Subclinical cardiac dysfunction in preschool children with a history of bronchopulmonary dysplasia: a pilot cohort study

Abstract

Background

Bronchopulmonary dysplasia (BPD) is a prevalent complication of prematurity associated with long-term respiratory and cardiovascular sequelae. While adolescent and adult outcomes have been extensively documented, early childhood cardiac function in BPD survivors remains poorly characterized. This study aimed to evaluate subclinical cardiac alterations in preschool-aged children with a history of BPD using detailed echocardiography and 24-hour Holter monitoring.

Methods

In this prospective cohort study, 122 children were classified into three groups: preschool children with BPD (≤ 32 weeks gestation or < 1500 g; Group 1), gestational age- and birth weight-matched preterm controls without BPD (Group 2), and healthy term controls (Group 3). Perinatal and neonatal data were extracted from medical records. Comprehensive echocardiography including M-mode, Doppler, and tissue Doppler imaging (TDI) assessed right and left ventricular systolic and diastolic function, interventricular septal mechanics, and myocardial performance index. Autonomic regulation was evaluated using 24-hour Holter monitoring. Statistical significance was defined as p < 0.05.

Results

Demographics including age, sex, height, and weight were comparable across groups. Chronic pulmonary changes on chest radiography were present in 31.25% of BPD children, significantly higher than in preterm controls (p = 0.013). Conventional systolic echocardiographic indices (ejection fraction, fractional shortening) were within normal limits in all groups. However, BPD children exhibited right ventricular diastolic dysfunction, with decreased E/A ratio, prolonged isovolumic relaxation time (IVRT), and altered systolic-diastolic timing. TDI revealed subclinical interventricular septal systolic impairment. Left ventricular systolic function was preserved, with mild prolongation of LV diastolic relaxation. No significant differences were observed in heart rate variability or blood pressure percentiles among groups.

Conclusions

Preschool children with a history of BPD exhibit subclinical right ventricular and septal dysfunction despite preserved left ventricular systolic performance, normal autonomic regulation, and age-appropriate blood pressure. These findings highlight the early cardiovascular impact of BPD-related pulmonary pathology and underscore the importance of longitudinal cardiac surveillance in this high-risk population to guide preventive interventions.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s12887-026-07311-6.

Introduction

Bronchopulmonary dysplasia (BPD), remains one of the most critical complications associated with prematurity. The incidence of BPD has continued to rise as more infants born before 28 weeks of gestation survive [1]. Improvements in obstetric and neonatal care, such as antenatal corticosteroids, surfactant therapy, and neonatal intensive care advancements, have increased survival in infants at lower gestational ages. Consequently, BPD incidence decreased in more mature infants, while extremely preterm infants often develop BPD [2, 3]. Originally described by Northway et al. in 1967 as a fibrotic and inflammatory lung condition resulting from prolonged mechanical ventilation and high oxygen exposure in premature infants [4].

Although the definition of BPD has been revised multiple times over the past 50 years due to increasing survival of extremely preterm infants and the development of new respiratory support modalities, the NICHD 2001 definition remains the most widely used in both clinical practice and research [3–5]. Despite concerns that this definition may not reliably predict long-term outcomes, it continues to serve as the standard framework in many studies, including the present one.

Because BPD is associated with significant long-term respiratory, cardiovascular, neurodevelopmental, and growth complications, accurate early diagnosis and severity grading are essential for predicting outcomes and identifying high-risk infants who may benefit from timely interventions [6, 7]. Morbidity and mortality are highest in the first year, gradually declining thereafter. Lung morbidity remains high throughout life, with recurrent wheezing affecting roughly 50% of low birth weight infants, continuing in 33% of school-aged children. Residual volume improves by 8–10 years, yet airway resistance may remain elevated into adulthood [8, 9]. BPD not only affects the respiratory system but may also impact cardiovascular function. Pulmonary hypertension (PH) is a major cardiac complication, resulting from chronic hypoxia and structural changes in pulmonary vessels, which may persist into school age and increase right heart load [7]. Echocardiographic evaluation of PH in early childhood can reduce the risk of long-term cardiopulmonary complications [10]. Right ventricular hypertrophy is observed in up to 50% of school-aged children with BPD, and mortality can reach 40% in patients with severe BPD who develop cor pulmonale [11, 12]. Other potential cardiac issues include systemic hypertension and arrhythmias, warranting careful monitoring [11].

