Reference values for cord blood N-terminal pro-B-type natriuretic peptide in preterm neonates

Q: What are the key findings of this study?

Cord blood NT-proBNP levels differed significantly by gestational age (p=0.003), decreasing from median 1,950 pg/mL at <=30+6 weeks to 1,010 pg/mL at 34-36+6 weeks.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Preterm birth (26-36 weeks of gestation) (n=174). Intervention: Gestational age and perinatal factors vs. Comparison across gestational age strata (<=30+6 weeks, 31-33+6 weeks, and 34-36+6 weeks). Primary outcome: Reference intervals (5th-95th percentiles) and concentrations of umbilical cord blood NT-proBNP (pg/mL) stratified by gestational age (p=0.003).

Q: What does this research mean for the field?

Cord blood NT-proBNP concentrations in preterm neonates decrease significantly as gestational age and birth weight increase. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

Chao Tong; 蔡琛; Yi Zhao; Shiyi Jiang; Hua Peng; Yalan Liu; Jie Liu; Cong Zhao; Lin Wang; Yan Chen

doi:10.3389/fped.2026.1822173

November 2, 2026Frontiers in PediatricsOpen Access

Reference values for cord blood N-terminal pro-B-type natriuretic peptide in preterm neonates

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Key result

Cord blood NT-proBNP levels decline ~48% from early preterm to near-term gestational age.

P=0.003
n=174

Why the study?

The study aimed to establish reference values for cord blood NT-proBNP in preterm neonates and examine associations between NT-proBNP concentrations and perinatal factors.

What are the reference intervals for umbilical cord blood NT-proBNP across gestational age strata in healthy preterm neonates (26–36 weeks), and how do perinatal factors associate with NT-proBNP levels?

Key Points

To establish reference values for cord blood N-terminal pro-brain natriuretic peptide (NT-proBNP) in preterm neonates and evaluate relationships between NT-proBNP concentrations and perinatal factors.
Prospectively evaluated 174 preterm infants born at 26–36 weeks of gestation admitted to a neonatal intensive care unit in Wuhan, China, excluding infants with congenital heart disease, severe asphyxia, maternal chronic or systemic disease, abnormal fetal heart rate, or early ejection fraction ≤50%.
Measured umbilical cord blood NT-proBNP concentrations using an electrochemiluminescence sandwich immunoassay and calculated reference intervals using the 5th–95th percentiles stratified by gestational age subgroups.
Cord blood NT-proBNP levels differed across gestational age groups (p = 0.003) and correlated negatively with gestational age (r = −0.229), birth weight (r = −0.278), 1-min Apgar score (r = −0.264), and 5-min Apgar score (r = −0.290; all P < 0.01).
Multiple linear regression identified gestational age as an independent positive predictor (β = 0.299, P = 0.027) and birth weight as an independent negative predictor (β = −0.337, P = 0.007), whereas 1- and 5-min Apgar scores were not significantly associated (P > 0.05).
No significant associations were detected between NT-proBNP concentrations and infant sex, cord blood pH, premature rupture of membranes, delivery mode, or early ejection fraction.

Study Design

Type

Cohort (n=174)

Multicenter

No

Structured PICO

What are the reference intervals for umbilical cord blood NT-proBNP across gestational age strata in healthy preterm neonates (26–36 weeks), and how do perinatal factors associate with NT-proBNP levels?

P

Population

174 healthy preterm neonates born at 26–36 weeks of gestation (mean 31.7 weeks, 42.5% female) without major congenital heart disease, severe asphyxia, or maternal systemic disease, evaluated at birth and within 7 days postnatally in China.

E

Exposure

Umbilical cord blood N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement at delivery using an electrochemiluminescence sandwich immunoassay (Roche Cobas 6000), stratified by gestational age and analyzed against perinatal factors (gestational age, birth weight, Apgar scores, sex, cord blood pH, PROM, delivery mode, early ejection fraction).

C

Comparator

Comparison across gestational age subgroups: <=30+6 weeks (n=44), 31–33+6 weeks (n=94), and 34–36+6 weeks (n=36).

O

Outcome

Umbilical cord blood NT-proBNP reference intervals (5th–95th percentiles) stratified by gestational age at birth.surrogate

Main Result

p-value: p=0.003

Establishes gestational-age-stratified reference intervals for umbilical cord blood NT-proBNP in preterm neonates (26–36 weeks) and demonstrates that vaginal delivery and premature rupture of membranes do not independently elevate cord blood NT-proBNP.

Limitations

Enrolling truly healthy preterm infants was challenging, as many require medical intervention shortly after birth, potentially introducing selection bias.
The sample size was relatively small for calculating completely reliable reference ranges, with no subjects under 26 weeks of gestational age.
Single-center study design; larger multicenter studies are needed to improve precision and reliability.
Difficulty enrolling truly 'healthy' preterm infants as many require medical intervention shortly after birth, potentially introducing selection bias
Relatively small sample size for establishing definitive reference ranges, with no infants born at <26 weeks of gestation
Single-center study requiring validation in larger multicenter cohorts

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Implication

Supports gestational age-specific interpretation of cord blood NT-proBNP in preterm neonates; leaves open whether applying these thresholds improves neonatal cardiac risk stratification.

Abstract

Purpose The aim of this work is to establish reference values for cord blood N-terminal pro-brain natriuretic peptide (NT-proBNP) in preterm neonates and to examine the associations between NT-proBNP concentrations and perinatal factors. Methods Cord blood NT-proBNP levels were measured in 174 preterm infants born at 26–36 weeks of gestation. Infants were stratified by gestational age (GA), and reference intervals for cord blood NT-proBNP were calculated as the 5th–95th percentiles for each GA subgroup. Correlations between NT-proBNP concentrations and selected perinatal variables were also assessed. Results The study revealed that NT-proBNP levels showed negative correlations with GA, birth weight (BW), and Apgar scores at 1 and 5 min, with correlation coefficients of −0.229, −0.278, −0.264, and −0.290, respectively, all statistically significant at P < 0.01. However, no significant associations were observed between NT-proBNP concentrations and infant gender, cord blood pH, premature rupture of membranes (PROM), mode of delivery, or early ejection fraction (EF). Conclusion Reference intervals for cord blood NT-proBNP in preterm infants should be stratified by GA, with levels decreasing as GA and BW increase. Neither vaginal delivery nor PROM was associated with elevated NT-proBNP levels, suggesting that these perinatal factors do not independently induce significant cardiovascular stress in the fetus.

Discussion

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Cite This Study

Tong et al. (2026) conducted a cohort in Preterm birth (26-36 weeks of gestation) (n=174). Gestational age and perinatal factors vs. Comparison across gestational age strata (<=30+6 weeks, 31-33+6 weeks, and 34-36+6 weeks) was evaluated on Reference intervals (5th-95th percentiles) and concentrations of umbilical cord blood NT-proBNP (pg/mL) stratified by gestational age (p=0.003). Cord blood NT-proBNP levels differed significantly by gestational age (p=0.003), decreasing from median 1,950 pg/mL at <=30+6 weeks to 1,010 pg/mL at 34-36+6 weeks.

synapsesocial.com/papers/6aea772189a8acbed9c87b02 https://doi.org/10.3389/fped.2026.1822173

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Reference values for cord blood N-terminal pro-B-type natriuretic peptide in preterm neonates

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Reference values for cord blood N-terminal pro-B-type natriuretic peptide in preterm neonates

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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