 nmol/L (complications) 4.95 nmol/L (high-severity group) | 90 100 | 66.6 92 | - 78.9/92.1 | Pro-ADM may offer additional risk/severity stratification in children with CAP and may be helpful in predicting the development of complications (need for PICU admission and intervention procedures). |
Pyelonephritis | |||||||||||
Dötsch J. et al. (1998) [23] | CC, SC | 2 w–8 yr n = 22 (11 patients with UTI, 11 controls) | Urine ADM | To investigate whether UTIs are associated with increased urine ADM excretion. | Culture | ADM levels in children with UTIs were significantly higher than in controls (0.6 ± 0.41 vs. 0.15 ± 0.14 ng/μmol creatinine p < 0.001) There was a significant correlation between WBC count and ADM in urine (r = 0.78, p < 0.001). | Urinary tract infections possibly promote increased ADM release from urinary tissue, although the mechanism is unclear. | ||||
Kalman S. et al. (2005) [24] | CC, SC | 6–18 mo n = 35 (19 patients with APN, 16 controls) | Plasma and urine ADM | To determine plasma and urine ADM levels in children with APN and compare the results with a control group. | Culture, DMSA | The plasma ADM levels were lower in APN patients than in the control group (p < 0.001). Urine ADM levels were higher in APN patients than in the control group (p < 0.001). The correlations between urine ADM levels and C-reactive protein and white blood cells were statistically significant. | Urine ADM may have a role in APN. The importance of plasma ADM in the pathogenesis of acute pyelonephritis remains to be determined. | ||||
Sharifian M. et al. (2013) [25] | CC, SC | 1 mo-10 yr n = 60 (31 with APN, 30 healthy controls) | Urine ADM | To evaluate the association between APN and urine ADM, as well as the effect of treatment on ADM levels. | DMSA | - | Urine ADM > 100 pg/dL (APN diagnosis) | 67.7 | 70 | 70/67.7 | This marker can be used for confirming the diagnosis and evaluating response to treatment in combination with other biomarkers. |
Cetin N. et al. (2020) [26] | CC, SC | 2–18 yr n = 82 (38 with APN, 24 with UTI, 20 healthy controls) | PSP pro-ADM TREM-1 | To investigate the diagnostic values of presepsin, pro-ADM, and TREM-1 levels in children with APN and lower UTI. | Culture, standard biomarkers (ESR, CRP, WBC) | 0.83 | 63.86 pg/mL (APN prediction) | - | - | 92.1/87.5 | Plasma pro-ADM could be a useful biomarker for the early diagnosis of acute pyelonephritis in children. |
Peñalver R. et al. (2021) [27] | P, O, SC | <16 yr n = 62 Patients diagnosed with fUTI at ED | Plasma and urine MR-proADM | To study the usefulness of MR-proADM as a biomarker of acute and chronic renal parenchyma damage in fUTI. | Culture, DMSA | 0.92 | 0.66 nmol/L (P-MR-proADM, for predicting RS) | 83.3 | 81.8 | - | P-MR-ProADM appears to have prognostic utility as a predictor of RS. |
Febrile Neutropoenia | |||||||||||
Demirkaya et al. (2015) [28] | P, O, SC | <18 yr 50 episodes of fever in 37 neutropenic oncology patients | ADM PCT CRP | To determine differences in serum ADM in febrile neutropoenia patient categories (CDI, FUO, MDI, sepsis). | Radiological imaging, cultures, clinical signs, Goldstein 2005 sepsis definitions | In the MDI group, ADM levels on day 3 were significantly higher than those in the CDI and FUO groups. | A correlation between serum adrenomedullin levels and the severity of febrile neutropoenia could not be demonstrated. Among adrenomedullin, CRP, and PCT, PCT demonstrates the highest correlation with the severity of infection. | ||||
Kesik V. et al. (2016) [29] | P, O, SC | 10 yr (1.66–16) * 36 febrile episodes in 14 neutropenic children with solid tumours | ADM | To evaluate the role of ADM in predicting the prognosis for patients with FN. | Culture Risk categories, as described by Alexander et al., 2002 | 0.76 0.628 | 263.5 ng/L (High-risk patients) 505.5 ng/L (Culture positivity) | 88 85.7 | 60 50 | 84.6/66.7 30/93 | ADM levels at admission were useful in identifying those at high risk and culture positivity in patients with solid tumours. |
Agnello L. et al. (2020) [30] | P, O, SC | 10 yr (0–17) * 36 febrile neutropenic episodes in 26 children being treated by oncology | PSP MR-proADM | To evaluate MR-proADM and PSP plasma levels and their kinetics in paediatric oncology patients with FN to assess their usefulness in the management of these patients. | Culture and clinical signs | 0.62 | . | - | - | - | MR-proADM had low diagnostic accuracy for blood culture positivity. |