In this study, we examined pulmonary and cardiac complications in preschool-aged children with BPD. Given the challenges of performing pulmonary function tests in children younger than five years, right ventricular function was evaluated using detailed echocardiographic measurements. Through this combined assessment, we aimed to identify early cardiovascular effects associated with BPD.

Materials and methods

This prospective cohort study was conducted in the pediatric cardiology outpatient clinic of a tertiary care center. Children aged 3–6 years who had previously been followed in the same institution’s neonatal intensive care unit (NICU) were invited to participate. The study was approved by the local institutional ethics committee, and written informed consent was obtained from the parents or legal guardians of all participants.

Study population

A total of 122 children were enrolled and classified into three groups:

• Group 1 (BPD group): Forty-eight preterm children born at ≤ 32 weeks of gestation or with a birth weight < 1500 g and diagnosed with bronchopulmonary dysplasia according to the NICHD 2001 criteria.

• Group 2 (Preterm control group): Forty-four preterm children with similar gestational age and birth weight but without a diagnosis of BPD.

• Group 3 (Term control group): Thirty healthy children born at term (≥ 37 weeks gestation) with appropriate birth weight.

Inclusion and exclusion criteria

Inclusion criteria

Preterm infants with very low birth weight (< 1500 g) or extremely low birth weight (< 1000 g), followed up regularly in NICU and outpatient clinics, and aged between 3 and 6 years at the time of evaluation.

Exclusion criteria

Children with congenital heart disease, multiple congenital anomalies, chromosomal abnormalities, inborn metabolic disorders, or significant neurological impairment were excluded.

Data collection

Perinatal and neonatal data were retrieved from hospital electronic medical records and included gestational age, birth weight, sex, mode of delivery, antenatal and postnatal steroid exposure, surfactant therapy, duration of mechanical ventilation and oxygen supplementation, and neonatal morbidities such as respiratory distress syndrome (RDS), sepsis, necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA), and retinopathy of prematurity (ROP).

Clinical evaluation

All children underwent standardized clinical evaluation. Blood pressure measurements were obtained under resting conditions at three different time points using an appropriately sized cuff, and values were interpreted according to age-, sex-, and height-specific percentiles. However, these children may exhibit masked hypertension despite having normal office blood pressure readings. Masked hypertension can only be accurately identified through 24-hour ambulatory blood pressure monitoring (ABPM), which was not performed in our study population.

Echocardiographic assessment

Comprehensive transthoracic echocardiography was performed by an experienced pediatric cardiologist using a commercially available ultrasound system (e.g., Vivid S70, GE Healthcare, Horten, Norway) equipped with a phased-array transducer (3–8 MHz).

All measurements were obtained with the patient in the left lateral decubitus position and were recorded simultaneously with electrocardiographic (ECG) monitoring to ensure accurate timing within the cardiac cycle.

Standard M-mode, two-dimensional, pulsed-wave Doppler, and tissue Doppler imaging (TDI) techniques were applied according to the recommendations of the American Society of Echocardiography.

Conventional Echocardiographic Measurements Left ventricular (LV) systolic function was assessed using: Left ventricular systolic function was assessed using ejection fraction (EF, %), calculated by the modified Simpson method, and fractional shortening (FS, %), obtained from M-mode echocardiography. Diastolic function was evaluated by measuring transmitral and transtricuspid inflow velocities with pulsed-wave Doppler, from which early diastolic velocity (E, cm/s), late diastolic velocity (A, cm/s), and the E/A ratio were derived; deceleration time (DT, ms) and isovolumic relaxation time (IVRT, ms) were additionally recorded. Tissue Doppler Imaging (TDI) was performed by positioning the sample volume at the lateral and septal mitral annulus and the lateral tricuspid annulus, enabling measurement of peak systolic velocity (S′, cm/s), early and late diastolic velocities (E′ and A′, cm/s), the E′/A′ ratio, isovolumic contraction velocity (IVC, cm/s), isovolumic contraction time (IVCT, ms), and isovolumic relaxation time (IVRT, ms). Finally, the myocardial performance index (MPI) was calculated using the formula MPI = (IVCT + IVRT) / ET, where ET denotes ejection time, providing an integrated measure of both systolic and diastolic ventricular performance independent of geometric assumptions.

