Maternal Plasma Pro-atrial and C-type Natriuretic Peptide Levels and Their Associations with Cardiovascular and Renal Function in the Second Half of Normal Pregnancy: a Longitudinal Study

Background: Physiological adaptation in pregnancy is characterized by remodeling of endocrine, cardiovascular and renal functions leading to fluid retention, volume expansion, altered cardiac loading conditions and hyperdynamic circulation. Natriuretic peptides have been used as biomarkers of cardiovascular function, but their associations with gestational age-related changes in maternal cardiac, endothelial and renal function have not been elucidated. The aim of this study was to establish longitudinal reference values for maternal plasma atrial natriuretic peptide (proANP) and C-type natriuretic peptide (CNP) and investigate their temporal association with cardiovascular and renal function in the second half of pregnancy.

Methods: This study was a prospective longitudinal study of 53 low-risk pregnancies. Women were examined every 3-5 weeks during 22-40 weeks of gestation (252 observations). Fasting maternal blood samples were obtained to measure proANP, CNP, creatinine, cystatin C, uric acid, and fibrinogen levels. Cardiac function and systemic hemodynamics were assessed noninvasively by impedance cardiography (ICG) and vascular endothelial function by flow-mediated vasodilation of brachial artery (FMD).

Results: The plasma proANP (Radj = 0.79; P = 0.007), CNP (R2adj = 0.54; P = 0.005) decreased between 22 and 40 weeks. The creatinine (Radj = 0.90; P < 0.001), cystatin C (Radj = 0.93; P = < 0.001) and uric acid (Radj = 0.83; P < 0.001) increased significantly, whereas the estimated glomerular filtration rate (Radj = 0.93; P < 0.001) decreased with gestational age. The FMD did not change significantly but fibrinogen (Radj = 0.79; P < 0.001) increased with advancing gestation. The maternal systemic vascular resistance index (Radj = 0.50; P < 0.001) increased, stroke index (Radj = 0.62; P < 0.001) decreased, whereas the cardiac index (Radj = 0.62; P = 0.438) and thoracic fluid content (Radj = 0.72; P = 0.132) did not change significantly with gestation. The proANP was associated with thoracic fluid content (Radj = 0.74; P < 0.001) and fibrinogen (Radj = 0.78; P = 0.034) but not with other variables of systemic hemodynamics, endothelial function, or renal function. The CNP was not associated significantly with parameters of cardiovascular or renal function.

Conclusion: Longitudinal reference values for maternal plasma proANP and CNP were established. These natriuretic peptides decreased slightly with advancing gestation, but they did not reflect the temporal physiological changes in maternal systemic hemodynamics, vascular endothelial function and renal function during the second half of pregnancy. The proANP correlated with the thoracic fluid content reflecting volume load in pregnancy.