Paediatrica Indonesiana p-ISSN 0030-9311.
e-ISSN 2338-476X.
Vol.
No.
DOI: https://doi.
org/10.
14238/pi65.
Original Article Hemodynamically significant patent ductus arteriosus and tissue oxygenation in preterm infants Lissaberti Amaliah.
Indrayady.
Afifa Ramadanti.
Ria Nova.
Atika Akbari Abstract Background One of the most common side effects of preterm birth is hemodynamically significant patent ductus arteriosus .
sPDA), with a prevalence of approximately 70% among preterm infants.
The clinical consequences of hsPDA are impaired tissue perfusion and oxygenation to organs.
Near-infrared spectroscopy (NIRS), a validated non-invasive method for determining regional oxygen saturation .
SO.
, can identify early changes in organ perfusion and oxygenation.
Cerebral and renal tissues as these vital organs are highly susceptible to systemic hypoperfusion caused by hsPDA, which can lead to serious complications such as brain injury and renal We used NIRS to clarify the impact of hsPDA on regional oxygenation in the brains and kidneys of preterm infants.
Objective To compare oxygenation of cerebral and renal regional tissues in preterm infants with and without hsPDA Methods A cross-sectional study was conducted at Mohammad Hoesin Hospital.
Forty preterm infants .
estational age <37 week.
, born between November 2023 and September 2024, who were diagnosed with PDA and had a chronological age >24 hours and <7 days, were enrolled.
Infants with multiple congenital anomalies, ductal-dependent cyanotic congenital heart disease, early-onset sepsis, or without parental consent were excluded.
Cerebral and renal oxygenation were assessed using NIRS Statistical analysis was performed with unpaired T-test.
Results Based on echocardiographic criteria, 22 of the 40 infants had hsPDA, while 18 had non-hsPDA.
The mean cerebral rSO2 values in the hsPDA and non-hsPDA groups were 79.
5 (SD
% and 80.
9 (SD 4.
%, respectively.
The mean renal rSO2 values were 70.
4 (SD 17.
% and 77.
8 (SD 6.
%, respectively.
The mean cerebral fractional tissue oxygen extraction (FTOE) values of the hspda and non-hsPDA groups were 0.
1 to 0.
The mean renal FTOE values were 0.
3 (SD 0.
2 (SD
, respectively.
There were no significant differences between the two groups in renal and cerebral rSO2 and FTOE.
Conclusion Preterm infantsAo cerebral and ren a l t i s s u e ox y g e n a t i o n i s w e r e n o t s i g n i f i c a n t l y different in those with and without hsPDA.
[Paediatr Indones.
65:364-72.
DOI: https://doi.
org/10.
364-72 ].
Keywords: tissue oxygenation.
NIRS.
hsPDA.
364 A Paediatr Indones.
Vol.
No.
September 2025 atent ductus arteriosus (PDA), a common congenital condition in preterm infants, occurs when the blood vessel connecting the pulmonary artery to the aorta fails to close after birth.
1 Persistent PDA leads to excessive blood flow to the lungs .
eft-to-right shun.
and hypoperfusion throughout the body.
This can develop into a hemodynamically significant PDA .
sPDA), which has a prevalence of approximately 70% among preterm infants.
2-5 Complications from hsPDA include pulmonary issues like congestion, edema, bleeding, and bronchopulmonary dysplasia (BPD), as well as systemic effects such as decreased oxygenation and critical organ perfusion, resulting in severe conditions like necrotizing enterocolitis (NEC) or even infant
3,4,6
A non-invasive tool, near-infrared spectroscopy (NIRS), has been instrumental in assessing regional oxygen saturation .
SO .
and fractional tissue oxygen extraction (FTOE) to evaluate tissue perfusion and oxygen delivery in hsPDA cases.
NIRS can detect systemic hypoperfusion and track therapeutic responses effectively.
7 For instance, a study demonstrated that renal oxygen saturation From the Department of Child Health.
Universitas Sriwijaya Medical School/Dr.
Mohammad Hoesin Hospital.
Palembang.
South Sumatera.
Indonesia.
Corresponding author: Indrayady.
Neonatology Division.
Faculty of Medicine.
Universitas Sriwijaya/Dr.
