Patent ductus arteriosus is persistent postnatal patency of the fetal ductus arteriosus, the vascular connection between the pulmonary artery and aorta. It is especially common in preterm infants, where persistent shunting can become hemodynamically significant, contribute to pulmonary overcirculation or systemic hypoperfusion, and complicate respiratory and neonatal outcomes.
Ask a research question about Patent Ductus Arteriosus. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
name: Patent Ductus Arteriosus
creation_date: "2026-05-05T01:33:38Z"
updated_date: "2026-05-05T04:25:15Z"
description: >-
Patent ductus arteriosus is persistent postnatal patency of the fetal ductus
arteriosus, the vascular connection between the pulmonary artery and aorta.
It is especially common in preterm infants, where persistent shunting can
become hemodynamically significant, contribute to pulmonary overcirculation or
systemic hypoperfusion, and complicate respiratory and neonatal outcomes.
category: Congenital
disease_term:
preferred_term: patent ductus arteriosus
term:
id: MONDO:0011827
label: patent ductus arteriosus
parents:
- Vascular disorder
synonyms:
- PDA
- Persistent ductus arteriosus
pathophysiology:
- name: Prostaglandin and oxygen-tension ductal closure signaling
description: >-
Fetal ductal patency is maintained by vasoactive signaling, including
prostaglandin-mediated relaxation. The postnatal fall in prostaglandin tone
and rise in oxygen tension normally shift the ductus arteriosus toward
functional constriction; persistent pro-patency signaling contributes to PDA.
cell_types:
- preferred_term: vascular smooth muscle cell
term:
id: CL:0000359
label: vascular associated smooth muscle cell
biological_processes:
- preferred_term: prostaglandin biosynthetic process
modifier: INCREASED
term:
id: GO:0001516
label: prostaglandin biosynthetic process
- preferred_term: response to oxygen levels
modifier: ABNORMAL
term:
id: GO:0070482
label: response to oxygen levels
evidence:
- reference: PMID:23055849
reference_title: "Patent ductus arteriosus: an overview."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Normal physiologic mechanisms contributing to closure - oxygen tension and decreased prostaglandins-are altered in prematurity.
explanation: This review explicitly supports oxygen tension and decreased prostaglandins as closure mechanisms altered in premature PDA.
- reference: PMID:23055849
reference_title: "Patent ductus arteriosus: an overview."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The maintenance of ductal patency is essential for the normal development of the fetus.
explanation: This supports active fetal ductal patency regulation as the normal precursor state that fails to close in PDA.
downstream:
- target: Persistent postnatal ductus arteriosus patency
description: Abnormal persistence of fetal pro-patency signaling impairs normal postnatal ductal closure.
- name: Persistent postnatal ductus arteriosus patency
description: >-
The ductus arteriosus normally functions as a fetal vascular connection and
closes after birth through coordinated ductal constriction and remodeling.
Failure of this patency-control program leaves an aortopulmonary channel.
cell_types:
- preferred_term: endothelial cell
term:
id: CL:0000115
label: endothelial cell
- preferred_term: vascular smooth muscle cell
term:
id: CL:0000359
label: vascular associated smooth muscle cell
biological_processes:
- preferred_term: vasculature development
modifier: ABNORMAL
term:
id: GO:0001944
label: vasculature development
- preferred_term: blood vessel diameter maintenance
modifier: ABNORMAL
term:
id: GO:0097746
label: blood vessel diameter maintenance
evidence:
- reference: DOI:10.3390/jcdd11040113
reference_title: Ductus Arteriosus in Fetal and Perinatal Life
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The ductus arteriosus represents an essential vascular structure connecting the pulmonary artery and the aorta.
explanation: This review supports the anatomic vascular channel that remains patent in PDA.
- reference: DOI:10.3390/jcdd11040113
reference_title: Ductus Arteriosus in Fetal and Perinatal Life
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
the regulatory mechanisms governing ductal patency in critical stages such as the fetal and the perinatal period
explanation: This supports a ductal patency-control mechanism spanning fetal and perinatal life.
downstream:
- target: Hemodynamically significant ductal shunting
description: A persistently patent ductus arteriosus permits ongoing aortopulmonary shunting after birth.
- name: Ductus arteriosus smooth muscle contractility program
description: >-
Developmental evidence indicates that ductus arteriosus smooth muscle
identity and contractility are necessary for ductal closure; impaired
contractility can produce a patent ductus arteriosus phenotype.
cell_types:
- preferred_term: vascular smooth muscle cell
term:
id: CL:0000359
label: vascular associated smooth muscle cell
biological_processes:
- preferred_term: smooth muscle contraction
modifier: DECREASED
term:
id: GO:0006939
label: smooth muscle contraction
evidence:
- reference: PMID:36749647
reference_title: Prdm6 drives ductus arteriosus closure by promoting ductus arteriosus smooth muscle cell identity and contractility.
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
Prdm6 depletion in Wnt1-expressing cells during development resulted in perinatal lethality and a completely penetrant patent ductus arteriosus (DA) phenotype.
explanation: This mouse developmental genetics study supports impaired smooth muscle developmental regulation as a PDA mechanism.
- reference: PMID:36749647
reference_title: Prdm6 drives ductus arteriosus closure by promoting ductus arteriosus smooth muscle cell identity and contractility.
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
Prdm6 depletion significantly reduced DA tone and contractility.
explanation: This directly supports reduced ductus arteriosus contractility as a mechanistic failure point.
downstream:
- target: Persistent postnatal ductus arteriosus patency
description: Reduced ductus arteriosus smooth muscle tone and contractility impairs functional closure.
- name: Hemodynamically significant ductal shunting
description: >-
When persistent ductal flow is large enough, pulmonary overcirculation and
systemic hypoperfusion can define hemodynamically significant PDA and
increase risk for adverse neonatal outcomes.
evidence:
- reference: DOI:10.1371/journal.pone.0306769
reference_title: Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. A multicenter cohort study
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A diagnosis of hemodynamically significant PDA (hsPDA) was established when the PDA diameter was ≥ 1.6 mm at the pulmonary end with growing or pulsatile flow pattern, and at least 2 of 3 indexes of pulmonary overcirculation and/or systemic hypoperfusion were present.
explanation: This cohort defines hsPDA by ductal size, flow pattern, and overcirculation or hypoperfusion indices.
phenotypes:
- category: Cardiovascular
name: Patent ductus arteriosus
diagnostic: true
description: Persistent ductal patency is the defining cardiovascular lesion.
phenotype_term:
preferred_term: Patent ductus arteriosus
term:
id: HP:0001643
label: Patent ductus arteriosus
evidence:
- reference: PMID:36749647
reference_title: Prdm6 drives ductus arteriosus closure by promoting ductus arteriosus smooth muscle cell identity and contractility.
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
Prdm6 depletion in Wnt1-expressing cells during development resulted in perinatal lethality and a completely penetrant patent ductus arteriosus (DA) phenotype.
explanation: This provides direct experimental support for the PDA phenotype.
