Symptomatic Patent Ductus Arteriosus Research Articles

Efficacy of inhaled nitric oxide in preterm infants ≤ 34weeks: a systematic review and meta-analysis of randomized controlled trials.

Background: The effect of inhaled nitric oxide (iNO) in neonates >34 weeks on improving respiration is well documented. However, the efficacy of iNO in preterm infants ≤34 weeks remains controversial. Objectives: The main purpose of this review is to assess the effectiveness and safety of iNO treatment in preterm infants ≤34 weeks. Search methods: We systematically searched PubMed, Embase and Cochrane Libraries from their inception to 1 June 2023. We also reviewed the reference lists of retrieved studies. Selection criteria: Our study involved randomized controlled trials on preterm infants ≤34 weeks, especially those receiving iNO treatment, and mainly assessed outcomes such as bronchopulmonary dysplasia (BPD) and mortality. Two authors independently reviewed these trials, extracted data, and evaluated study biases. Disagreements were resolved by consensus. We used the GRADE method to assess evidence quality. Results: Our research included a total of 17 studies involving 4,080 neonates and 7 follow-up studies. The synthesis of results showed that in neonates, iNO treatment reduced the incidence of BPD (RR: 0.92; 95% CI: 0.86-0.98). It also decreased the composite outcome of death or BPD (RR: 0.94; 95% CI: 0.90-0.98), without increasing the risk of short-term (such as intraventricular hemorrhage, periventricular leukomalacia) and long-term neurological outcomes (including Bayley mental developmental index <70, cerebral palsy and neurodevelopmental impairment). Furthermore, iNO did not significantly affect other neonatal complications like sepsis, pulmonary hemorrhage, necrotizing enterocolitis, and symptomatic patent ductus arteriosus. Subgroup analysis revealed that iNO significantly reduced BPD incidence in neonates at 36 weeks under specific intervention conditions, including age less than 3 days, birth weight over 1,000g, iNO dose of 10ppm or higher, or treatment duration exceeding 7 days (p < 0.05). Conclusion: Inhaled NO reduced the incidence of BPD in neonates at 36 weeks of gestation, and the effect of the treatment depended on neonatal age, birth weight, duration and dose of iNO. Therefore, iNO can be considered a promising treatment for the potential prevention of BPD in premature infants. More data, however, would be needed to support nitric oxide registration in this specific patient population, to minimize its off-label use.

International Online Survey on the Management of Patent Ductus Arteriosus

Introduction: There is uncertainty and lack of consensus regarding optimal management of patent ductus arteriosus (PDA). We aimed to determine current clinical practice in PDA management across a range of different regions internationally. Materials and Methods: We surveyed PDA management practices in neonatal intensive care units using a pre-piloted web-based survey, which was distributed to perinatal societies in 31 countries. The survey was available online from March 2018 to March 2019. Results: There were 812 responses. The majority of clinicians (54%) did not have institutional protocols for PDA treatment, and 42% reported variable management within their own unit. Among infants <28 weeks (or <1,000 g), most clinicians (60%) treat symptomatically. Respondents in Australasia were more likely to treat PDA pre-symptomatically (44% vs. 18% all countries [OR 4.1; 95% CI 2.6–6.5; p < 0.001]), and respondents from North America were more likely to treat symptomatic PDA (67% vs. 60% all countries [OR 2.0; 95% CI 1.5–2.6; p < 0.001]). In infants ≥28 weeks (or ≥1,000 g), most clinicians (54%) treat symptomatically. Respondents in North America were more likely to treat PDAs in this group of infants conservatively (47% vs. 38% all countries [OR 2.3; 95% CI 1.7–3.2; p < 0.001]), and respondents from Asia were more likely to treat the PDA pre-symptomatically (21% vs. 7% all countries [OR 5.5; 95% CI 3.2–9.8; p < 0.001]). Discussion/Conclusion: There were marked international differences in clinical practice, highlighting ongoing uncertainty and a lack of consensus regarding PDA management. An international conglomeration to coordinate research that prioritises and addresses these areas of contention is indicated.

Prophylaxis of Patent Ductus Arteriosus with Paracetamol in Extremely Low Gestational Age Newborns (ELGANs): A Single-Institution Observational Study in Vietnam.

