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

CONTEXT: 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. OBJECTIVES: To define trimester-specific 95% reference intervals for BNP and NT-pro BNP in pregnancy. METHODS: Longitudinal study of 260 healthy pregnant women, with sampling in each trimester. 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 = .0001), which supports the partitioning of reference intervals by body mass index (BMI). The upper limit for BNP was 50 pg/mL, with no detectable trimester-related differences. Although other biomarkers (hemoglobin 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 hemodilution. NT-pro BNP in the first trimester was inversely associated with neonatal birthweight at term (P = .011). CONCLUSION: 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.