Comparison of Umbilical Serum Copeptin Relative to Erythropoietin and S100B as Asphyxia Biomarkers at Birth

Summanen, Milla; Seikku, Laura; Rahkonen, Petri; Stefanović, Vedran; Teramo, Kari; Andersson, Sture; Kaila, Kai; Rahkonen, Leena

doi:10.1159/000456063

Cited by 23 publications

(25 citation statements)

References 23 publications

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“…Unfortunately, we did not have AVP samples available before 1 h and therefore our AVP measurements were taken a mean of 30 min after the peak appearance of sinusoidal activity, potentially reducing the strength of the relationship. Nonetheless, AVP levels 1 h after HI were strongly associated with loss of EEG power by day 3 (r 2 = 0.61), consistent with clinical studies suggesting that AVP or its more stable co-metabolite copeptin may have value as a standalone biomarker for HIE (Evers & Wellmann, 2016;Summanen et al 2017). Further studies are needed to understand the relationship between AVP levels after HI and neural injury.…”

Section: Figure 3 Spectral Power and Sample Entropy Of Fetal Heart Rsupporting

confidence: 90%

“…Nonetheless, AVP levels 1 h after HI were strongly associated with loss of EEG power by day 3 ( r 2 = 0.61), consistent with clinical studies suggesting that AVP or its more stable co‐metabolite copeptin may have value as a standalone biomarker for HIE (Evers & Wellmann, ; Summanen et al . ). Further studies are needed to understand the relationship between AVP levels after HI and neural injury.…”

Section: Discussionmentioning

confidence: 97%

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Early sinusoidal heart rate patterns and heart rate variability to assess hypoxia–ischaemia in near‐term fetal sheep

Kasai

Lear

Davidson

et al. 2019

The Journal of Physiology

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Key points •Therapeutic hypothermia needs to be started as early as possible in the first 6 h after acute injury caused by hypoxia–ischaemia (HI), but the severity and timing of HI are often unclear. In this study we evaluated whether measures of heart rate variability (HRV) might provide early biomarkers of HI. •The duration but not magnitude of suppression of HRV power and conversely increased sample entropy of the heart rate were associated with severity of HI, such that changes in the first 3 h did not discriminate between groups. •Relative changes in HRV power bands showed different patterns between groups and therefore may have the potential to evaluate the severity of HI. •Aberrant fetal heart rate patterns and increased arginine vasopressin levels in the first hour after moderate and severe HI were correlated with loss of EEG power after 3 days’ recovery, suggesting potential utility as early biomarkers of outcome. Abstract Therapeutic hypothermia is partially neuroprotective after acute injury caused by hypoxia–ischaemia (HI), likely because the timing and severity of HI are often unclear, making timely recruitment for treatment challenging. We evaluated the utility of changes in heart rate variability (HRV) after HI as biomarkers of the timing and severity of acute HI. Chronically instrumented fetal sheep at 0.85 gestational age were exposed to different durations of umbilical cord occlusion to produce mild (n = 6), moderate (n = 8) or severe HI (n = 8) or to sham occlusion (n = 5). Heart rate (HR) and HRV indices were assessed until 72 h after HI. All HI groups showed suppressed very low frequency HRV power and elevated sample entropy for the first 3 h; more prolonged changes were associated with greater severity of HI. Analysis of relative changes in spectral power showed that the moderate and severe groups showed a shift towards higher HRV frequencies, which was most marked after severe HI. This shift was associated with abnormal rhythmic HR patterns including sinusoidal patterns in the first hour after HI, and with elevated plasma levels of arginine vasopressin, which were correlated with subsequent loss of EEG power by day 3. In conclusion, absolute changes in HRV power in the first 3 h after acute HI were not significantly related to the severity of HI. The intriguing relative shift in spectral power towards higher frequencies likely reflects greater autonomic dysfunction after severe HI. However, sinusoidal HR patterns and elevated vasopressin levels may have utility as biomarkers of severe HI.

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Section: Figure 3 Spectral Power and Sample Entropy Of Fetal Heart Rsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 97%

Early sinusoidal heart rate patterns and heart rate variability to assess hypoxia–ischaemia in near‐term fetal sheep

Kasai

Lear

Davidson

et al. 2019

The Journal of Physiology

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“…Umbilical cord serum EPO levels did not correlate with the duration of the labor nor that of the second stage of the labor in the current study. This is consistent with the findings of a recent study on term asphyxiated neonates [15].…”

Section: Commentsupporting

confidence: 93%

Amniotic fluid and umbilical cord serum erythropoietin in term and prolonged pregnancies