Fawsi M.M. et al. (2021) [31] | P, O, SC | 1–15 yr 100 neutropenic patients due to hematologic malignancies | MR-proADM CRP | To assess the utility of MR-proADM as an early marker for sepsis in severely neutropenic patients with hematologic malignancies. | Culture, Goldstein 2005 sepsis criteria | 0.939 | 2.4 nmol/L (bacteraemia/sepsis discrimination) | 91.6 | 85.1 | 83.3/92.4 | MR-proADM is a promising early marker for sepsis in severely neutropenic young patients with hematologic malignancies. |
Other Infections | |||||||||||
Michels M. et al. (2011) [32] | CC, SC | <15 yr n = 88 (43 children with DHF, 28 children with DSS, 17 controls) | MR-proADM CoPEP | To determine the relationship of MR-proADM and CoPEP to outcomes and their potential as biomarkers of plasma leakage in children with DHF and DSS. | WHO criteria, low albumin, pleural effusion | Plasma MR-proADM concentrations were significantly higher in the DHF and DSS groups at enrolment than in the healthy controls. MR-proADM concentrations in the DHF group had decreased by day 2, remaining elevated in the DSS group. Inverse correlation between MR-proADM and serum albumin at enrolment. MR-proADM concentrations were positively correlated with the pleural effusion index at day 2. | MR-proADM may have a functional role in limiting endothelial hyperpermeability during DHF/DSS. MR-proADM may be a candidate biomarker to predict the development of DHF/DSS. | ||||
Benito, J. et al. (2013) [33] | P, O, MC (7 ED) | 1–36 mo n = 1035 ED well-appearing children with FWS | MR-proADM CT-pro-ET-1 | To assess the usefulness of MR-pro-ADM and CT-pro-ET-1 in predicting BI and IBI in well-appearing infants with FWS. | PCT | 0.59 0.63 | ≥0.6 nmol/L (predicting BI) 0.7 nmol/L (predicting IBI) | - - | - - | - - | The overall performance of MR-proADM as a diagnostic marker of BI and IBI is poor. |
Bueno-Campaña, M. et al. (2018) [34] | P, O, MC (N = 2) | < 6 mo n = 33 Children with bronchiolitis | MR-proADM | To explore the relationship between the need for respiratory support and MR-proADM. | - | Children who needed nasal cPAP or MV presented higher MR-proADM levels than the group that required just high-flow therapy or no extra support (p < 0.05). | MR-proADM could be a potential biomarker for the severity of acute bronchiolitis. | ||||
Girona-Alarcón, M. (2021) [35] | P, O, SC | Adults/children n = 24 (20 adults with ARDS, 4 children with MIS-C) | MR-proADM PCT CRP Troponins NT-proBNP | To describe the characteristics of the disease in each specific population and to analyse the differences between adults and children. | - | MR-proADM levels were higher in children than in adults: 1.72 vs. 0.78 nmol/L (p = 0.017). | MR-proADM use should be studied in larger samples, since it could be helpful to pinpoint the risk of MIS-C in children infected with COVID. |
Scheme | Type of Study | Setting | Biomarkers Studied | Aim | Gold Standard | AUC | Cut-Off | Se | Sp | PPV/ NPV | Conclusion |
Congenital Heart Disease | |||||||||||
Yoshibayashi M. et al. (1999) [36] | CC, SC | 0.8–18 yr n = 28 (16 cyanotic w/CHD, 12 KD patients as controls) | ADM | To investigate the pathophysiological significance of ADM in hypoxaemia caused by cyanotic CHD. | - | Patients with cyanotic CHD showed significantly higher concentrations of ADM and an increased uptake of adrenomedullin in the pulmonary circulation (compared to arterial-venous levels of ADM) was also detected. | ADM levels may function as a compensatory mechanism for hypoxaemia in cyanotic congenital heart disease. | ||||
Watanabe K. et al. (2003) [37] | CC, SC | 8.3 ± 7.2 yr * n = 89 82 children with CHD, 7 healthy controls | ADM-m ADM-Gly | To investigate the pathophysiological role of two forms of ADM, ADM-m and ADM-Gly, in CHD. | Echocardiography and cardiac catheterisation | Plasma ADM-m and ADM-Gly were examined in cyanotic CHD and intracardiac repair with PH. They were negatively correlated with SAsat and mixed venous oxygen saturation, and positively correlated with Rp. In the multiple regression analysis, SAsat and Rp were independently correlated with ADM. Venous ADM-m levels were significantly higher than arterial ADM-m levels. | ADM levels may play beneficial roles in reducing pulmonary arterial resistance or alleviating hypoxaemia in these patients. Results also suggest that the mature form is extracted in pulmonary circulation. | ||||
Zhu X.B. et al. (2006) [38] | CC, SC | n = 48 (42 children with CHD, 6 recovered KD patients as controls) | ADM | To investigate the pathophysiological role of ADM in CHD. | Echocardiography and cardiac catheterisation | Plasma ADM levels are increased in congenital heart disease with high pulmonary blood flow and hypertension or with cyanosis, p < 0.01. Plasma ADM levels are positively correlated with pulmonary vascular resistance (r = 0.406, p < 0.01). | Increased ADM levels may play a role in reducing the pulmonary arterial resistance and alleviating hypoxaemia in these patients. | ||||
