Serum concentration of copeptin in newborns with congenital heart defect
Anna Tarko 1, 2  
,   Anna Suchojad 1, 2  
,   Julia Kordyś 1  
,   Svetlana Simonova 1  
,   Iwona Maruniak-Chudek 1, 2  
More details
Hide details
Oddział Neonatologii, Patologii i Intensywnej Terapii Noworodka, Górnośląskie Centrum Zdrowia Dziecka im. św. Jana Pawła II, Samodzielny Publiczny Szpital Kliniczny nr 6 Śląskiego Uniwersytetu Medycznego w Katowicach
Klinika Neonatologii, Patologii i Intensywnej Terapii Noworodka, Wydział Nauk Medycznych w Katowicach, Śląski Uniwersytet Medyczny w Katowicach
Iwona Maruniak-Chudek   

Klinika Neonatologii, Patologii i Intensywnej Terapii Noworodka, Wydział Nauk Medycznych w Katowicach, Śląski Uniwersytet Medyczny w Katowicach, ul. Medyków 16, 40-752 Katowice
Ann. Acad. Med. Siles. 2021;75:41–48
Neonates with congenital heart defects (CHD) require careful fluid management due to the risk of cardiovascular failure. Routine laboratory parameters are not the optimal tool to detect fluid overload; therefore the search for novel markers is justified. Copeptin (pre-pro-vasopressin – CTproAVP) may be one of them. The aim of the study was to analyze the influence of the current protocol of hydration in neonates with CHD on the physiological volume homeostasis measured with CTproAVP.

Material and methods:
Ten term newborns with CHD hospitalized in neonatal intensive care before cardiac surgery were enrolled in the study. Four of them presented symptoms of respiratory insufficiency and all except two received alprostadil. Clinical management was routine, with the exception of CTproAVP measurement in the first five days of life with evaluation of serum and urine osmolality. Fluid intake was within the normal range for age. Term, healthy neonates (N = 200) served as the control.

The current hydration protocol did not cause an increase in serum and urine osmolality compared to the controls. The effective osmolality of the analyzed body fluids was even lower in the neonates with CHD. The concentration of CTproAVP was also lower in the study group, but the difference was not statistically significant. There were no clinical signs of cardiovascular distress or overhydration. No factors explaining the variability in CTproAVP concentration were identified.

These preliminary data suggest that the protocol of hydration does not cause dehydration or stimulation of CTproAVP release. It seems that even more restrictive protocols of fluid management can be applied in newborns with CHD at the risk of pulmonary congestion. A longer observation period is needed, including the postoperative period, to obtain more reliable information on optimal fluid management and the role of CTproAVP in monitoring volemia.