- category: Cardiovascular
name: Pulmonary arterial hypertension
description: Longstanding or severe ductal shunting can contribute to pulmonary vascular disease and elevated pulmonary arterial pressure.
phenotype_term:
preferred_term: Pulmonary arterial hypertension
term:
id: HP:0002092
label: Pulmonary arterial hypertension
evidence:
- reference: DOI:10.1371/journal.pone.0306769
reference_title: Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. A multicenter cohort study
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
The increased risk of mortality in neonates with non-hsPDA underscores the potential inadequacy of criteria for defining hsPDA within the first 3 postnatal days (as they may be adversely affected by other clinically severe factors, i.e. persistent pulmonary hypertension and mechanical ventilation).
explanation: This supports pulmonary hypertension as an important confounder and associated cardiopulmonary context rather than proving it is caused by PDA in all patients.
- category: Respiratory
name: Respiratory distress
description: Hemodynamically significant PDA in preterm infants is clinically tied to respiratory morbidity and ventilatory status.
phenotype_term:
preferred_term: Respiratory distress
term:
id: HP:0002098
label: Respiratory distress
evidence:
- reference: DOI:10.1371/journal.pone.0306769
reference_title: Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. A multicenter cohort study
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
persistent pulmonary hypertension and mechanical ventilation
explanation: This supports severe respiratory and pulmonary vascular context in early PDA assessment, although the abstract does not isolate respiratory distress as a standalone phenotype.
- category: Respiratory
name: Bronchopulmonary dysplasia
description: Hemodynamically significant PDA in very low birth weight infants is associated with higher occurrence of bronchopulmonary dysplasia.
phenotype_term:
preferred_term: Bronchopulmonary dysplasia
term:
id: HP:0006528
label: Chronic lung disease
evidence:
- reference: DOI:10.1371/journal.pone.0306769
reference_title: Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. A multicenter cohort study
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The occurrence of BPD was 6-fold higher among neonates with hsPDA
explanation: This multicenter cohort directly supports BPD as an associated adverse neonatal outcome in hsPDA.
- category: Cardiovascular
name: Heart murmur
description: A continuous or machinery-like murmur is a common clinical sign of ductal shunting.
phenotype_term:
preferred_term: Heart murmur
term:
id: HP:0030148
label: Heart murmur
evidence:
- reference: PMID:23055849
reference_title: "Patent ductus arteriosus: an overview."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Clinical signs of ductal patency include murmur, tachycardia, bounding peripheral pulses, and congestive heart failure and associated symptoms.
explanation: This review directly lists murmur among clinical signs of ductal patency.
- category: Cardiovascular
name: Bounding pulses and widened pulse pressure
description: Large ductal shunts can produce bounding pulses and widened pulse pressure as clinical signs of runoff physiology.
phenotype_term:
preferred_term: Bounding pulse
term:
id: HP:0032555
label: Bounding pulse
evidence:
- reference: PMID:23055849
reference_title: "Patent ductus arteriosus: an overview."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Clinical signs of ductal patency include murmur, tachycardia, bounding peripheral pulses, and congestive heart failure and associated symptoms.
explanation: This review directly lists bounding peripheral pulses among clinical signs of ductal patency.
- category: Neurological
name: Intraventricular hemorrhage
description: Severe hemodynamic patterns in hsPDA are associated with increased risk of high-grade intraventricular hemorrhage in very low birth weight infants.
phenotype_term:
preferred_term: Intraventricular hemorrhage
term:
id: HP:0030746
label: Intraventricular hemorrhage
evidence:
- reference: DOI:10.1371/journal.pone.0306769
reference_title: Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. A multicenter cohort study
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The risk of IVH (grade ≥ 3) and ROP (grade ≥ 3) increased by 8.7-fold and 18-fold, respectively, when both systemic hypoperfusion and pulmonary overcirculation were present in hsPDA.
explanation: This cohort directly supports association between severe hsPDA physiology and high-grade IVH.
- category: Ophthalmologic
name: Retinopathy of prematurity
description: Severe hemodynamic patterns in hsPDA are associated with increased risk of high-grade retinopathy of prematurity.
phenotype_term:
preferred_term: Retinopathy of prematurity
term:
id: HP:0500049
label: Retinopathy of prematurity
evidence:
- reference: DOI:10.1371/journal.pone.0306769
reference_title: Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. A multicenter cohort study
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The risk of IVH (grade ≥ 3) and ROP (grade ≥ 3) increased by 8.7-fold and 18-fold, respectively, when both systemic hypoperfusion and pulmonary overcirculation were present in hsPDA.
explanation: This cohort directly supports association between severe hsPDA physiology and high-grade ROP.
genetic:
- name: PRDM6 developmental susceptibility mechanism
association: Predisposing
presence: Positive
gene_term:
preferred_term: PRDM6
term:
id: hgnc:9350
label: PRDM6
notes: >-
PRDM6 evidence is strongest from developmental model systems and a candidate
human GWAS locus; it is not curated here as a deterministic Mendelian cause
of isolated PDA.
evidence:
- reference: PMID:36749647
reference_title: Prdm6 drives ductus arteriosus closure by promoting ductus arteriosus smooth muscle cell identity and contractility.
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
we identified an SMC-selective enhancer within the Prdm6 third intron that exhibited allele-specific activity, providing evidence that rs17149944 may be the causal SNP for a cardiovascular disease GWAS locus identified within the human PRDM6 gene.
explanation: This supports PRDM6 as a plausible developmental susceptibility locus while preserving uncertainty about human causality.
diagnosis:
- name: Echocardiographic assessment of ductal patency and hemodynamic significance
description: >-
Echocardiography is used to identify PDA and classify hemodynamic
significance, but diagnostic criteria and timing vary across neonatal
centers.
evidence:
- reference: DOI:10.1007/s00431-025-06485-y
reference_title: Diagnosis of patent ductus arteriosus by different echocardiographic methods in very preterm infants
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
There is no consensus regarding the timing and diagnostic criteria for identifying hemodynamically significant patent ductus arteriosus (hsPDA).
explanation: This supports the need to document criteria and timing in hsPDA diagnosis.
- reference: DOI:10.1007/s00431-025-06485-y
reference_title: Diagnosis of patent ductus arteriosus by different echocardiographic methods in very preterm infants
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Our results suggest that more attention should be paid to the choice of diagnostic criteria for individuating hsPDA in very preterm infants.
explanation: This directly supports criteria selection as a key diagnostic issue.
- name: Serum biomarker adjuncts to echocardiography
description: >-
Natriuretic peptides, cardiac troponin, vasoactive markers, and inflammatory
biomarkers have been studied as adjuncts to echocardiography for assessing
ductal patency and treatment decisions in preterm infants.
evidence:
- reference: DOI:10.3390/biomedicines13030670
reference_title: "Serum Biomarkers in Patent Ductus Arteriosus in Preterm Infants: A Narrative Review"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Results: Out of the 813 identified articles, 85 were included in our review of cardiac biomarkers: Natriuretic peptides (NPs), Cardiac troponin T (cTnT), vasoactive biomarkers (Mid-regional pro-adrenomedullin (MR-proADM), Endothelin-1 (ET-1), Copeptin, and Isoprostanes (IPs)), and inflammatory biomarkers (Interleukin-6 (IL-6), IL-8, IL-10, Growth Differentiation Factor 15 (GDF-15), Monocyte Chemoattractant Protein-1 (MCP-1/CCL2), Macrophage Inflammatory Protein-1α (MIP-1α/CCL3)) in relation to PDA.
explanation: This review lists biomarker classes evaluated in relation to PDA.
treatments:
- name: Ibuprofen pharmacologic closure
description: >-
Cyclooxygenase inhibitor therapy with ibuprofen is a common medical closure
strategy in premature infants, with evidence varying by route of
administration.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: ibuprofen
term:
id: CHEBI:5855
label: ibuprofen
target_mechanisms:
- target: Prostaglandin and oxygen-tension ductal closure signaling
treatment_effect: INHIBITS
description: Ibuprofen inhibits cyclooxygenase-dependent prostaglandin production to favor ductal constriction.
evidence:
- reference: DOI:10.7717/peerj.16591
reference_title: "The impact of the route of administration on the efficacy and safety of the drug therapy for patent ductus arteriosus in premature infants: a systematic review and meta-analysis"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
oral ibuprofen may offer certain advantages in closing PDA without increasing the risk of adverse events.
explanation: This meta-analysis supports oral ibuprofen as an evidence-backed pharmacologic closure route.
