Plasma copeptin in preterm infants: a highly sensitive marker of fetal and neonatal stress.

CONTEXT: Copeptin is a stable by-product of arginine-vasopressin synthesis and reflects its secretion by the pituitary. OBJECTIVE: The objective of the study was to investigate perinatal factors affecting copeptin concentrations in preterm infants at birth and at 3 d of life. DESIGN AND SETTING: This was a prospective cross-sectional study at two Swiss university hospitals. PATIENTS: One hundred sixty-seven preterm infants were enrolled, 59 infants born between 24 and 31 wk gestational age, 50 infants between 32 and 34 wk, and 58 between 35 and 36 wk. MAIN OUTCOME MEASURE: Plasma copeptin concentrations, determined by a CT-proAVP-luminescence-immunoassay, were measured. RESULTS: Copeptin at birth was significantly higher in preterm infants born vaginally [median (range) 366 (1-2900) pmol/liter, n = 43] than those born by cesarean section [6.9 (2-1580), n = 124]. In infants born after cesarean without prior labor (n = 66), estimated fetal weight less than the fifth percentile, suspect fetal heart rate, compromised placental perfusion, and chorioamnionitis were each associated with significantly elevated cord copeptin. Copeptin at 3 d of life was not associated with cord blood copeptin but inversely related to gestational age (Rs = -0.6, P < 0.001) and birth weight (Rs -0.612, P < 0.001). Day 3 copeptin increased alongside the level of mechanical respiratory support. CONCLUSION: Copeptin is a highly sensitive marker of perinatal stress.

Copeptin in the differential diagnosis of the polydipsia-polyuria syndrome--revisiting the direct and indirect water deprivation tests.

BACKGROUND: The water deprivation test (WDT) with direct or indirect measurement of plasma arginine vasopressin (AVP) is the method of choice for the differential diagnosis of the polydipsia-polyuria syndrome. In theory, direct measurement of AVP is highly attractive but is hampered by technical difficulties. OBJECTIVE: The aim of the study was to evaluate the utility of copeptin, a surrogate of AVP secretion, in the diagnostic work-up of the polyuria-polydipsia syndrome and to compare its performance with the current diagnostic standard. SETTING AND DESIGN: In two tertiary referral centers, 20 healthy subjects and 50 patients with polydipsia-polyuria syndrome underwent WDT with measurements of both plasma AVP and copeptin levels. The reference diagnosis was based on clinical information and treatment response. RESULTS: Twenty-two patients (44%) were diagnosed with primary polydipsia, 17 (34%) with partial central diabetes insipidus (DI), nine (18%) with complete central DI, and two (4%) with nephrogenic DI. The indirect WDT led to a correct diagnosis in 35 of 50 patients (70%). The direct WDT with AVP or copeptin measurement correctly diagnosed 23 patients (46%) or 36 patients (72%), respectively. Baseline copeptin values greater than 20 pmol/liter identified patients with nephrogenic DI, and concentrations below 2.6 pmol/liter indicated complete central DI. The ratio between Δ copeptin (0800 to 1600 h) and serum sodium concentration at 1600 h yielded optimal diagnostic accuracy, allowing us to also discern partial central DI from primary polydipsia (sensitivity 86%, and specificity 100%). CONCLUSION: Copeptin holds promise as a diagnostic tool in the polyuria-polydipsia syndrome, improving significantly the diagnostic accuracy of the direct WDT.

High copeptin concentrations in umbilical cord blood after vaginal delivery and birth acidosis.

CONTEXT: The pituitary-secreted nonapeptide arginine-vasopressin (AVP) is unstable and therefore unsuited for diagnostic use, but its secretion can be estimated by measuring copeptin, the C-terminal portion of the AVP precursor (pro-AVP). OBJECTIVE: Our objective was to investigate perinatal factors affecting copeptin concentrations in infants at birth and at 3 d of life. DESIGN AND SETTING: We conducted a prospective cross-sectional study at a tertiary university hospital. PATIENTS: Copeptin plasma concentrations were evaluated in 177 infants at birth, including 117 paired arterial/venous umbilical cord and 102 venous blood samples obtained at 3 d of life. MAIN OUTCOME MEASURE: Copeptin concentrations were determined by a C-terminal pro-AVP luminescence immunoassay. RESULTS: Arterial umbilical cord copeptin concentrations were consistently higher than matched venous ones (median 18 vs. 10 pmol/liter, P < 0.001), but both values were closely related (R(s) = 0.825; P < 0.001), and both were negatively related to arterial umbilical cord pH (R(s) arterial/venous = -0.578/-0.639; P < 0.001). Although exceedingly high copeptin concentrations were observed after vaginal birth in umbilical cord arterial [median (5-95% range) = 1610 (85-5000) pmol/liter] and venous [793 (6-4836) pmol/liter] plasma, copeptin concentrations were low after primary cesarean section [arterial/venous = 8 (3-907)/5 (5-504) pmol/liter]. Postnatal body weight loss was associated with increased copeptin concentrations at d 3 (R(s) = 0.438; P < 0.001) and was inversely related to copeptin concentrations at birth (R(s) = -0.289 and -0.309; both P = 0.001). CONCLUSION: Vaginal birth is associated with a large release of copeptin that exceeds all values published so far, including those in critically ill adult patients with shock or brain injury. Thus, vaginal birth is arguably the most intense stressor in life.