Impact of different hemodynamic states of patent ductus arteriosus on cerebral, mesenteric, and renal perfusion in preterm infants: a doppler ultrasound analysis

Abstract

Objective

To compare end organ hemodynamic in hemodynamically significant (hs) and non-hemodynamically significant (non-hs) patent ductus arteriosus (PDA).

Methods

This retrospective study enrolled preterm infants with PDA who were admitted to the neonatal intensive care unit (NICU) of our center between January 2021 and December 2024. According to comprehensive evaluations of echocardiographic findings and clinical parameters, infants were classified into hemodynamically significant PDA (hsPDA) and non-hsPDA groups. Clinical characteristics and bedside Doppler ultrasound measurements of the anterior cerebral artery (ACA), superior mesenteric artery (SMA), and renal artery (RA) were collected to evaluate the effects of different PDA hemodynamic states on organ blood flow.

Results

A total of 103 preterm infants with PDA were analyzed, including 50 in the hsPDA group and 53 in the non-hsPDA group. There were no significant differences in demographic or clinical variables between the two groups. Compared with the non-hsPDA group, the hsPDA group exhibited lower end-diastolic velocity (EDV) and mean velocity (MV) and higher resistance index (RI) in both the SMA and RA, while parameters of the ACA showed no significant differences. The incidence of necrotizing enterocolitis was higher in the hsPDA group, whereas other complications did not differ significantly between groups.

Conclusions

Different hemodynamic states of PDA have distinct impacts on organ perfusion in preterm infants. Bedside Doppler ultrasound provides a sensitive tool for early detection of these hemodynamic alterations.

Introduction

Patent ductus arteriosus (PDA) is a common congenital cardiac anomaly in preterm infants, with an incidence exceeding 30% in those born before 32 weeks of gestation [1]. Persistent PDA allows blood to shunt from the aorta to the pulmonary circulation, leading to pulmonary overperfusion and systemic hypoperfusion, which may consequently impair blood flow and normal function of vital organs such as the brain, intestine, and kidneys. [2, 3] Previous studies have shown that PDA is closely associated with several severe complications in preterm infants, including intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and acute kidney injury [4–6]. However, the underlying mechanisms and causal relationships between PDA and adverse organ outcomes remain incompletely understood. Recent evidence suggests that not all PDAs exert identical effects on the circulatory system. The degree and direction of the left-to-right shunt, as well as the hemodynamic significance of PDA, may result in varying degrees of organ perfusion impairment and clinical manifestations [7].

Doppler ultrasound, as a noninvasive, real-time, and repeatable bedside monitoring tool, has been widely used in neonatal intensive care units (NICUs) to evaluate hemodynamics of major organs such as the brain, lungs, intestines, and kidneys [8]. By assessing hemodynamic parameters of the anterior cerebral artery (ACA), superior mesenteric artery (SMA), and renal artery (RA), clinicians can indirectly reflect organ perfusion and vascular resistance. Although several studies have indicated that PDA may affect cerebral, intestinal, and renal perfusion in neonates, systematic comparative studies focusing on organ hemodynamic differences between hemodynamically significant PDA (hsPDA) and non-hsPDA preterm infants remain limited [9]. Therefore, this study aimed to analyze and compare the cerebral, intestinal, and renal hemodynamics of preterm infants with different hemodynamic types of PDA using Doppler ultrasound, in order to explore the variations in organ perfusion associated with different PDA hemodynamic states.

Methods

This single-center retrospective study was conducted in the NICU of Longyan First Hospital. Preterm infants with PDA who were admitted between June 2021 and December 2024 and underwent bedside Doppler ultrasound evaluation were included. A total of 2420 preterm infants (gestational age < 37 weeks) were admitted to the NICU during the study period. Routine screening for PDA was performed on all preterm infants within the first week of admission. According to echocardiographic findings, infants were classified into hsPDA and non-hsPDA groups. The diagnostic criteria for hsPDA were defined as one or more of the following: a left atrium-to-aortic root ratio > 1.4, a left pulmonary artery end-diastolic velocity > 0.2 m/s, or the presence of growing or pulsatile ductal flow patterns [10]. The study protocol was approved by the institutional ethics committee of Longyan First Affiliated Hospital of Fujian Medical University. The requirement for written informed consent was waived by the ethics committee, in accordance with national regulations.

