Soluble receptor fms-like tyrosine kinase-1 testing: analytical performances of the new B•R•A•H•M•S sFlt-1 KRYPTOR automated immunoassay

Objective Soluble fms-like tyrosine kinase-1 (sFlt-1) participates to the physiopathology of pre-eclampsia by complexing the placental growth factor(PlGF) and blunting its biological action. Measurement of sFlt-1 levels contributes to the risk assessment of pre-eclampsia but only few automated assays for sFlt-1 testing are available. The aim of our study was to evaluate the analytical performances of the Thermo Scientific B•R•A•H•M•S sFlt-1 KRYPTOR immunoassay on KRYPTOR® compact PLUS instrument, a recently developed automated immunoassay. Methods Imprecision of the B•R•A•H•M•S sFlt-1 KRYPTOR (Thermo Scientific) immunoassay was determined with three levels of manufacturer’s control materials and seven pools of serum covering a broad spectrum of sFlt-1 concentrations, ran in duplicates two times a day for 5 days. The linearity of the sFlt-1 assay was determined through a 20 points dilution test. Matrix commutability was evaluated in paired EDTA and serum samples collected from second and third trimester pregnant women (n=47). PlGF concentrations were also determined in this set of patient samples with the B•R•A•H•M•S PlGF KRYPTOR immunoassay. Results The between run coefficients of variation (CV) for the quality control materials were 0. 8, 1. 1 and 1. 0% for mean concentrations of 1540,2988 and 9666 pg/mL, respectively. The 20 points dilution test covered a range of concentrations ranging from 92391 to 41 pg/mL anddemonstrated a reduced mean bias of 6. 2%, confirming the linearity of the assay. In the pregnant women samples, the median concentrations of sFlt-1 in serum and EDTA were respectively 1072 pg/mL (range: 166. 3 - 3400) and 1122 pg/mL (326 – 3099). The Spearman correlation coefficient between the 2 matrixes was 0. 97 and Passing and Bablok regression analysis showed a slope of 0. 97 and an intercept of 30. 31. For PlGF, the median concentrations in serum and EDTA were respectively 220. 3 pg/mL (range: 88. 6 – 928. 3) and 214. 5 pg/mL (76. 3 – 948. 4). The Spearman correlation coefficient between serum and EDTA was 0. 96 and Passing and Bablokregression analysis between the 2 matrixes showed a slope of 0. 94 and an intercept of 8. 02. The ratios between sFlt-1 and PlGF were not significantly different between serum and EDTA. Conclusion Our study demonstrated that the sFlt-1 automated immunoassay developed on the B•R•A•H•M•S KRYPTOR® compact PLUS has excellent analytical performances. Furthermore, a limited bias was observed between serum and EDTA samples, indicating the potential matrix commutability

Plasma midregional proadrenomedullin in newborn infants: impact of prematurity and perinatal infection

INTRODUCTION: Adrenomedullin (ADM) is one of the strongest endogenous vasodilating hormones. Its stable by-product midregional-proADM (MR-proADM) is an established indicator of systemic infection and cardiovascular compromise in adult patients. METHODS: A prospective cross-sectional study was performed to investigate the perinatal factors affecting MR-proADM plasma concentrations in 328 newborn infants with a gestational age (GA) between 24 and 41 wk. RESULTS: Blood samples were obtained in 270 infants from umbilical veins (with additional 108 paired samples from umbilical arteries), and at 2-3 d of life in 183 infants. Paired venous and arterial umbilical cord MR-proADM concentrations were closely related (Spearman's rank order correlation coefficient (R(s)) = 0.825, P < 0.001). MR-proADM concentrations at birth and at 2-3 d were inversely related to GA (R(s) = -0.403 and R(s) = -0.541, respectively) and birth weight (BW; R(s) = -0.421 and R(s) = -0.530, respectively; all P < 0.001). On stepwise regression analysis, clinical chorioamnionitis and umbilical arterial blood base excess retained a significant impact on MR-proADM cord venous blood concentrations. At 2-3 d of life, histologic chorioamnionitis and GA at delivery were significantly associated with MR-proADM levels. DISCUSSION: As compared with adults, MR-proADM concentrations are elevated in neonates, especially those born very preterm. Immaturity and infection, which both feature low systemic vascular resistance, are related to increased MR-proADM concentrations