Bronchopulmonary dysplasia (BPD) is a chronic lung disease that predominantly affects preterm infants, with pathological features characterized by alveolar simplification and impaired pulmonary vascular development [1,2]. A 2021 multicenter study in the United States reported a 40.6 % incidence among extremely preterm infants (22–29 gestational weeks) [3], while contemporaneous Chinese data showed a 29.2 % prevalence in preterm neonates born before 32 weeks. With the advancement of perinatal technologies [4–6], the survival rate of extremely preterm infants has improved markedly, which has consequently made BPD one of the most prevalent complications in this vulnerable population. Notably, BPD is frequently complicated by pulmonary hypertension (pH) and cardiac dysfunction, both of which are associated with significantly increased mortality. Current research primarily focuses on identifying risk factors for BPD, optimizing respiratory management, and developing pharmaceutical treatments. Given that the pathophysiology of BPD remains unclear and specific treatments are lacking [7], early prevention and prompt intervention for this disorder should be prioritized.

Recent advancements in echocardiography technology have led to the increasing adoption of targeted neonatal echocardiography (TNE), which is performed by neonatologists in neonatal intensive care units (NICU) [8]. This diagnostic approach provides real-time hemodynamic assessment for preterm infants and offers valuable guidance for the management of critically ill newborns. Emerging evidence suggests TNE exhibits significant potential in identifying cardiovascular abnormalities in preterm infants and optimizing neonatal cardiovascular care. The development of BPD is associated with progressive structural and functional changes in the heart, and severe BPD may potentially exacerbate cardiac deterioration [9]. Clinically, TNE has been proven effective in diagnosing and evaluating various conditions, including pericardial effusion, neonatal shock, patent ductus arteriosus (PDA), and persistent pulmonary hypertension of the newborn (PPHN). However, its application in BPD research remains limited, as relatively few studies have investigated the relationship between TNE parameters in preterm infants and the development of BPD.

The authors hypothesize that preterm infants with BPD may have systemic cardiac dysfunction. This form of cardiac dysfunction may directly or indirectly increase the infants' requirements for respiratory support, thereby contributing to the development of persistent respiratory complications. The primary objective of this study is to identify differences in echocardiographic parameters between preterm infants with BPD and healthy preterm infants, with the aim of providing a foundation for further investigating the interaction between cardiac and pulmonary function in infants with BPD.

This study systematically analyzed alterations in TNE parameters among pediatric patients with BPD. Comparative analysis identified statistically significant differences between BPD and non-BPD cohorts across key cardiac function indices: FAC, TAPSE, LVEF, MV-E, MV-E/A ratio, and tricuspid valve-related tissue Doppler imaging (TDI) parameters (TV-E′, TV-A′, TV-S′, and TV-E/E′).

BPD-related pulmonary vascular remodeling initiates a pathological cascade involving increased vascular tension, altered reactivity, vasoconstriction, and elevated pulmonary vascular resistance [14], leading to significantly elevated RV afterload. Chronic afterload elevation, coupled with hypoxic episodes, can progress to RV dysfunction, hypertrophy, and severe ventricular failure [15], Notably, early signs of BPD and respiratory insufficiency may emerge as early as postnatal day 7 [16]. A cohort study of 1735 preterm infants (23–30 weeks’ gestation) revealed a biphasic oxygen requirement pattern: initial decline from birth to day 7, followed by a resurgence in the second postnatal week [17]. Additionally, Czernik et al. [18] suggested that BPD-associated pulmonary vascular disease may impair RV function within 2 weeks of birth, though further research is needed for validation.

