Patent ductus arteriosus (PDA) is one of the most frequently encountered cardiovascular conditions in preterm neonates, particularly those born before 32 weeks of gestation. The ductus arteriosus, a vital fetal structure, normally undergoes functional closure within the first 72 hours after birth. However, in preterm infants, this closure is often delayed or absent, resulting in a persistent left-to-right shunt that can significantly compromise cardiopulmonary function (1,2).

Persistent PDA has been associated with increased pulmonary blood flow, left atrial and ventricular volume overload, and reduced systemic perfusion, all of which contribute to respiratory and hemodynamic instability in the neonatal period (3). While medical and surgical management strategies are commonly employed to address hemodynamically significant PDAs, the long-term effects of persistent ductal patency, especially when left untreated or minimally responsive to therapy, remain an area of growing clinical concern (4,5).

Emerging evidence suggests that prolonged ductal patency in preterm infants is linked to chronic pulmonary morbidities such as bronchopulmonary dysplasia (BPD), recurrent lower respiratory tract infections, and the development of pulmonary hypertension (PH) in infancy and early childhood (6,7). Furthermore, the chronic left-to-right shunting and altered pulmonary hemodynamics may influence long-term right ventricular function and overall cardiopulmonary outcomes (8).

Despite advances in neonatal intensive care, the criteria for PDA intervention remain inconsistent across centers, and data on the long-term cardiopulmonary sequelae are limited. Therefore, there is a pressing need to elucidate the impact of persistent PDA on cardiopulmonary health beyond the neonatal period. This study aims to evaluate the long-term respiratory and cardiovascular complications in preterm infants with persistent PDA compared to those without PDA, with follow-up extending to 24 months of corrected age.

Study Design and Setting

A prospective cohort study was conducted at the neonatal intensive care unit (NICU) of a tertiary care teaching hospital. Preterm infants born at <32 weeks gestation and admitted to the NICU within the first 24 hours of life were screened for eligibility. Infants with major congenital anomalies, chromosomal abnormalities, or congenital heart defects (other than PDA) were excluded.

Eligible infants were divided into two groups:

• PDA Group (Study Group): Infants with a persistent PDA diagnosed on echocardiography beyond 14 days of life.
• Non-PDA Group (Control Group): Gestational age- and weight-matched preterm infants with no evidence of PDA at or beyond 14 days of life.

A total of 120 infants were enrolled, with 60 in each group.

Data Collection and Follow-up

Baseline demographic and perinatal data were recorded, including birth weight, gestational age, Apgar scores, and antenatal steroid exposure. Echocardiographic evaluation was performed by a pediatric cardiologist using a standardized protocol at three time points: at discharge, 6 months, and 24 months corrected age.

Pulmonary artery systolic pressure (PASP) was estimated using Doppler echocardiography. Cardiac function was assessed through measurements of left ventricular ejection fraction (LVEF). Respiratory outcomes such as the incidence of bronchopulmonary dysplasia (BPD), number of lower respiratory tract infections (LRTIs) requiring hospitalization, and the need for supplemental oxygen were documented.

• Persistent PDA was defined as ductal patency confirmed by echocardiography beyond 14 days of life with evidence of a left-to-right shunt.
• Bronchopulmonary dysplasia was diagnosed based on oxygen dependence at 36 weeks postmenstrual age.
• Pulmonary hypertension was defined as a PASP >30 mmHg at 6 or 24 months, with supportive echocardiographic features.

Statistical Analysis

Statistical analysis was carried out using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (SD) and compared using the independent t-test. Categorical variables were analyzed using the chi-square test or Fisher’s exact test, as appropriate. A p-value <0.05 was considered statistically significant.

A total of 120 preterm infants were included in the final analysis, with 60 infants in the persistent PDA group and 60 in the control group. Both groups were matched for gestational age, birth weight, and gender distribution, with no statistically significant differences in baseline characteristics (Table 1).

Table 1: Baseline Demographic and Perinatal Characteristics

At the time of discharge, a significantly higher proportion of infants in the PDA group required prolonged respiratory support compared to the control group (58.3% vs. 31.7%, p=0.003). The incidence of bronchopulmonary dysplasia (BPD) was also notably higher among infants with PDA (48.3%) than in the control group (21.7%) (p=0.004), as shown in Table 2.

Table 2: Respiratory Outcomes at Discharge

Follow-up echocardiography at 6 months corrected age revealed elevated pulmonary artery systolic pressure (PASP) in the PDA group (mean PASP: 34.7 ± 5.9 mmHg) compared to the control group (28.3 ± 4.6 mmHg), with the difference being statistically significant (p<0.001) (Table 3). By 24 months, persistent pulmonary hypertension was identified in 36.7% of the PDA group, whereas only 13.3% of controls exhibited similar findings (p=0.008).

Table 3: Cardiopulmonary Parameters at Follow-Up

Additionally, recurrent lower respiratory tract infections requiring hospitalization within 2 years were reported in 55% of the PDA group versus 26.7% of controls (p=0.002). However, no significant differences were observed in left ventricular ejection fraction (LVEF) between the groups at 24 months (66.8% ± 5.2 vs. 68.2% ± 4.9, p=0.210).

In summary, as demonstrated in Tables 2 and 3, infants with persistent PDA experienced significantly more adverse respiratory and cardiovascular outcomes compared to their counterparts without PDA.

This prospective cohort study provides compelling evidence that persistent PDA in preterm infants is significantly associated with adverse long-term cardiopulmonary outcomes, including higher rates of bronchopulmonary dysplasia (BPD), pulmonary hypertension (PH), and recurrent respiratory infections. Our findings support the growing body of literature that suggests untreated or refractory PDA can have lasting physiological consequences extending well beyond the neonatal period.