- name: Acetaminophen pharmacologic closure
description: >-
Acetaminophen is used as an alternative pharmacologic closure or prophylaxis
strategy in preterm infants, with clinical trials evaluating prevention of
ductal patency and severe morbidity.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: acetaminophen
term:
id: CHEBI:46195
label: paracetamol
target_mechanisms:
- target: Prostaglandin and oxygen-tension ductal closure signaling
treatment_effect: INHIBITS
description: Acetaminophen is used to suppress prostaglandin-mediated ductal patency signaling.
evidence:
- reference: DOI:10.7717/peerj.16591
reference_title: "The impact of the route of administration on the efficacy and safety of the drug therapy for patent ductus arteriosus in premature infants: a systematic review and meta-analysis"
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
the use of paracetamol demonstrated no significant difference in PDA closure and the risk of adverse events between oral and intravenous administration.
explanation: This supports acetaminophen/paracetamol as an evaluated PDA pharmacotherapy, while preserving uncertainty about route-specific efficacy.
- name: Transcatheter device closure
description: >-
In selected premature infants with hemodynamically significant PDA,
transcatheter closure has emerged as an alternative to surgical ligation.
treatment_term:
preferred_term: transcatheter device closure
term:
id: MAXO:0025001
label: surgical procedure on cardiovascular system
evidence:
- reference: PMID:39263415
reference_title: "Device Closure of Hemodynamically Significant Patent Ductus Arteriosus in Premature Infants."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In recent years, there has been rapid development in transcatheter patent ductus arteriosus closure primary with the use of the Amplatzer Piccolo Occluder, and this has gained widespread acceptance as a safe and effective alternative to surgical ligation in extremely low-birth-weight infants weighing over 700 g.
explanation: This review supports transcatheter device closure as a selected-treatment option in very small premature infants.
- name: Surgical ligation
description: >-
Surgical ligation remains part of the PDA management landscape, particularly
as an alternative or rescue option when pharmacologic or catheter-based
closure is unsuitable.
treatment_term:
preferred_term: surgical procedure on cardiovascular system
term:
id: MAXO:0025001
label: surgical procedure on cardiovascular system
evidence:
- reference: PMID:23055849
reference_title: "Patent ductus arteriosus: an overview."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Three management strategies are currently available for PDA: fluid restriction and diuretics (as clinically appropriate), medical intervention, and surgical ligation.
explanation: This review explicitly includes surgical ligation among PDA management strategies.
- reference: PMID:39263415
reference_title: "Device Closure of Hemodynamically Significant Patent Ductus Arteriosus in Premature Infants."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In recent years, there has been rapid development in transcatheter patent ductus arteriosus closure primary with the use of the Amplatzer Piccolo Occluder, and this has gained widespread acceptance as a safe and effective alternative to surgical ligation in extremely low-birth-weight infants weighing over 700 g.
explanation: This contemporary device-closure review supports surgical ligation as the comparator treatment that transcatheter closure may replace in selected infants.
clinical_trials:
- name: NCT04459117
phase: PHASE_III
status: COMPLETED
description: >-
TREOCAPA randomized trial evaluating prophylactic acetaminophen treatment of
the ductus arteriosus in extremely preterm infants.
target_phenotypes:
- preferred_term: Patent ductus arteriosus
term:
id: HP:0001643
label: Patent ductus arteriosus
evidence:
- reference: clinicaltrials:NCT04459117
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
TREOCAPA is a Phase II/III European Multicentre study concerning the prophylactic treatment by Acetaminophen of extremely preterm infant during the first five days after birth.
explanation: This trial registry summary supports disease-specific prophylactic acetaminophen evaluation.
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.
Please provide a comprehensive research report on Patent Ductus Arteriosus covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.
For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.
Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed
Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Search first: CTD, PubMed, PheGenI, GxE databases
Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC
For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities
For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype
Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser
Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases
Search first: CDC databases, WHO, PubMed, NHANES
Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON
Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc
Search first: Gene Ontology (GO), Reactome, KEGG, PubMed
Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold
Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA
Search first: ImmPort, Immunome Database, IEDB, Gene Ontology
Search first: PubMed, Gene Ontology, Reactome
Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types
Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Search first: OMIM, Orphanet, HPO, PubMed
Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.
Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
Search first: CDC, WHO, behavioral intervention databases, Cochrane Library
Search first: NSGC resources, ACMG guidelines, GeneReviews
Search first: Clinical guidelines, FDA approvals, PubMed
Search first: NCBI Taxonomy
Search first: VBO (Vertebrate Breed Ontology)
Search first: NCBI Gene
Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease
This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details
Patent ductus arteriosus (PDA) is the postnatal persistence of the fetal ductus arteriosus (DA), a conduit between the pulmonary artery and descending aorta. In preterm infants, PDA is common and strongly related to gestational age/birth weight; controversy persists regarding what constitutes a hemodynamically significant PDA (hsPDA), optimal timing of treatment, and whether early pharmacologic closure improves longer-term outcomes. Recent work emphasizes physiology-guided diagnosis (targeted neonatal echocardiography and combined hemodynamic models), increasing real-world use of transcatheter closure in very small infants, and active investigation of prophylactic/targeted acetaminophen strategies. (chen2025combinationofechocardiography pages 1-2, dani2025diagnosisofpatent pages 1-2, trahan2025patentductusarteriosus pages 4-5, baruteau2024deviceclosureof pages 1-2)
Patent ductus arteriosus is persistence of patency of the DA after birth, resulting in (typically) a left-to-right shunt from the aorta to pulmonary artery once pulmonary vascular resistance falls. The DA is defined as a fetal vessel connecting the main pulmonary artery to the proximal descending aorta. (cucerea2025serumbiomarkersin pages 1-2)
Synonyms/alternate names in contemporary literature: “PDA”, “persistent ductus arteriosus”, and “ductal patency/persistent patency of the ductus arteriosus” are used interchangeably in recent reviews and trials. (cucerea2025serumbiomarkersin pages 1-2, ursino2025treocapaprophylactictreatment pages 1-2)
ICD/MeSH/MONDO/OMIM/Orphanet identifiers: Not reliably retrievable from the full-text evidence captured in the current tool session; therefore, no identifier values are asserted here to avoid uncited claims.
