Biventricular Reference Values Define Early Hemodynamic Stability in Preterm Infants

A newly published retrospective investigation from neonatology researchers at the First Affiliated Hospital of Nanjing Medical University has established first-week biventricular reference values and statistical growth curves for extremely preterm infants, demonstrating that conventional clinical thresholds frequently misclassify cardiovascular stability during early postnatal life. Extremely preterm neonates face their highest clinical vulnerabilities during the critical window known as the golden hour, an initial transitional phase encompassing delivery-room resuscitation, physiologic stabilization, and transport to the neonatal intensive care unit. Although the fundamental objective of these intensive golden hour protocols is to deliver a hemodynamically stable neonate to specialized intensive care, clinical stability has historically remained a subjective bedside impression rather than an objectively quantified physiological state.

This lack of objective measurement stems largely from an absence of reference values for the right-sided cardiac structures and pulmonary vascular parameters that define stability. While normative pediatric echocardiographic data have been published extensively for left-sided cardiovascular anatomy, equivalent benchmarks for right ventricular geometry and pulmonary vascular performance have been conspicuously absent, and very few existing normative datasets extend below 24 completed weeks of gestation. To address this long-standing clinical uncertainty, the research team conducted a single-center study examining 104 preterm infants born between 22 weeks 0 days and 29 weeks 6 days of gestation who had successfully emerged from the golden hour in a clinically stable condition, evaluating each infant via comprehensive echocardiography between days three and seven of life.

The investigators systematically recorded a broad profile of 38 distinct echocardiographic parameters, ultimately deriving GAMLSS z-score equations for 11 key cardiovascular metrics. To account for normal growth and maturational differences, birth weight was selected as the explanatory covariate for the two purely structural anatomical parameters analyzed, whereas gestational age was utilized as the primary modeling covariate for the remaining nine functional hemodynamic parameters. Measurement reproducibility was rigorously evaluated using intraclass correlation coefficients, establishing that inter-operator agreement remained remarkably high across 10 of the 11 modeled parameters and confirming the technical reliability of the scanning protocols across independent observers.

The physiological observations demonstrated that cardiac diastolic immaturity was near-universal across the cohort while simultaneously exhibiting pronounced gestational-age dependencies. Specifically, E/A was measured below 1 in 94 percent to 96 percent of infants born between 24+0 and 29+6 weeks of gestation, and Ar-A exceeded 0 in 100 percent of the evaluated infants. While E/A remained independent of gestational age across the cohort, IVRT lengthened with it (ρ = 0.644, P < 0.001).

Equally critical maturational trajectories were observed in the pulmonary circulation, where the pulmonary vascular resistance index—calculated as pulmonary artery acceleration time divided by right ventricular ejection time—exhibited a significant decline with advancing gestational age among infants born prior to 28 weeks (n = 69; Spearman rank correlation coefficient ρ = -0.472, P < 0.001). When the researchers evaluated conventional diagnostic standards against this stable cohort, they found that applying the traditional clinical cutoff of less than 0.25 would have falsely classified 10.7 percent of these stable neonates as having elevated pulmonary vascular resistance, an error rate that reached 26.3 percent among infants born between 26 weeks 0 days and 27 weeks 6 days. By comparison, gestational-age-specific values flagged only 1.9 percent of the cohort overall, and infants flagged by the reference were missed by the conventional cutoff.

Only 5.8 percent of the stable infants fell below the 4.8 mm TAPSE threshold linked to death or severe morbidity. To confirm that the derived reference values reflected intrinsic developmental biology rather than differences in medical therapy or circulatory shunting, the researchers performed detailed sensitivity analyses stratified by respiratory support modalities and ductal status. After statistically adjusting for gestational age, neither the mode of respiratory support nor the presence of an open ductus arteriosus showed any significant association with any of the 11 echocardiographic parameters, with all resulting P values exceeding 0.08.

Because static conventional cutoffs misclassify preterm hemodynamic status in both directions—erroneously diagnosing healthy preterm infants with vascular pathology while overlooking genuine developmental outliers—these gestational-age-specific models clarify what true cardiovascular stability looks like during the first week of life. Published in the journal Frontiers in Pediatrics, the study provides a robust developmental framework for interpreting early neonatal hemodynamics from 22 weeks of gestation onward. The authors noted that establishing these validated biventricular reference curves and GAMLSS z-score equations delivers a critical baseline for recognizing early circulatory instability and offers an essential foundation for future prospective clinical validation across neonatal intensive care units.

Subject of Research: Biventricular reference values and echocardiographic z-scores in stable preterm infants

Article Title: Biventricular reference values and GAMLSS z-scores in hemodynamically stable preterm infants born at 22+0–29+6 weeks: a first-week baseline for recognizing early circulatory instability

Article References: Zhou, J., Xia, X., & Lu, C. (2026). Biventricular reference values and GAMLSS z-scores in hemodynamically stable preterm infants born at 22+0–29+6 weeks: a first-week baseline for recognizing early circulatory instability. Frontiers in Pediatrics, 14, 2004784. https://doi.org/10.3389/fped.2026.2004784

Image Credits: AI Generated

DOI: 10.3389/fped.2026.2004784

Keywords: echocardiography, GAMLSS z-scores, preterm infants, hemodynamic stability, diastolic function, pulmonary vascular resistance, golden hour, gestational age, birth weight, tricuspid annular plane systolic excursion, isovolumetric relaxation time, neonatal intensive care unit, biventricular reference values, ductal status, respiratory support, pulmonary artery acceleration time, right ventricular ejection time, intraclass correlation