Inclusion criteria were as follows: (1) gestational age < 37 weeks; (2) echocardiographic confirmation of PDA after admission; (3) availability of Doppler ultrasound data for cerebral, intestinal, and renal hemodynamics; and (4) all examinations performed by qualified and experienced sonographers. Exclusion criteria included: (1) other congenital heart defects or major structural anomalies; (2) systemic or cerebral disorders that could markedly affect circulation, such as severe infection or respiratory distress syndrome; (3) preexisting organ lesions before examination, including IVH, cerebral infarction, nephritis, or NEC; and (4) incomplete clinical or ultrasound data. A sample size calculation was performed using GPower 3.1.9.2. Based on the results of previous preliminary surveys, we assumed a medium effect size for our analysis. The alpha value was set at 0.05, and the statistical power was set at 0.90. According to the calculation, at least 98 participants were required for the study, with 49 infants in the hsPDA group and 49 infants in the non-hsPDA group.

Routine screening for PDA was performed on all preterm infants within the first week of admission. The first echocardiographic evaluation was carried out during this period. If PDA was detected during the initial examination, a follow-up echocardiographic evaluation was performed one week later to assess the progression or resolution of the PDA. All enrolled infants underwent Doppler ultrasound assessments of the brain, intestines, and kidneys within one week after admission. Cerebral blood flow parameters were obtained via the anterior fontanelle to measure the ACA peak systolic velocity (PSV), end-diastolic velocity (EDV), and mean velocity (MV), and the resistance index (RI = [PSV-EDV]/PSV) was calculated. Intestinal perfusion was evaluated through SMA measurements of PSV, EDV, MV, and RI; renal perfusion was assessed via the RA using the same parameters. Each measurement was averaged over 4–5 consecutive cardiac cycles. Doppler ultrasound measurements of the anterior cerebral artery (ACA), superior mesenteric artery (SMA), and renal artery (RA) were performed using Philips Ultrasound EPIQ5 device with L12-5, L18-5 linear array transducer and an S8-3 sector transducer. Measurements of the ACA were taken through the anterior fontanelle, and measurements of the SMA and RA were taken at the appropriate vascular sites [11]. Echocardiography was performed by pediatric sonographers, and the results were interpreted by neonatologists with expertise in neonatal echocardiography. All ultrasound examinations were performed using the same equipment (Philips Ultrasound EPIQ5) by pediatric sonographers blinded to the infants’ group allocation.

Data collection

Clinical information was obtained from the hospital’s electronic medical record system. Data collected included general characteristics (sex, age, gestational age, apgar score at 5 min, birth weight, Ibuprofen treatment, and inotrope use), blood pressure (systolic and diastolic), and respiratory support type at the time of examination. Acute kidney injury (AKI) was defined as a significant increase in serum creatinine levels (greater than 1.5 times the baseline value) or a decrease in urine output to less than 0.5 mL/kg/hour, in accordance with established neonatal guidelines [12]. The blood pressure data were collected at times close to the Doppler ultrasound examinations to ensure they reflected the same clinical condition during the measurements. If multiple BP readings were taken, the measurement closest to the Doppler examination was used for analysis. Doppler parameters of the ACA (PSV, EDV, MV, RI), SMA (PSV, EDV, MV, RI), and RA (PSV, EDV, MV, RI) were collected, with each value averaged over 4–5 cardiac cycles. All measurements were performed within a small time window (within 24 h) during the same echocardiographic session to minimize variability. Both sides of the ACA and RA were measured. When available, the right ACA measurements were taken for analysis. In 2 infants, only the left ACA measurements were available and those were used instead. The first set of PDA measurements obtained during the initial assessment within the first week of admission was chosen for analysis. All infants were managed by the same neonatal care team under standardized protocols during NICU hospitalization. Two independent researchers entered and cross-checked all data to ensure accuracy and completeness.

