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Persistent Newborn Pulmonary Hypertension

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Generation of three iPSC lines from two patients with heterozygous FOXF1 mutations associated to Alveolar Capillary Dysplasia with Misalignment of the Pulmonary Veins.

Evelien Slot, Annelies de Klein, Robbert J Rottier,

Diagnosing Alveolar Capillary Dysplasia with Misalignment of the Pulmonary Veins (ACD/MPV) based on a genetic alteration in the FOXF1 gene, is complicated by the poor understanding of the causal relation between FOXF1 variants and the ACD/MPV phenotype. Here, we report the generation of human iPSC lines from two ACD/MPV patients, ... Read more >>

Stem Cell Res (Stem cell research)
[2020, 44:101745]

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Complete closure of the ductus arteriosus in the foetus with transposition of the great arteries.

Agnieszka Grzyb, Adam Koleśnik, Dariusz Gruszfeld, Joanna Szymkiewicz-Dangel,

Prenatal restriction of the ductus arteriosus can manifest as persistent pulmonary hypertension in the newborn, especially dangerous with the transposition of the great arteries. Its aetiology has long been related to maternal intake of non-steroidal anti-inflammatory drugs; however, some other substances, including polyphenols, may have similar properties. We describe a ... Read more >>

Cardiol Young (Cardiology in the young)
[2020, :1-3]

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Milrinone Use in Persistent Pulmonary Hypertension of the Newborn.

Amna Qasim, Sunil K Jain,

Failure of the normal transition from in utero to ex utero physiology leads to "persistent" pulmonary hypertension of the newborn (PPHN). PPHN is frequently associated with low systemic blood pressure and low cardiac output because of increased right ventricular afterload and myocardial dysfunction. The general management of newborns with PPHN ... Read more >>

Neoreviews (NeoReviews)
[2020, 21(3):e165-e178]

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Point-of-care ultrasound in the neonatal ICU.

Laura E Miller, Jason Z Stoller, María V Fraga,

PURPOSE OF REVIEW:Point-of-care ultrasound (POCUS) is an emerging clinical tool in the neonatal intensive care unit (NICU). Recent literature describing the use of POCUS for various applications in the NICU has garnered increased interest among neonatologists. RECENT FINDINGS:Diagnostic applications for POCUS in the NICU include the evaluation and serial monitoring ... Read more >>

Curr. Opin. Pediatr. (Current opinion in pediatrics)
[2020, 32(2):216-227]

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Neonatal functional echocardiography.

Cecile Tissot, Yogen Singh,

PURPOSE OF REVIEW:The role of echocardiography has dramatically changed over the past decade and use of functional echocardiography has become increasingly popular among neonatologists and pediatric intensivists in making clinical decisions in sick infants and children. The purpose of this review is to outline the current capabilities and limitations of ... Read more >>

Curr. Opin. Pediatr. (Current opinion in pediatrics)
[2020, 32(2):235-244]

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Frequent mutation of hypoxia-related genes in persistent pulmonary hypertension of the newborn.

Mingbang Wang, Deyi Zhuang, Mei Mei, Haiyan Ma, Zixiu Li, Fusheng He, Guoqiang Cheng, Guang Lin, Wenhao Zhou,

AIMS:Persistent pulmonary hypertension of the newborn (PPHN) is characterized by sustained high levels of pulmonary vascular resistance after birth with etiology unclear; Arterial blood oxygen saturation of Tibetan newborns at high latitudes is higher than that of Han newborns at low latitudes, suggesting that genetic adaptation may allow sufficient oxygen ... Read more >>

Respir. Res. (Respiratory research)
[2020, 21(1):53]

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Highly Sensitive Blocker Displacement Amplification and Droplet Digital PCR Reveal Low-Level Parental FOXF1 Somatic Mosaicism in Families with Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins.

Justyna A Karolak, Qian Liu, Nina G Xie, Lucia R Wu, Gustavo Rocha, Susana Fernandes, Luk Ho-Ming, Ivan F Lo, David Mowat, Elizabeth K Fiorino, Morris Edelman, Joyce Fox, Denise A Hayes, David Witte, Ashley Parrott, Edwina Popek, Przemyslaw Szafranski, David Y Zhang, Pawel Stankiewicz,

Detection of low-level somatic mosaicism [alternate allele fraction (AAF) ≤ 10%] in parents of affected individuals with the apparent de novo pathogenic variants enables more accurate estimate of recurrence risk. To date, only a few systematic analyses of low-level parental somatic mosaicism have been performed. Herein, highly sensitive blocker displacement ... Read more >>

J Mol Diagn (The Journal of molecular diagnostics : JMD)
[2020, :]

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Living-donor single-lobe lung transplantation for pulmonary hypertension due to alveolar capillary dysplasia with misalignment of pulmonary veins.

