Pregnancy-specific Reference Intervals for BNP and NT-pro BNP—Changes in Natriuretic Peptides Related to Pregnancy

Abstract

Background Cardiac disease is the leading cause of maternal mortality in the UK, so accurate cardiovascular diagnoses in pregnancy are essential. BNP (B-type natriuretic peptide) and NT-pro BNP (N-terminal-pro BNP) are useful clinical tools for investigating suspected peripartum cardiomyopathy but, as the pregnancy-specific reference intervals are undefined, it is uncertain how they should be interpreted in pregnant women. Methods Longitudinal study of 260 healthy pregnant women, with sampling in each trimester to define 95% reference intervals. Results The upper reference limit for NT-pro BNP was 200 pg/mL in the first and second trimesters, and 150 pg/mL in the third. Levels were significantly reduced in overweight women in the third trimester (p=0.0001), which supports the partitioning of reference intervals by BMI. The upper limit for BNP was 50 pg/mL, with no detectable trimester-related differences. Whilst other biomarkers (haemoglobin and platelets) fell throughout pregnancy, both natriuretic peptides were initially elevated before falling by the third trimester, suggesting that the observed changes in natriuretic peptides are driven by dynamic interplay between cardiac strain and progressive haemodilution. NT-pro BNP in the first trimester was inversely associated with neonatal birthweight at term (p=0.011). Conclusions Cardiac biomarkers have an important role for investigating suspected disease in high-risk pregnant women, but a robust assessment of the levels expected in healthy pregnant women is an essential prerequisite to their application in clinical practice. This study has defined trimester- and BMI-specific reference intervals for NT-pro BNP and BNP, which may improve how women with suspected cardiovascular disease are investigated in pregnancy.

Serum miR-204 and miR-451 Expression and Diagnostic Value in Patients with Pulmonary Artery Hypertension Triggered by Congenital Heart Disease

“…It participates in the regulation of blood pressure, blood volume, and water-salt balance. And more importantly, it can reflect cardiac function [ 29 ]. ADMA is an endogenous nitric oxide synthase inhibitor, which could induces endothelial dysfunction, and plays an important role in the occurrence and development of cardiovascular diseases for a new risk factor [ 30 ].…”

Association of N-Terminal Pro–Brain Natriuretic Peptide Concentration in Early Pregnancy With Development of Hypertensive Disorders of Pregnancy and Future Hypertension

“…There are limited normative data in pregnancy to establish a threshold for elevated NT-proBNP; thus, we used normative values for nonpregnant adults . Elevated NT-proBNP concentration was defined as a concentration greater than 125 pg/mL (nonpregnant adult threshold; to convert to nanograms per liter, multiply by 1) and greater than 200 pg/mL in sensitivity analyses (recently published pregnancy reference interval) . Results are presented as adjusted ORs with corresponding 95% CIs.…”

“…21 Elevated NT-proBNP concentration was defined as a concentration greater than 125 pg/mL (nonpregnant adult threshold; to convert to nanograms per liter, multiply by 1) and greater than 200 pg/mL in sensitivity analyses (recently published pregnancy reference interval). 22 Results are presented as adjusted ORs with corresponding 95% CIs. We used t tests for normally distributed continuous variables, Wilcoxon tests for medians, and χ 2 tests for categorical variables.…”

Prevalence and Correlates of Elevated NT-proBNP in Pregnant Women in the General U.S. Population

“… 15 , 23 In women free of pre-existing cardiovascular disease, studies by Dockree et al and Umazume et al showed lower NT-proBNP and BNP levels in the third trimester compared to the first trimester, while one by Furenäs et al showed no differences in NT-proBNP. 15 , 23 , 24 However, these were (N < 300), and in clinical populations that were not racially/ethnically diverse. On the other hand, a recent longitudinal of 307 pregnant women with existing cardiovascular disease showed stable NT-proBNP levels until labor and delivery, when a transient rise occurred, followed again by return to baseline NT-proBNP levels.…”