Prophylactic paracetamol for extremely low gestation age neonates (ELGAN, <27 weeks' gestation) with symptomatic patent ductus arteriosus (sPDA) in high-income countries (HIC) reduces medical and surgical interventions. Its effectiveness in low-to-middle-income countries (LMIC) remains uncertain. This study assesses prophylactic paracetamol's impact on sPDA interventions in ELGANs in an LMIC. This is a retrospective cohort study that compared a historical cohort of ELGANs that were treated with oral ibuprofen or intravenous paracetamol after diagnosis of sPDA (n = 104) with infants (n = 76) treated with prophylactic paracetamol (20 mg/kg loading, 7.5 mg/kg qid for 4 days), in a tertiary neonatal intensive care unit (NICU) in Vietnam. Oral ibuprofen or intravenous therapeutic paracetamol were administered if prophylactic paracetamol failed to close sPDA. Surgical ligation was conducted if targeted medical intervention failed, or the infant deteriorated from conditions attributable to sPDA. In the historical cohort, 57 (55%) infants died within 7 days of life compared to 18 (24%) from the prophylactic cohort (p < 0.01). Of the survivors, 21 (45%) of the historical and 23 (39.7%) of the prophylactic cohort required surgical ligation (p = 0.6). Duration of hospitalization for survivors was lower in the prophylactic cohort (mean 74 vs. 97 days, p = 0.01). In the prophylactic cohort, 24 (41%) infants did not need further treatment while 34 (59%) required further treatment including ibuprofen and/or paracetamol 28 (48%) and surgical ligation 22 (38%). Prophylactic paracetamol for ELGAN in LMIC does not reduce the need for surgical ligation, sPDA rates, and other PDA-related morbidities in infants who survive beyond 7 days of age. It may reduce the risk of death and the duration of hospitalization but further study into the reasons behind this need to be determined with larger studies.

Second nationwide survey of bilirubin encephalopathy in preterm infants in Japan

ObjectivesTo determine the clinical features of bilirubin encephalopathy in preterm infants (pBE) in Japan. MethodsWe performed a retrospective, nationwide questionnaire-based survey. The initial survey determined the number of children with pBE who were born after 2000. Using a structured questionnaire, the second survey clarified the clinical manifestations and characteristics of children with pBE, including demographic data, neurological symptoms, and MRI and auditory brainstem response (ABR) findings. ResultsThe initial survey identified 41 pBE infants from 18 institutions. After exclusion of patients included in previous studies, clinical information was collected from 30 patients (21 boys and 9 girls) during the secondary survey. The median gestational age was 26 weeks and the median birthweight was 846 g. Chronic lung disease and symptomatic patent ductus arteriosus were common neonatal complications. Head control was observed in 63% and functional gait in 17% of patients. Purposeful hand use was seen in 57% and verbal communication in 50% of patients. MRI showed T2 hyperintensities in the globus pallidus of 29 of 30 patients. ABR abnormalities were present in 11 of 15 patients. None of the variables were significantly different between the 2017 and 2021 surveys. ConclusionsThe pBE infants had severely impaired gross motor function and relatively preserved manual function and verbal communication. MRI and ABR findings aid in the diagnosis of pBE.

What are the effects of prostaglandin inhibitor drugs for the treatment of symptomatic patent ductus arteriosus (PDA)?

What are the effects of prostaglandin inhibitor drugs for the treatment of symptomatic patent ductus arteriosus (PDA)?

Association of patent ductus arteriosus with extubation failure among preterm infants.

Mechanical ventilation is associated with mortality/morbidities in preterm infants. Nearly a third of these infants fail extubation, and this may increase morbidities. To evaluate the association of moderate to large symptomatic patent ductus arteriosus (PDA) with failure of extubation among preterm infants. This was a retrospective study on preterm infants (birth weight <1250 g and gestational age ≥23 weeks) born between January 2009 and December 2016, who were mechanically ventilated and extubated within the first 60 days of age. Three hundred and sixty infants were evaluated, of these, 26% failed, and 74% succeeded in the initial extubation attempt. On adjusted analysis, symptomatic PDA was associated with an increased risk of extubation failure. The presence of symptomatic patent ductus arteriosus was associated with extubation failure. Further investigations are needed to establish whether there is a causal relationship between PDA and extubation failure and whether proactive screening for presence of PDA and treatment of the same, before extubation among these infants, improves chances of successful extubation and cardiorespiratory outcomes.

Relationship of cerebral blood volume with arterial and venous flow velocities in extremely low-birth-weight infants.