All Doppler and TDI measurements were obtained at end-expiration to minimize respiratory variation and averaged over three consecutive cardiac cycles. Additionally, TDI measurements were performed at a heart rate range of 90–120 bpm, and the Nyquist limit, gain, and filter settings were optimized and recorded for reproducibility.

Holter electrocardiography

Twenty-four-hour ambulatory electrocardiographic monitoring was performed using a digital Holter system (e.g., GE SEER Light Holter system, GE Healthcare, USA). Recordings were analyzed using dedicated software by an experienced cardiologist blinded to group allocation.

The following heart rate variability (HRV) parameters were assessed: Time-domain parameters: Twenty-four-hour ambulatory electrocardiographic monitoring was performed using a digital Holter system (GE SEER Light Holter system, GE Healthcare, USA). The Holter recordings were sampled at 1000 Hz, and all artifacts and ectopic beats were automatically detected and manually verified prior to analysis. Subsequently, the recordings were analyzed using dedicated software by an experienced cardiologist blinded to group allocation. To evaluate heart rate variability (HRV), time-domain parameters—including the standard deviation of all normal RR intervals (SDNN, ms), the standard deviation of 5-minute average NN intervals (SDANN, ms), the root mean square of successive differences (rMSSD, ms), and pNN50 (%) were assessed. Additionally, frequency-domain parameters consisting of very low frequency (VLF, ms²), low frequency (LF, ms²), high frequency (HF, ms²) and the LF/HF ratio were determined. The Holter recordings were sampled at 1000 Hz, and all artifacts and ectopic beats were automatically detected and manually verified prior to analysis.

Statistical analysis

Statistical analyses were performed using SPSS software (version 25.0, IBM Corp., Armonk, NY, USA). Data distribution was assessed using visual (histograms, Q–Q plots) and analytical methods (Shapiro–Wilk test). Continuous variables were expressed as mean ± standard deviation (SD) or median (min–max) depending on distribution. Categorical variables were expressed as frequencies and percentages. Between-group comparisons were performed using: Student’s t-test or one-way ANOVA for normally distributed variables, Mann–Whitney U test or Kruskal–Wallis test for non-normally distributed variables, Chi-square or Fisher’s exact test for categorical variables, correlation analyses were conducted using Pearson or Spearman correlation coefficients as appropriate. A p-value < 0.05 was considered statistically significant.

Results

The demographic characteristics of the patients enrolled in the study, including age, sex, weight, height, and gestational age, were compared. No significant differences were observed among the groups in terms of age, sex, height, or weight. The demographic characteristics of the groups are presented in Table 1. Patients in group 1 were evaluated at a mean age of 63.9 ± 22 months, with similar evaluation ages in the other groups. However, gestational ages of groups 1 and 2 were significantly lower than those of group 3. Additionally, the gestational age of group 1 was significantly lower than that of group 2. No significant differences were found between groups 1 and 2 in terms of mode of delivery, birth weight, or prenatal steroid administration.

Table 1.