Cardiovascular Surgery | |||||||||||
Komai H. et al. (1998) [39] | P, O, SC | 2–8 mo children n = 21
| ADM | To evaluate ADM in patients undergoing CPB as a marker of pulmonary vascular damage. | - | The plasma ADM level increased significantly after CPB in each group. The high pulmonary arterial flow group had significantly lower ADM levels before and after CPB compared to other groups. In this group, there was a significant negative correlation between pre-CPB mPAP and ADM levels after CPB. | ADM may provide information regarding CPB-induced endothelial damage. The difference in ADM production in the high pulmonary arterial flow group may have been a consequence of the pre-existing pulmonary damage in these patients. | ||||
Szekely L. et al. (2000) [40] | P, O, SC | 1–99 mo n = 19 Children undergoing surgical CHD repair | ADM | To study whether perioperative myocardial injury could be altered by the presence of ADM. | Troponin-I | Preoperative ADM levels in the group with little or no evidence of myocardial injury after the surgery were significantly greater than the groups with either moderate or severe injury. | Higher preoperative ADM levels are associated with lower levels of myocardial injury (as assessed by troponin-I release) during surgery for congenital heart defects. | ||||
Takeuchi M. et al. (2001) [41] | P, O, SC | 7 mo–6 yr n = 13 Children with CHD during CPB | ADM VP ANP BNP ALD | To elucidate the effects of ADM on fluid homeostasis during CPB. | - | ADM levels increased gradually, with a peak 60 min after CPB, and decreased 24 h after the operation. ADM levels were correlated with urine volume and with brain natriuretic peptide during CPB. | ADM plays an important role in fluid homeostasis during CBP, in cooperation with other hormones. | ||||
Florio P. et al. (2008) [42] | P, O, SC | 126 ± 110 d * n = 50 Infants with CHD undergoing CPB | ADM | To determine whether ADM measurement is useful for monitoring cerebral distress during CPB. | Neurological signs at physical examination using the Amiel–Tison test | 0.897 | 17.4 ng/L (predicting brain damage) | 100 | 73 | - | Infants who developed abnormal neurologic sequelae had significantly higher MCA PI values and lower ADM concentrations; thus, these indicators may be useful for the early identification of infants at risk for brain damage. |
Abella R. et al. (2012) [43] | P, O, SC | 0–9 mo n = 48 Children undergoing CPB | ADM | To investigate whether perioperative ADM levels can predict risk of LCOS. | Clinical/laboratory findings, inotropic score, cardiac death, echocardiography | 0.842 | 27 pg/L (predicting LCOS) | 100 | 64.1 | 39.1/100 | ADM might be, alone or in combination with standard parameters, a promising predictor of LCOS in infants subjected to open-heart surgery with CPB. |
Arkader R. et al. (2013) [44] | P, O, SC | 39 ± 16 mo * n = 19 Children undergoing CPB and receiving 30 mg/kg MP after anaesthesia | C-peptide CRP IL-6 ADM | To improve our understanding of the metabolic and inflammatory factors that are involved in glucose regulation in children after CPB. | - | The ADM levels before CPB were slightly higher than normal, and increases of 323% were observed on day 1 after CPB; levels returned to baseline on day 3. ADM was correlated to insulin variations and was an independent factor associated with lower insulin concentrations in the multiple regression model. | ADM may be a predictor of low insulin concentration after CPB. | ||||
Pérez-Navero J. et al. (2017) [45] | P, O, SC | 10 d–15 yr n = 117 Children after CPB | ANP BNP CoPEP MR-proADM cTn-I | To assess biomarkers as indicators of LCOS in children undergoing CPB. | Echocardiography (LVEF), PiCCO (CI), clinical and analytical criteria | 0.848 | 1.5 nmol/L 24 h post-CPB (predicting LCOS) | 88 | 66 | 50/93 | cTn-I at 2 h post-CPB and ADM at 24 h post-CPB were independent predictors of LCOS. |
Pérez-Navero J. et al. (2018) [46] | P, O, SC | 10 d–15 yr n = 117 Children after CPB | MR-proADM cTn-I | To determine the predictive value of IS, VIS, MR-proADM, and cTn-I for LCOS in children undergoing CPB. | Echocardiography (LVEF), PiCCO (CI), clinical and analytical criteria | 0.81 0.850 | Prediction model 1 (age, CPB > 120 min, VIS) Prediction model 2 (model 1 + cTn-I, MR-proADM) | 55.5 61.3 | 92.9 5.7 | 74.7/79.59 61.3/85.7 | The VIS score at 2 h post-CPB was identified as an independent early predictor of LCOS. This predictive value was not significantly increased when associated with cardiac biomarkers for LCOS. |