Mohammad Hosein Hospital.
Jalan Jendral Sudirman KM 3.
Palembang.
South Sumatera.
Indonesia.
Email:
indrayady@yahoo.
Submitted July 6, 2025.
Accepted October 9, 2025.
Lissaberti Amaliah et al.
: Hemodynamically significant patent ductus arteriosus and tissue oxygenation in preterm infants below 66% strongly correlates with hsPDA in preterm 5 Other studies observed differing impacts of hsPDA on tissue oxygenation in vital organs like the brain and kidneys, revealing variability and occasionally controversial findings.
In Indonesia, research on the effects of hsPDA and regional tissue oxygenation using NIRS is still More studies are needed to better understand the impact of hemodynamic disturbances caused by PDA in preterm infants .
Such research could provide invaluable insights to improve early diagnosis and targeted interventions for this vulnerable population.
Methods This cross-sectional study was conducted in the neonatal intensive care unit (NICU) and Neonatology Division of Mohammad Hoesin Hospital.
Palembang.
South Sumatra, between November 2023 to September The study subjects were preterm infants .
estational age <37 week.
born in November 2023 and September 2024 who had been diagnosed with PDA and met the inclusion criteria of chronological age >24 hours and <7 days.
Exclusion criteria were multiple congenital anomalies ductal-dependent cyanotic congenital heart disease, early-onset sepsis, and no parental consent.
This study employed a consecutive sampling technique based on the sequence of diagnoses.
The sample size was calculated using a formula for continuous data and the classified into hsPDA and non-hsPDA groups.
All preterm infants who met the inclusion criteria and had no exclusion criteria, whether born at Mohammad Hoesin Hospital or elsewhere, underwent echocardiographic examination within the first 7 days of life .
t a chronological age of >24 hours to 7 day.
The examinations were performed by a pediatric cardiology consultant using a Philips EPIQ CVx-3D system (Koninklijke Philips N.
Netherland.
Hemodynamically significant patent ductus arteriosus .
sPDA) was diagnosed based on the following echocardiographic criteria: ductus arteriosus diameter >1.
5 mm in the constriction phase, left pulmonary artery to aortic diameter (LA/A.
ratio >1.
4, and presence of left-to-right shunt.
The INVOSE 5100C near-infrared spectrometer with neonatal sensors (OxyAlertE) was used to monitor cerebral and renal tissue oxygen saturation .
SO.
Normal rSO2 values were considered to be between >55% and <85%.
9 Fractional tissue oxygen extraction (FTOE) is the amount of oxygen extracted from tissues.
It reflects the balance between oxygen supply and tissue demand.
FTOE is obtained using the following formula: FTOE= [(SpO2 or arterial oxygen saturation-rSO.
/SpO.
), the normal value of FTOE is 0.
1 to 0.
10 A decrease in rSO2 indicates a decrease in blood flow, resulting in a decrease in oxygen delivery to tissues and an increase in oxygen extraction by tissues.
Statistical analysis of the differences in regional oxygen saturation and FTOE between the two groups was performed using an unpaired t-test if the distribution was normal.
A P value less than 0.
(P<0.
was considered to be statistically significant.
SPSS for Windows version 25 software was used for data processing and results.
This study was approved by the Health Research Ethics Committee of Faculty of Medicine Universitas Sriwijaya/Dr.
Mohammad Hoesin Hospital Palembang.
Results Echocardiography of 398 preterm infants identified 99 cases of patent ductus arteriosus (PDA), of which 75 were classified as hsPDA and 24 as non-hsPDA.
From the hsPDA group, 44 infants were excluded due to age >7 days .
, ductal-dependent cyanotic congenital heart disease .
, multiple congenital anomalies .
, early-onset sepsis .
, and nearinfrared spectroscopy (NIRS) device malfunction during data collection .
In the non-hsPDA group, 6 infants were excluded due to age >7 days .
and NIRS malfunction .
Thus, 22 hsPDA and 18 non-hsPDA infants were included in the final analysis (Figure .
Of the 40 participants in the study, 23 preterm infants were male .
%), and 17 were female .
%).
The majority of patients were at 32-37 weeks gestation .
%).
The mean birth weight was 1,384 (SD 472.
grams for patients in the hsPDA group and 1,888.