Daisuke Nakajima, Hiromi Oda, Katsutaka Mineura, Tatsuya Goto, Itaru Kato, Shiro Baba, Tadashi Ikeda, Toyofumi F Chen-Yoshikawa, Hiroshi Date,

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). A 6-year-old boy underwent living-donor single-lobe transplantation with the right lower lobe from his 31-year-old mother. The pretransplantation graft size matching was acceptable: the estimated ... Read more >>

Am. J. Transplant. (American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons)
[2019, :]

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AMP-Kinase Dysfunction Alters Notch Ligands to Impair Angiogenesis in Neonatal Pulmonary Hypertension.

Ujala Rana, Emily Callan, Brianna Entringer, Teresa Michalkiewicz, Amit Joshi, Abdul K Parchur, Ru-Jeng Teng, Girija G Konduri,

OBJECTIVE:Decreased angiogenesis contributes to Persistent pulmonary hypertension of the newborn (PPHN); mechanisms remain unclear. 5'AMP activated protein kinase (AMPK) is a key regulator of cell metabolism. We investigated the hypothesis that a decrease in AMPK function leads to mitochondrial dysfunction and altered balance of notch ligands, delta-like 4 (DLL4) and ... Read more >>

Am. J. Respir. Cell Mol. Biol. (American journal of respiratory cell and molecular biology)
[2020, :]

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Getting an Early Start in Understanding Perinatal Asphyxia Impact on the Cardiovascular System.

Mihaela Roxana Popescu, Anca Maria Panaitescu, Bogdan Pavel, Leon Zagrean, Gheorghe Peltecu, Ana-Maria Zagrean,

Perinatal asphyxia (PA) is a burdening pathology with high short-term mortality and severe long-term consequences. Its incidence, reaching as high as 10 cases per 1000 live births in the less developed countries, prompts the need for better awareness and prevention of cases at risk, together with management by easily applicable ... Read more >>

Front Pediatr (Frontiers in Pediatrics)
[2020, 8:68]

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Ophthalmic findings in neonates receiving sildenafil.

Hamish P Dunn, Leah N Kim, Himanshu Popat, Karen Walker, Jane Lock, James Smith,

AIM:To determine the risk of ocular complications of sildenafil therapy in neonates. METHODS:Retrospective case review of neonates with persistent pulmonary hypertension of the newborn who received sildenafil therapy between 2010 and 2015 in a single, tertiary surgical neonatal intensive care unit in Australia. Ophthalmic examination findings in the neonatal intensive ... Read more >>

J Paediatr Child Health (Journal of paediatrics and child health)
[2020, :]

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A homozygous missense variant of SUMF1 in the Bedouin population extends the clinical spectrum in ultrarare neonatal multiple sulfatase deficiency.

Orna Staretz-Chacham, Lars Schlotawa, Ohad Wormser, Inbal Golan-Tripto, Ohad S Birk, Carlos R Ferreira, Thomas Dierks, Karthikeyan Radhakrishnan,

BACKGROUND:Multiple sulfatase deficiency (MSD, MIM #272200) is an ultrarare congenital disorder caused by SUMF1 mutation and often misdiagnosed due to its complex clinical presentation. Impeded by a lack of natural history, knowledge gained from individual case studies forms the source for a reliable diagnosis and consultation of patients and parents. ... Read more >>

Mol Genet Genomic Med (Molecular genetics & genomic medicine)
[2020, :e1167]

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Presumed prenatal closure of foramen ovale and persistent pulmonary hypertension of the newborn.

Katharina Stock, Miriam Michel, Elisabeth Schermer, Elisabeth Ralser, Ursula Kiechl-Kohlendorfer, Ralf Geiger, Tomaž Podnar,

Prenatal closure of foramen ovale without CHD is a rarely reported entity. Therefore, clinical and echocardiographic findings are poorly defined in these patients. We report a patient with prenatal closure of foramen ovale that presented with severe pulmonary hypertension of the newborn and left ventricular failure. Judicious management strategies were ... Read more >>

Cardiol Young (Cardiology in the young)
[2019, :1-3]

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Inhaled nitric oxide use in neonates: Balancing what is evidence-based and what is physiologically sound.