Demographic characteristics of the groups

Variable	Group 1 (BPD)	Group 2 (Preterm control)	Group 3 (Term control)	p-value
Age (mean month)	63,9±22	64,27±17,5	64,06±19,68	0,998
Weight (mean kg)	16,33±4,42	16,73±3,11	16,88±3,96	0,879
Height (mean cm)	102,17±11,45	105,07±8,23	103,94±9,6	0,610
Gestational Age	27,38±1,89	29±1,73	38,06±0,68	0,0001
Gestational age (weeks)	27.4 ± 1.9	29.0 ± 1.7	38.1 ± 0.7	<0.001
Delivery type (C/S / VD)	30 (62.5%) / 18 (37.5%)	21 (73.3%) / 7 (26.7%)	–	0.263
Birth weight <750 g / 750–1250 g / >1250 g	9 / 32 / 7	2 / 18 / 8	–	0.181
Antenatal steroid (Yes/No)	43/48 (89.6%)	26/28 (92.9%)	–	0.634
RDS (Yes/No)	44/48 (91.7%)	19/28 (67.9%)	–	0.008
Surfactant therapy (Yes/No)	44/48 (91.7%)	19/28 (67.9%)	–	0.008
Mechanical ventilation (Yes/No)	46/48 (95.8%)	20/28 (71.4%)	–	0.002
Postnatal steroid (Yes/No)	48/48 (100%)	0/28 (0%)	–	<0.001
Sepsis (Yes/No)	42/48 (87.5%)	18/27 (66.7%)	–	0.03
Systolic blood pressure (mmHg)	93.2 ± 7.3	94.1 ± 5.1	93.8 ± 6.5	0.78
Diastolic blood pressure (mmHg)	53.1 ± 4.1	53.1 ± 4.3	54.2 ± 3.9	0.9

Data are presented as mean ± standard deviation (SD)

In group 1, statistically significant differences were observed regarding the presence of RDS, requirement for mechanical ventilation, surfactant therapy, and postnatal steroid use. Specifically, the risk of developing RDS, the need for surfactant therapy, the requirement for mechanical ventilation, and postnatal steroid use were all significantly higher in group 1.

Blood pressure measurements were evaluated across the term, preterm, and bronchopulmonary dysplasia (BPD) groups. There were no statistically significant differences among the three groups in terms of systolic or diastolic blood pressure (p > 0.05). (Table 1)

Electrocardiographic evaluation revealed findings suggestive of Wolff–Parkinson–White syndrome in one patient from group 1. The diagnosis was confirmed with 24-hour Holter ECG monitoring, and medical treatment was initiated, with subsequent follow-up.

Chest radiographs of children in groups 1 and 2 were evaluated. Chronic changes were detected in 31.25% (15 cases) of chest X-rays in group 1, whereas no pathological findings were observed in group 2. This difference was statistically significant (p = 0.013). Chest radiographs were evaluated by pediatric radiologists. Chronic pulmonary changes were defined based on the presence of hyperinflation, flattened diaphragms, irregular parenchymal linear opacities (atelectatic bands or fibrotic strands), peribronchial thickening, and scattered (patchy) opacities. Cystic lung changes or prominent vascular markings observed in some cases were also recorded as pathological findings.

In all children with BPD, M-mode echocardiographic parameters were within normal limits. Echocardiographic assessment of systolic function revealed no statistically significant differences in mean ejection fraction or fractional shortening among the three groups. (Table 2).

Table 2.

Evaluation of cardiac measurements with echocardiography

	Group 1	Group 2	Group 3	p
IVSd	5,15±0,86	5,07±0,7	5,4±0,61	0,446
IVSs	7,43±1,06	8,53±0,74	8,19±1,05	0,0001
LVDd	32,17±3,37	33,27±2,63	37±3,33	0,0001
LVDs	18,66±2,49	19,33±2,23	21,69±2,55	0,0001
LVPWd	5,72±1,1	4,93±0,96	5,88±0,62	0,016
LVPWs	10,83±1,58	10,67±0,82	10,81±0,75	0,916
ESV	10,83±3,63	13,5±4,51	14,63±1,15	0,001
EDV	42,13±10,47	49±13,45	52,06±1,61	0,002
Ao	16,79±2,15	16,53±1,13	18,56±1,79	0,004
LA	21,74±3,03	23,07±2,09	24,64±1,65	0,002
PA	15,84±2,21	15,27±1,1	18,38±2,73	0,0001
PAldv	0,25±0,08	0,16±0,02	0,14±0,01	0,0001
PAv	0,95±0,13	0,86±0,11	0,73±0,1	0,0001
FS	41,74±5,75	40,73±4,7	40,75±3,97	0,712
EF	73,85±6,8	73,27±6,41	73,13±4,05	0,901