The information below is derived primarily from: - Aggregated disease-level resources (systematic reviews and narrative reviews) for mechanisms and treatment syntheses (baruteau2024deviceclosureof pages 1-2, luo2024theimpactof pages 1-2, pugnaloni2024ductusarteriosusin pages 5-8, cucerea2025serumbiomarkersin pages 1-2) - Human clinical cohorts/trials for quantified outcomes and practice variation (chesi2024patentductusarteriosus pages 1-2, dani2025diagnosisofpatent pages 1-2, chen2025combinationofechocardiography pages 1-2) - Model organism primary studies for causal molecular regulators of DA closure (mouse developmental genetics) (zou2023prdm6drivesductus pages 1-2)
PDA arises when normal physiologic DA constriction and subsequent anatomic remodeling/closure fail. Birth-related rise in oxygen tension and reduced circulating prostaglandins normally trigger DA vasoconstriction (via inhibition of potassium channels, increased Ca2+ influx) and later remodeling into the ligamentum arteriosum. (cucerea2025serumbiomarkersin pages 1-2)
Preterm DA tissue is described as thinner and less muscular with smooth muscle cells (SMCs) more sensitive to circulating vasodilators (PGE2 and nitric oxide), contributing to prolonged patency in prematurity. (pugnaloni2024ductusarteriosusin pages 5-8)
Prematurity / low birth weight: PDA prevalence inversely correlates with gestational age and birth weight. In one prospective cohort background, PDA affected ~65% of very-low-birth-weight infants (<1500 g), and hsPDA prevalence has been reported to reach ~50% in infants <28 weeks. (chen2025combinationofechocardiography pages 1-2)
Perinatal/clinical risk factors for hsPDA progression (early life): In a prospective study combining echocardiography and noninvasive hemodynamic monitoring, independent risk factors included maternal eclampsia/preeclampsia, surfactant use, echocardiographic size/LA:Ao metrics, and total body water percentage at 48–72 h. (chen2025combinationofechocardiography pages 1-2)
Systemic inflammation / mediator milieu: Reviews describe that systemic inflammation (e.g., TNFα) can increase vasodilatory mediators (PGE2, NO), increasing patency risk in preterms. (pugnaloni2024ductusarteriosusin pages 5-8)
Other proposed contributors in preterm infants: adrenal insufficiency/altered cortisol, thrombocytopenia/platelet dysfunction, and clinical interventions that affect transductal flow/diameter (e.g., surfactant) are discussed as contributors to prolonged patency and hemodynamic sequelae. (pugnaloni2024ductusarteriosusin pages 5-8)
No robust “protective factor” interventions with quantified effect sizes were identified in the retrieved evidence set. However, the physiologic transition itself—loss of placental prostaglandins and increased oxygen tension—acts as a natural pro-closure shift. (cucerea2025serumbiomarkersin pages 1-2)
Direct gene–environment interaction studies (formal GxE) were not clearly represented in the retrieved evidence set. The contemporary mechanistic framing supports interaction between genetic variation in prostaglandin/SMC programs and environmental/perinatal exposures that alter oxygen tension, inflammation, and vasodilator signaling, but specific interaction effect sizes were not available. (pugnaloni2024ductusarteriosusin pages 5-8, minta2025associationbetweengenetic pages 1-2, zou2023prdm6drivesductus pages 1-2)
In preterm infants, PDA phenotypes range from asymptomatic ductal patency to hemodynamically significant shunting with pulmonary overcirculation and systemic hypoperfusion. Contemporary echocardiography-based definitions operationalize “pulmonary overcirculation” and “systemic steal/hypoperfusion” patterns. (chesi2024patentductusarteriosus pages 2-4, mukherjee2025…paracetamoland pages 57-62)
Common phenotype domains and candidate HPO terms (suggestions): - Cardiac murmur (clinical sign): Heart murmur (HP:0001642) — described as “machinery murmur” in clinical descriptions embedded in trial methods. (mukherjee2025…paracetamoland pages 57-62) - Wide pulse pressure / bounding pulses (clinical signs): Increased pulse pressure (HP:0031232), Bounding pulse (HP:0025502) — described as common clinical signs in hsPDA screening contexts. (mukherjee2025…paracetamoland pages 57-62) - Respiratory morbidity association: Respiratory distress (HP:0002098), Bronchopulmonary dysplasia (HP:0012099). Persistent left-to-right shunt is linked to worse respiratory failure and higher BPD risk. (dani2025diagnosisofpatent pages 1-2, chesi2024patentductusarteriosus pages 1-2) - Neurologic/retinal complications (in preterm context): Intraventricular hemorrhage (HP:0001344), Retinopathy of prematurity (HP:0000593). (chesi2024patentductusarteriosus pages 1-2)
Frequency/severity notes: - hsPDA incidence estimates vary strongly with diagnostic criteria and timing. A study directly comparing criteria found hsPDA incidence ~34–35% across three approaches but emphasized that different criteria/timing diagnose different infants at different times. (dani2025diagnosisofpatent pages 1-2)
Direct patient-reported QoL instruments are uncommon in neonatal PDA literature; the principal QoL-related impacts discussed are mediated via prematurity complications (BPD, IVH, ROP) and long-term neurodevelopment. Persistent shunting is linked to pulmonary hypertension and impaired neurodevelopment in broad clinical association statements. (dani2025diagnosisofpatent pages 1-2)
PRDM6 (model organism causality; human relevance suggested): In a mouse developmental model, Wnt1-lineage deletion of Prdm6 caused perinatal lethality with a fully penetrant patent ductus arteriosus phenotype, attributed to reduced DA tone/contractility and downregulation of a DA-enriched smooth-muscle contractile gene program. The paper also maps an SMC-selective enhancer in Prdm6 with allele-specific activity and highlights a GWAS SNP (rs17149944) as potentially causal at the PRDM6 locus. (zou2023prdm6drivesductus pages 1-2)
Prostaglandin pathway genes (human association in preterms): A 2025 association study in 99 preterm neonates investigated prostaglandin-pathway polymorphisms (phospholipase A2, COX-1, prostaglandin synthase 2, EP4/PTGER4) and reported associations of selected polymorphisms with PDA risk; one excerpt notes rs1051931 in a phospholipase A2 gene associated with increased PDA risk (OR ~2.49) in their analysis. (minta2025associationbetweengenetic pages 1-2, minta2025associationbetweengenetic pages 7-9)
A synthesis of recent reviews: 1) Fetal patency maintenance: relative hypoxia + PGE2 signaling (EP4 receptor) and other vasodilatory pathways (cAMP/cGMP) maintain DA relaxation; NO and CO contribute. (cucerea2025serumbiomarkersin pages 1-2) 2) Immediate postnatal functional closure: increased oxygen tension and reduced prostaglandins promote DA SMC constriction through inhibition of K+ channels and increased Ca2+ influx; oxygen also increases endothelin-1 and reactive oxygen species, generating isoprostanes. (cucerea2025serumbiomarkersin pages 1-2) 3) Anatomic closure/remodeling: over days–weeks, closure involves SMC migration/proliferation, extracellular matrix production, endothelial proliferation, and disruption of the internal elastic lamina. (pugnaloni2024ductusarteriosusin pages 5-8) 4) Failure points in prematurity: immature DA structure (thinner/less muscular), heightened sensitivity to PGE2/NO, and inflammatory and endocrine perturbations increase risk of persistent patency and hsPDA physiology. (pugnaloni2024ductusarteriosusin pages 5-8)
Specific disease-associated DNA methylation/histone marks were not identified in the retrieved evidence set.
