Persistent Fetal Circulation Syndrome

A syndrome of persistent PULMONARY HYPERTENSION in the newborn infant (INFANT, NEWBORN) without demonstrable HEART DISEASES. This neonatal condition can be caused by severe pulmonary vasoconstriction (reactive type), hypertrophy of pulmonary arterial muscle (hypertrophic type), or abnormally developed pulmonary arterioles (hypoplastic type). The newborn patient exhibits CYANOSIS and ACIDOSIS due to the persistence of fetal circulatory pattern of right-to-left shunting of blood through a patent ductus arteriosus (DUCTUS ARTERIOSUS, PATENT) and at times a patent foramen ovale (FORAMEN OVALE, PATENT).

Also Known As:

ACD-MPV; ACDMPV; Alveolar Capillary Dysplasia With Misalignment Of Pulmonary Veins; Alveolar Capillary Dysplasia With Misalignment Of Pulmonary Veins And Other Congenital Anomalies; Circulation, Persistent Fetal; Familial Persistent Pulmonary Hypertension of the Newborn; Misalignment of the Pulmonary Vessels; Persistent Fetal Circulation; Pulmonary Hypertension, Familial Persistent, of the Newborn; ACD MPV; Fetal Circulation, Persistent; Hypertension, Pulmonary, of Newborn, Persistent; Persistent Pulmonary Hypertension of Newborn

Networked: 122 relevant articles (4 outcomes, 4 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Meconium Aspiration Syndrome
2.	Pulmonary Hypertension
3.	Diaphragmatic Hernia
4.	Persistent Fetal Circulation Syndrome
5.	Respiratory Insufficiency (Respiratory Failure)

Experts

1.	Szafranski, Przemyslaw: 14 articles (06/2022 - 01/2013)
2.	Stankiewicz, Paweł: 12 articles (06/2022 - 06/2009)
3.	Sen, Partha: 8 articles (01/2018 - 06/2009)
4.	Karolak, Justyna A: 6 articles (06/2022 - 12/2018)
5.	Popek, Edwina: 5 articles (07/2021 - 01/2016)
6.	Tibboel, Dick: 5 articles (01/2021 - 01/2013)
7.	de Klein, Annelies: 5 articles (01/2021 - 01/2013)
8.	Langston, Claire: 5 articles (05/2016 - 06/2009)
9.	Gambin, Tomasz: 4 articles (06/2022 - 05/2016)
10.	Kalin, Tanya V: 4 articles (11/2021 - 09/2014)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Persistent Fetal Circulation Syndrome:

1.	DNA (Deoxyribonucleic Acid)IBA 01/01/2021 - "To investigate the contribution of aberrant DNA methylation, genome wide methylation patterns of ACD/MPV lung tissues were compared with methylation patterns of control lung tissues using the recently developed technique Methylated DNA sequencing (MeD-seq). " 01/01/2021 - "Each amplicon of the FOXF1-targeted NGS panel was efficiently sequenced using DNA isolated from blood or cell lines of 15 ACD/MPV patients and 8 controls. " 06/01/2013 - "We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. " 04/09/2021 - "Non-invasive methods such as DNA sequencing and FOXF1 analysis are helpful in the clinical diagnosis of ACD/MPV especially in early infants with respiratory distress and pulmonary hypertension."
2.	Transcription Factors (Transcription Factor)IBA 07/01/2018 - "Since its first description, significant achievements in research have led to a better understanding of the underlying molecular mechanism of ACD/MPV and genetic studies have identified associations with genomic alterations in the locus of the transcription factor FOXF1. " 01/01/2020 - "ACDMPV is associated with haploinsufficiency of the transcription factor FOXF1, which plays an important role in the development of the lung and intestine. " 06/01/2009 - "Using array CGH analysis, we have identified six overlapping microdeletions encompassing the FOX transcription factor gene cluster in chromosome 16q24.1q24.2 in patients with ACD/MPV and MCA. " 01/01/2023 - "Rationale: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal developmental disorder of lung morphogenesis caused by insufficiency of FOXF1 (forkhead box F1) transcription factor function. " 11/01/2022 - "Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) results from haploinsufficiency of the mesenchymal transcription factor FOXF1 gene. "
3.	Tolazoline (Priscoline)FDA Link 01/01/1987 - "The effects of two doses of tolazoline have been compared in 2 groups of newborns suffering from the persistent fetal circulation syndrome. " 01/01/1979 - "In pediatric cardiology tcPO2 is useful in monitoring cyanotic children given high-risk therapy such as balloon septostomy or drugs with controversial effects such as tolazoline in persistent fetal circulation. " 10/01/1978 - "Transcutaneous PO2 monitoring in infants with persistent fetal circulation who are receiving tolazoline therapy." 01/01/1987 - "In a first time, the outcome was favourable after the correction of acidosis and treatment with tolazoline of a persistent fetal circulation. " 12/01/1980 - "There were 47 seriously-ill neonates with medical causes of respiratory distress and 10 infants with severe respiratory distress secondary to a congenital diaphragmatic hernia treated with tolazoline according to a strict protocol designed to manage persistent fetal circulation (PFC). "
4.	Nitric Oxide (Nitrogen Monoxide)FDA Link 07/01/2003 - "Persistent pulmonary hypertension of newborn (PPHN) is associated with decreased nitric oxide (NO) release and impaired pulmonary vasodilation. " 04/01/2001 - "Baby A presented persistent pulmonary hypertension of newborn, and received nitric oxide inhalation. " 11/01/1999 - "Nitric oxide (NO), and extracorporeal membrane oxygenation (ECMO) were instituted as supportive care because of profound persistent fetal circulation (PFC). " 02/01/2007 - "Inhaled nitric oxide should be used early in severe hypoxic respiratory failure with persistent pulmonary hypertension of newborn and can improve survival rates without any major immediate side effects." 01/01/2009 - "A 6-day old neonate with meconium aspiration syndrome and persistent pulmonary hypertension of newborn on high frequency oscillator ventilation and inhaled nitric oxide was referred to our hospital with a large pericardial effusion causing hemodynamic compromise. "
5.	Oxygen (Dioxygen)IBA 02/01/2017 - "Objective To evaluate practice variations amongst neonatologists regarding oxygen management in neonates with persistent pulmonary hypertension of newborn (PPHN). " 02/01/2017 - "Management of Supplemental Oxygen for Infants with Persistent Pulmonary Hypertension of Newborn: A Survey." 02/01/1981 - "When these changes occur in lungs with immature, thick saccular walls, there is a decreased surface for oxygen exchange and an increased pulmonary vascular resistance resulting in a persistent fetal circulation." 01/01/1984 - "The group 2 and 3 infants suffered clinical and neurological evidence of hypoxic-ischemic brain injury from perinatal asphyxia; however, the infants in group 2 suffered additional problems such as meconium aspiration, persistent fetal circulation with ongoing hypoxemia as measured by transcutaneous or umbilical arterial oxygen monitoring. " 01/01/2004 - "Risk factors of mortality by univariate analysis were: outborn babies, resuscitation before admission, first born baby, low pH, high oxygen index (OI), high alveolar-arterial oxygen tension gradient (AaDO2) at admission, high OI and AaDO2 at 2 hours after admission, shock, pneumothorax, asphyxia, pulmonary hemorrhage, persistent pulmonary hypertension of newborn (PPHN), and renal failure. "
