Reference Intervals for N-Terminal Pro-B-Type Natriuretic Peptide in Amniotic Fluid between 10 and 34 Weeks of Gestation

<div><p>Background</p><p>In adult and pediatric cardiology, n-terminal pro-B-type natriuretic peptide (nt-proBNP) serves as biomarker in the diagnosis and management of cardiovascular dysfunction. Elevated levels of circulating nt-proBNP are present in fetal conditions associated with myocardial pressure or volume load. Compared to fetal blood sampling, amniocentesis is technically easier and can be performed from early pregnancy onwards. We aimed to investigate amniotic fluid (AF) nt-proBNP concentrations in normal pregnancies between 10 and 34 weeks of gestation.</p><p>Methods</p><p>Nt-proBNP and total protein (TP) was measured in AF by chemiluminescence assay (photometry, respectively). To adjust for a potential dilutional effect, the AF-nt-proBNP/AF-TP ratio was analyzed. Reference intervals were constructed by regression modeling across gestational age.</p><p>Results</p><p>132 samples were analyzed. A negative correlation between AF-nt-proBNP/AF-TP ratio and gestational age was observed. Curves for the mean and the 5% and 95% reference interval between 10 and 34 weeks of gestation were established.</p><p>Conclusion</p><p>In normal pregnancy, nt-proBNP is present in AF and decreases during gestation. Our data provide the basis for research on AF-nt-proBNP as biomarker in fetal medicine.</p></div

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

<div><p>Background</p><p>Myocardial 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.</p><p>Methods</p><p>Ultrasound, 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.</p><p>Results</p><p>Specimen 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).</p><p>Conclusion</p><p>Amniotic 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.</p></div

Ln (AF-nt-proBNP/AF-TP) in cases (group 1, n = 171) and controls (group 2, n = 220).

<p>Lines represent the mean and the 5% and 95% reference interval.</p

Obstetric data (n = 128).

<p>*available for 31 women; ^§available for 24 women.</p><p>Obstetric data (n = 128).</p

Fetal data, including outcome (n = 128).

<p>*MoM, Multiples of the Median, available for 26 cases; ^§available for 31 cases.</p><p>Fetal data, including outcome (n = 128).</p

Study flow diagram.

<p>Study flow diagram.</p

Clinical, obstetric and laboratory details; cases and controls.

<p>Clinical, obstetric and laboratory details; cases and controls.</p

Fetal diagnoses at enrolment and delivery; cases and controls.

<p>Fetal diagnoses at enrolment and delivery; cases and controls.</p

Study flow diagram.

<p>Study flow diagram.</p

Curves for the mean and the 5% and 95% reference interval of ln(AF-nt-proBNP/AF-TP) between 10 and 34 weeks of gestation.

<p>Group 1, cases without malformations (n = 55); Group 2, cases with malformations (n = 73).</p