The structural basis of persistent pulmonary hypertension of the newborn infant

Murphy, John D.; Rabinovitch, Marlene; Goldstein, Jeffrey; Reid, Lynne

doi:10.1016/s0022-3476(81)80605-1

Cited by 289 publications

(103 citation statements)

References 12 publications

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…24 This may be related to an increase in pulmonary blood flow and pressure. One could speculate that the common occurrence of persistent pulmonary hypertension and early progression of pulmonary vascular disease in the infants with TGA and intact ventricular septum may be related to the prenatal increase in pulmonary blood flow and prenatal alteration of the pulmonary vascular bed.…”

Section: Prenatal Nature Of the Ductus Arteriosus And Pulmonary Vascumentioning

confidence: 99%

Prenatal Features of Ductus Arteriosus Constriction and Restrictive Foramen Ovale in d-Transposition of the Great Arteries

et al. 1999

View full text Add to dashboard Cite

Background-Although most neonates with d-transposition of the great arteries (TGA) have an uncomplicated preoperative course, some with a restrictive foramen ovale (FO), ductus arteriosus (DA) constriction, or pulmonary hypertension may be severely hypoxemic and even die shortly after birth. Our goal was to determine whether prenatal echocardiography can identify these high-risk fetuses with TGA. Methods and Results-We reviewed the prenatal and postnatal echocardiograms and outcomes of 16 fetuses with TGA/intact ventricular septum or small ventricular septal defect. Of the 16 fetuses, 6 prenatally had an abnormal FO (fixed position, flat, and/or redundant septum primum). Five of the 6 had restrictive FO at birth. Five fetuses had DA narrowing at the pulmonary artery end in utero, and 6 had a small DA (diameter z score of ϽϪ2.0). Of 4 fetuses with the most diminutive DA, 2 also had an abnormal appearance of the FO, and both died immediately after birth. One other fetus had persistent pulmonary hypertension. Eight fetuses had abnormal Doppler flow pattern in the DA (continuous high-velocity flow, nϭ1; retrograde diastolic flow, nϭ7). Conclusions-Abnormal

show abstract

Section: Prenatal Nature Of the Ductus Arteriosus And Pulmonary Vascumentioning

confidence: 99%

Prenatal Features of Ductus Arteriosus Constriction and Restrictive Foramen Ovale in d-Transposition of the Great Arteries

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Neonatal pulmonary vessels are known to exhibit greater vasoconstrictive responses than adult pulmonary arteries. 46 In addition, these vessels possess a unique ability to undergo rapid changes in architecture, particularly thickening of the media and the adventitia, distal extension of smooth muscle, 47 and increased tortuosity and muscularization of the alveolar septal arterioles. 48 The importance of this abnormal proliferation and excessive collagen synthesis by pulmonary vascular wall cells has been demonstrated by attenuation of the pulmonary hypertensive process by inhibitors of collagen synthesis in a rat model.…”

Section: Pathophysiology Of Meconium Passagementioning

confidence: 99%

Resuscitation of the Meconium-Stained Infant and Prevention of Meconium Aspiration Syndrome

Fuloria

Wiswell

1999

J Perinatol

View full text Add to dashboard Cite

The term meconium was originally coined by Aristotle who used the Greek word meconium-arion 1 meaning "opium-like," because he believed meconium induced fetal sleep. It is probable that he recognized the association between the presence of meconium in the amniotic fluid and the occurrence of fetal deaths and neonatal depression.Depending on the population studied, the frequency of meconium-stained amniotic fluid (MSAF) at the time of delivery is variable, ranging between approximately 8% and 19% of all term deliveries. [2][3][4][5][6][7][8] Alexander and colleagues 9 noted a 1.5-fold increased risk for MSAF in black women compared with white women. The authors recommended that maternal ethnicity be viewed as a risk indicator of, and not a causal factor for, MSAF. They also observed an increased likelihood of MSAF with increasing gestational age in both ethnic groups.Regardless of the reason for meconium passage, its presence may be associated with adverse fetal and neonatal outcomes, including death, acute respiratory complications, and long-term pulmonary and neurologic abnormalities. Depending on various factors, including the population studied and the criteria used for making a diagnosis, meconium aspiration syndrome (MAS) will develop in 2% to 33% of infants born through MSAF. 3,4,10,11 As many as 30% or more of infants with MAS require mechanical ventilation. 3,12 Accompanying persistent pulmonary hypertension of the newborn (PPHN) is present in approximately one-third of these infants. 13 The mortality associated with MAS is disturbingly high, ranging from 4% to 19% 3,12,14 ; a large proportion of this mortality is attributable to PPHN.Early-onset neonatal seizures, secondary to hypoxic events, have been reported in infants born through thick MSAF. 15 Berkus et al. 16 observed a sevenfold increased risk of neonatal seizures and a fivefold increased likelihood of hypotonia in infants born through moderate to thick compared with thin meconium-stained or clear amniotic fluid. Some investigators have noted an increased likelihood of cerebral palsy in surviving infants with a low Apgar score who were born through MSAF. 17 In addition, there may be long-term pulmonary sequelae associated with MAS. Yuksel et al. 18 have shown increased functional residual capacity and airway reactivity at 6 months of age in infants with MAS; infants who required more respiratory support in the neonatal period had significantly more symptoms and required bronchodilator therapy more often. MAS has also been implicated in increased airway reactivity and abnormal pulmonary function tests in later childhood. 19,20 PATHOPHYSIOLOGY OF MECONIUM PASSAGEMeconium is a viscous green substance composed primarily of water (72% to 80%). Other components of meconium include gastrointestinal secretions, bile, bile acids, mucus, pancreatic juice, cellular debris, and swallowed amniotic fluid, lanugo, vernix caseosa, and blood. 1,21 The substance may first be noted in the fetal gastrointestinal tract as early as 10 to 16 weeks' gestation. At birt...

