Fetal ultrasound parameters associated with N-terminal pro-B-type natriuretic peptide levels in umbilical cord blood: a cross-sectional study

Background Current Doppler and functional ultrasound parameters, such as the cardiovascular profile score, umbilical artery pulsatility index, and ductus venosus pulsatility index, are valuable for detecting advanced fetal cardiac decompensation; however, they have limited ability in identifying subtle hemodynamic changes. This critical gap in current fetal assessment highlights the need for reliable markers that can identify subtle cardiac stress before overt failure. In this study, we aimed to identify fetal ultrasound parameters associated with umbilical venous N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, a biomarker associated with fetal cardiac load. Methods We conducted a single-center, cross-sectional study at a tertiary perinatal medical center, recruiting women with singleton pregnancies undergoing cesarean delivery at ≥22 weeks of gestation. Fetal ultrasonographic examinations were performed within 7 days before delivery, and NT-proBNP levels were measured in umbilical venous blood collected immediately after birth. NT-proBNP values were natural log-transformed (Ln NT-proBNP) to address the non-normality of the residuals in the regression models, and gestational age-adjusted linear regression analyses were performed. Results A total of 202 pregnant women were included in the analyses. A higher left to right cardiac output (LCO/RCO) ratio was significantly associated with lower Ln NT-proBNP levels (estimate: −0.206; 95% confidence interval [CI]: −0.314 to −0.097), whereas a higher anterior tibial artery to renal artery peak systolic velocity (ATA-PSV/RA-PSV) ratio was significantly associated with higher Ln NT-proBNP levels (estimate: 0.149, 95% CI: 0.047 to 0.251). Conclusions LCO/RCO and ATA-PSV/RA-PSV were associated with NT-proBNP levels. LCO/RCO consistently improved model performance. While ATA-PSV/RA-PSV may reflect aspects of peripheral circulation not captured by conventional indices, its incremental value beyond gestational age was modest. Further studies are needed to validate these findings and clarify their clinical significance. Trial registration This study was prospectively registered for transparency in the UMIN Clinical Trials Registry (UMIN-CTR; ID: UMIN000047081, registered on March 4, 2022), as it was an observational cross-sectional study without any intervention or randomization.