RV function assessment is crucial in TNE, particularly for pulmonary hypertension patients. The RV's complex crescent shape challenges geometric modeling, complicating assessment [19]. ASE Pediatric Quantification Guidelines [20] suggest standardized measurements: basal/mid-cavity end-diastolic diameters, end-diastolic longitudinal length, apical four-chamber end-systolic/end-diastolic planar areas, FAC, and TAPSE. These validated metrics are valuable in neonatal care. While right ventricular end-diastolic area (RVEDA) and end-systolic area (RVESA) showed no statistically significant differences (p > 0.05), the fractional area change (FAC) was significantly lower in the BPD group (p = 0.006). This suggests that FAC, as a functional ratio, may be a more sensitive indicator of global RV systolic performance than individual planar dimensions, which can be subject to significant inter-patient geometric variability and may be underpowered in smaller cohorts. Interestingly, while only 6.8 % of our BPD cohort met the formal criteria for pH, significant reductions in FAC and TAPSE were observed. This suggests that RV systolic impairment may precede the clinical diagnosis of overt pH, possibly reflecting “subclinical” elevation in pulmonary vascular resistance or impaired RV-pulmonary arterial coupling in the early stages of alveolar simplification [21]. Furthermore, our results were compared against established preterm neonatal normative ranges (e.g., TAPSE values of 6–10 mm) rather than adult thresholds, confirming a true functional deficit in the BPD group [22–24]. Our findings regarding reduced TAPSE and FAC in BPD infants align with those recently reported by Chakr et al. [25], who identified early echocardiographic markers of pulmonary vascular disease in at-risk preterm infants. This consistency suggests that RV systolic impairment is a robust feature of the BPD cardiopulmonary phenotype from the early stages through to 36 weeks PMA.

Our analysis showed no significant intergroup differences in tricuspid valve (TV) Doppler parameters (TV-E, TV-A, TV-E/A ratio; all p > 0.05). This aligns with their role in assessing diastolic filling, not systolic function. Neonatal cardiovascular physiology likely explains the limited clinical impact of RV diastolic dysfunction on these indices. TNE allows for thorough qualitative and quantitative assessment of global and regional LV systolic function. A prospective study found elevated LVO in the first two postnatal weeks may predict BPD in preterm infants [26], though the role of PDA in this link needs further study. In our research, BPD and non-BPD cohorts showed no significant differences in LVSV or LVO (p > 0.05). Among chamber geometry indices, LVFS and LVEF are key for LV function evaluation in pediatric critical care [27,28], While some studies show age-related LVFS increases in BPD infants [29], others report no LVEF differences between BPD and non-BPD groups [30]. Our study noted a significant decrease in LVEF in BPD infants (p = 0.003) despite comparable LVFS (p = 0.50). This discrepancy likely stems from the fact that LVFS is a linear measurement that assumes a prolate ellipsoidal geometry, which may be less accurate in BPD infants due to altered ventricular interdependence and septal flattening. LVEF, calculated via the biplane Simpson’s method, more accurately reflects global contractility by accounting for volume changes, though it remains sensitive to the increased afterload common in BPD.

MV-E and MV-A are crucial echocardiographic markers for assessing LV diastolic function. MV-E reflects the left atrial (LA)-LV pressure gradient during early diastole, influenced by LV relaxation rate and LA pressure changes. Our study showed significantly lower MV-E values in BPD infants than controls (p < 0.05), indicating impaired LV diastolic function. Physiologically, MV-E should exceed MV-A, but BPD infants had a markedly reduced MV-E/A ratio (0.58), well below the normal threshold of 1, suggesting significant diastolic dysfunction that may worsen BPD pathology. Fetal and preterm infant myocardium shows A-wave dominance, and our analysis found no significant intergroup difference in MV-A (p > 0.05). While an MV-E/A ratio < 1 indicates dysfunction in adults, preterm infants need a stricter threshold of < 0.6, and our BPD cohort's mean ratio (0.58 ± 0.3) meets this criterion. As a multifactorial disease, BPD's inflammatory pathways may increase ventricular afterload, LA pressure, and disrupt filling patterns [31]. Our findings align with previous studies linking LV diastolic impairment in BPD infants to prolonged diastolic intervals, altering the MV-E/A balance. The observed LV diastolic dysfunction (lower MV-E and MV-E/A ratio) suggests impaired myocardial relaxation. While systemic blood pressure was within normal ranges for both groups, the potential role of occult systemic hypertension or increased LV afterload from chronic inflammation cannot be ruled out as a contributor to altered filling patterns.

