N-terminal pro-B-type natriuretic peptide in amniotic fluid of fetuses with known or suspected cardiac load

Abstract

BackgroundMyocardial dysfunction occurs in a variety of fetal disorders. Findings from adult cardiology, where n-terminal pro-B-type natriuretic peptide (nt-proBNP) is an established biomarker of left ventricular dysfunction have been extended to fetal life. Since fetal blood sampling is technically challenging we investigated amniotic fluid nt-proBNP for its suitability to diagnose fetal myocardial dysfunction.MethodsUltrasound, Doppler examination and echocardiography was applied to classify cases and controls. Amniotic fluid nt-proBNP to amniotic fluid total protein ratio was calculated and compared to the gestational age-dependent reference intervals. In a subset of cases, fetal and maternal plasma nt-proBNP levels were determined.ResultsSpecimen from 391 fetuses could be analyzed (171 cases, 220 controls). There was a high correlation between amniotic fluid and fetal blood nt-proBNP levels (r = 0.441 for cases; r = 0.515 for controls), whereas no correlation could be detected between maternal and fetal (blood and amniotic fluid) nt-proBNP concentrations. Specificity and positive likelihood ratio of amniotic fluid nt-proBNP to amniotic fluid total protein ratio were high (0.97 and 4.3, respectively).ConclusionAmniotic fluid nt-proBNP measurement allows diagnostic confirmation of fetal myocardial dysfunction. It may serve as a useful adjunct in addition and correlation to existing tests of myocardial function, particularly in the context of invasive fetal therapy, where access to the amniotic cavity is part of the procedure.

Myocardial injury in fetal aortic stenosis: Insights from amniotic fluid analysis

“…23 This is the first study to report elevated NT-BNP in response to LV pressure load in the human fetus. Our results are in agreement with prior studies that have shown higher BNP in human fetuses with volume loading lesions 16,17 and in animal models of LV pressure load. 18 In adults with AS, greater LV pressure leads to increased ventricular wall stress and myocyte stretch, both of which are responsible for adverse remodeling.…”

“…Troponin is a cardiac muscle protein that is integral in muscle contraction and is released in response to myocardial cell injury or death. Amniotic fluid BNP has been shown to correlate with fetal blood BNP levels 17 and to be elevated in fetal volume overload states, including twin-twin transfusion and congenital cardiac defects. 16,17 In a fetal sheep model of supravalvar AS, amniotic fluid BNP levels were elevated compared with controls and the degree of BNP elevation correlated with AS severity and LV hypertrophy.…”

“…Amniotic fluid BNP has been shown to correlate with fetal blood BNP levels 17 and to be elevated in fetal volume overload states, including twin-twin transfusion and congenital cardiac defects. 16,17 In a fetal sheep model of supravalvar AS, amniotic fluid BNP levels were elevated compared with controls and the degree of BNP elevation correlated with AS severity and LV hypertrophy. 18 In this study we evaluate if NT-BNP and troponin are elevated in mid-gestation fetuses with severe AS.…”

Fetal NT-proBNP levels and their course in severe anemia during intrauterine treatment

“…In contrast to image-based diagnostics, there is no inter- or intraobserver variability. The correlation between cardiac stress and NT-proBNP concentration also appears to be strong in the fetal organism [ 7 , 11 , 16 , 17 ]. Although MCA-PSV measurement shows high reliability for anemia diagnosis, it cannot reliably predict the occurrence of hydrops fetalis [ 18 ] and the severity of cardiac compromise and is affected during IUT therapy by transfused adult erythrocytes [ 19 ].…”

Prognostic value of heart failure biomarkers in the assessment of cardiac dysfunction in the fetus and newborn

“…C. Leufgen [41] в исследовании установил, что определение NT-proBNP в околоплодных водах служит методом диагностики дисфункции миокарда у плода. Хроническая перегрузка объемом, предили постнагрузка приводят к вторичной экспрессии генов, участвующих в развитии сердца плода, с последующим ремоделированием сердца, которое опосредуется через BNP.…”