Unstable cerebral blood flow is theorised to contribute to the occurrence of intraventricular haemorrhage (IVH) in extremely low-birth-weight infants (ELBWIs), which can be caused by increased arterial flow, increased venous pressure, and impaired autoregulation of brain vasculature. As a preliminary step to investigate such instability, we aimed to check for correlations of cerebral blood volume (CBV), as measured using near-infrared spectroscopy, with the flow velocities of the anterior cerebral artery (ACA) and internal cerebral vein (ICV), as measured using Doppler ultrasonography.Data were retrospectively analysed from 30 ELBWIs uncomplicated by symptomatic patent ductus arteriosus, which can influence ACA velocity, and severe IVH (grade ≥ 3), which can influence ICV velocity and CBV. The correlation between tissue oxygen saturation (StO2) and mean blood pressure was also analysed as an index of autoregulation.CBV was not associated with ACA velocity; however, it was significantly correlated with ICV velocity (Pearson R = 0.59 [95% confidence interval: 0.29-0.78], P = 0.00061). No correlation between StO2 and mean blood pressure was observed, implying that autoregulation was not impaired. Conclusion:Although our findings are based on the premise that cerebral autoregulation was unimpaired in the ELBWIs without complications, the same result cannot be directly applied to severe IVH cases. However, our results may aid future research on IVH prediction by investigating the changes in CBV when severe IVH occurs during ICV velocity fluctuation. What is Known: • The pathogenesis of IVH includes unstable cerebral blood flow affected by increased arterial flow, increased venous pressure, and impaired cerebral autoregulation. • The approaches that can predict IVH are under discussion. What is New: • ACA velocity is not associated with CBV, but ICV velocity is significantly correlated with CBV. • CBV measured using NIRS may be useful in future research on IVH prediction.

Interventions for patent ductus arteriosus (PDA) in preterm infants: an overview of Cochrane Systematic Reviews.

Interventions for patent ductus arteriosus (PDA) in preterm infants: an overview of Cochrane Systematic Reviews.

Fluid restriction for treatment of symptomatic patent ductus arteriosus in preterm infants

Fluid restriction for treatment of symptomatic patent ductus arteriosus in preterm infants

Newborn Periventricular Nodular Heterotopia with Persistent Feeding Cyanosis and Apneic Spell: A Case Report

Periventricular nodular heterotopia (PNH) is a neuronal migration disorder that occurs during early brain development. Patients with PNH may be asymptomatic and have normal intelligence; however, PNH is also known to cause various symptoms such as seizures, dyslexia, and cardiovascular anomalies. PNH is not commonly diagnosed during early infancy because of the lack of clinical manifestations during this period. We present the case of a female infant diagnosed with PNH based on brain magnetic resonance imaging, who had symptomatic patent ductus arteriosus that had to be ligated surgically and had prolonged feeding cyanosis with frequent apneic spells.

Comparison of neonatal morbidity and mortality between single-room and open-bay care: a retrospective cohort study

ObjectiveIn response to the increasing focus on family-centred care, neonatal intensive care unit (NICU) environments have gradually shifted towards the single-room design. However, the assumed benefits of this emerging design...

Management of the patent ductus arteriosus in preterm infants.

Management of the patent ductus arteriosus (PDA) is one of the most contentious topics in the care of preterm infants. PDA management can be broadly divided into prophylactic and symptomatic therapy. Prophylaxis with intravenous indomethacin in extremely low birth weight infants may reduce severe intraventricular hemorrhage. Echocardiography should be routinely used to confirm the presence of a PDA before considering symptomatic therapy. A symptomatic PDA can be managed conservatively, using pharmacotherapy or with procedural closure. Ibuprofen should be considered as the pharmacotherapy of choice for a symptomatic PDA. High-dose ibuprofen may be preferable, especially for preterm infants beyond the first 3 to 5 days of age. If pharmacotherapy fails (after two courses) or is contraindicated, procedural closure may be considered for infants with a persistent PDA with significant clinical symptoms in addition to echocardiographic signs of a large PDA shunt volume and pulmonary over-circulation.

What are the benefits and harms of indomethacin for treating symptomatic patent ductus arteriosus (PDA) in infants?

What are the benefits and harms of indomethacin for treating symptomatic patent ductus arteriosus (PDA) in infants?

Risk factor analysis for symptomatic patent ductus arteriosus in extremely low birth weight infants.

Risk factor analysis for symptomatic patent ductus arteriosus in extremely low birth weight infants.