Bobillo-Pérez S. et al. (2019) [47] | P, O, SC | 1 mo–16 yr n = 111 Children after CPB | PCT MR-proADM pro-ANP | To assess the usefulness of PCT, pro-ADM, and pro-ANP as predictors of need for MV, inotropic support, and bacterial infection in patients after CPB. | - | 0.721 0.738 | 1.22 nmol/L immediately after CPB (predicting MV need) 1.01 nmol/L 24–36 h after CPB (predicting MV need) | 69.5 72.9 | 87 64.8 | 80.2/78.9 51.9/82.2 | Pro-ADM and pro-ANP are good predictors of need for MV and LOS after CPB. Procalcitonin is useful for predicting bacterial infection. |
Bobillo-Pérez S. et al. (2020) [48] | P, O, SC | 2.1 yr (0.6–6.6) ** n = 113 Children undergoing cardiac surgery | MRpro-ADM pro-ANP | To evaluate the utility of pro-ANP and pro-ADM levels prior to CPB for predicting the need for intensive post-CPB support. | - | 0.724 0.855 | pro-ADM for predicting increased respiratory support pro-ADM for predicting increased inotropic support | - | - | - | In the multivariable analysis, pro-ADM wasn’t identified as an independent predictor for increased need for respiratory or inotropic support. |
Fontan Surgery | |||||||||||
Hiramatsu T. et al. (1999) [49] | CC, SC | 1–14 yr n = 16 8 Fontan procedures, 8 biventric. repair with normal CVP | ET-1 ADM | To examine the time course of ET-1 and ADM and to explore their influence on pulmonary vascular tone. | Cardiac catheterisation | ET-1 and ADM increased after CPB in both groups. However, plasma ET-1 levels were significantly elevated and ADM levels were significantly lower at 6 and 24 h after CPB in the Fontan group when compared with the control group. | An imbalance between increased ET-1 and decreased ADM after CPB during the Fontan procedure induces vasoconstriction. | ||||
Watanabe K. et al. (2007) [50] | CC, SC | 1.4–22.6 yr n = 40 29 Fontan procedures, 11 recovered KD | ADM-m ADM-Gly ADM-T | To investigate the significance of molecular forms of ADM in patients after the Fontan procedure. | Follow-up cardiac catheterisation (period between the Fontan procedure and the examination was 5.8 ± 4.9 yr) | Fontan patients had significantly higher venous concentrations of ADM-T, ADM-Gly, and ADM-m than controls. There was a significant difference in ADM-m levels in the pulmonary artery and femoral artery. The venous concentration of ADM-m correlated negatively with cardiac output. | ADM may be involved in the regulation of pulmonary arterial tone following Fontan surgery. | ||||
Kaiser R. et al. (2014) [51] | CC, SC | 4–36 yr n = 65 53 after Fontan procedure, 12 healthy subjects | MR-proADM | To assess the utility of MR-proADM as a predictor of Fontan procedure failure. | Echocardiography, abdominal and pleural ultrasound, NYHA classification | 0.985 | >0.520 nmol/L (predicting Fontan failure) | 100 | 93.9 | 57.1/100 | Serial measurements of MR-proADM levels may help identify patients at risk for a failing Fontan circulation, especially when these exceed 0.520 nmol/L. |
Heart Failure | |||||||||||
Randa Abdel Kader M. et al. (2007) [52] | CC, SC | n = 84 38 adults w/CHF 21 children w/CHF 15 adult and 10 paediatric healthy controls | ADM ANP | To evaluate ADM and ANP in patients with CHF and investigate their relationship with haemodynamic variables. | NYHA functional classification, echocardiography | Plasma levels of ADM and ANP increased in adult and paediatric patients with CHF, irrespective of the cause. They were positively correlated with each other and negatively correlated with LVEF and FS. | ADM and ANP may be used to identify high-risk subjects for HF during more invasive procedures. | ||||
Hauser J. et al. (2016) [53] | CC, MC (N = 2) | 0–24 yr n = 203 114 patients w/HF, 89 controls | MR-proANP sST2 GDF-15 MR-proADM NT-proBNP | To assess the diagnostic utility of four novel biomarkers in paediatric HF. | Presence of HF symptoms, abnormal systolic ventricular function via MRI or echocardiography | ROC analysis showed poor accuracy for MR-proADM (AUC 0.61, 95% CI 0.48–0.69, p = 0.029). In a subset of patients with DCM, MR-proADM was associated with poor LV function, but showed poor accuracy for its diagnosis. | MR-proADM shows unsatisfactory diagnostic power. | ||||
Dilated Cardiomyopathy | |||||||||||
Kılınc M. et al. (2003) [54] | CC, SC | 5 mo–14 yr n = 21 11 DCM, 10 healthy controls | Plasma and urine ADM and NO | To determine plasma and urine AM and NO in children with idiopathic DCM and correlate these with other clinical and laboratory findings. | Echocardiography, signs and symptoms of DCM | Plasma and urine ADM levels were significantly lower than in the healthy controls. Plasma and urine ADM levels were negatively correlated with EF and FS. | Low ADM levels may be a bad prognostic factor for children with DCM in advanced stages. | ||||