IVSd diastolic diameter of the interventricular septum (mm), IVSs systolic diameter of the interventricular septum (mm), LVDd left ventricular end-diastolic diameter (mm), LVDs left ventricular end-systolic diameter (mm), LVPWd left ventricular posterior wall diastolic diameter (mm), LVPWs left ventricular posterior wall systolic diameter (mm), ESV end-systolic volume (mL), EDV end-diastolic volume (mL), Ao aortic root diastolic diameter (mm), LA left atrium diameter (mm), PA pulmonary artery diameter (mm), PAldv pulmonary artery late diastolic velocity (cm/s), PAv pulmonary artery velocity (cm/s), EF ejection fraction (%), FS fractional shortening (%), E early diastolic velocity (cm/s), A late atrial velocity (cm/s), E/A ratio of early to late filling (unitless), IVRT isovolumic relaxation time (ms), IVCT isovolumic contraction time (ms), DECt deceleration time (ms), Dt total diastolic time (ms), Sv systolic velocity (cm/s), St systolic time (ms). Data are presented as mean ± standard deviation (SD)

Tricuspid and pulmonary flows were assessed by PW and CW Doppler. Right ventricular systolic pressure (via tricuspid regurgitation) and pulmonary artery diastolic pressure (via pulmonary regurgitation) were measured, and all patients exhibited normal pulmonary artery pressures. Systolic and diastolic functions of the right ventricle (RV), left ventricle (LV), and interventricular septum (IVS) were assessed using tissue Doppler echocardiography. In BPD patients of group 1, compared to groups 2 and 3, RV systolic and diastolic functions showed significant increases in RV E, A, IVRT, IVCT, and Sv parameters, whereas E/A ratio, deceleration time (Dect), total time (Tt), and St parameters were significantly decreased (Fig. 1). Regarding LV function, the E/A ratio was significantly reduced, and IVRT was significantly increased in group 1. No significant differences were observed in LV systolic parameters among the groups (Fig. 2).

Fig. 1.

Tissue Doppler ımaging(TDI) measurements obtained from the lateral segment of the tricuspid annulus demonstrate normal right ventricular systolic function with reduced diastolic function (E=A)

Fig. 2.

Normal left ventricular systolic and diastolic function are demonstrated by tissue Doppler ımaging (TDI) measurements obtained from the lateral mitral annulus

Assessment of IVS systolic and diastolic functions revealed significant differences in IVSDtı St and IVSDtı Sv values between group 1 and groups 2 and 3. IVS systolic functions were reduced in group 1, and this reduction was statistically significant (Table 3).

Table 3.

Evaluation of interventricular septum, right and left ventricular systolic and diastolic functions with tissue Doppler imaging

	Group 1	Group 2	Group 3	p
RV	0,17±0,03	0,15±0,02	0,16±0,02	0,042
RV A	0,11±0,04	0,08±0,02	0,08±0,01	0,001
RV E/A	1,65±0,46	1,93±0,35	1,93±0,24	0,013
RV IVRT	18,24±3,12	16,33±1,4	17,31±1,74	0,048
RV DECt	19,94±3,41	21,07±3,01	19,19±0,83	0,218
RVDt	293,37±37,58	340,13±41,07	361,5±47,11	0,0001
RV IVC	0,09±0,02	0,06±0,01	0,08±0,02	0,0001
RV Sv	0,13±0,02	0,11±0,03	0,12±0,01	0,002
RV St	284,37±27,06	303,07±23,87	313,5±13,13	0,0001
LV E	0,16±0,02	0,17±0,01	0,17±0,02	0,722
LV A	0,07±0,02	0,06±0,01	0,07±0,01	0,095
LV E/A	2,58±0,6	3,06±0,39	2,68±0,55	0,018
LV IVRT	17,22±2,47	15,53±1,51	15,25±0,58	0,001
LV DE	16,93±2,75	17,2±2,11	16,94±1,18	0,928
LV Dt	291,56±48,45	311,4±47,63	319,69±39,22	0,082
LV IVC	0,04±0,01	0,04±0,01	0,04±0,01	0,107
LV Sv	0,08±0,02	0,07±0,01	0,08±0,01	0,041
LV St	275,82±26,17	305,87±17,03	300,69±11,52	0,0001
IVS E	0,13±0,02	0,12±0,01	0,13±0,01	0,179
IVS A	0,06±0,01	0,06±0,01	0,05±0,01	0,026
IVS E/A	2,26±0,47	2,21±0,27	2,55±0,46	0,059
IVS IVRT	17,69±2,59	16,27±1,71	15,19±1,05	0,001
IVS Dt	295,48±43,02	312,87±31,77	369,75±61,62	0,0001
IVS DECt	17,19±2,8	16±2,67	16,13±0,89	0,158
IVS IVC	0,04±0,01	0,04±0,01	0,04±0,01	0,695
IVS St	284,27±23,59	295,07±20,82	309,75±14,14	0,0001
IVS Sv	0,07±0,02	0,06±0,01	0,06±0,01	0,004