Artificial intelligence model comparison for risk factor analysis of patent ductus arteriosus in nationwide very low birth weight infants cohort

Despite the many comorbidities and high mortality rate in preterm infants with patent ductus arteriosus (PDA), therapeutic strategies vary depending on the clinical setting, and most studies of the related risk factors are based on small sample populations. We aimed to compare the performance of artificial intelligence (AI) analysis with that of conventional analysis to identify risk factors associated with symptomatic PDA (sPDA) in very low birth weight infants. This nationwide cohort study included 8369 very low birth weight (VLBW) infants. The participants were divided into an sPDA group and an asymptomatic PDA or spontaneously close PDA (nPDA) group. The sPDA group was further divided into treated and untreated subgroups. A total of 47 perinatal risk factors were collected and analyzed. Multiple logistic regression was used as a standard analytic tool, and five AI algorithms were used to identify the factors associated with sPDA. Combining a large database of risk factors from nationwide registries and AI techniques achieved higher accuracy and better performance of the PDA prediction tasks, and the ensemble methods showed the best performances.

Ductus Arteriosus of Extremely Preterm Twins is More Resistant to Cyclooxygenase Inhibitors Than Those of Singletons.

Symptomatic patent ductus arteriosus (sPDA) is common among preterm infants, and can lead to several complications. This is particularly true for extremely preterm infants, as closure of the ductus arteriosus using cyclooxygenase inhibitors is often difficult. A recent study using a preterm sheep model showed that intimal thickening—required for anatomical closure of the ductus arteriosus—is less developed in twins than in singletons. Therefore, this study primarily aimed to prove that the ductus arteriosus of extremely preterm twins is more resistant to cyclooxygenase inhibitors than those of extremely preterm singletons. Its secondary aim was to assess whether the resistance against cyclooxygenase inhibitors differed according to chorionicity. In this retrospective case–control study, medical records of 162 extremely preterm infants (gestational age < 28 weeks) were reviewed, and the treatment course of sPDA was subsequently compared between singletons (n = 131) and twins (n = 31). The median indomethacin doses for sPDA and the necessity for surgical ligation were significantly higher in twins than in singletons (5 vs 2 [p < 0.001] and 42% vs 21% [p = 0.018], respectively). No significant differences in sPDA treatment, including the number of indomethacin doses and the necessity for surgical ligation, were observed between monochorionic diamniotic and dichorionic diamniotic twins. This study confirms that the ductus arteriosus of extremely preterm twins is more resistant to cyclooxygenase inhibitors than those of singletons. However, there was no significant difference in sPDA treatment by chorionicity.

Risk factors and prognosis in very low birth weight infants treated for hypotension during the first postnatal week from the Korean Neonatal Network.

Hypotension in the early stages of life appears in 20% of very low birth weight (VLBW) infants. The gestational age and birth weight are the risk factors highly related to the postnatal hypotension. Other risk factors slightly differ between different studies. So, we evaluated the risk factors and prognosis that are associated with infants treated with hypotension in the early stages of life, after excluding the influences of gestational age and small for gestational age (SGA). VLBW infants registered in the Korean Neonatal Network between 2013 and 2015 treated for hypotension within a week after their birth were selected as study subjects. The rest were used as a control group. Risk factors and the prevalence of severe complications, including mortality, were investigated and compared after matching for gestational age and SGA. The treatment rate for hypotension within the first postnatal week was inversely related to decreasing gestational ages and birth weights. In particular, 63.4% of preterm infants born at ≤ 24 weeks’ gestation and 66.9% of those with a birth weight < 500 g were treated for hypotension within a week of birth. Regression analysis after matching showed that 1-minute Apgar score, neonatal cardiac massage or epinephrine administration, symptomatic patent ductus arteriosus, early onset sepsis, and chorioamnionitis were significantly associated with hypotension. In the hypotension group, mortality, grade 3 or higher intraventricular hemorrhage, periventricular leukomalacia, and moderate to severe bronchopulmonary dysplasia rates were significantly higher after the matching for gestational age and SGA. Hypotension during the first postnatal week is very closely related to the prematurity and the condition of the infant shortly after birth. Regular prenatal care including careful monitoring and appropriate neonatal resuscitation are very crucial to decrease the risk of hypotension in the early stages of life.