Orthostatic Tachycardia | |||||||||||
Zhang F. et al. (2012) [55] | CC, SC | 7–14 yr n = 77 57 children with POTS, 20 healthy children as controls | MR-proADM | To explore the predictive value of MR-proADM in assessing the therapeutic efficacy of midodrine hydrochloride for children with POTS. | Symptom scoring and HUT/HUTT test | 0.879 | 61.5 pg/mL (predicting efficacy of midodrine hydrochloride) | 100 | 71.6 | -/- | MR-proADM can help guide midodrine hydrochloride therapy in the management of POTS in children, identifying those who will have a good response to the drug. |
Li H. et al. (2015) [56] | P, O, SC | 14.5 ± 4.5 yr * n = 53 children with POTS | MR-proADM | To explore the predictive value of baseline plasma MR-proADM for the long-term survival of children with POTS treated with midodrine hydrochloride. | Orthostatic intolerance symptom score and symptom-free survival | At the 60-month follow-up, patients with baseline MR-proADM of >61.5 ng/L had a significantly lower symptom score. At the 72-month follow-up, the symptom score was similar, while symptom-free survival was significantly higher if baseline MR-proADM was >61.5 ng/L. | The baseline plasma MR-proADM level is valuable for predicting the long-term survival of children with POTS treated with midodrine hydrochloride. | ||||
Transcatheter PDA Closure | |||||||||||
Wu R.Z. et al. (2010) [57] | CC, SC | n = 115 55 children w/transcatheter PDA closure, 60 normal children | ADM BNP | To observe changes in ADM and BNP before and after transcatheter closure in children with PDA. | - | Before transcatheter closure, concentrations of plasma ADM were significantly higher in patients with PDA compared to the control group. Plasma ADM was significantly reduced at day 3 and month 3 after transcatheter closure. | Plasma ADM levels decreased significantly after transcatheter closure in children with PDA. |
Study | Type of Study | Setting | Biomarkers Studied | Aim | Gold Standard | AUC | Cut-Off | Se | Sp | PPV/ NPV | Conclusion |
---|---|---|---|---|---|---|---|---|---|---|---|
Yoshibayashi M. et al. (1997) [58] | CC, SC | 9 mo–19 yr n = 51 25 C-PH, 10 P-PH, 16 no PH | ADM-LI | To elucidate the pathophysiological significance of ADM in PH. | Cardiac catheterisation | Plasma AM-LI concentrations in the C-PH group and the P-PH group were significantly higher than in the no PH group. There is a significant decrease in the plasma AM-LI concentration between the PA and PV. There is a significant correlation between plasma AM-LI in the PA and pulmonary artery pressure. | ADM may be involved in the cardiovascular regulation or homeostasis of pulmonary circulation in pulmonary hypertension. | ||||
Vijay P. et al. (1998) [59] | P, O, SC | 9 yr n = 30 Patients w/CHD | ADM ET-1 NO2 NO3 | To examine the influence of these biomarkers in the development of postoperative PH. | Cardiac catheterisation or echocardiography | ADM levels were significantly higher in LF groups compared to HF groups (p < 0.0001). Upon initiating CPB, ADM levels in the LF group declined from their preoperative value to a level similar to that seen in the HF group. The levels of ADM gradually increased during the first 12 h post-op in all groups (p ≤ 0.05) | ADM appears to affect baseline vascular tone in patients with intact endothelial function. | ||||
Nakayama, T. (2001) [60] | P, O, SC | 12 ± 4 yr * n = 17 Children w/P-PH | ANP BNP ET-1 ADM | To investigate whether plasma levels of ADM are useful for assessing the severity of P-PH. | NYHA classification, pulmonary haemodynamics, and 6 min. walk test | ADM significantly decreased at 1 month and at 3 months. There was a significant relationship between the changes in adrenomedullin at 3 months compared to values upon initiating PGI2 therapy and the changes in mean pulmonary arterial pressure. | ADM was valuable for evaluating both cardiac performance and pulmonary haemodynamics after long-term treatment with PGI2 in patients with primary pulmonary hypertension. | ||||
Lu H. et al. (2003) [61] | CC, SC | 2 mo–16 yr n = 48 33 patients w/CHD, 15 healthy children | ADM ET-1 NO | To investigate their role in CHD with PH. | - | Plasma ADM levels were significantly higher in patients with CHD than in the control group (p < 0.05) and increased significantly as PH severity increased from non-PH to mild to moderate-severe (p < 0.05, p < 0.01). On the 7th day after CPB, plasma ADM levels in the PH group were significantly decreased in comparison with those before the operation. Plasma ADM levels in CHD were positively correlated with PASP. | ADM may play an important role in the development of PH in patients with CHD. ADM may be involved in the defence mechanism against further increases in pulmonary arterial pressure. | ||||