Statistical analysis

Continuous variables were presented as mean ± standard deviation or median (interquartile range), and categorical variables as frequencies and percentages. Data normality was assessed using the Shapiro-Wilk test. Group comparisons were performed using one-way analysis of variance for normally distributed data and the Kruskal-Wallis test for non-normally distributed data. Categorical variables were compared using the chi-square or Fisher’s exact test, as appropriate. All statistical analyses were conducted using SPSS version 25.0 (IBM Corp., Armonk, NY, USA), and a two-tailed P < 0.05 was considered statistically significant.

Results

A total of 103 preterm infants with PDA met the inclusion criteria and were included in the study, comprising 50 infants with hsPDA and 53 without hsPDA (Fig. 1). The demographic and clinical characteristics of the two groups are summarized in Table 1. There were no significant differences in sex, age, gestational age, birth weight, Apgar score at 5 min, type of respiratory support, or use of inotropes (P > 0.05). The number of magnesium sulfate (MgSO4) treated infants was 15 (30%) in the hsPDA group and 12 (22.6%) in the non-hsPDA group, with no significant difference (P > 0.05). The number of SGA infants was 5 (10%) in the hsPDA group and 1 (1.9%) in the non-hsPDA group, with no significant difference (P > 0.05). Systolic blood pressure did not differ significantly between groups (P > 0.05), whereas diastolic blood pressure was significantly lower in the hsPDA group compared with the non-hsPDA group (Table 1).

Fig. 1.

Flow chart of patient inclusion in the study

Table 1.

General clinical data of HsPDA group and non-hsPDA group

Male gender, n (%)	hsPDA group(n = 50)	Non-hsPDA group(n = 53)	p value
	27 (54.0)	28 (52.8)	0.905
Age, d	6.5 ± 2.8	6.9 ± 3.1	0.402
Gestational age, w	29.1 ± 1.5	29.6 ± 1.7	0.653
Apgar score at 5 min	7.9 ± 1.1	8.3 ± 1.4	0.388
Weight, kg	1.25 ± 0.2	1.32 ± 0.2	0.653
MgSO4, n (%)	15 (30.0)	12 (22.6)	0.396
Small for gestational age, n (%)	5 (10.0)	1 (1.9)	0.106
Ductal diameter, mm	2.5 ± 0.4	1.6 ± 0.2	< 0.001
Transfer origin, n (%)	8 (16.0)	7 (13.2)	0.688
Respiratory support, n (%)
Invasive respiratory support	11 (22.0)	9 (17.0)	0.520
Non-invasive respiratory support	39 (78.0)	44 (83.0)
Ibuprofen, n (%)	8 (16.0)	5 (9.4)	0.381
Inotropes, n (%)	4 (8.0)	2 (3.8)	0.428
SBP, mmHg	55.7 ± 5.3	58.5 ± 9.5	0.095
DBP, mmHg	28.2 ± 3.9	33.6 ± 3.5	< 0.001

Transfer origin: infants who were transferred from external hospitals to our NICU

SBP Systolic blood pressure, DBP Diastolic blood pressure

Table 2 summarizes the differences in ACA, SMA, and RA hemodynamic parameters between the two groups. In the ACA, there were no significant differences in PSV, EDV, MV, or RI between the hsPDA and non-hsPDA groups. In the SMA, infants in the hsPDA group had significantly lower EDV (5.7 ± 2.9 cm/s vs. 8.8 ± 2.1 cm/s, P < 0.001) and MV (16.0 ± 2.4 cm/s vs. 18.6 ± 2.2 cm/s, P < 0.001), whereas the RI was significantly higher (0.85 ± 0.08 vs. 0.77 ± 0.05, P < 0.001) compared with the non-hsPDA group. Similarly, in the RA, the hsPDA group exhibited significantly lower EDV (7.2 ± 2.2 cm/s vs. 10.1 ± 2.1 cm/s, P < 0.001) and MV (17.6 ± 2.3 cm/s vs. 20.0 ± 2.4 cm/s, P < 0.001), accompanied by a markedly higher RI (0.81 ± 0.06 vs. 0.75 ± 0.05, P < 0.001).

Table 2.