Data are presented as mean ± standard deviation (SD)

Abbreviations RV right ventricle, LV left ventricle, IVS interventricular septum, E peak early diastolic velocity(cm/s), A peak late diastolic velocity(cm/s), E/A ratio of peak early to late diastolic velocity, IVRT isovolumic relaxation time(ms), IVC isovolumic contraction velocity (cm/s), DECt deceleration time(ms), Dt total duration(ms), St systolic time(ms), Sv peak systolic velocity(cm7s), p p-value*

Analysis of 24-hour Holter ECG parameters revealed no significant differences among the groups in terms of total power, VLF, LF, HF, 24HSDNN, SDNNI, SDANNI, RMSSD, PNN50, mean heart rate, or LF/HF ratio (Table 4).

Table 4.

Assessment of heart rate variables

	Group 1	Group 2	P
SDNN 24	109,21±25,34	128±2,45	0,112
SDANN	99,04±26,85	120,2±6,3	0,093
SDNN	53,29±14,24	52,8±4,87	0,941
rMSSD	37,71±12,96	45,8±9,91	0,196
PNN50	14,5±8,74	16,6±2,7	0,602
Tpow	2829,39±1539,72	2198,4±93,48	0,373
VLF	1746,71±1100,78	1315,8±179,6	0,395
LF	610,75±322,27	581,2±180,3	0,844
HF	416,43±277,27	415,2±131,91	0,992
HF/LF	0,69±0,33	0,71±0,02	0,889
MHR	99±7,46	102±4,95	0,396

SDNN standard deviation of NN intervals (ms), SDANN standard deviation of averages of NN intervals for 5-min segments (ms), rMSSD root mean square of successive differences (ms), PNN50 percentage of adjacent NN intervals >50 ms (%), Tpow total power (ms²), VLF/LF/HF very low / low / high frequency components (ms²), HF/LF autonomic balance (unitless), MHR mean heart rate (beats per minute, bpm). Data are presented as mean ± standard deviation (SD)

Correlation analysis did not demonstrate any significant association between the primary outcome parameter and clinical variables, including age, gestational age, birth weight, and body mass index (p > 0.05 for all). In multivariable linear regression analysis, none of the evaluated variables were identified as independent predictors of the outcome parameter (p > 0.05 for all).

Discussion

In this study, we evaluated cardiac function in preschool-aged children with a history of BPD and compared them with healthy preterm and term controls. Although the long-term adverse consequences of BPD are well established, data specifically addressing early childhood outcomes remain limited [3, 4]. Our study contributes to this knowledge gap by assessing cardiac and indirectly pulmonary parameters in a particularly vulnerable preschool population. The primary finding of our study is that preschool children with a history of BPD exhibit significant subclinical right ventricular (RV) diastolic dysfunction compared to both healthy term and premature controls. In Group 1 (BPD group), a decrease in the E/A ratio and a prolongation of the IVRT duration were observed compared to the other two groups. These observations support the presence of subclinical RV diastolic dysfunction, likely reflecting pulmonary pathology–related hemodynamic burden, while preserved systolic indices suggest an early-stage process. Furthermore, assessment of the interventricular septum (IVS) showed prolonged IVRT, increased deceleration time, and reduced systolic annular velocity (s’), consistent with septal dysfunction secondary to RV impairment. In summary, septal dysfunction is often secondary to RV impairment. Because the septum is a shared wall, any diastolic stiffness or pressure increase in the right ventricle directly disrupts the septal geometry and its mechanical performance, eventually affecting the filling and performance of the entire heart.