The retrieved evidence emphasizes perinatal physiologic environment (oxygen tension, inflammation, endocrine milieu) over classic adult-style lifestyle exposures.
Hemodynamic significance is a physiology construct. There is “no consensus regarding the timing and diagnostic criteria for identifying hemodynamically significant PDA (hsPDA)” and different criteria identify different infants at different postnatal times, which contributes to inter-center variability. (dani2025diagnosisofpatent pages 1-2)
Composite echocardiographic approaches: Recent clinical studies operationalize hsPDA through DA diameter/flow patterns plus indices of pulmonary overcirculation and systemic hypoperfusion. For example, one multicenter cohort defined hsPDA as PDA ≥1.6 mm with pulsatile/growing flow plus ≥2/3 indices of overcirculation/hypoperfusion. (chesi2024patentductusarteriosus pages 1-2)
A prospective study combining echocardiographic and systemic hemodynamic parameters within 72 h showed that a combined model (maternal factors + surfactant + DA diameter/weight ratio + LA/Ao + TBW%) achieved AUC 0.981 with sensitivity 100% and specificity 90.0% for predicting hsPDA development. (chen2025combinationofechocardiography pages 1-2)
The cohort definitions and adjusted odds ratios for outcomes by PDA category are tabulated in the Chesi 2024 paper (see extracted tables). (chesi2024patentductusarteriosus media 56412072, chesi2024patentductusarteriosus media 692abe13)
Congenital: DA is physiologically present in utero; PDA refers to failure of closure after birth.
Anatomic closure typically requires days to weeks via remodeling processes (SMC/EC/ECM changes). (pugnaloni2024ductusarteriosusin pages 5-8)
Early postnatal time (first 72–84 hours) is a key window in preterm infants for echocardiographic assessment; however, criteria/timing materially alter hsPDA classification. (dani2025diagnosisofpatent pages 1-2)
A heritable component is supported by twin and animal-model evidence (cited in the prostaglandin-pathway association paper), and by developmental gene-regulatory causality (PRDM6 mouse model). However, specific Mendelian inheritance patterns for “isolated PDA” were not established from the retrieved evidence set. (minta2025associationbetweengenetic pages 1-2, zou2023prdm6drivesductus pages 1-2)
Diagnosis and hemodynamic assessment are echo-based, with emphasis on ductal size and flow direction/pattern, pulmonary overcirculation indices (e.g., LA/Ao), and systemic hypoperfusion indices. (chen2025combinationofechocardiography pages 1-2, chesi2024patentductusarteriosus pages 1-2, mukherjee2025…paracetamoland pages 57-62)
Practice variation / criteria uncertainty: Comparing different criteria sets shows stable overall incidence (~34–35%) but changing concordance and patient-level classification by time and criteria, underscoring the need for standardized definitions for hsPDA. (dani2025diagnosisofpatent pages 1-2)
A 2025 narrative review summarizes candidate serum biomarkers (e.g., natriuretic peptides, troponin, vasoactive and inflammatory markers) as correlates of PDA physiology, but emphasizes that clinical judgment must integrate these with echocardiography. (cucerea2025serumbiomarkersin pages 1-2)
Not comprehensively covered in the retrieved evidence set. Clinically, confounding early-day factors (persistent pulmonary hypertension, ventilator pressures, vasoactive infusions) can mask shunt direction/magnitude and complicate interpretation. (chesi2024patentductusarteriosus pages 10-11)
A multicenter VLBW cohort study reported strong adjusted associations between PDA categories and outcomes: - Non-hsPDA vs no PDA: ~15-fold higher risk of death. (chesi2024patentductusarteriosus pages 1-2) - hsPDA vs no PDA: ~6-fold higher BPD occurrence. (chesi2024patentductusarteriosus pages 1-2) - Most significant hsPDA physiology (systemic hypoperfusion + pulmonary overcirculation): grade ≥3 IVH risk increased 8.7-fold and grade ≥3 ROP risk increased 18-fold. (chesi2024patentductusarteriosus pages 1-2)
These associations and the exact categorization/criteria are presented in the paper’s tables (image-extracted). (chesi2024patentductusarteriosus media 56412072, chesi2024patentductusarteriosus media 692abe13)
Route effects (ibuprofen): A 2024 systematic review/meta-analysis (n=630) found oral ibuprofen had higher initial-course closure rates than IV ibuprofen (RR 1.27; 95% CI 1.13–1.44; p<0.0001) without statistically significant differences in adverse events or need for surgery after a full course. (luo2024theimpactof pages 1-2)
Route effects (acetaminophen/paracetamol): The same meta-analysis found no significant difference between oral vs IV acetaminophen/paracetamol for closure (RR 0.86; 95% CI 0.38–1.91). (luo2024theimpactof pages 1-2)
Contemporary overview (extremely preterm): A 2025 review reports that acetaminophen response rates exceed 50% across gestational ages in some series (with 47% response at 21–22 weeks in one cohort cited), but ductal reopening and nonresponse remain common (e.g., 37% reopening among initial responders; 20–30% remain patent despite therapy). The same review highlights diminishing returns with repeated courses (failure rates after first/second/third courses reported as 38%/76%/92% for ibuprofen or acetaminophen courses). (trahan2025patentductusarteriosus pages 4-5)
Expert consensus framing: A 2024 device-closure review states that first-line medical therapy (COX inhibitors or acetaminophen) has “moderate closure success” around 60–70%, and notes important adverse event concerns (bleeding, NEC, renal impairment) that contribute to conservative strategies and interventional escalation. (baruteau2024deviceclosureof pages 1-2)
MAXO suggestions (treatment actions): - Pharmacologic closure of PDA (COX inhibition; acetaminophen therapy) - Transcatheter closure of PDA - Surgical ligation of PDA (These are ontology suggestions; not asserted as exact MAXO IDs due to lack of identifier evidence in retrieved texts.)
Transcatheter closure outcomes (Piccolo trial follow-up): 3-year follow-up of 200 infants ≥700 g undergoing transcatheter PDA closure with Amplatzer Piccolo reported implant success 95.5% (191/200), and among those evaluated at 3 years, PDA closure 100% (33/33); overall survival >95% with 9 deaths not adjudicated device/procedure-related; notable events included aortic obstruction (2, requiring stent) and increased tricuspid regurgitation (5). (francescato2023transcatheterclosurein pages 1-2)
Real-world implementation trends (Children’s Hospitals Neonatal Consortium, 2011–2022): Among 54,813 infants (23–32 weeks), 36% had PDA; pharmacotherapy use increased 44% (relative) over time, “mostly with increased acetaminophen use”; transcatheter closure increased from 0 to 20.3%, and surgical ligation decreased from 25.1% to 3.6%. (trahan2025patentductusarteriosus pages 4-5)
Practice shift / expert opinion: Contemporary reviews emphasize rapid adoption of transcatheter closure (particularly after approval of Amplatzer Piccolo) and its role as an alternative to surgical ligation in experienced centers, while acknowledging ongoing questions around timing, patient selection, and complications at extremely low weights. (baruteau2024deviceclosureof pages 1-2, francescato2023transcatheterclosurein pages 1-2)
No established population-level primary prevention strategy was identified in the retrieved evidence set (PDA in prematurity reflects developmental physiology). The active research direction is secondary prevention / early targeted therapy to prevent severe morbidity.
