Albumin determined by bromocresol green leads to erroneous results in routine evaluation of patients with chronic kidney disease

Objectives: Measurement of plasma albumin is pivotal for clinical decision-making in patients with chronic kidney disease (CKD). Routinely used methods as bromocresol green (BCG) and bromocresol purple (BCP) can suffer from aselectivity, but the impact of aselectivity on the accuracy of plasma albumin results of CKD-patients is still unknown. Therefore, we evaluated the performance of BCG-, BCP- and JCTLM-endorsed immunological methods in patients with various stages of CKD. Methods:We evaluated the performance of commonly used albumin methods in patients with CKD stages G1 through G5, the latter divided in two groups based on whether they received hemodialysis treatment. In total, 163 patient plasma samples were measured at 14 laboratories, on six different BCG and BCP-platforms, and four different immunological platforms. The results were compared with an ERM-DA-470k-corrected nephelometric assay. The implications on outcome is evaluated by the proportion of patient results &lt;38g/L for the diagnosis of protein energy wasting. Results:Albumin results determined with BCP- and immunological methods showed the best agreement with the target value (92.7 and 86.2%, respectively vs. 66.7% for BCG, namely due to overestimation). The relative agreement of each method with the target value was platform-dependent, with larger variability in agreement between platforms noted for BCG and immunological methods (3.2-4.6 and 2.6-5.3%) as opposed to BCP (0.7-1.5%). The stage of CKD had similar effects on the variability in agreement for the three method-groups (0.6-1.8% vs. 0.7-1.5% vs. 0.4-1.6%). The differences between methods cause discrepancies in clinical decision-making, as structurally fewer patients were diagnosed with protein energy wasting upon using BCG-based albumin results. Conclusions: Our study shows that BCP is fit for the intended use to measure plasma albumin levels in CKD patients from all stages, including patients on hemodialysis. In contrast, most BCG-based platforms falsely overestimate the plasma albumin concentration.</p

Fetal volume measurements with three dimensional ultrasound in the first trimester of pregnancy, related to pregnancy outcome, a prospective cohort study

BACKGROUND: First trimester growth restriction is associated with an increased risk of adverse birth outcomes (preterm birth, low birth weight and small for gestational age at birth). The differences between normal and abnormal growth in early pregnancy are small if the fetal size is measured by the crown-rump-length. Three-dimensional ultrasound volume measurements might give more information about fetal development than two-dimensional ultrasound measurements. Detection of the fetus with a small fetal volume might result in earlier detection of high risk pregnancies and a better selection of high risk pregnancies. METHODS: A prospective cohort study, performed at the Máxima Medical Centre, in Eindhoven-Veldhoven, the Netherlands. During the routine first trimester scan with nuchal translucency measurement 500 fetal volumes will be obtained. The gestational age is based on the first day of the last menstrual period in a regular menstrual cycle and by the crown-rump-length. The acquired datasets are collected and stored on a hard disk for offline processing and volume calculation. The investigator who performs the volume measurements is blinded for the results of the first trimester scan. The manual mode will be used to outline the Region Of Interest, the fetal head and rump, in all cross sections. The fetal volumes are calculated with a rotational step of 9°. First, the relation between fetal volume and gestational age, for a set of participants with normal pregnancies (training set), will be assessed. This model will then be used to determine expected values of fetal volume for a normal pregnancy, which will be referred to as expected normal values. Secondly, for a new set of participants with normal pregnancies and a set of participants with complicated pregnancies (together defined as validation set), the observed fetal volumes (FV(observed)) are compared with their expected normal values (FV(expected)) and expressed as a percentage of the expected normal value. The mean difference in percentage error between the set of normal versus complicated pregnancies will then be compared using the independent-samples t-test. Finally, logistic regression analysis will be applied to the validation set of participants to analyze the possibility of predicting the pregnancy outcome after fetal volume calculation in the first trimester, using this percentage error. DISCUSSION: After this study it is clear whether FV measurement in the first trimester can detect high risk pregnancies. If it is possible to detect these pregnancies, more intensive follow up in these pregnancies might result in fewer complicated pregnancies and fewer fetal morbidities

The predictive value of first trimester fetal volume measurements, a prospective cohort study