This study was supported by a grant from Medical University of Silesia (KNW – 2-K20/N/6/N)
The authors declare that there is no conflict of interests regarding the publication of this paper.
Morgenthaler N.G. Copeptin: a biomarker of cardiovascular and renal function. Congest. Heart Fail. 2010; 16(suppl 1): S37–44, doi: 10.1111/j.1751-7133.2010.00177.x.
Katan M., Christ-Crain M. The stress hormone copeptin: a new prognostic biomarker in acute illness. Swiss Med. Wkly 2010; 140: w13101, doi: 10.4414/smw.2010.13101.
Holwerda D.A. A glycopeptide from the posterior lobe of pig pituitaries. I. Isolation and characterization. Eur. J. Biochem. 1972; 28(3): 334–339, doi: 10.1111/j.1432-1033.1972.tb01918.x.
Struck J., Morgenthaler N.G., Bergmann A. Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients. Peptides 2005; 26(12): 2500–2504, doi: 10.1016/j.peptides.2005.04.019.
Stoiser B., Mörtl D., Hülsmann M., Berger R., Struck J., Morgenthaler N.G., Bergmann A., Pacher R. Copeptin, a fragment of the vasopressin precursor, as a anovel predictor of outcome in heart failure. Eur. J. Clin. Invest. 2006; 36(11): 771–778, doi: 10.1111/j.1365-2362.2006.01724.x.
Morgenthaler N.G., Müller B., Struck J., Bergmann A., Redl H., Christ-Crain M. Copeptin, a stable peptide of the arginine vasopressin precursor, is elevated in hemorrhagic and septic shock. Shock 2007; 28(2): 219–226, doi: 10.1097/SHK.0b013e318033e5da.
Katan M., Morgenthaler N.G., Widmer I., Puder J.J., König C., Müller B., Christ-Crain M. Copeptin, a stable peptide derived from the vasopressin precursor, correlates with the individual stress level. Neur. Endocrinol. Lett. 2008; 29(3): 341–346.
Lipinski M.J., Escárcega R.O., D’Ascenzo F., Magalhães M.A., Baker N.C., Torguson R. et al. A systematic review and collaborative meta-analysis to determine the incremental value of copeptin for rapid rule-out of acute myocardial infarction. Am. J. Cardiol. 2014; 113(9): 1581–1591, doi: 10.1016/j.amjcard.2014.01.436.
Alehagen U., Dahlström U., Rehfeld J.F., Goetze J.P. Association of copeptin and N-terminal proBNP concentrations with risk of cardiovascular death in older patients with symptoms of heart failure. JAMA 2011; 305(20): 2088–2095, doi: 10.1001/jama.2011.666.
Nickel N.P., Lichtinghagen R., Golpon H., Olsson K.M., Brand K., Welte T., Hoeper M.M. Circulating levels of copeptin predict outcome in patients with pulmonary arterial hypertension. Respir. Res. 2013; 14(1): 130, doi: 10.1186/1465-9921-14-130.
Neuhold S., Huelsmann M., Strunk G., Stoiser B., Struck J., Morgenthaler N.G. et al. Comparison of copeptin, B-type natriuretic peptide, and amino-terminal pro-B-type natriuretic peptide in patients with chronic heart failure: prediction of death at different stages of the disease. J. Am. Coll. Cardiol. 2008; 52(4): 266–272, doi: 10.1016/j.jacc.2008.03.050.
Furman L., Schanler R.J. Nutrition. [In:] Gleason Ch.A., Devaskar Sh.U. Avery’s diseases of the newborn. 9th Ed. Elsevier Saunders. Philadelphia 2012; pp. 937–959.
Katan M., Müller B., Christ-Crain M. Copeptin: a new and promising diagnostic and prognostic marker. Crit. Care 2008; 12(2): 117, doi: 10.1186/cc6799.
Tenderenda-Banasiuk E., Wasilewska A., Filonowicz R., Jakubowska U., Waszkiewicz-Stojda M. Serum copeptin levels in adolescents with primary hypertension. Pediatr. Nephrol. 2014; 29(3): 423–429, doi: 10.1007/s00467-013-2683-5.
Itoi K., Jiang Y.Q., Iwasaki Y., Watson S.J. Regulatory mechanisms of corticotropin-releasing hormone and vasopressin gene expression in the hypothalamus. J. Neuroendocrinol. 2004; 16(4): 348–355, doi: 10.1111/j.0953-8194.2004.01172.x.
Reichlin T., Hochholzer W., Stelzig C., Laule K., Freidank H., Morgenthaler N.G. et al. Incremental value of copeptin for rapid rule out of acute myocardial infarction. J. Am. Coll. Cardiol. 2009; 54(1): 60–68, doi: 10.1016/j.jacc.2009.01.076.
Chenevier-Gobeaux C., Freund Y., Claessens Y.E., Guérin S., Bonnet P., Doumenc B. et al. Copeptin for rapid rule out of acute myocardial infarction in emergency department. Int. J. Cardiol. 2013; 166(1): 198–204, doi: 10.1016/j.ijcard.2011.10.098.
Dedic A., ten Kate G.J., Rood P.P., Galema T.W., Ouhlous M., Moelker A. et al. Copeptin in acute chest pain: identification of acute coronary syndrome and obstructive coronary artery disease on coronary CT angiography. Emerg. Med. J. 2013; 30(11): 910–913, doi: 10.1136/emermed-2012-201596.
Griebel G., Stemmelin J., Gal C.S., Soubrié P. Non-peptide vasopressin V1b receptor antagonists as potential drugs for the treatment of stress-related disorders. Curr. Pharm. Des. 2005; 11(12): 1549–1559, doi: 10.2174/1381612053764797.
Mizia-Stec K., Lasota B., Mizia M., Chmiel A., Adamczyk T., Chudek J., Gasior Z. Copeptin constitutes a novel biomarker of degenerative aortic stenosis. Heart Vessels 2013; 28(5): 613–619, doi: 10.1007/s00380-012-0293-y.
Goldsmith S.R. Congestive heart failure: potential role of arginine vasopressin antagonists in the therapy of heart failure. Congest. Heart Fail. 2002; 8(5): 251–256, doi: 10.1111/j.1527-5299.2002.01158.x.
Katan M., Fluri F., Morgenthaler N.G., Schuetz P., Zweifel Ch., Bingisser R. et al. Copeptin: a novel, independent prognostic marker in patients with ischemic stroke. Ann. Neurol. 2009; 66(6): 799–808, doi: 10.1002/ana.21783.
Pérez-Navero J.L., de la Torre-Aguilar M.J., de la Rosa I.I., Gil-Campos M., Gómez-Guzmán E., Merino-Cejas C. et al. Cardiac Biomarkers of Low Cardiac Output Syndrome in the Postoperative Period After Congenital Heart Disease Surgery in Children. Rev. Esp. Cardiol. 2017; 70(4): 267–274, doi: 10.1016/j.rec.2016.09.011.
Rouatbi H., Zigabe S., Gkiougki E., Vranken L., Van Linthout C., Seghaye M.C. Biomarkers of neonatal stress assessment: A prospective study. Early Hum. Dev. 2019; 137: 104826, doi: 10.1016/j.earlhumdev.2019.104826.
Kasser S., Hartley C., Rickenbacher H., Klarer N., Depoorter A., Datta A.N. et al. Birth experience in newborn infants is associated with changes in nociceptive sensitivity. Sci. Rep. 2019; 9(1): 4117, doi: 10.1038/s41598-019-40650-2.
Wrotek A., Jackowska T., Pawlik K. Sodium and copeptin levels in children with community acquired pneumonia. Adv. Exp. Med. Biol. 2015; 835: 31–36, doi: 10.1007/5584_2014_41.
Hoorn E.J., Geary D., Robb M., Halperin M.L., Bohn D. Acute hyponatremia related to intravenous fluid administration in hospitalized children: an observational study. Pediatrics 2004; 113(5): 1279–1284, doi: 10.1542/peds.113.5.1279.