Laurie G Sherlock, Clyde J Wright, John P Kinsella, Cassidy Delaney,

Inhaled nitric oxide is a powerful therapeutic used in neonatology. Its use is evidenced-based for term and near-term infants with persistent pulmonary hypertension; however, it is frequently used off-label both in term and preterm babies. This article reviews the off-label uses of iNO in infants. Rationale is discussed for a ... Read more >>

Nitric Oxide (Nitric oxide : biology and chemistry)
[2020, 95:12-16]

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ECMO for Neonatal Sepsis in 2019.

Warwick Wolf Butt, Roberto Chiletti,

Sepsis and septic shock in newborns causes mortality and morbidity depending on the organism and primary site. ECMO provides cardiorespiratory support to allow adequate organ perfusion during the time for antibiotics and source control surgery (if needed) to occur. ECMO mode and cannulation site vary depending on support required and ... Read more >>

Front Pediatr (Frontiers in pediatrics)
[2020, 8:50]

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Therapies that enhance pulmonary vascular NO-signaling in the neonate.

Julie Dillard, Marta Perez, Bernadette Chen,

There are several pulmonary hypertensive diseases that affect the neonatal population, including persistent pulmonary hypertension of the newborn (PPHN) and bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH). While the indication for inhaled nitric oxide (iNO) use is for late-preterm and term neonates with PPHN, there is a suboptimal response to this ... Read more >>

Nitric Oxide (Nitric oxide : biology and chemistry)
[2020, 95:45-54]

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Association of rare non-coding SNVs in the lung-specific FOXF1 enhancer with a mitigation of the lethal ACDMPV phenotype.

Przemyslaw Szafranski, Qian Liu, Justyna A Karolak, Xiaofei Song, Nicole de Leeuw, Brigitte Faas, Romana Gerychova, Petr Janku, Marta Jezova, Iveta Valaskova, Kathleen A Gibbs, Lea F Surrey, Virginie Poisson, Denis Bérubé, Luc L Oligny, Jacques L Michaud, Edwina Popek, Paweł Stankiewicz,

Haploinsufficiency of FOXF1 causes alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a lethal neonatal lung developmental disorder. We describe two similar heterozygous CNV deletions involving the FOXF1 enhancer and re-analyze FOXF1 missense mutation, all associated with an unexpectedly mitigated disease phenotype. In one case, the deletion of the ... Read more >>

Hum. Genet. (Human genetics)
[2019, 138(11-12):1301-1311]

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B4GALT1-congenital disorders of glycosylation: Expansion of the phenotypic and molecular spectrum and review of the literature.

Orna Staretz-Chacham, Iris Noyman, Ohad Wormser, Abed Abu Quider, Guy Hazan, Iris Morag, Noam Hadar, Kimiyo Raymond, Ohad S Birk, Carlos R Ferreira, Arie Koifman,

A congenital disorder of glycosylation due to biallelic mutations in B4GALT1 has been previously reported in only three patients with two different mutations. Through homozygosity mapping followed by segregation analysis in an extended pedigree, we identified three additional patients homozygous for a novel mutation in B4GALT1, expanding the phenotypic spectrum ... Read more >>

Clin. Genet. (Clinical genetics)
[2020, :]

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Perinatal Management of Bart's Hemoglobinopathy: Paradoxical Effects of Intrauterine, Transplacental, and Partial Exchange Transfusions.

Mark Curran, Michel Mikhael, Wang-Dar Sun, Jina Lim, Anna Leung, Gira Morchi, Ramen H Chmait,

We describe a fetus at 24 3/7 weeks' gestation that showed ultrasound evidence of anemia, hydrops, and severe growth restriction. Both parents were known to be cis heterozygous carriers for SEA α-thalassemia deletion (αα/-). Cordocentesis confirmed fetal anemia and homozygous α-thalassemia (-/-) in the fetus. Fetal intrauterine transfusions corrected the ... Read more >>

AJP Rep (AJP reports)
[2020, 10(1):e11-e14]

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Multiorgan involvement and management in children with Down syndrome.