Wang, T. (2005) [62] | P, O, SC | n = 52 children with CHD | ADM UII | To evaluate the effects and clinical significance of ADM and UII as regards PH. | - | As pulmonary hypertension increases in severity, the plasma levels of ADM increase. There is a positive correlation between PSAP and plasma ADM levels. Plasma levels of ADM in each group after CPB is lower than that of each group before the operation. | Measuring the levels of ADM may be a reliable method to monitor changes in pulmonary pressure and the worsening of pulmonary hypertension. |
Study | Type of Study | Setting | Biomarkers Studied | Aim | Gold Standard | AUC | Cut-Off | Se | Sp | PPV/ NPV | Conclusion |
---|---|---|---|---|---|---|---|---|---|---|---|
Balat et al. (2000) [63] | CC, SC | 6 mo–10 yr n = 25 10 w/Bartter syndrome, 5 w/pseudo-Bartter, 10 healthy controls | Urine and plasma total nitrite and ADM | To verify whether NO and ADM play a role in the reduced vascular response seen in Bartter syndrome. | - | Plasma ADM levels were higher in those with Bartter syndrome than in the other groups (p > 0.05). Urine ADM was increased in children with Bartter syndrome and pseudo-Bartter syndrome as compared with healthy controls during the pre-treatment period (p < 0.05) and in Bartter syndrome compared to pseudo-Bartter syndrome after 6 month of therapy (p < 0.05). | The increased production of ADM may have a role in the reduced vascular response seen in Bartter syndrome. | ||||
Balat A. et al. (2000) [64] | CC, SC | 2–10 yr n = 23 13 w/clinical MCNS, 10 healthy controls | Urinary and plasma total nitrite and ADM | To study plasma and urine ADM and NO concentrations in children w/MCNS during relapse and remission. | Clinical criteria | Plasma ADM concentrations during relapse were significantly lower than in remission and controls, and urine ADM levels were significantly higher in relapse than in remission and controls. | The important changes in plasma and urine ADM levels in relapse suggested that these changes may be compensatory when the body experiences severe proteinuria. | ||||
Balat A. et al. (2002) [65] | CC, SC | 8.05 ± 1.61 yr * n = 41 30 children w/PNE, 18 healthy controls | Urinary and plasma total nitrite and ADM | To investigate if plasma and urine ADM and nitrite levels are altered in children with PNE. | Clinical criteria | Plasma and urine ADM levels were significantly lower in children with PNE than in controls (p < 0.001 and p < 0.01). There was a negative correlation between 24-h urinary K+ excretion and ADM levels (r = −0.47, p < 0.01). No correlation was found between the number of bedwetting episodes per week/duration of enuresis with urinary ADM levels. | Decreased ADM levels may be a compensatory response when there is abnormal electrolyte and water excretion. | ||||
Balat A. et al. (2003) [66] | CC, SC | 6.43 ± 2.62 yr n = 20 14 patients w/DI, 6 patients w/VUR as controls | Tissue levels of NO and ADM | To determine the tissue levels of NO and ADM in children with DI and compare them with children with normal bladder activity. | Urodynamic testing | ADM levels measured via bladder biopsy (pmol/g tissue) were increased in children with DI (p < 0.001). | Increased ADM appears to be compensatory for decreased NO production in the smooth muscle of the bladder in DI patients. | ||||
Kalman S. et al. (2005) [67] | CC, SC | 1–13 yr n = 74 w/recurrent UTI: 25 w/RPS and w/VUR, 16 w/RPS and w/o VUR, 12 w/o RPS and w/VUR, 21 healthy children | Plasma and urine ADM | To determine plasma and urine ADM levels in children with RPS and VUR. | Cystoureterography DMSA | Plasma ADM levels were not significantly higher in the control group than in the rest of the groups (p = 0.162). Urine ADM levels were higher in the control group than in the three study groups (p < 0.005). | Urine ADM can be a prognostic factor in the long-term follow-up of paediatric cases with VUR. |
Study | Type of Study | Setting | Biomarkers Studied | Aim | Gold Standard | AUC | Cut-Off | Se | Sp | PPV/ NPV | Conclusion |
---|---|---|---|---|---|---|---|---|---|---|---|