A major example is prophylactic acetaminophen in extremely preterm infants (TREOCAPA) to improve survival without severe morbidity. (ursino2025treocapaprophylactictreatment pages 1-2)
The evidence set primarily addresses human PDA, but mechanistic conclusions are supported by animal models (mouse developmental genetics; cited animal evidence for prostaglandin/EP4 pathway disruption). (minta2025associationbetweengenetic pages 1-2, zou2023prdm6drivesductus pages 1-2)
1) Quantified outcome associations even in “non-hsPDA”: A 2024 multicenter cohort reported strong associations between PDA categories and mortality/BPD/IVH/ROP, and highlighted potential inadequacy of early hsPDA criteria in the first days of life. (chesi2024patentductusarteriosus pages 1-2, chesi2024patentductusarteriosus pages 10-11) 2) Evolving transcatheter closure evidence base: 2023–2024 work and reviews emphasize Piccolo-enabled closure in very small infants and continued follow-up on safety/complications. (francescato2023transcatheterclosurein pages 1-2, baruteau2024deviceclosureof pages 1-2) 3) Route-of-administration evidence for ibuprofen: 2024 meta-analysis suggests oral ibuprofen may be more effective than IV for initial closure without increased adverse events. (luo2024theimpactof pages 1-2)
The following table is designed for direct knowledge-base ingestion.
| Domain | Key points (with numbers) | Population/context | Source (first author year, journal) | URL |
|---|---|---|---|---|
| hsPDA definition/criteria | Chesi 2024: hsPDA defined as PDA ≥1.6 mm at pulmonary end with growing/pulsatile flow plus ≥2/3 indices of pulmonary overcirculation and/or systemic hypoperfusion; early treatment decisions remained partly discordant with ultrasound, with up to 40% treated in week 1 not meeting hsPDA criteria on ultrasound. (chesi2024patentductusarteriosus pages 1-2, chesi2024patentductusarteriosus pages 2-4) | Multicenter prospective cohort of 218 VLBW infants | Chesi 2024, PLOS ONE | https://doi.org/10.1371/journal.pone.0306769 |
| hsPDA definition/criteria | Dani 2025: Florence criteria = left-to-right shunt + ductal size ≥1.4 mm/kg plus ≥2 other echocardiographic criteria; Paris criteria use 2 echocardiographic criteria + gestational age; incidence of hsPDA was similar across methods: 35% (Florence), 34% (Paris), 35% (El-Khuffash score). (dani2025diagnosisofpatent pages 1-2) | Very preterm infants <32 weeks; echo at 24–48 h and 72–84 h | Dani 2025, European Journal of Pediatrics | https://doi.org/10.1007/s00431-025-06485-y |
| Epidemiology by GA/BW | PDA prevalence is inversely related to maturity: at day 4, about 10% in infants 30–37 weeks, ~80% in 25–28 weeks, and >90% at 24 weeks; 2024 VON data cited: 31% of infants <30 weeks received pharmacologic treatment and 3% had surgical closure. (dani2025diagnosisofpatent pages 1-2) | Preterm infants, especially very preterm | Dani 2025, European Journal of Pediatrics | https://doi.org/10.1007/s00431-025-06485-y |
| Epidemiology by BW/GA | PDA affected ~65% of VLBW infants (<1,500 g); hsPDA prevalence may reach ~50% in infants <28 weeks. In the prospective cohort, 85/98 had PDA at 24 h, and 30/98 progressed to hsPDA. (chen2025combinationofechocardiography pages 1-2) | Prospective cohort, GA ≤32 weeks, BW ≤1,500 g | Chen 2025, Frontiers in Pediatrics | https://doi.org/10.3389/fped.2025.1616706 |
| Echo/hemodynamic markers | Infants progressing to hsPDA had larger DA diameter, higher DA diameter/weight ratio at 48 and 72 h, higher LA/Ao at 24, 48, and 72 h; systemic hemodynamics showed increased stroke index, cardiac output index, TBW%, and reduced TPRI at 48–72 h. (chen2025combinationofechocardiography pages 1-2) | Same Chen cohort; serial echo + NICaS monitoring in first 72 h | Chen 2025, Frontiers in Pediatrics | https://doi.org/10.3389/fped.2025.1616706 |
| Independent risk factors/prediction | Independent predictors of hsPDA included maternal eclampsia/preeclampsia, surfactant use, DA diameter/weight ratio, LA/Ao, and TBW% at 48–72 h. Combined echo + hemodynamic model performance: AUC 0.981, sensitivity 100%, specificity 90.0%. (chen2025combinationofechocardiography pages 1-2) | Same Chen cohort | Chen 2025, Frontiers in Pediatrics | https://doi.org/10.3389/fped.2025.1616706 |
| Outcome associations | Non-hsPDA carried a 15-fold higher risk of death vs no PDA; by contrast, mortality risk in hsPDA was similar to no PDA in adjusted analyses. (chesi2024patentductusarteriosus pages 1-2, chesi2024patentductusarteriosus pages 10-11, chesi2024patentductusarteriosus pages 11-13) | Multicenter VLBW cohort | Chesi 2024, PLOS ONE | https://doi.org/10.1371/journal.pone.0306769 |
| Outcome associations | BPD occurrence was 6-fold higher with hsPDA vs no PDA; when both systemic hypoperfusion and pulmonary overcirculation were present, risk of grade ≥3 IVH increased 8.7-fold and grade ≥3 ROP increased 18-fold. (chesi2024patentductusarteriosus pages 1-2, chesi2024patentductusarteriosus pages 10-11, chesi2024patentductusarteriosus pages 11-13) | Multicenter VLBW cohort | Chesi 2024, PLOS ONE | https://doi.org/10.1371/journal.pone.0306769 |
Table: This table condenses recent, quantitative evidence for defining hemodynamically significant PDA, estimating risk by prematurity, and interpreting echocardiographic/hemodynamic predictors and outcome associations. It is designed as a compact knowledge-base-ready summary anchored to recent cohort studies and diagnostic comparisons.
References
(chen2025combinationofechocardiography pages 1-2): Cuie Chen, Yuechong Cui, Shujun Chen, Jiaonv Chen, Lirong Zhao, Yuanyuan Sun, Liuqing Ji, and Guoliang Wang. Combination of echocardiography with systemic hemodynamic parameters for early risk stratification of hemodynamically significant patent ductus arteriosus in preterm infants. Frontiers in Pediatrics, Sep 2025. URL: https://doi.org/10.3389/fped.2025.1616706, doi:10.3389/fped.2025.1616706. This article has 0 citations.
(dani2025diagnosisofpatent pages 1-2): Carlo Dani, Davide Sarcina, Iuri Corsini, Simone Pratesi, Chiara Poggi, Simona Montano, Barbara Loi, Giulia Regiroli, and Daniele De Luca. Diagnosis of patent ductus arteriosus by different echocardiographic methods in very preterm infants. European Journal of Pediatrics, Sep 2025. URL: https://doi.org/10.1007/s00431-025-06485-y, doi:10.1007/s00431-025-06485-y. This article has 3 citations and is from a peer-reviewed journal.