The observed increase in BPD incidence among infants with persistent PDA aligns with previous studies, where prolonged left-to-right shunting led to pulmonary overcirculation, pulmonary edema, and compromised alveolar development (1,2). The mechanical strain and oxygen toxicity from prolonged ventilator use further exacerbate the risk of chronic lung disease in this population (3,4). In our study, 48.3% of infants in the PDA group developed BPD, a figure consistent with earlier reports showing rates between 40% and 60% in similar cohorts (5,6).

Elevated pulmonary artery pressures at both 6 and 24 months of corrected age in the PDA group highlight the long-standing hemodynamic burden placed on the pulmonary vasculature. Persistent volume overload and shear stress are known contributors to vascular remodeling and subsequent PH in preterm infants (7). Studies by Sehgal et al. and Mourani et al. have demonstrated that early PDA-associated PH is a predictor of long-term cardiopulmonary compromise and may persist into early childhood if not adequately managed (8,9).

The significantly higher incidence of recurrent lower respiratory tract infections in our PDA cohort suggests that pulmonary morbidity may persist even after the ductus closes or is surgically managed. Structural changes to the airways and impaired mucociliary clearance following chronic lung disease likely predispose these infants to infections (10). Additionally, repeated hospitalizations contribute to poor neurodevelopmental outcomes and increased healthcare utilization (11).

Interestingly, while our study identified substantial pulmonary and right heart involvement, left ventricular systolic function, as assessed by ejection fraction, remained within normal limits in both groups. This finding suggests that left heart function is relatively preserved, which aligns with previous echocardiographic studies showing that early neonatal adaptation often compensates for increased volume load without overt systolic dysfunction (12).

One of the central debates in neonatal care revolves around the optimal timing and criteria for PDA intervention. Several randomized trials, including the PDA-TOLERATE and PDA RCT studies, have shown variable results regarding the benefits of early closure versus conservative management (13,14). Our findings emphasize the potential long-term respiratory burden of persistent PDA, reinforcing the need for individualized, physiology-based treatment approaches rather than gestational age–driven protocols (15).

Persistent PDA in preterm infants is significantly associated with increased long-term cardiopulmonary complications, including higher rates of bronchopulmonary dysplasia, pulmonary hypertension, and recurrent respiratory infections. Early identification and individualized management strategies are essential to reduce morbidity and improve long-term outcomes in this high-risk population.

1. Ashfaq A, Rettig RL, Chong A, Sydorak R. Outcomes of patent ductus arteriosus ligation in very low birth weight premature infants: A retrospective cohort analysis. J Pediatr Surg. 2022 Jul;57(7):1201–4.
2. Kang SL, Samsudin S, Kuruvilla M, Dhelaria A, Kent S, Kelsall WA. Outcome of patent ductus arteriosus ligation in premature infants in the East of England: a prospective cohort study. Cardiol Young. 2013 Oct;23(5):711–6.
3. Kitaoka H, Konishi T, Shitara Y, Ito A, Kashima K, Fujita A, et al. Effects of Milrinone on Neonates after Patent Ductus Arteriosus Ligation: A Retrospective Nationwide Database Study. Neonatology. 2023;120(6):751–9.
4. Mosalli R, Alfaleh K. Prophylactic surgical ligation of patent ductus arteriosus for prevention of mortality and morbidity in extremely low birth weight infants. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD006181.
5. Malviya M, Ohlsson A, Shah S. Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic patent ductus arteriosus in preterm infants. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD003951.
6. Ohlsson A, Walia R, Shah S. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD003481.
7. Härkin P, Marttila R, Pokka T, Saarela T, Hallman M. Morbidities associated with patent ductus arteriosus in preterm infants: Nationwide cohort study. J Matern Fetal Neonatal Med. 2018 Oct;31(19):2576–83.
8. Fujii AM, Brown E, Mirochnick M, O'Brien S, Kaufman G. Neonatal necrotizing enterocolitis with intestinal perforation in extremely premature infants receiving early indomethacin treatment for patent ductus arteriosus. J Perinatol. 2002 Oct–Nov;22(7):535–40.
9. Duboue PM, Padovani P, Bouteiller XP, Martin-Kabore F, Benbrik N, Gronier CG, et al. Post-ligation cardiac syndrome after surgical versus transcatheter closure of patent ductus arteriosus in low body weight premature infants: A multicenter retrospective cohort study. Eur J Pediatr. 2024 May;183(5):2193–201.
10. Weisz DE, Mirea L, Rosenberg E, Jang M, Ly L, Church PT, et al. Association of Patent Ductus Arteriosus Ligation With Death or Neurodevelopmental Impairment Among Extremely Preterm Infants. JAMA Pediatr. 2017 May 1;171(5):443–9.
11. Evans P, O'Reilly D, Flyer JN, Soll R, Mitra S. Indomethacin for symptomatic patent ductus arteriosus in preterm infants. Cochrane Database Syst Rev. 2021 Jan 15;1(1):CD013133.
12. Ohlsson A, Walia R, Shah S. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD003481.
13. Castaldo MP, Neary E, Bischoff AR, Resende MHF, Weisz DE, Jain A, et al. Rectal Acetaminophen Improves Shunt Volume and Reduces Patent Ductus Arteriosus Ligation in Extremely Preterm Infants. Am J Perinatol. 2023 Aug;40(11):1223–31.
14. Ohlsson A, Walia R, Shah S. Ibuprofen for the treatment of a patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2003;(2):CD003481.
15. Malviya M, Ohlsson A, Shah S. Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic patent ductus arteriosus in preterm infants. Cochrane Database Syst Rev. 2003;(3):CD003951.