show abstract

“…56,57 PPHN is associated with diverse cardiac and pulmonary disorders or can occur as an idiopathic disorder and is characterized by abnormal pulmonary vascular tone and reactivity, hypertensive vascular remodeling, and, in severe cases, decreased vascular growth. [58][59][60] Autopsy studies of the lungs of newborns with fatal PPHN have revealed severe vascular remodeling even in newborns who die shortly after birth, suggesting that severe disease is associated with chronic intrauterine stress. [61][62][63][64][65][66] The exact intrauterine events that alter pulmonary vascular reactivity and growth in PPHN are poorly understood, but perinatal stresses, including chorioamnionitis, placental vascular lesions, and intrauterine growth restriction, are associated with PPHN.…”

Section: Impaired Lung Vascular Development In Pediatric Pah General mentioning

confidence: 99%

The Robyn Barst Memorial Lecture: Differences between the Fetal, Newborn, and Adult Pulmonary Circulations: Relevance for Age‐Specific Therapies (2013 Grover Conference Series)

et al. 2014

View full text Add to dashboard Cite

Pulmonary arterial hypertension (PAH) contributes to poor outcomes in diverse diseases in newborns, infants, and children. Many aspects of pediatric PAH parallel the pathophysiology and disease courses observed in adult patients; however, critical maturational differences exist that contribute to distinct outcomes and therapeutic responses in children. In comparison with adult PAH, disruption of lung vascular growth and development, or angiogenesis, plays an especially prominent role in the pathobiology of pediatric PAH. In children, abnormalities of lung vascular development have consequences well beyond the adverse hemodynamic effects of PAH alone. The developing endothelium also plays critical roles in development of the distal airspace, establishing lung surface area for gas exchange and maintenance of lung structure throughout postnatal life through angiocrine signaling. Impaired functional and structural adaptations of the pulmonary circulation during the transition from fetal to postnatal life contribute significantly to poor outcomes in such disorders as persistent pulmonary hypertension of the newborn, congenital diaphragmatic hernia, bronchopulmonary dysplasia, Down syndrome, and forms of congenital heart disease. In addition, several studies support the hypothesis that early perinatal events that alter lung vascular growth or function may set the stage for increased susceptibility to PAH in adult patients ("fetal programming"). Thus, insights into basic mechanisms underlying unique features of the developing pulmonary circulation, especially as related to preservation of endothelial survival and function, may provide unique therapeutic windows and distinct strategies to improve short-and long-term outcomes of children with PAH.Keywords: pulmonary vascular development, angiogenesis, alveolarization, persistent pulmonary hypertension of the newborn, congenital diaphragmatic hernia, bronchopulmonary dysplasia, Down syndrome, pediatric pulmonary hypertension. Pulmonary arterial hypertension (PAH) is a devastating and progressive disease that is characterized by abnormalities of vascular tone and reactivity, vessel wall structure, growth, and thrombosis. 1 Mechanisms contributing to PAH and its progression are complex and remain incompletely understood. Insights into vascular biology over the past few decades have led to remarkable improvements in the clinical course, outcomes, and survival in adults with PAH, yet relatively few studies have been performed in children. As in adults, PAH contributes to poor outcomes in diverse cardiac, pulmonary, and systemic diseases in newborns, infants, and children (Table 1). 2 There is a clear need to define the natural history of pediatric PAH in diverse settings; to develop new strategies to identify at-risk patients early in their course; and to establish novel approaches to better diagnose, evaluate, and treat children with PAH. 3,4 Despite many similarities between pediatric and adult PAH, critical differences exist that currently limit our clinical appr...

show abstract

The structural basis of persistent pulmonary hypertension of the newborn infant

Cited by 289 publications

References 12 publications

Prenatal Features of Ductus Arteriosus Constriction and Restrictive Foramen Ovale in d-Transposition of the Great Arteries

Prenatal Features of Ductus Arteriosus Constriction and Restrictive Foramen Ovale in d-Transposition of the Great Arteries

Resuscitation of the Meconium-Stained Infant and Prevention of Meconium Aspiration Syndrome

The Robyn Barst Memorial Lecture: Differences between the Fetal, Newborn, and Adult Pulmonary Circulations: Relevance for Age‐Specific Therapies (2013 Grover Conference Series)

Contact Info

Product

Resources

About