Objectives To determine if fetal volume (FV) measurements with three-dimensional ultrasound in the first trimester of pregnancy can detect the fetus at risk for preterm birth and/or low birth weight. Methods In this prospective cohort study, 538 participants were included during the routine first trimester ultrasound examination. Volume measurements were performed with VOCAL (9°). Firstly, the relation between FV and gestational age for a set of participants with normal pregnancies (training set), was assessed using multiple linear regression analysis, which was then used to determine the expected normal values. Secondly, for a new set of participants with normal pregnancies and a set of participants with complicated pregnancies (preterm birth and/or low birth weight), i.e. the validation set, the observed fetal volumes (FVobserved) were compared with their expected normal values (FVexpected) and expressed as a percentage of the expected normal value. The difference in mean percentage was then assessed with independent-samples t-test. Finally, logistic regression analysis was applied to the validation set to analyze the ability to predict the pregnancy outcome with FV calculation. Results Linear regression analysis of FV as a predictor of preterm birth and/or low birth weight did not result in significant (p = 0.630 and 0.290, respectively) or clinical relevant results (standardized effect sizes of 0.061 and 0.179, respectively). The predicting quality was also very low (AUC = 0.508 and 0.545 respectively). Conclusions Fetal volume measurements in the first trimester of pregnancy are not useful as a prognostic tool for predicting pregnancies of high risk for preterm birth or a low birth weight

The predictive value of first trimester fetal volume measurements, a prospective cohort study

Objectives: To determine if fetal volume (FV) measurements with three-dimensional ultrasound in the first trimester of pregnancy can detect the fetus at risk for preterm birth and/or low birth weight. Methods: In this prospective cohort study, 538 participants were included during the routine first trimester ultrasound examination. Volume measurements were performed with VOCAL (9 degrees). Firstly, the relation between FV and gestational age for a set of participants with normal pregnancies (training set), was assessed using multiple linear regression analysis, which was then used to determine the expected normal values. Secondly, for a new set of participants with normal pregnancies and a set of participants with complicated pregnancies (preterm birth and/or low birth weight), i.e. the validation set, the observed fetal volumes (FVobserved) were compared with their expected normal values (FVexpected) and expressed as a percentage of the expected normal value. The difference in mean percentage was then assessed with independent-samples t-test. Finally, logistic regression analysis was applied to the validation set to analyze the ability to predict the pregnancy outcome with Pi calculation. Results: Linear regression analysis of FV as a predictor of preterm birth and/or low birth weight did not result in significant (p = 0.630 and 0.290, respectively) or clinical relevant results (standardized effect sizes of 0.061 and 0.179, respectively). The predicting quality was also very low (AUC = 0.508 and 0.545 respectively). Conclusions: Fetal volume measurements in the first trimester of pregnancy are not useful as a prognostic tool for predicting pregnancies of high risk for preterm birth or a low birth weight

Reference values for the external genitalia of full-term and pre-term female neonates

International audienceBackground and objectives Identifying virilisation of the genitalia in female newborns early during the neonatal period is important to diagnose pathologies. However, there is no clear threshold for clitoromegaly or for the anogenital ratio. The objective of this study was to define reference values for the external genitalia of full-term and pre-term female neonates. Design This was a prospective study of all females born in the study centre between May 2014 and July 2016. Clitoral length and anogenital ratio were measured in 619 newborns with a gestational age of 24+2 to 41+3 weeks during their first 3 days of life. Associations between the values at day 3 and gestational age, birth weight and other newborn characteristics were examined by linear regression. Results The mean clitoral length at day 3 of life was 3.69±1.53 mm (n=551; 95th percentile, 6.5 mm; maximum, 8 mm), and the mean anogenital ratio was 0.42±0.09 (95th percentile, 0.58). There was no significant variation with gestational age or birth weight, and no significant difference between the results at day 0 and day 3. Conclusion These results suggest that clitoromegaly can be defined as a clitoral length >6.5 mm. Values ≥8 mm should prompt further investigations. An anogenital ratio >0.6 should be considered a sign of virilisation. Since clitoral size does not vary with gestational age or birth weight, clitoromegaly should not be attributed to prematurity