Seikku

Stefanović

Rahkonen

et al. 2019

European Journal of Obstetrics & Gynecology and Reproductiv

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Objective. Erythropoietin-a hormone regulating erythropoiesis-is a biomarker of chronic fetal hypoxia. High erythropoietin levels in fetal plasma and amniotic fluid are associated with increased risk of adverse neonatal outcome. Since the risk of perinatal morbidity and mortality is increased in pregnancies beyond 41 gestational weeks, we evaluated erythropoietin levels in amniotic fluid and umbilical cord serum in apparently low-risk term (≥37 gestational weeks) and prolonged pregnancies (≥41 gestational weeks) with labor induction. Study Design. This prospective cohort study comprised 93 singleton pregnancies at 37 +0-42 +1 gestational weeks, of which prolonged pregnancies numbered 63 (67.7%). Amniotic fluid samples were collected at time of labor induction by amniotomy. Umbilical cord blood samples for evaluation of pH, base excess, and umbilical cord serum erythropoietin were collected at birth. Erythropoietin levels were measured by immunochemiluminometric assay. Normal value of amniotic fluid erythropoietin level was defined as ≤3 IU/L, and abnormal value as ≥27 IU/L. Normal umbilical cord serum erythropoietin was defined as <40 IU/L. Data on maternal pregnancy and delivery characteristics and short-term neonatal outcomes such as Apgar score were obtained from the hospital charts. Associations were calculated using Spearman's rank correlation coefficient. The Chi-square test, Fisher's exact test and the Mann-Whitney U test were utilized to determine differences in the study groups. Results. Amniotic fluid erythropoietin levels correlated with gestational age (r=0.261, p=0.012) and were higher among prolonged pregnancies as compared to term pregnancies (p=0.005). There were 78 (83.9%) vaginal deliveries, and among these erythropoietin levels in amniotic fluid correlated with the levels in umbilical cord serum (r=0.513, p<0.000). Umbilical cord serum erythropoietin levels correlated with gestational age among vaginal deliveries (r=0.250, p=0.027). Erythropoietin levels in amniotic fluid and umbilical cord serum did not correlate with umbilical artery pH or base excess, or other adverse pregnancy outcome. Conclusions. In vaginal deliveries erythropoietin levels in amniotic fluid correlated with the levels in umbilical cord serum. Erythropoietin levels correlated with gestational age, probably due to weakening placental function and relative hypoxemia occurring in advanced gestation. However, in this relatively low-risk study population erythropoietin was not related to adverse delivery outcome.

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“…Higher S100B concentrations were associated with cord blood acidosis, aEEG pattern severity, HIE severity, and correlated with neurodevelopmental sequelae at 6-year follow-up and death) [62]. In contrast, Summanen et al found cord blood S100B to be a poor NB of PA in term newborns [63] (Table 2).…”

Section: Bloodmentioning

confidence: 95%

Early predictors of perinatal brain damage: the role of neurobiomarkers

Bersani

Pluchinotta

Dotta

et al. 2019

Clinical Chemistry and Laboratory Medicine (CCLM)

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The early detection of perinatal brain damage in preterm and term newborns (i.e. intraventricular hemorrhage, periventricular leukomalacia and perinatal asphyxia) still constitute an unsolved issue. To date, despite technological improvement in standard perinatal monitoring procedures, decreasing the incidence of perinatal mortality, the perinatal morbidity pattern has a flat trend. Against this background, the measurement of brain constituents could be particularly useful in the early detection of cases at risk for short-/long-term brain injury. On this scenario, the main European and US international health-care institutions promoted perinatal clinical and experimental neuroprotection research projects aimed at validating and including a panel of biomarkers in the clinical guidelines. Although this is a promising attempt, there are several limitations that do not allow biomarkers to be included in standard monitoring procedures. The main limitations are: (i) the heterogeneity of neurological complications in the perinatal period, (ii) the small cohort sizes, (iii) the lack of multicenter investigations, (iv) the different techniques for neurobiomarkers assessment, (iv) the lack of consensus for the validation of assays in biological fluids such as urine and saliva, and (v), the lack of reference curves according to measurement technique and biological fluid. In the present review we offer an up-to-date overview of the most promising developments in the use of biomarkers in the perinatal period such as calcium binding proteins (S100B protein), vasoactive agents (adrenomedullin), brain biomarkers (activin A, neuron specific enolase, glial fibrillary acidic protein, ubiquitin carboxyl-terminal hydrolase-L1) and oxidative stress markers.

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Comparison of Umbilical Serum Copeptin Relative to Erythropoietin and S100B as Asphyxia Biomarkers at Birth

Cited by 23 publications

References 23 publications

Early sinusoidal heart rate patterns and heart rate variability to assess hypoxia–ischaemia in near‐term fetal sheep

Early sinusoidal heart rate patterns and heart rate variability to assess hypoxia–ischaemia in near‐term fetal sheep

Amniotic fluid and umbilical cord serum erythropoietin in term and prolonged pregnancies

Early predictors of perinatal brain damage: the role of neurobiomarkers

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