Fetal growth restriction and neonatal-pediatric lung diseases: Vascular mechanistic links and therapeutic directions

Arvind Sehgal; Theodore Dassios; Marcel F. Nold; Claudia A. Nold-Petry; Anne Greenough

doi:10.1016/j.prrv.2022.09.002

Fetal growth restriction and neonatal-pediatric lung diseases: Vascular mechanistic links and therapeutic directions

Arvind Sehgal^*, Theodore Dassios, Marcel F. Nold, Claudia A. Nold-Petry, Anne Greenough

^*Corresponding author for this work

Women & Children's Health

Research output: Contribution to journal › Review article › peer-review

8 Citations (Scopus)

Abstract

Bronchopulmonary dysplasia (BPD) is the most common respiratory sequela of prematurity, and infants born with fetal growth restriction (FGR) are disproportionately represented in BPD statistics, as factors which affect somatic growth may also affect pulmonary growth. Effects of in-utero hypoxia underlying FGR on lung parenchymal architecture predisposing to BPD are well documented, but the pulmonary vascular constructs are not well appreciated. Disruption of angiogenesis during critical periods of lung growth impairs alveolarization, contributing to BPD pathogenesis. Pulmonary artery thickness/stiffness has been noted in FGR in the initial postnatal weeks, and also in well-grown infants with established BPD. The lack of waveform cushioning by the major arteries exposes the pulmonary resistance vessels to higher pulsatile stress, thereby accelerating microvascular disease. Reactive oxygen species, increased sympathetic activity and endothelial dysfunction are common mediators in FGR and BPD; each putative targets for prevention and/or therapeutics using interleukin (IL)-1 receptor antagonist (IL-1Ra), melatonin or inhibition of renin–angiotensin–aldosterone system. While BPD is the archetypal respiratory disease of infancy, effects of FGR on pulmonary function are long-term, extending well into childhood. This narrative links FGR in very/extremely preterm infants with BPD through the vascular affliction as a mechanistic and potentially, therapeutic pathway. Our objectives were to depict the burden of disease for FGR and BPD amongst preterm infants, portray vascular involvement in the placenta in FGR and BPD cohorts, provide high resolution vascular ultrasound information in both cohorts with a view to address therapeutic relevance, and lastly, link this information with paediatric age-group lung diseases.

Original language	English
Pages (from-to)	19-30
Number of pages	12
Journal	Paediatric Respiratory Reviews
Volume	44
DOIs	https://doi.org/10.1016/j.prrv.2022.09.002
Publication status	Published - Dec 2022

Keywords

Arterial stiffness
Bronchopulmonary dysplasia
Fetal growth restriction
Mechanisms
Placenta

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10.1016/j.prrv.2022.09.002

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title = "Fetal growth restriction and neonatal-pediatric lung diseases: Vascular mechanistic links and therapeutic directions",

abstract = "Bronchopulmonary dysplasia (BPD) is the most common respiratory sequela of prematurity, and infants born with fetal growth restriction (FGR) are disproportionately represented in BPD statistics, as factors which affect somatic growth may also affect pulmonary growth. Effects of in-utero hypoxia underlying FGR on lung parenchymal architecture predisposing to BPD are well documented, but the pulmonary vascular constructs are not well appreciated. Disruption of angiogenesis during critical periods of lung growth impairs alveolarization, contributing to BPD pathogenesis. Pulmonary artery thickness/stiffness has been noted in FGR in the initial postnatal weeks, and also in well-grown infants with established BPD. The lack of waveform cushioning by the major arteries exposes the pulmonary resistance vessels to higher pulsatile stress, thereby accelerating microvascular disease. Reactive oxygen species, increased sympathetic activity and endothelial dysfunction are common mediators in FGR and BPD; each putative targets for prevention and/or therapeutics using interleukin (IL)-1 receptor antagonist (IL-1Ra), melatonin or inhibition of renin–angiotensin–aldosterone system. While BPD is the archetypal respiratory disease of infancy, effects of FGR on pulmonary function are long-term, extending well into childhood. This narrative links FGR in very/extremely preterm infants with BPD through the vascular affliction as a mechanistic and potentially, therapeutic pathway. Our objectives were to depict the burden of disease for FGR and BPD amongst preterm infants, portray vascular involvement in the placenta in FGR and BPD cohorts, provide high resolution vascular ultrasound information in both cohorts with a view to address therapeutic relevance, and lastly, link this information with paediatric age-group lung diseases.",

keywords = "Arterial stiffness, Bronchopulmonary dysplasia, Fetal growth restriction, Mechanisms, Placenta",

author = "Arvind Sehgal and Theodore Dassios and Nold, {Marcel F.} and Nold-Petry, {Claudia A.} and Anne Greenough",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

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doi = "10.1016/j.prrv.2022.09.002",

language = "English",

volume = "44",

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T1 - Fetal growth restriction and neonatal-pediatric lung diseases

T2 - Vascular mechanistic links and therapeutic directions

AU - Sehgal, Arvind

AU - Dassios, Theodore

AU - Nold, Marcel F.