Del Ry S. et al. (2016) [68] | CC, SC | 12.5 ± 0.4 yr * n = 83 51 obese adolescents, 32 healthy adolescents | MR-proADM | To assess plasma MR-proADM levels in obese adolescents compared to normal-weight subjects. | National BMI reference data specific for age and sex | Plasma MR-proADM levels were significantly higher in obese adolescents than in normal-weight ones (p < 0.0001). MR-proADM correlated with BMI z-score, fat mass, circulating insulin, HOMA-IR, total cholesterol, and LDL cholesterol. Fat mass and BMI z-score were independent determinants of circulating MR-proADM. | Obese adolescents have higher circulating levels of MR-proADM compared to those of normal weight, suggesting its important involvement in obese patients. | ||||
Metwalley K.A. et al. (2018) [69] | CC, SC | 9.76 ± 2.21 yr * n = 120 60 obese children, 60 non-obese children | ADM | To determine the plasma levels of ADM in obese children and their relationship to LV function. | Echocardiography | - | 52 pg/mL (predicting LV hypertrophy) | 94.3 | 92.5 | - | Measuring plasma ADM levels in obese children may help to identify those at high risk of developing LV hypertrophy and dysfunction. |
El-Habashy S. et al. (2010) [70] | CC, SC | 13.9 ± 3.2 yr * n = 85 55 children w/T1DM, 30 healthy controls | ADM HbA1c | To assess ADM levels in children and adolescents with T1DM and their correlation with diabetic MVC. | Indirect ophthalmoscope examination of the fundus | ADM levels were significantly increased in patients with and without MVC compared to the control group, with higher levels in those with MVC. Plasma ADM levels were positively correlated with both duration of diabetes and HbA1c. | ADM may have a role in the diabetic vasculopathy of children and adolescents with T1DM. | ||||
Semeran K. et al. (2013) [71] | CC, SC | 8–18 yr n = 62 41 patients with T1DM, 21 healthy controls | HbA1c Lipid profile IL-17 VEGF ADM | To assess the use of biomarkers in patients with T1DM with no visible lesions for predicting retinal dysfunction. | S-cone ERG protocol | A statistically significant finding was that the ADM level in the diabetes group was lower than in the control group (p < 0.05). | The changes observed in the ADM levels support its possible involvement in the microvascular complications of diabetes. Different-than-expected study results as regards ADM concentration indicate that further studies are needed. |
Study | Type of Study | Setting | Biomarkers Studied | Aim | Gold Standard | AUC | Cut-Off | Se | Sp | PPV/ NPV | Conclusion |
---|---|---|---|---|---|---|---|---|---|---|---|
Nishida K. et al. (2001) [72] | P, O, SC | 0.4–2.6 yr n = 6 Children with acute KD | ADM | To test ADM as an early detection biomarker of coronary artery vasculitis in KD. | Echocardiography | ADM levels were markedly elevated before treatment, especially in patients with coronary artery dilation. After treatment, plasma adrenomedullin levels substantially decreased. | ADM may be useful to monitor Kawasaki disease patients during its acute phase and may help to diagnose coronary artery involvement. | ||||
Islek I. et al. (2003) [73] | CC, SC | 11.4 ± 3.1 * n = 28 16 children with HSP, 12 healthy controls | Plasma and urine NO and ADM | To measure ADM and NO levels in children with HSP. | Diagnostic criteria | Plasma and urine ADM levels were significantly higher in the acute phase of HSP than in the controls. No difference was seen between remission phase levels and control ADM levels. | ADM may have a role in the immune-inflammatory process of HSP, especially in the active stage. | ||||
Balat A. et al. (2005) [54] | CC, SC | 7–14 yr n = 25 11 children with ARF, 14 healthy controls | Plasma and urine NO and AM | To investigate whether an association between levels of ADM/NO and ARF exists. | Diagnostic criteria | Plasma and urine ADM levels were significantly higher in children with ARF, irrespective of whether they were in the acute or convalescent phases. Plasma and urine levels of ADM in the acute phase showed positive correlation with ESR and negative correlation with EF. | ADM may play a role in the immune-inflammatory process of ARF. However, increased levels may also be the result of inflammatory injury in ARF. | ||||
Balat A. et al. (2006) [74] | CC, SC | 3–16 yr n = 15 w/FMF, 15 healthy controls | Plasma and urine NO and ADM | To determine the levels of ADM and NO in children w/FMF and compare with the healthy controls. | Diagnostic criteria | Plasma and urine levels were significantly higher in FMF patients than in controls. | ADM may have a role in the immuno-inflammatory process of FMF, although whether these act to promote or protect against further inflammatory injury is not clear. | ||||