Comparison of hemodynamics parameters between HsPDA group and non-hsPDA group

Anterior cerebral artery	hsPDA group(n = 50)	Non-hsPDA group(n = 53)	p value
PSV, cm/s	34.8± 3.9	34.1± 3.4	0.331
EDV, cm/s	7.4± 2.1	8.0± 1.8	0.144
MV, cm/s	16.7 ± 2.1	17.4 ± 2.3	0.114
RI	0.79±0.06	0.77±0.04	0.072
Superior mesenteric artery
PSV, cm/s	36.8± 3.4	38.1± 4.0	0.074
EDV, cm/s	5.7± 2.9	8.8± 2.1	< 0.001
MV, cm/s	16.0±2.4	18.6±2.2	< 0.001
RI	0.85±0.08	0.77±0.05	< 0.001
Renal artery
PSV, cm/s	38.7± 4.2	39.8± 4.1	0.221
EDV, cm/s	7.2± 2.2	10.1± 2.1	< 0.001
MV, cm/s	17.6±2.3	20.0± 2.4	< 0.001
RI	0.81±0.06	0.75±0.05	< 0.001

PSV Peak systolic velocity, EDV End-diastolic velocity, MV Mean velocity, RI Resistance index

Table 3 presents the comparison of complications between the two groups. No significant differences were found in the incidences of IVH, severe IVH, or renal insufficiency (P > 0.05). However, the incidence of Stage II/III NEC was significantly higher in the hsPDA group than in the non-hsPDA group (P = 0.024).

Table 3.

Comparison of complication incidence between the two groups

Any grade intraventricular hemorrhage, n (%)	hsPDA group(n = 50)	Non-hsPDA group(n = 53)	p value
	18 (36.0)	13 (24.5)	0.205
Severe intraventricular hemorrhage (Grade III–IV), n (%)	5 (10.0)	2 (3.8)	0.261
Any stage necrotizing enterocolitis, n (%)	9 (18.0)	2 (3.8)	0.025
Stage II/III NEC, n (%)	5 (10)	0 (0)	0.024
Renal insufficiency, n (%)	4 (8.0)	1 (1.9)	0.196

Discussion

This study compared cerebral, intestinal, and renal Doppler hemodynamic parameters as well as clinical complications between preterm infants with hsPDA and those without hsPDA. The findings revealed no significant differences in cerebral hemodynamics between the two groups. In contrast, infants with hsPDA showed reduced EDV and increased RI in the intestinal and renal circulations, indicating impaired perfusion in these organs. Regarding complications, intestinal morbidity was significantly higher in the hsPDA group, while the incidences of cerebral and renal complications did not differ between groups.

Cerebral Doppler parameters showed no significant differences between the two groups, which may be explained by the autoregulatory capacity of cerebral vessels. Previous studies have shown that cerebral blood flow in preterm infants remains relatively stable through vasomotor regulation within a certain range, buffering systemic circulatory fluctuations [13]. Even when PDA induces systemic hemodynamic alterations, cerebral autoregulation can preserve perfusion within a compensatory range. The present findings therefore suggest that variations in PDA hemodynamic state do not substantially affect cerebral blood flow, indicating that cerebral perfusion remains relatively stable despite systemic changes. This observation is consistent with the results reported by Kim et al., who found that hsPDA does not necessarily produce significant alterations in cerebral hemodynamics [14]. However, this stability does not imply that hsPDA has no cerebral impact; excessive ductal shunting or concomitant factors such as hypotension and infection may exceed the limits of autoregulation, thereby increasing the risk of intraventricular hemorrhage and other complications [15].

When a PDA produces a large left-to-right shunt, significant systemic-to-pulmonary diversion occurs, leading to pulmonary overperfusion and systemic hypoperfusion, which in turn reduce mesenteric blood flow and increase the risk of intestinal ischemia and hypoxia [5]. In the present study, Doppler evaluation of the SMA revealed significantly increased RI and reduced diastolic flow in the hsPDA group, indicating compromised intestinal perfusion. Previous studies have reported that intestinal vascular autoregulation in preterm infants is immature and highly sensitive to systemic hemodynamic fluctuations. When systemic perfusion is impaired by hsPDA-related shunting, intestinal blood flow becomes particularly vulnerable. [16, 17] These hemodynamic findings provide a physiological explanation for the higher incidence of NEC observed in hsPDA infants. Consistent with this, our complication analysis showed that intestinal complications occurred significantly more often in the hsPDA group than in the non-hsPDA group. Therefore, continuous monitoring of intestinal hemodynamics is essential in the management of preterm infants with hsPDA.