Cesarean section was not associated with mortality or morbidities advantage in very low birth weight infants: a nationwide cohort study

This study investigated the role of cesarean section (CS) in mortality and morbidity of very-low-birth-weight infants (VLBWIs) weighing less than 1500 g. This nationwide prospective cohort study of the Korean Neonatal Network consisted of 9,286 VLBWIs at 23–34 gestational weeks (GW) of age between 2013 and 2017. The VLBWIs were stratified into 23–24, 25–26, 27–28 and 29–34 GW, and the mortality and morbidity were compared according to the mode of delivery. The total CS rate was 78%, and was directly proportional to gestational age. The CS rate was the lowest at 61% in case of infants born at 23–24 GW and the highest at 84% in VLBWIs delivered at 29–34 GW. Contrary to the significantly lower total mortality (12%) and morbidities including sepsis (21%) associated with CS than vaginal delivery (VD) (16% and 24%, respectively), the mortality in the 25–26 GW (26%) and sepsis in the 27–28 GW (25%) and 29–34 GW (12%) groups were significantly higher in CS than in VD (21%, 20% and 8%, respectively). In multivariate analyses, the adjusted odds ratios (ORs) for mortality (OR 1.06, 95% CI 0.89–1.25) and morbidity including sepsis (OR 1.12, 95% CI 0.98–1.27) were not significantly reduced with CS compared with VD. The adjusted ORs for respiratory distress syndrome (1.89, 95% CI 1.59–2.23) and symptomatic patent ductus arteriosus (1.21, 95% CI 1.08–1.37) were significantly increased with CS than VD. In summary, CS was not associated with any survival or morbidity advantage in VLBWIs. These findings indicate that routine CS in VLBWIs without obstetric indications is contraindicated.

Conservative Treatment Without Any Intervention Compared With Other Therapeutic Strategies for Symptomatic Patent Ductus Arteriosus in Extremely Preterm Infants: A Nationwide Cohort Study in Korea.

Objective: Although symptomatic treatment is the most preferred treatment strategy for proven symptomatic patent ductus arteriosus (PDA), a considerable number of infants only received conservative treatment without any pharmacological or surgical interventions in the lower gestational age and lower birth weight group in Korea. We compared in-hospital outcomes of infants treated conservatively without any intervention and those of infants managed by other therapeutic strategies in extremely preterm infants with symptomatic PDA.Methods: A prospectively collected cohort study for 2,303 infants with gestational ages <28 weeks from the Korean Neonatal Network database. These infants were classified into four groups according to the presence of PDA-related symptoms and therapeutic treatment strategy: prophylactic treatment group, pre-symptomatic treatment (PST) group, symptomatic treatment (ST) group, and conservative treatment (CT) without any intervention group.Results: In multivariable logistic regression analysis, the risk of death was significantly decreased in the PST group (adjusted odds ratio [aOR] = 0.507; 95% confidence interval [CI] 0.311–0.826) and ST group (aOR = 0.349; 95% CI: 0.230–0.529) compared with the CT group. However, the risk of composite outcome of severe bronchopulmonary dysplasia or death had not increased in the PST group and ST group. Neonatal death due to pulmonary hemorrhage or neurological disease was significantly higher in the CT group than in the PST group or ST group.Conclusion: In extremely preterm infants, who are at highest risk of PDA-related morbidities and mortality, even less interventional approach for PDA can be allowed; the rescued pharmacological or surgical interventions are necessary if they met the criteria for hemodynamically significant PDA.

Trans-catheter closure of large PDA in adult patients with Amplatzer device: case series.

Ductus arteriosus is a physiological structure if not closed after birth, may lead to many complications. Today, trans-catheter closure of patent ductus arteriosus with Occluder devices is the preferred method. Surgical ligation is used only in certain cases such as large symptomatic patent ductus arteriosus in very small infants and premature babies; unfavourable structure of the duct or economic considerations. In this article, we described haemodynamic and morphological characteristics of five patients with large patent ductus arteriosus which were occluded with Amplatzer device.From 23 January, 2010 to 31 July, 2018, five patients referred to our clinic with large patent ductus arteriosus and pulmonary arterial hypertension for further evaluation. After assessing them with various diagnostic methods, we decided to close defect with ventricular septal defect Occluder device. Patients aged 21-44 years and one of them was male. Ductus closure was successfully done with ventricular septal defect Occluder device. Closure was successful for all of them but in one case, whose device was embolized to pulmonary artery after 24 hr and he underwent surgery.Trans-catheter closure of large patent ductus arteriosus in adult patients with pulmonary hypertension is feasible. Despite the fact that complications may occur even with the most experienced hands, the 'double disk' Amplatzer ventricular septal defect muscular Occluder could be advantageous in this setting.