6.	Long Noncoding RNAIBA 08/01/2014 - "RNAi-mediated knock-down of LINC01081 in normal fetal lung fibroblasts showed that this lncRNA positively regulates FOXF1 transcript level, further indicating that decrease in LINC01081 expression can contribute to development of ACDMPV." 08/01/2014 - "Two deletions overlapping a distant FOXF1 enhancer unravel the role of lncRNA LINC01081 in etiology of alveolar capillary dysplasia with misalignment of pulmonary veins." 01/01/2013 - "We identify overlapping deletions 250 kb upstream of FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete lung-specific lncRNA genes. " 01/01/2021 - "The FOXF1 gene, causative for a neonatal lethal lung developmental disorder alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), maps 1.7 kb away from the long noncoding RNA gene FENDRR on the opposite strand, suggesting they may be coregulated. " 05/01/2016 - "Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. "
7.	NucleotidesIBA 01/01/2023 - "Measurements and Main Results: Pathogenic single-nucleotide variants and copy-number variant deletions involving the FOXF1 gene locus in all subjects with ACDMPV (n = 6) were accompanied by marked changes in lung structure, including deficient alveolar development and a paucity of pulmonary microvasculature. " 01/01/2023 - "Heterozygous single-nucleotide variants or copy-number variant (CNV) deletions involving the FOXF1 gene and/or its lung-specific enhancer are found in the vast majority of ACDMPV patients. " 07/27/2021 - "Causative heterozygous single nucleotide variants (SNVs) or copy-number variant (CNV) deletions involving FOXF1 or its distant lung-specific enhancer on chromosome 16q24.1 have been identified in 80-90% of ACDMPV patients. " 11/01/2019 - "Here, we present a third unrelated ACDMPV family with the same de novo variant and propose that a direct tandem repeat of eight consecutive nucleotides GCGGCGGC within the ~4 kb CpG island in FOXF1 exon 1 is a novel mutation hotspot causative for ACDMPV." 10/01/2022 - "Heterozygous single nucleotide variants (SNVs) or copy-number variant deletions involving FOXF1 or its distant lung-specific enhancer on chromosome 16q24.1 have been identified in 80-90% of patients with Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a lethal neonatal lung developmental disorder. "
8.	Vasodilator Agents (Vasodilators)IBA 01/01/2022 - "Treatment of neonates with persistent pulmonary hypertension of newborn includes optimization of ventilatory support, use of pulmonary vasodilators, and/or inotropic support. " 05/01/1980 - "We suggest that persistent fetal circulation may complicate this disorder and that vasodilator theapy is justified when other therapeutic measures fail." 04/01/1981 - "The effectiveness and safety of ECMO is convincing enough to warrant its consideration as therapy for congenital diaphragmatic hernia and persistent fetal circulation prior to the use of vasodilators." 02/01/2023 - "Based on the disease course, histopathology, and outcomes of this case, we believe ACDMPV should be considered a possibility in an infant presenting with hypoxemic respiratory failure, resistant pulmonary hypertension, and vasodilator-induced pulmonary edema. " 04/01/1981 - "This encouraging experience indicates that the pattern of persistent fetal circulation in the newborn infant who has undergone repair of a diaphragmatic hernia can be successfully managed with ECMO even when efforts to lower pulmonary hypertension and improve oxygenation with vasodilators (tolazoline, phenothiazine, acetylcholine, or prostaglandin E1) and have been ineffective. "
9.	Epoprostenol (Prostacyclin)FDA LinkGeneric 01/01/1992 - "[Prostacyclin in the treatment of persistent fetal circulation syndrome]." 09/22/1979 - "Use of prostacyclin in persistent fetal circulation." 06/23/1979 - "Use of prostacyclin in persistent fetal circulation." 01/01/2023 - "Two cases of pediatric PH patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) and congenital diaphragmatic hernia (CDH) with bronchopulmonary dysplasia (BPD), respectively, treated with epoprostenol above 100 ng/kg/min are presented. "
10.	Dopamine (Intropin)FDA LinkGeneric 01/01/2001 - "Although epinephrine preserves the SAP/PAP ratio, dopamine shows preferential pulmonary vasoconstriction, which might be detrimental if it also occurs during the management of infants with persistent fetal circulation. " 08/05/1984 - "[Tolazoline and dopamine in the management of persistent fetal circulation]." 10/01/1983 - "The combined application of Tolazoline and Dopamine for the treatment of the persistent fetal circulation syndrome showed that Dopamine prevented the most common side effects of Tolazoline i.e. " 10/01/1983 - "[Tolazoline and dopamine in the treatment of the persistent fetal circulation syndrome]." 01/01/1997 - "Plasma lactate levels were significantly elevated with epinephrine infusion 3.2 microg/kg/min. The differential responses of dopamine and epinephrine on pulmonary and mesenteric circulations may be significant in the pathophysiology and management of persistent fetal circulation and necrotizing enterocolitis."