(SD 485.
grams in the non-hsPDA group.
The majority .
%) of pregnancies were Respiratory support was mostly NIPPV .
%) and invasive ventilation .
%).
No subjects Paediatr Indones.
Vol.
65 No.
September 2025 A 365 Lissaberti Amaliah et al.
: Hemodynamically significant patent ductus arteriosus and tissue oxygenation in preterm infants 398 preterm infants Echocardiography:
99 PDA preterm infants 75 hsPDA Excluded:
A 17 infants >7 days of age A 8 infants with ductal-dependent cyanotic congenital heart disease A 5 infants with multiple congenital anomaly infants.
A 1 infant with early onset sepsis 24 non-hsPDA Excluded:
A 3 infants >7 days of age 44 hsPDA infants 21 non-hsPDA infants 22 patients were excluded due to NIRS 3 patients were excluded due to NIRS malfunction 22 hsPDA 18 non-hsPDA Figure 1.
Flow chart of patients used inotropes.
The earliest NIRS data collection was when the patient was one day old, and the latest was when the patient was 6 days old.
NIRS data were collected mostly at 2 days .
%) and 5 days .
%).
The most common comorbidities of infants were hyaline membrane disease (HMD) .
%).
There was one patient with seizure comorbidity, four patients with hyperbilirubinemia, and one patient with APGAR score at 5 minutes was 3.
All non-hsPDA patient groups were born by caesarean section, while in the hsPDA group, one patient was delivered vaginally.
most infants were born with clear amniotic fluid .
5%).
There were no maternal comorbidities such as hypertension, obesity, antenatal 366 A Paediatr Indones.
Vol.
No.
September 2025 SubjectsAo characteristics are shown in Table 1.
Mean cerebral and renal regional oxygen saturation .
SO .
and fractional tissue oxygen extraction (FTOE) were assessed across clinical Oxygenation values were comparable between sexes.
Extremely preterm tended to have lower rSO 2 and slightly higher FTOE, whereas moderate late preterm showed better oxygenation profiles with lower cerebral FTOE .
95%CI 0.
Multiple gestation was associated with higher renal rSO2 and lower cerebral FTOE.
Infants on nasal cannula had the lowest cerebral rSO2 .
and highest cerebral FTOE .
, while NIPPV users Lissaberti Amaliah et al.
: Hemodynamically significant patent ductus arteriosus and tissue oxygenation in preterm infants Table 1.
Characteristics of subjects hsPDA Non-hsPDA Total (N=.
Gender, n Male Female Gestational age, n Extremely preterm (< 28 week.
Very preterm .
- < 32 week.
Moderate late preterm .
-37 week.
Birth weight, n ELBW (< 1,000 .
VLBW (< 1,500 .
LBW (< 2,500 g.
Number of fetuses carried, n Singleton
Multiple Respiratory support, n Nasal cannula
CPAP
NIPPV
Invasive ventilation Inotropic administration, n Yes
Age at time of data collection, n 1 day
2 days 3 days 4 days 5 days 6 days Infant comorbidities*, n HMD
TTN
Pneumonia
PPHN
Hyperbilirubinemia Anemia Seizure APGAR score, n O3 Delivery, n Normal Caesarean section Amniotic fluid, n Clear Absent Meconium-stained Characteristics *one patient can have more than one comorbidity.
ELBW=extremely low birth weight.
VLBW=very low birth weight.
LBW=low birth weight.
CPAP= Continous positive airway pressure.
NIPPV= Noninvasive positive pressure ventilation.
TTN=transient tachypnea of the newborn.
PPHN=persistent pulmonary hypertension of the newborn had the highest cerebral rSO2 .
9%).
Inotropic use was not reported.
infants without inotropes showed cerebral FTOE of 0.
%CI 0.
12 to 0.
Oxygenation was generally stable across postnatal Paediatr Indones.
Vol.
65 No.
September 2025 A 367 Lissaberti Amaliah et al.
: Hemodynamically significant patent ductus arteriosus and tissue oxygenation in preterm infants days, with peaks in rSO2 on days 4 .
and 6 .
The HMD was associated with lower cerebral FTOE, while hyperbilirubinemia showed the highest cerebral rSO2 .