Niamh Lagan, Dean Huggard, Fiona Mc Grane, Timothy Ronan Leahy, Orla Franklin, Edna Roche, David Webb, Aengus O' Marcaigh, Des Cox, Afif El-Khuffash, Peter Greally, Joanne Balfe, Eleanor J Molloy,

AIM:To review multiorgan involvement and management in children with Down syndrome (DS). METHODS:A literature review of articles from 1980 to 2019 using the MEDLINE interface of PubMed was performed using the following search terms- [Down syndrome] or [Trisomy 21] AND [Cardiology] or [Respiratory] or [neurodevelopment] or [epilepsy] or [musculoskeletal] or ... Read more >>

Acta Paediatr. (Acta paediatrica (Oslo, Norway : 1992))
[2020, :]

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Methemoglobin and the response to inhaled nitric oxide in persistent pulmonary hypertension of the newborn.

R Dadiz, J Nair, C T D'Angio, R M Ryan, S Lakshminrusimha,

BACKGROUND:We aimed to investigate whether the change in methemoglobin levels (ΔMHb) predicts oxygenation response to inhaled nitric oxide (iNO) in persistent pulmonary hypertension of the newborn (PPHN) with lung disease, with or without pulmonary hypoplasia. METHODS:In this prospective observational study, infants were categorized based on ΔMHb and oxygenation response (ΔPaO2/FiO2) ... Read more >>

J Neonatal Perinatal Med (Journal of neonatal-perinatal medicine)
[2019, :]

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Disruption of normal patterns of FOXF1 expression in a lethal disorder of lung development.

Laurie A Steiner, Michael Getman, Gillian M Schiralli Lester, M Anwar Iqbal, Philip Katzman, Przemyslaw Szafranski, Pawel Stankiewicz, Soumyaroop Bhattacharya, Thomas Mariani, Gloria Pryhuber, Xin Lin, Jennifer L Young, David A Dean, Kristin Scheible,

BACKGROUND:Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) is a lethal disorder of lung development. ACDMPV is associated with haploinsufficiency of the transcription factor FOXF1, which plays an important role in the development of the lung and intestine. CNVs upstream of the FOXF1 gene have also been associated ... Read more >>

J. Med. Genet. (Journal of medical genetics)
[2019, :]

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Cerebral Insufficiency Caused by Diazoxide in a Premature Neonate with Congenital Hyperinsulinism.

Seigo Okada, Shinnosuke Fukunaga, Haruka Ohta, Takashi Furuta, Reiji Hirano, Takahiro Motonaga, Yuichi Ishikawa,

Diazoxide is a peripheral vasodilator that has been used for intravenous treatment of hypertensive emergencies. However, it is currently used mainly for hyperinsulinemic hypoglycemia in lower dose orally, and its major side effects are edema and pulmonary hypertension. Herein, we report the first association between periventricular leukomalacia (PVL) and intractable ... Read more >>

Neuropediatrics (Neuropediatrics)
[2019, :]

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Maternal Diabetes Mellitus and Persistent Pulmonary Hypertension of the Newborn: Accumulated Evidence From Observational Studies.

Lin-Ping Shu, Rui-Heng Zhang, Yao-Hua Cai, Jian-Bo Zhou, Jin-Kui Yang, Lu Qi,

OBJECTIVES:Maternal diabetes mellitus (including pre-existing and gestational diabetes mellitus) is linked with adverse infant outcomes. However, the question of whether maternal diabetes increases the risk of persistent pulmonary hypertension of the newborn (PPHN) is unclear. Herein, we conducted a systematic review and meta-analysis to summarize clinical evidence to determine the ... Read more >>

Can J Diabetes (Canadian journal of diabetes)
[2019, :]

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Hydrocortisone Improves Oxygenation Index and Systolic Blood Pressure in Term Infants With Persistent Pulmonary Hypertension.

Mahdi Alsaleem, Aysha Malik, Satyan Lakshminrusimha, Vasantha Hs Kumar,

Persistent pulmonary hypertension of the newborn (PPHN) is an essential cause for hypoxic respiratory failure with significant morbidity and mortality in term and near-term neonates. Hydrocortisone has been shown to decrease oxygen dependency and pulmonary hypertension in neonates with meconium aspiration syndrome and animal studies, respectively. We hypothesize that hydrocortisone ... Read more >>

Clin Med Insights Pediatr (Clinical medicine insights. Pediatrics)
[2019, 13:1179556519888918]

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