AU - Nold-Petry, Claudia A.

AU - Greenough, Anne

PY - 2022/12

Y1 - 2022/12

N2 - Bronchopulmonary dysplasia (BPD) is the most common respiratory sequela of prematurity, and infants born with fetal growth restriction (FGR) are disproportionately represented in BPD statistics, as factors which affect somatic growth may also affect pulmonary growth. Effects of in-utero hypoxia underlying FGR on lung parenchymal architecture predisposing to BPD are well documented, but the pulmonary vascular constructs are not well appreciated. Disruption of angiogenesis during critical periods of lung growth impairs alveolarization, contributing to BPD pathogenesis. Pulmonary artery thickness/stiffness has been noted in FGR in the initial postnatal weeks, and also in well-grown infants with established BPD. The lack of waveform cushioning by the major arteries exposes the pulmonary resistance vessels to higher pulsatile stress, thereby accelerating microvascular disease. Reactive oxygen species, increased sympathetic activity and endothelial dysfunction are common mediators in FGR and BPD; each putative targets for prevention and/or therapeutics using interleukin (IL)-1 receptor antagonist (IL-1Ra), melatonin or inhibition of renin–angiotensin–aldosterone system. While BPD is the archetypal respiratory disease of infancy, effects of FGR on pulmonary function are long-term, extending well into childhood. This narrative links FGR in very/extremely preterm infants with BPD through the vascular affliction as a mechanistic and potentially, therapeutic pathway. Our objectives were to depict the burden of disease for FGR and BPD amongst preterm infants, portray vascular involvement in the placenta in FGR and BPD cohorts, provide high resolution vascular ultrasound information in both cohorts with a view to address therapeutic relevance, and lastly, link this information with paediatric age-group lung diseases.

AB - Bronchopulmonary dysplasia (BPD) is the most common respiratory sequela of prematurity, and infants born with fetal growth restriction (FGR) are disproportionately represented in BPD statistics, as factors which affect somatic growth may also affect pulmonary growth. Effects of in-utero hypoxia underlying FGR on lung parenchymal architecture predisposing to BPD are well documented, but the pulmonary vascular constructs are not well appreciated. Disruption of angiogenesis during critical periods of lung growth impairs alveolarization, contributing to BPD pathogenesis. Pulmonary artery thickness/stiffness has been noted in FGR in the initial postnatal weeks, and also in well-grown infants with established BPD. The lack of waveform cushioning by the major arteries exposes the pulmonary resistance vessels to higher pulsatile stress, thereby accelerating microvascular disease. Reactive oxygen species, increased sympathetic activity and endothelial dysfunction are common mediators in FGR and BPD; each putative targets for prevention and/or therapeutics using interleukin (IL)-1 receptor antagonist (IL-1Ra), melatonin or inhibition of renin–angiotensin–aldosterone system. While BPD is the archetypal respiratory disease of infancy, effects of FGR on pulmonary function are long-term, extending well into childhood. This narrative links FGR in very/extremely preterm infants with BPD through the vascular affliction as a mechanistic and potentially, therapeutic pathway. Our objectives were to depict the burden of disease for FGR and BPD amongst preterm infants, portray vascular involvement in the placenta in FGR and BPD cohorts, provide high resolution vascular ultrasound information in both cohorts with a view to address therapeutic relevance, and lastly, link this information with paediatric age-group lung diseases.

KW - Arterial stiffness

KW - Bronchopulmonary dysplasia

KW - Fetal growth restriction

KW - Mechanisms

KW - Placenta

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U2 - 10.1016/j.prrv.2022.09.002

DO - 10.1016/j.prrv.2022.09.002

M3 - Review article

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AN - SCOPUS:85140647349

SN - 1526-0542

VL - 44

SP - 19

EP - 30

JO - Paediatric Respiratory Reviews

JF - Paediatric Respiratory Reviews

ER -

Fetal growth restriction and neonatal-pediatric lung diseases: Vascular mechanistic links and therapeutic directions

Abstract

Keywords

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