8%) and lowest FTOE .
Vaginal delivery resulted in the most favorable oxygenation parameters.
Meconium-stained amniotic fluid was linked to lower rSO2 and elevated FTOE .
95% CI 0.
, suggesting increased tissue oxygen extraction under hypoxic stress (Table .
Analysis was conducted to evaluate the mean values of cerebral and renal regional oxygen saturation .
SO .
and fractional tissue oxygen extraction (FTOE) between the hsPDA and non-hsPDA groups.
The mean cerebral rSO2 was 79.
1%) in the hsPDA group and 80.
3%) in the non-hsPDA group, while mean renal rSO2 was 70.
8%) and 8 .
4%), respectively.
No statistically significant differences were observed in cerebral rSO2 (P=0.
or renal rSO2 (P=0.
Cerebral and renal FTOE showed the same mean value of 0.
The mean renal FTOE was 0.
in the hsPDA group 2 .
in the non-hsPDA group.
There were no significant differences in cerebral FTOE (P=0.
or renal FTOE (P=0.
between groups (Table .
Discussion The majority of infants diagnosed with PDA were male .
58%), both from the hsPDA group and from the non-hsPDA group, while 17 subjects .
%) were female.
A cross-sectional study design regarding risk factors for patent ductus arteriosus in patients for the period January 2014 to June 2017, 8% were men who suffered from PDA.
12 Another study evaluated several risk factors for the incidence of PDA in preterm infants and found that the risk of developing PDA was slightly higher for males than But their meta-analysis included only 28 of 45 studies in the analysis of sex differences.
Gestational age was divided into three groups, namely, extremely preterm (<28 week.
, very preterm .
to <32 week.
, and moderate late preterm .
to 37 week.
The majority of patients were at 32 to 37 weeks of gestation .
%).
Samosir et al.
14 reported that gestational age 28 to <32 weeks was the most common pre-term hsPDA patient category.
This finding was also consistent with a previous study 368 A Paediatr Indones.
Vol.
No.
September 2025 which noted a hsPDA prevalence of 20% at 32 weeks of gestation and increased to more than 90% at 26 weeks of gestation.
Mean birth weight was 1,384 (SD 472.
grams in the hsPDA group and 1,888.
grams in the non-hsPDA group.
Similarly, a previous study reported that most hsPDA patients were VLBW .
%).
14 Most pregnancies were singleton .
%), consistent with a study which showed that 77.
4% of hsPDA cases were In our study, the hsPDA group required more advanced respiratory support, with a higher number of infants receiving NIPPV and invasive ventilation, compared to the non-hsPDA group.
These findings suggest a greater degree of cardiorespiratory compromise in the hsPDA population, likely due to the left-to-right shunting associated with significant ductal patency, which can lead to pulmonary overcirculation and respiratory distress.
In contrast, a previous study reported that CPAP was the most commonly used mode of respiratory support in the non-hsPDA group, indicating potentially less severe clinical presentation.
A Furthermore, while the previous study found inotropic use in both groups .
hree subjects eac.
, no infants in our study required inotropes.
This may reflect differences in patient selection, clinical thresholds for intervention, or overall hemodynamic stability in the population studied.
The absence of inotropic use in our sample suggests that despite the need for respiratory support, systemic perfusion may have remained adequate without pharmacologic cardiovascular support.
We performed echocardiography and measured regional oxygen saturation values using NIRS in preterm infants aged >24 hours and <7 days.
Pulmonary vascular resistance decreases after >24 hours of life, thus, left to right ductal shunting can be detected using echocardiography.
A study opted to conduct echocardiography after the third day of life to avoid potential bidirectional shunting during the transitional period, their chosen timeframe remains within our defined window (>24 hours and <7 day.
Therefore, our approach supports the clinical validity of earlier evaluation without delaying diagnosis until after day three.
Moreover, earlier detection within this period may optimize therapeutic interventions, as treatment initiated beyond 7 days of age has been shown to be less effective.
17,18
Gestational age Extremely preterm (< 28 week.
Very preterm .
- < 32 week.
Moderate late preterm .
Ae37 week.
Birth weight ELBW (< 1,000 .
VLBW (< 1,500 .