Therapies and Procedures

1.	Extracorporeal Membrane Oxygenation 12/03/1988 - "Persistent fetal circulation and extracorporeal membrane oxygenation." 04/01/2003 - "Whereas reversible neonatal processes such as meconium aspiration and persistent fetal circulation have fostered clinical trials demonstrating the efficacy of extracorporeal life support, adult cardiopulmonary failure extracorporeal life support trials have proved less compelling. " 10/01/1982 - "A retrospective analysis of 93 consecutive children with congenital posterolateral diaphragmatic hernia (CDH) was performed to determine outcome, ability to predict the development of persistent fetal circulation (PFC) requiring pharmacologic or extracorporeal membrane oxygenation (ECMO), and whether drugs or ECMO have improved survival. " 08/01/1996 - "Six newborns (age range, 0 to 5 days; weight, 2.4 to 3.1 kg) were treated with venoarterial ECMO, with additional placement of a cephalic venous catheter, for meconium aspiration (4) or persistent fetal circulation (2). " 11/10/1990 - "We report the successful treatment with extracorporeal membrane oxygenation of two Dutch neonates with severe respiratory insufficiency, due to meconium aspiration syndrome and persistent fetal circulation respectively. "
2.	Therapeutics 01/01/2023 - "In conclusion, npFOXF1 has a very good safety profile and combined with preceding studies showing therapeutic efficacy, npFOXF1 can be considered as a good candidate therapy for ACDMPV in human neonates." 02/11/2023 - "Owing to the poor response to the established therapy, ACD/MPV was suspected. " 11/01/2021 - "We will review knowledge related to cell surface markers, signature gene expression, and key transcriptional regulators and will explore the translational potential of EPCs for cell-based therapy for BPD and ACDMPV. " 01/01/2021 - "Nanoparticle therapies increasing neonatal pulmonary angiogenesis may be considered to prevent PH in ACDMPV." 01/01/2021 - ": Cell-based therapy using donor or ESC/induced pluripotent stem cell-derived FOXF1+cKIT+ endothelial progenitors may be considered for treatment of human ACDMPV."
3.	Lung Transplantation 01/01/2018 - "We reviewed clinical history, diagnostic studies, explant histology, genetic sequence results, and post-transplant course for 6 infants with atypical ACDMPV who underwent bilateral lung transplantation at St. Louis Children's Hospital. " 01/01/2018 - "To describe disease course, histopathology, and outcomes for infants with atypical presentations of alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) who underwent bilateral lung transplantation. " 01/01/2020 - "This is a case report of a successful single-lobe lung transplantation for pulmonary hypertension secondary to alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). "
4.	Intravenous Administration 01/01/2023 - "The aim of the present study is to investigate the safety of intravenous administration of FOXF1-expressing PEI-PEG nanoparticles (npFOXF1), our pioneering treatment for ACDMPV. "
5.	Catheters 08/01/1985 - "We have described two cases in which persistent fetal circulation was mistakenly diagnosed because umbilical artery catheters were placed in too high a position. " 08/01/1985 - "False diagnosis of persistent fetal circulation caused by misplacement of umbilical artery catheter." 12/01/1977 - "Our meager experience was with four neonates diagnosed as having persistent fetal circulation monitored by the use of this PA catheter. " 10/01/1983 - "The management of persistent fetal circulation (PFC) in 3 neonates was facilitated by continuous monitoring of either pulmonary artery (PAP) or right ventricular pressure using an umbilical catheter with a catheter-tip electrode. " 04/01/1989 - "In nine critically ill neonates with persistent fetal circulation, femoral venous catheters were inserted at the bedside to initiate treatment and provide venous access. "