Radiographic analysis revealed chronic lung changes in 31.25% of children in Group 1, whereas no abnormalities were found in Group 2; this difference was statistically significant (p = 0.013). Given the limited feasibility of reliable spirometry in preschool-aged children, cardiopulmonary interaction was primarily evaluated using echocardiography.

In our cohort, children with BPD exhibited smaller left ventricular (LV), left atrial (LA), and pulmonary artery diameters compared with their healthy peers, although all measurements remained within normal reference ranges. Similar findings have been reported in other studies of extremely preterm and BPD populations, suggesting mild cardiac remodeling [13–15].

Similar studies have likewise reported smaller LV and LA dimensions in extremely preterm children, albeit generally within normal ranges [13]. Furthermore, BPD children exhibited right ventricular (RV) diastolic dysfunction with preserved systolic function, consistent with previously published data [10]. While smaller left heart dimensions were observed in our cohort, the underlying etiology remains speculative. This finding may reflect cardiac remodeling secondary to altered pulmonary hemodynamics; however, it could also be a direct consequence of premature birth on myocardial development and maturation, independent of pulmonary function.

Tissue Doppler imaging demonstrated RV diastolic impairment characterized by reduced E/A ratio, prolonged IVRT, and shortened systolic–diastolic time intervals—findings indicative of impaired early diastolic relaxation and incomplete ventricular filling. These observations support the presence of subclinical RV diastolic dysfunction, likely reflecting pulmonary pathology–related hemodynamic burden, while preserved systolic indices suggest an early-stage process.

Assessment of the interventricular septum (IVS) showed prolonged IVRT, increased deceleration time, and reduced systolic annular velocity (s′), consistent with septal dysfunction secondary to RV impairment. LV TDI parameters revealed isolated IVRT prolongation, suggesting delayed early relaxation and possible Grade 1 diastolic dysfunction without evidence of elevated filling pressures or impaired systolic performance.

Persistent subclinical cardiac dysfunction in BPD can be mechanistically explained by chronic alterations in pulmonary vascular development, alveolarization deficits, and pulmonary vascular remodeling. These changes increase right ventricular afterload, induce myocardial wall stress, and promote subclinical myocardial remodeling. Long-term exposure to intermittent hypoxia, inflammation, and oxidative stress may further exacerbate RV diastolic dysfunction. Recent studies demonstrate that early hemodynamic alterations in preterm infants with BPD, including decreased pulmonary artery acceleration time (PAAT) and reduced TAPSE, correlate with later subclinical RV impairment [16, 17]. Additionally, BPD-related pulmonary vascular disease may influence LV diastolic function through interventricular interactions, explaining isolated LV IVRT prolongation observed in our cohort [18, 19]. These findings highlight the complex cardiopulmonary interplay in BPD and support longitudinal cardiac monitoring.

Persistent systemic hypertension observed in school-age children with a history of BPD is considered a manifestation of long-term cardiovascular and renal remodeling that originates in neonatal life. Reduced nephron endowment, heightened sympathetic activity, RAAS dysregulation, vascular remodeling, chronic lung disease, and intermittent hypoxia contribute to this process [20, 21]. Accordingly, children with BPD constitute a high-risk group requiring careful monitoring for hypertension. In the present study, however, no systemic hypertension was detected in any group based on the 2017 AAP criteria [22].