LBW (< 2,500 g.
Number of fetuses carried Singleton
Multiple Respiratory support
Nasal cannula
CPAP
NIPPV
Invasive ventilation Inotropic administration Yes
Age at time of data collection 1 day
2 days 3 days 4 days 5 days 6 days Infant comorbidities HMD
TTN
Pneumonia Hyperbilirubinemia Seizure APGAR score Mean cerebral rSO2 (SD), % Gender Male Female Characteristics Table 2.
Characteristics of subjects based on rSO2 and FTOE 6 .
Mean renal rSO2 (SD), % 17* .
05 to 0.
13* .
1 to 0,.
13* .
07 to 0,.
12 to 0.
14* .
12 to 0.
14* .
10 to 0.
14* .
10 to 0.
Mean cerebral FTOE (SD) or geometric mean .
%CI) 18* .
14 to 0.
18* .
14 to 0.
Mean renal FTOE (SD) or geometric mean .
%CI) Lissaberti Amaliah et al.
: Hemodynamically significant patent ductus arteriosus and tissue oxygenation in preterm infants Paediatr Indones.
Vol.
65 No.
September 2025 A 369 18* .
13 to 0.
16* .
12 to 0.
*Geometric mean .
% CI) 8 .
Amniotic fluid Clear Absent Meconium-stained 8 .
18* .
14 to 0.
15* .
13 to 0.
Delivery Normal Caesarean section Mean renal rSO2 (SD), % Mean cerebral rSO2 (SD), % Characteristics Table 2.
Characteristics of subjects based on rSO2 and FTOE .
Mean cerebral FTOE (SD) or geometric mean .
%CI) Mean renal FTOE (SD) or geometric mean .
%CI) Lissaberti Amaliah et al.
: Hemodynamically significant patent ductus arteriosus and tissue oxygenation in preterm infants 370 A Paediatr Indones.
Vol.
No.
September 2025 The HMD was the most common comorbidity in both groups, with 20 subjects in the hsPDA group, and 12 subjects in the non-hsPDA group.
One subject in the hsPDA group presented with an APGAR score of less than 3.
The majority of subjects in both groups underwent Caesarean section deliveries, with the majority having clear amniotic fluid .
%).
maternal comorbidities were found in either group.
Similarly.
Utomo et al.
3 noted HMD as the most common infant comorbidity .
6%).
Caesarean section delivery .
%), and clear amniotic fluid .
4%), but the maternal comorbidity of hypertension was found in 32.
7% of their subjectsAo mothers.
This study investigated the differences in cerebral and renal oxygen saturation .
SO.
and fractional tissue oxygen extraction (FTOE) between preterm infants with hemodynamically significant patent ductus arteriosus .
sPDA) and those without .
on-hsPDA).
The results showed no statistically significant differences in cerebral rSO2 .
5 (SD
% vs.
9 (SD 4.
P=0.
, renal rSO2 .
4 (SD 17.
% vs.
8 (SD 6.
P=0.
, cerebral FTOE .
95%CI 0.
10 to 0.
P=0.
, or renal FTOE .
3 (SD 0.
2 (SD 0.
P=0.
between the two groups.
Importantly, the observed rSO2 values fell within the upper limit of the normal physiological range .
-84%), potentially influenced by the administration of supplemental oxygen through respiratory support modalities, resulting in hyperoxic 19 Elevated rSO2 is known to be inversely related to FTOE,20 as also reflected in the current study, particularly in the cerebral region where FTOE values were uniformly low across both groups.
Although the renal FTOE appeared higher in the hsPDA group, indicating a compensatory increase in oxygen extraction in response to relatively lower renal rSO2, this difference was not statistically significant.
These results reinforce existing evidence that cerebral autoregulation is relatively well-maintained in preterm infants, even in the presence of hsPDA, whereas renal perfusion may exhibit greater sensitivity to changes in systemic hemodynamics.
The mean difference in cerebral oxygen saturation between the two groups was not significant in our study.
A previous study also reported a lack of significant difference in mean cerebral oxygen saturation between hsPDA and non-hsPDA groups .
27 (SD 9.
% vs.
03 (SD 9.
Lissaberti Amaliah et al.