Kalman S. et al. (2012) [75] | CC, SC | 9.2 ± 4.7 yr * n = 37 (16 homozygous M694V, 10 heterozygous M694V, 11 other mutations) | Urine and plasma ADM | To compare plasma and urine ADM levels of FMF patients who exhibit M694V homozygosity and patients with other genotypes. | - | Plasma ADM levels were higher in FMF patients w/homozygous M694V than other patients (heterozygous M694V and other mutations). No differences between heterozygous M694V and other mutation groups, nor in urine ADM levels. | Although the results are favourable, more studies are needed to demonstrate the association between homozygous M694V mutation and ADM levels. | ||||
Polat A. (2015) [76] | CT, SC | 7.8 ± 2 yr n = 37 Children with confirmed FMF | ADM | To investigate ADM as a marker for inflammation in paediatric patients with FMF who are using colchicine at different doses. | ESR and CRP levels | ADM levels were similar in all visits (p = 0.954) and did not show any differences between the first 3 visits and following 3 visits i.e., before and after changing the dosage. | No alterations in ADM levels were demonstrated at any visits, which may suggest the continuation of subclinical inflammation in these patients. |
Study | Type of Study | Setting | Biomarkers Studied | Aim | Gold Standard | AUC | Cut-Off | Se | Sp | PPV/ NPV | Conclusion |
---|---|---|---|---|---|---|---|---|---|---|---|
Özgür B.G. et al. (2017) [77] | CC, SC | 9.2 ± 2.8 yr * n = 90 45 children with ADHD, 45 healthy children | ADM NO | To compare plasma ADM and NO levels of newly diagnosed, treatment-naive patients with ADHD and healthy children. | K-SADS-PL-T schedule | There were no statistically significant differences in NO and ADM levels, neither between the groups nor ADHD subtypes. | The role of ADM in the pathophysiology of ADHD could not be demonstrated. | ||||
Zoroglu S.S. et al. (2003) [78] | CC, SC | 2–12 yr n = 48 26 autistic patients, 22 healthy controls | ADM NO | To assess the role of NO and ADM in autism. | DSM-IV diagnostic criteria | The mean values of plasma total nitrite and ADM levels in the autistic group were significantly higher than control values. | ADM may have a pathophysiological role in autism; this subject requires much further research. | ||||
Kucukosmanoglu E. et al. (2012) [79] | CC, SC | 5–15 yr n = 47 27 children with acute asthma attack, 20 controls | ADM | To determine changes in ADM levels during an acute asthma attack and its association with allergen sensitivity. | GINA classification, prick tests | No significant differences were found in ADM levels between the controls and patients in either the acute attack or remission period. ADM levels were higher in the acute attack period in those patients with a severe attack, patients sensitive to an allergen, and patients with history of atopic dermatitis. | ADM may play a role in children with atopic dermatitis and may also have a role in the immuno-inflammatory process of asthma. | ||||
Piccin A. et al. (2015) [80] | CC, SC | n = 128 111 children with SCA, 17 controls | MP PC PS NO pro-ADM ET-1 | To investigate the relationship between MP, PC, PS, NO, ET-1, and pro-ADM in paediatric patients with SCA. | - | Pro-ADM levels were elevated in acute chest syndrome versus steady state and controls. | During an acute chest crisis, ADM and ET-1 were elevated, suggesting a role for therapy inhibiting ET-1. | ||||
Robertson C.L. et al. (2001) [81] | CC, SC | 1.5 mo–11 yr n = 31 21 patients with TBI, 10 controls without TBI or meningitis | CSF ADM | To investigate whether post- traumatic CSF ADM concentration was associated with relevant clinical variables (CBF). | Glasgow scale CBF measured using Xenon CT | ADM concentration was markedly increased in the CSF of infants and children after severe TBI versus controls. CBF increased one unit for every 0.893 unit increase in ADM concentration. Assessment of the relationship between ADM and outcomes did not reveal a significant association. | ADM may participate in the regulation of CBF after severe TBI. |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Solé-Ribalta, A.; Bobillo-Pérez, S.; Jordan-García, I. A Review of Adrenomedullin in Pediatric Patients: A Useful Biomarker. Children 2022, 9, 1181. https://doi.org/10.3390/children9081181
Solé-Ribalta A, Bobillo-Pérez S, Jordan-García I. A Review of Adrenomedullin in Pediatric Patients: A Useful Biomarker. Children. 2022; 9(8):1181. https://doi.org/10.3390/children9081181
Chicago/Turabian StyleSolé-Ribalta, Anna, Sara Bobillo-Pérez, and Iolanda Jordan-García. 2022. "A Review of Adrenomedullin in Pediatric Patients: A Useful Biomarker" Children 9, no. 8: 1181. https://doi.org/10.3390/children9081181