Tissue Doppler imaging (TDI) has emerged as a valuable tool for evaluating myocardial development in preterm infants. In our study, mitral annular TDI parameters—including MV-S′, MV-E′, MV-A′, and the MV-E/E′ — were comparable between BPD and non-BPD groups (all p > 0.05). By contrast, BPD infants exhibited significantly reduced tricuspid annular velocities (TV-S′, TV-E′, TV-A′) relative to controls (all p < 0.05), suggesting targeted RV dysfunction.

TV-S′ is a reliable marker of global RV systolic function. While adult studies define impaired RV systolic function as TV-S′ < 9 cm/s, normative data for preterm infants remain limited. Our findings align with prior research [28] which reported lower TV-S′ velocities in mild BPD infants at postnatal day 1 (6.2 ± 1.1 cm/s) and day 28 (9.3 ± 1.3 cm/s, p < 0.01) compared to non-BPD peers. Existing evidence indicates an age-dependent increase in TV-S′ during childhood, with neonates showing the most pronounced progression — likely reflecting concurrent cardiac growth and functional maturation. Furthermore, the significantly lower TV-S′ velocities observed in our BPD cohort are supported by the findings of Chakr et al. [25], further validating the utility of tricuspid annular dynamics as a sensitive indicator of targeted RV dysfunction in this population.

Among TDI parameters, the TV-E/E′ ratio is the most clinically validated measure of RV filling pressure. It directly reflects the hemodynamic consequences of diastolic dysfunction: elevated ventricular filling pressure manifests as a marked increase in TV-E/E′. Adult studies have established TV-E/E′ as a reliable correlate of elevated end-diastolic pressure and an independent predictor of heart failure. Supporting this, Akcan et al. [29] demonstrated via retrospective analysis that TV-E/E′ not only distinguishes BPD preterm infants from healthy controls but also quantifies BPD severity. Our data corroborate these observations, with statistically significant differences in TV-E/E′ ratios between BPD and control groups (p < 0.05).

This retrospective study has three limitations that should be considered when interpreting our findings. First, the relatively small size of our infant cohort may restrict statistical power, which could limit our ability to detect subtle intergroup differences; additionally, as is inherent to retrospective designs, our study is susceptible to selection bias and unmeasured confounders — such as variations in clinical management protocols not captured in medical records — that may have influenced the observed outcomes. Second, given that the study was conducted exclusively at a single tertiary care center over a 6-year period, the findings may be constrained by institutional-specific practices, including standardized TNE imaging protocols and approaches to comorbidity management; further, the authors were unable to fully account for comorbidities like pulmonary hypertension, which are known to affect cardiac function and could thus confound TNE parameter measurements. Third, our inclusion criteria were restricted to very low birth weight infants with available TNE data at 36 weeks PMA, which excluded infants with early BPD diagnoses; this focus on late-stage assessment may omit clinically relevant early-stage cardiac functional changes associated with BPD, ultimately limiting the generalizability of our results to only infants with established, late-stage BPD.

In conclusion, TNE is a viable noninvasive method for assessing BPD. Clinically, these findings emphasize that BPD management should transition from a purely “lung-centric” approach to a “cardiopulmonary” model. Early detection of biventricular dysfunction via TNE can guide precision interventions. Yet, prospective multicenter studies with standardized protocols are required to validate its efficacy in early BPD detection.

Conceptualization: Lie Huang, Jianhui Wang; Data curation: Meile Cheng, Lei Luo, Yongping Li; Formal analysis: Xi Xu; Resources: Meile Cheng; Writing – original draft: Xi Xu; Writing – review & editing: Lie Huang.

None.

The datasets are not publicly available due to ethical restrictions and institutional privacy policies. The data contains sensitive information that could compromise the anonymity of the participants. Requests to access the data should be directed to the corresponding author.