: Hemodynamically significant patent ductus arteriosus and tissue oxygenation in preterm infants Table 3.
Analysis of cerebral and renal rSO2 and FTOE values between the hsPDA and non-hsPDA groups Variables hsPDA Non-hsPDA P value Mean cerebral rSO2 (SD), % 5 .
Mean renal rSO2 (SD), % 4 .
10 to 0.
10 to 0.
Mean cerebral FTOE .
%CI) Mean renal FTOE (SD) *Geometric mean.
**unpaired T-test.
P<0.
, in their study in preterm infants aged 3 to 7 days with a gestational age of 24 to 34 weeks.
A study of 45 subjects with gestational age <29 weeks found no significant difference between the hsPDA and non-hsPDA groups, with mean cerebral oxygen saturation of 68 (SD .
% and 73 (SD .
%, 5 In contrast, a prospective observational study on 123 preterm infants .
estational age <32 weeks and chronological age >72 hour.
The NIRS revealed a significant difference in regional cerebral oxygenation saturation between the hsPDA and non-hsPDA groups (P=0.
Their findings were in agreement with the theory that in infants with hsPDA, abnormal blood flow caused by shunting from the aorta to the pulmonary artery can overload the pulmonary circulation and reduce blood flow to vital organs.
This results in decreased perfusion and oxygenation of tissues such as the brain and kidneys.
The hsPDA group had a mean renal oxygen saturation value of 70.
%, and the non-hsPDA group had a mean of 77.
%, but the difference was not significant (P=0.
Similarly, a previous study reported that renal oxygen saturation were not significantly different between the hsPDA and nonhsPDA groups, with a mean value of renal oxygen saturation .
41 (SD 14.
%vs.
61 (SD 10.
(P=0.
3 In contrast, another study noted a significant difference in renal oxygenation saturation between the hsPDA and non-hsPDA groups (P=0.
8 Likewise, another study reported that in 45 research subjects with gestational age <29 weeks, there was a significant difference between the hsPDA and non-hsPDA groups (P=0.
The mean cerebral FTOE values were not significantly different between the two groups in our Fractional tissue oxygen extraction (FTOE) is the amount of oxygen extracted from tissues.
It reflects the balance between the oxygen supply and the needs of the underlying tissue.
In our study, both groups had higher than normal mean cerebral rSO2 .
SO2 hsPDA 5 .
% and non-hsPDA rSO2 80.
The mean FTOE values from the two groups were less than the normal (FTOE hsPDA 0.
05 and non-hsPDA Similarly.
Utomo et al.
3 reported that FTOE was not significantly different between groups (P=0.
as did Navikiene et al.
8 (P=0.
Mean renal FTOE was 0.
in the hsPDA group and 0.
in the non-hsPDA group, which were not significantly different.
Similarly.
Utomo et al.
3 found no significant difference (P=0.
, but Navikiene et al.
8 did (P=0.
This study had several limitations.
First, the NIRS examination was not performed together with echocardiography.
Second, we identified the characteristics of subjects without looking at the influence of these characteristics on the saturation value of cerebral and renal tissue oxygenation.
Third, the gestational age range of the subjects was quite wide due to the limited sample size.
There were more patients with moderate late preterm than very preterm and extremely preterm.
In conclusion, a preterm infant's cerebral and renal tissue oxygenation were similar between those with and without hsPDA.
Conflict of interest None declared.
Acknowledgment We would like to thank the Department of Child Health at Sriwijaya University Medical School and Mohammad Hoesin Hospital.
Palembang, for their support.
Paediatr Indones.
Vol.
65 No.
September 2025 A 371 Lissaberti Amaliah et al.
: Hemodynamically significant patent ductus arteriosus and tissue oxygenation in preterm infants Funding acknowledgment S c h n e i d e r D J.
M o o r e J W.
Pa t e n t d u c t u s a r t e r i o s u s .
Circulation.
114:1873-82.
DOI: https://doi.
org/ 10.
The authors received no specific grants from any funding agency in the public, commercial, or not-for-profit sectors.
CIRCULATIONAHA.
Trisa A.
Faktor risiko paten duktus arteriosus pada pasien yang dirawat di bagian anak RSUP DR.
Mohammad Hoesin Palembang
References