Copeptin and MR-proADM in umbilical cord plasma reflect perinatal stress in neonates born to mothers with diabetes and MR-proANP reflects maternal diabetes Plasma measurement of cardiovascular peptide hormones and their biosynthetic precursors has gained clinical interest in neonates. Natriuretic peptide (NT) concentrations in neonates with congenital heart disease remain increased in the first days of life and appear to be promising prognostic biomarkers in preterm neonates with patent ductus arteriosus [1,2] . Recent studies have also shown that copeptin, a vasopressin surro- gate marker, is markedly increased by perinatal stress, for example after vaginal delivery and asphyxia [3,4] . Contemporary clinical relevance of cardiovascular biomarkers also applies to neo- nates born to mothers with diabetes, which have an even higher risk of postnatal morbidity and mortality [5] . Vasopressin, adrenomedullin (ADM) and NT are all involved in fluid homeostasis through either water retention or renal natri- uresis [6–9] . As vasopressin is highly labile in plasma, the C-terminal fragment from pro- vasopressin, copeptin, has emerged as a stable surrogate measure of vasopressin release [10] . So far, copeptin is a promising plasma marker in cardiovascular disease [7,11] . Interestingly, copeptin plasma concentrations in adults are also associated with metabolic syndrome, where they are associated with hyperinsulinemia, high fat intake, low physical activity and future devel- opment of diabetes mellitus [12,13] . NT concen- trations are also related to glucose metabolism, where low concentrations predict development of diabetes in healthy individuals [14] . The precur- sor midregional pro-A-type NT (MR-proANP) is not believed to play any physiological role, but is suggested to be a biomarker of higher reliability than bioactive ANP [15] . ADM is diffusely produced in human tissues, including the heart and blood vessels [16,17] . It correlates with the more stable prohormone midregional pro-ADM (MR-proADM) with no known bioactivity [18] , and measurement is suggested to predict future risk of cardiovascular morbidity and death in adult patients [19] . Aim: To examine concentrations of three cardiovascular propeptides in umbilical cord plasma of neonates born to mothers with Type 1, Type 2 and gestational diabetes. Measurement of cardiovascular markers in umbilical cord plasma may potentially help identify neonates at risk of postnatal complications. Neonates born to mothers with diabetes have an increased risk of neonatal morbidity and mortality, and measurement of these new biomarkers may potentially help identify neonates at risk of these complications. Subjects & methods: Copeptin, midregional proadrenomedullin (MR-proADM) and mid- regional pro-A-type natriuretic peptide (MR-proANP) were measured in cord plasma of neonates (n = 63) born to mothers with the three types of diabetes. Associations with maternal glycemic control, mode of delivery and neonatal metabolic acidosis were examined. Results: Umbilical cord plasma copeptin concentrations were lowest in neonates after elective cesarean sections (6.1 pmol/l; interquartile range [IQR]: 4.5–9.1) compared with emergency cesarean sections (156 pmol/l; IQR: 9.6–311; p = 0.019) and vaginal delivery (831 pmol/l; IQR: 107–2407; p < 0.0001). MR-proADM was also affected by mode of delivery; however, this seemed more likely to be caused by an inverse association with the acid–base balance. In this population, only MR-proANP plasma concentrations were related to type of diabetes. Neonates born to mothers with Type 1 diabetes had higher concentrations (median 260 pmol/l; IQR: 222–318) compared with Type 2 diabetes (175 pmol/l; IQR: 169–200; p = 0.003) and gestational diabetes (200 pmol/l; IQR: 149–276; p = 0.009). Conclusion: Umbilical cord plasma copeptin and MR-proADM concentrations primarily reflect perinatal stress associated with mode of delivery and the degree of fetal acidosis, whereas MR-proANP concentrations are higher in neonates born to mothers with Type 1 diabetes. KEYWORDS: adrenomedullin n ANP n copeptin n MR-proADM n MR-proANP n natriuretic peptide n neonate n maternal diabetes n umbilical cord plasma n vasopressin Julie Smith, Karen G Halse, Peter Damm, Marie LS Lindegaard, Isis Amer-Wåhlin, Steen Hertel, Marianne Johansen, Elizabeth R Mathiesen, Lars B Nielsen & Jens P Goetze* *Author for correspondence: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark Tel.: +45 3545 2202 Fax: +45 3545 2880 jpg@dadlnet.dk See page 146 for a full list of ailiaions 139 ISSN 1752-0363 10.2217/BMM.12.79 © 2013 Future Medicine Ltd Biomarkers Med. (2013) 7(1), 139–146 Preliminary Communication part of