This study also found that hsPDA significantly affected renal hemodynamics in preterm infants. Because renal blood flow is highly dependent on perfusion pressure and preterm infants have immature renal vascular autoregulation, the kidneys are particularly susceptible to hemodynamic disturbances in the presence of a significant PDA. Insufficient renal perfusion can reduce glomerular filtration rate and precipitate acute kidney injury. [18, 19] In accordance with previous studies, including that of Borysova et al.,[6] we found that the presence of hsPDA was associated with notable changes in Doppler parameters, particularly in the renal arteries, highlighting the significant role of hemodynamic alterations in renal complications. Although no significant difference in the incidence of renal insufficiency was observed between the two groups, this may be due to the limited sample size, which could have reduced statistical power. Moreover, the diagnosis of renal dysfunction in preterm infants relies on serum creatinine levels and urine output, both of which are influenced by multiple factors, potentially affecting the observed results. [7, 20] Despite this, the negative impact of hsPDA on renal hemodynamics warrants attention. Doppler assessment of renal blood flow may help identify preterm infants with PDA who require earlier intervention.

We used the LA/Ao ratio and LPA EDV as primary echocardiographic indices for determining hsPDA due to their reliable association with volume overload and increased pulmonary blood flow. While LVO and PDA diameter are also valuable indicators, they were not included in our analysis due to limitations in accurately measuring LVO in a retrospective study and the variable correlation of PDA diameter with hemodynamic significance. The role of ductal size in determining the hemodynamic significance of PDA is well-established in the literature. While this study did not include ductal size as a criterion for defining hsPDA, it remains an important factor in many definitions of hsPDA, often used in conjunction with the shunt pattern. In line with previous studies, the hsPDA group in this study exhibited a significantly larger ductal size, supporting the association between ductal diameter and significant shunting. Despite this, the definition of hsPDA continues to evolve, and there is no universally accepted standard for its diagnosis. Further research is needed to reach a consensus on the optimal criteria for defining and managing hsPDA. As new evidence emerges, ongoing efforts to refine these diagnostic criteria will be crucial for advancing our understanding of hsPDA and improving clinical management.

This study has several limitations. First, as a single-center retrospective study with a small sample size, evaluating complex interactions among multiple factors was limited. Second, the potential interobserver and intra-observer variability due to the involvement of multiple sonographers over the course of 4 years. Although standardized protocols were followed, no formal analysis of interobserver or intra-observer variability was conducted. Our study did not specifically focus on infants with bi-directional or right-to-left shunting PDA. The clinical and hemodynamic implications of bi-directional or right-to-left shunting PDA could be explored in future studies. We did not collect additional data on diastolic flow reversal in the descending aorta. This is an important functional marker of hsPDA and could provide valuable insights into its severity. However, due to the study’s design, this was not further explored. Due to the inclusion of some outborn infants, we were unable to perform a separate analysis of outcomes between inborn and outborn infants. Differences in management prior to transfer may have impacted the outcomes. Finally, advanced real-time techniques like near-infrared spectroscopy or amplitude-integrated electroencephalography were not used, limiting the assessment of perfusion function.

Conclusion

Different hemodynamic states of PDA have distinct impacts on organ perfusion in preterm infants. Bedside Doppler ultrasound provides a sensitive tool for early detection of these hemodynamic alterations.

Authors’ contributions

QZH designed the study, performed the statistical analysis, participated in the operation, and drafted the manuscript. LLP and ZX collected the clinical data. HXW supervised the study. All authors read and approved the final manuscript.

Funding

There is no funding.

Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Declarations

Ethical approval and consent to participate

The present study was approved by the Ethics Committee of Longyan First Affiliated Hospital of Fujian Medical University. All procedures were conducted in accordance with the Declaration of Helsinki. As this is a retrospective study, the requirement for written informed consent was waived by the ethics committee, in accordance with national regulations. Therefore, informed consent was not obtained from the parents or legal guardians of participants under the age of 16.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.