(trahan2025patentductusarteriosus pages 4-5): Kimberly Fernandez Trahan, Elaine L. Shelton, and Maria Gillam-Krakauer. Patent ductus arteriosus in extremely preterm infants: update on current diagnostic and treatment options. Current Treatment Options in Cardiovascular Medicine, Jul 2025. URL: https://doi.org/10.1007/s11936-025-01101-6, doi:10.1007/s11936-025-01101-6. This article has 3 citations and is from a peer-reviewed journal.
(baruteau2024deviceclosureof pages 1-2): Alban-Elouen Baruteau, Mathilde Méot, Nadir Benbrik, Céline Grunenwald, Naychi Lwin, Juliana Patkai, Jean-Christophe Rozé, Damien Bonnet, and Sophie Malekzadeh-Milani. Device closure of hemodynamically significant patent ductus arteriosus in premature infants. JACC: Advances, 3:101211, Oct 2024. URL: https://doi.org/10.1016/j.jacadv.2024.101211, doi:10.1016/j.jacadv.2024.101211. This article has 16 citations.
(cucerea2025serumbiomarkersin pages 1-2): Manuela Cucerea, Raluca Marian, Marta Simon, Madalina Anciuc-Crauciuc, Andreea Racean, Andrea Toth, Zsuzsánna Simon-Szabó, Mihaela-Georgiana Fadur, Valeriu Moldovan, and Elena Moldovan. Serum biomarkers in patent ductus arteriosus in preterm infants: a narrative review. Biomedicines, 13:670, Mar 2025. URL: https://doi.org/10.3390/biomedicines13030670, doi:10.3390/biomedicines13030670. This article has 4 citations.
(ursino2025treocapaprophylactictreatment pages 1-2): Moreno Ursino, Corinne Alberti, Gilles Cambonie, Ruth Kemp, Aure Vanhecke, Lea Levoyer, Alpha Diallo, Mikko Hallman, Jean-Christophe Rozé, Corine Alberti, Ricardo Carbajal, Pierre Kuhn, Alban Baruteau, Andrei Morgan, Pierre-Yves Ancel, Jennifer Zeilin, Naim Bouazza, Olivier Baud, Olivier Claris, Jean-Charles Picaud, Pierre-Henri Jarreau, Gene Dempsey, Naouel Bouafia, Regis Hankard, Tobias Muehlbacher, Aline Rideau, Kevin Leduc, Sebastien Joye, Cyril Flamant, Geraldine Gascoin, Isabelle Ligi, Juliana Patkai, Charlotte Kruse, Heloise Torchin, Pille Andresson, Antoine Bouissou, Elisa Proenca, Marine Vincent, Evgeniya Babacheva, Nadia Mazille, Magali Reynold De Seresin, Mirka Lumia, Christoph Rüegger, Claudia Knoepfli, Marco Bartocci, Georgi Nellis, Kim Nguyen, Ulla Sankilampi, Vincent Rigo, Francisca Barcos, Christoph Binder, Laure Simon, Hanna Soukka, Arnaud Callies, Maria Fintzou, Andre Graça, Marina Malakozi, Marie Moreau, Anne Murray, Katja Ovaskainen, Sauli Palmu, Manon Tauzin, Outi Aikio, Siw Helen Eger, Barthelemy Tosello, Louis Baraton, Alain Beuchee, Susanne Kirschenhofer, Kelly Mellul, Gaelle Sorin, Ludovic Treluyer, David Healy, Mari Liis Ilmoja, Elsa Kermorvant, Vito Mondì, Dimitrios Rallis, Nuria Torre, Helene Yager, Elodie Zana-Taieb, Laure Carneiro, Cecile Cipierre, Araceli Corredera, Gilles Dassieu, Rim Debbiche, Fabrice Decobert, Leif Evaggelidis, Aurelie Garbi, Maarja Hallik, Emilie Jourdes, Claire Langlet Muteau, Bertrand Leboucher, Jurate Panaviene, Marion Plourde, Outi Tammela, Geraldine Apprioual, Clemence Auzet, Claire Bellanger, Melinda Benard, Valerie Biran, Farid Boubred, Marine Butin, Melissa David, Marie Amelie Detristan, Odile Dicky, Laurence Dillenseger, Izaskun Dorronsoro, Xavier Durrmeyer, Sophie Laborie, Carine Lallemant, Noemie Lefevre, Sandra Lescure, Nathalie Montjaux, Corinne Ragouilliaux, Marta Sarda, Helene Schieber, Hans Jorgen Stensvold, Kenneth Strommen, Joao Virtuoso, Noura Zayat, Julie Abbal, Nahla Ahmed, Alberto Berenguer, Roberto Chioma, Yshwarya Stapleton, Sophie Delorme, Elodie Garnier, Joana Gil, Raquel Gouveia, Isabelle Grand Vuillemin, Shushanik Hovhannisyan, Andrei Morgan, Piermichele Paoulillo, Chiara Passarella, Anne Sophie Pellot, Simonetta Picone, Nikolaos Podimatas, Ana Rita Prior, Monica Rebelo, Angela Sainz, Edmundo Santos, Juliette Suhard, Camille Theveniaut, Tiina Ukkonen, and Mathilde Yverneau. Treocapa: prophylactic treatment of the ductus arteriosus in preterm infants by acetaminophen—statistical analysis plan for the randomized phase iii group sequential trial. Trials, Feb 2025. URL: https://doi.org/10.1186/s13063-025-08751-8, doi:10.1186/s13063-025-08751-8. This article has 5 citations and is from a peer-reviewed journal.
(luo2024theimpactof pages 1-2): Hanwen Luo, Jianghua He, Xiaoming Xu, Hongju Chen, and Jing Shi. The impact of the route of administration on the efficacy and safety of the drug therapy for patent ductus arteriosus in premature infants: a systematic review and meta-analysis. PeerJ, 12:e16591, Jan 2024. URL: https://doi.org/10.7717/peerj.16591, doi:10.7717/peerj.16591. This article has 6 citations and is from a peer-reviewed journal.
(pugnaloni2024ductusarteriosusin pages 5-8): Flaminia Pugnaloni, Daniela Doni, Mariella Lucente, Stefano Fiocchi, and Irma Capolupo. Ductus arteriosus in fetal and perinatal life. Journal of Cardiovascular Development and Disease, 11:113, Apr 2024. URL: https://doi.org/10.3390/jcdd11040113, doi:10.3390/jcdd11040113. This article has 17 citations.
(chesi2024patentductusarteriosus pages 1-2): Elena Chesi, Katia Rossi, Gina Ancora, Cecilia Baraldi, Mara Corradi, Francesco Di Dio, Giorgia Di Fazzio, Silvia Galletti, Giovanna Mescoli, Irene Papa, Agostina Solinas, Luca Braglia, Antonella Di Caprio, Riccardo Cuoghi Costantini, Francesca Miselli, Alberto Berardi, and Giancarlo Gargano. Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. a multicenter cohort study. PLOS ONE, 19:e0306769, Jul 2024. URL: https://doi.org/10.1371/journal.pone.0306769, doi:10.1371/journal.pone.0306769. This article has 11 citations and is from a peer-reviewed journal.