Consistent with previous literature, our study did not demonstrate elevated blood pressure levels in preschool-aged children with a history of BPD. Previous studies with long-term follow-up have shown that children born preterm may develop hypertension later in life, although this is not usually evident in early childhood [21, 23, 24]. The absence of hypertension in our cohort likely reflects the early stage of cardiovascular remodeling. Nevertheless, given the known long-term risk, our findings further emphasize the importance of continued blood pressure monitoring as part of longitudinal follow-up in children with BPD.

Although prematurity and BPD can disrupt early autonomic nervous system (ANS) maturation, partial recovery or adaptive compensation may occur as children grow. While some autonomic alterations persist into adulthood in individuals born preterm, overall long-term regulatory capacity may remain largely preserved [25, 26]. Early-life stressors including oxygen dependence, hypoxia, and mechanical ventilation can disrupt autonomic nervous system (ANS) balance in infants with BPD, as evidenced by studies reporting altered heart rate variability (HRV) patterns during infancy [27]. HRV abnormalities observed in early childhood have been associated with later manifestations of autonomic dysfunction [28]. In young adults born preterm, impaired cardiac response and exercise capacity have also been reported [29]. Some evidence suggests that ANS dysfunction may be mild or normalize in childhood. Consistent with this, HRV parameters in our study did not differ significantly between groups, aligning with studies indicating limited early ANS impairment in preschool-aged children [25].

Long-term follow-up studies show that subclinical cardiac dysfunction and reduced exercise capacity may still emerge later in life among individuals born preterm, including those with BPD [30]. Thus, the absence of HRV differences in our cohort does not indicate absence of risk; rather, it underscores the need for longitudinal cardiovascular and ANS monitoring. Clinical follow-up should incorporate age-appropriate blood pressure assessments, ambulatory BP monitoring when indicated, serial echocardiography, and HRV analysis to detect early subclinical alterations and guide preventive management.

This study has several limitations that should be acknowledged. First, the relatively small sample size, particularly in Group 2 (n = 28) and Group 3 (n = 30), may limit the statistical power to detect subtle differences in some parameters. Second, the cross-sectional design precludes causal inference and limits our ability to assess the trajectory of cardiac changes over time. Third, pulmonary function testing was not performed due to the challenges of spirometry in children under five years of age; therefore, a direct correlation between pulmonary function and echocardiographic parameters could not be established. Fourth, 24-hour ambulatory blood pressure monitoring (ABPM) was not performed, which means that masked hypertension cannot be excluded despite normal office blood pressure readings. Finally, this study was conducted at a single tertiary center, which may limit the generalizability of the findings to other populations. Despite these limitations, this study provides novel echocardiographic data in a preschool BPD cohort and highlights the importance of early and longitudinal cardiovascular surveillance in this high-risk population.

Conclusion

In preschool-aged children with a history of bronchopulmonary dysplasia (BPD), we identified subclinical impairments in both systolic and diastolic function of the right ventricle and the interventricular septum, whereas left ventricular function remained largely preserved. Mild deviations in cardiac morphometric parameters further suggest early structural cardiac involvement linked to BPD. In contrast, comparable heart rate variability and blood pressure measurements across groups indicate that autonomic regulation may remain relatively preserved in early childhood. Recognition of these subtle yet meaningful cardiac alterations is clinically important, as they underscore the need for long-term cardiovascular and respiratory surveillance, inform structured follow-up strategies, and support timely preventive interventions in this high-risk population.

Authors’ contributions

Medical Practices: KÖ, SK, TKÇ, EYA, HB,
MÇ, MP, SÖ, Concept: TKÇ,SK, KÖ Design: TKÇ,SK, KÖ,MÇ Data Collection orProcessing: TKÇ, EYA, SÖ,HB Analysis or Interpretation: KÖ,EK, TKÇ Literature Search: TKÇ,EK, KÖ Writing: TKÇ,EK, KÖ. All authors reviewed the manuscript.

Funding

This research received no external funding.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

This study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the İstanbul Kanuni Sultan Süleyman research and traning hospital (Approval Number:3). Written informed consent to participate was obtained from the parent(s)/legal guardian(s) of all participants.

Consent for publication

Written informed consent for publication was obtained from the parent(s)/legal guardian(s).

Competing interests

The authors declare no competing interests.