(zou2023prdm6drivesductus pages 1-2): Meng Zou, Kevin D. Mangum, Justin C. Magin, Heidi H. Cao, Michael T. Yarboro, Elaine L. Shelton, Joan M. Taylor, Jeff Reese, Terrence S. Furey, and Christopher P. Mack. Prdm6 drives ductus arteriosus closure by promoting ductus arteriosus smooth muscle cell identity and contractility. JCI Insight, Mar 2023. URL: https://doi.org/10.1172/jci.insight.163454, doi:10.1172/jci.insight.163454. This article has 13 citations and is from a domain leading peer-reviewed journal.
(minta2025associationbetweengenetic pages 1-2): Marcin Minta, Grażyna Kurzawińska, Zuzanna-Banach Minta, Agnieszka Seremak Mrozikiewicz, and Dawid Szpecht. Association between genetic polymorphisms in the prostaglandin pathway and the development of patent ductus arteriosus in preterm infants. International Journal of Molecular Sciences, 26:9274, Sep 2025. URL: https://doi.org/10.3390/ijms26199274, doi:10.3390/ijms26199274. This article has 0 citations.
(chesi2024patentductusarteriosus pages 2-4): Elena Chesi, Katia Rossi, Gina Ancora, Cecilia Baraldi, Mara Corradi, Francesco Di Dio, Giorgia Di Fazzio, Silvia Galletti, Giovanna Mescoli, Irene Papa, Agostina Solinas, Luca Braglia, Antonella Di Caprio, Riccardo Cuoghi Costantini, Francesca Miselli, Alberto Berardi, and Giancarlo Gargano. Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. a multicenter cohort study. PLOS ONE, 19:e0306769, Jul 2024. URL: https://doi.org/10.1371/journal.pone.0306769, doi:10.1371/journal.pone.0306769. This article has 11 citations and is from a peer-reviewed journal.
(mukherjee2025…paracetamoland pages 57-62): A Mukherjee. … paracetamol and ibuprofen research) trial: a comparative study on the use of paracetamol versus ibuprofen in treating patent ductus arteriosus in premature infants. Unknown journal, 2025.
(minta2025associationbetweengenetic pages 7-9): Marcin Minta, Grażyna Kurzawińska, Zuzanna-Banach Minta, Agnieszka Seremak Mrozikiewicz, and Dawid Szpecht. Association between genetic polymorphisms in the prostaglandin pathway and the development of patent ductus arteriosus in preterm infants. International Journal of Molecular Sciences, 26:9274, Sep 2025. URL: https://doi.org/10.3390/ijms26199274, doi:10.3390/ijms26199274. This article has 0 citations.
(chesi2024patentductusarteriosus media 56412072): Elena Chesi, Katia Rossi, Gina Ancora, Cecilia Baraldi, Mara Corradi, Francesco Di Dio, Giorgia Di Fazzio, Silvia Galletti, Giovanna Mescoli, Irene Papa, Agostina Solinas, Luca Braglia, Antonella Di Caprio, Riccardo Cuoghi Costantini, Francesca Miselli, Alberto Berardi, and Giancarlo Gargano. Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. a multicenter cohort study. PLOS ONE, 19:e0306769, Jul 2024. URL: https://doi.org/10.1371/journal.pone.0306769, doi:10.1371/journal.pone.0306769. This article has 11 citations and is from a peer-reviewed journal.
(chesi2024patentductusarteriosus media 692abe13): Elena Chesi, Katia Rossi, Gina Ancora, Cecilia Baraldi, Mara Corradi, Francesco Di Dio, Giorgia Di Fazzio, Silvia Galletti, Giovanna Mescoli, Irene Papa, Agostina Solinas, Luca Braglia, Antonella Di Caprio, Riccardo Cuoghi Costantini, Francesca Miselli, Alberto Berardi, and Giancarlo Gargano. Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. a multicenter cohort study. PLOS ONE, 19:e0306769, Jul 2024. URL: https://doi.org/10.1371/journal.pone.0306769, doi:10.1371/journal.pone.0306769. This article has 11 citations and is from a peer-reviewed journal.
(chesi2024patentductusarteriosus pages 10-11): Elena Chesi, Katia Rossi, Gina Ancora, Cecilia Baraldi, Mara Corradi, Francesco Di Dio, Giorgia Di Fazzio, Silvia Galletti, Giovanna Mescoli, Irene Papa, Agostina Solinas, Luca Braglia, Antonella Di Caprio, Riccardo Cuoghi Costantini, Francesca Miselli, Alberto Berardi, and Giancarlo Gargano. Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. a multicenter cohort study. PLOS ONE, 19:e0306769, Jul 2024. URL: https://doi.org/10.1371/journal.pone.0306769, doi:10.1371/journal.pone.0306769. This article has 11 citations and is from a peer-reviewed journal.
(francescato2023transcatheterclosurein pages 1-2): Gaia Francescato, Daniela Doni, Giuseppe Annoni, Irma Capolupo, Elena Ciarmoli, Iuri Corsini, Italo Francesco Gatelli, Sabrina Salvadori, Alberto Testa, and Gianfranco Butera. Transcatheter closure in preterm infants with patent ductus arteriosus: feasibility, results, hemodynamic monitoring and future prospectives. Italian Journal of Pediatrics, Nov 2023. URL: https://doi.org/10.1186/s13052-023-01552-2, doi:10.1186/s13052-023-01552-2. This article has 7 citations and is from a peer-reviewed journal.
(NCT04205877 chunk 1): Shyam K. Sathanandam, MD. The U.S. PDA Registry. Le Bonheur Children's Hospital. 2020. ClinicalTrials.gov Identifier: NCT04205877
(NCT06587282 chunk 1): PREEMIE: Study for Treatment of PDA in Premature Infants. Merit Medical Systems, Inc.. 2025. ClinicalTrials.gov Identifier: NCT06587282
(NCT06601114 chunk 1): Arooj Khan. The Effectiveness of Paracetamol Versus Ibuprofen in Management of Patent Ductus Arteriosus in Preterm Neonates. Arooj Khan. 2024. ClinicalTrials.gov Identifier: NCT06601114
(chesi2024patentductusarteriosus pages 11-13): Elena Chesi, Katia Rossi, Gina Ancora, Cecilia Baraldi, Mara Corradi, Francesco Di Dio, Giorgia Di Fazzio, Silvia Galletti, Giovanna Mescoli, Irene Papa, Agostina Solinas, Luca Braglia, Antonella Di Caprio, Riccardo Cuoghi Costantini, Francesca Miselli, Alberto Berardi, and Giancarlo Gargano. Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. a multicenter cohort study. PLOS ONE, 19:e0306769, Jul 2024. URL: https://doi.org/10.1371/journal.pone.0306769, doi:10.1371/journal.pone.0306769. This article has 11 citations and is from a peer-reviewed journal.
(trahan2025patentductusarteriosus pages 2-4): Kimberly Fernandez Trahan, Elaine L. Shelton, and Maria Gillam-Krakauer. Patent ductus arteriosus in extremely preterm infants: update on current diagnostic and treatment options. Current Treatment Options in Cardiovascular Medicine, Jul 2025. URL: https://doi.org/10.1007/s11936-025-01101-6, doi:10.1007/s11936-025-01101-6. This article has 3 citations and is from a peer-reviewed journal.