Effects of intra-uterine growth restriction on the control of breathing and lung development after birth

R. Harding, M. L. Tester, T. J. Moss, M. G. Davey, Samantha Louey, B. Joyce, S. B. Hooper, G. Maritz

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

1. Low birthweight is now recognized as an important risk factor for early postnatal respiratory illness and it is becoming evident that low birthweight can increase the risk for airway dysfunction in children and adults. Our studies have been aimed at determining how low birthweight, resulting from intra-uterine growth restriction (IUGR), affects the control of breathing and the structural and functional development of the lung. 2. We have measured ventilatory responsiveness to progressive hypoxia and progressive hypercapnia during the first weeks after birth in postnatal lambs in which IUGR was induced by chronic placental insufficiency. It was found that the postnatal increase in ventilatory sensitivity to hypoxia observed in control lambs was diminished in low birthweight lambs; in contrast, the sensitivity to hypercapnia was not affected. In other studies, we found that IUGR caused by maternal anaemia led to elevated CO2 levels during sleep and wakefulness. 3. Our findings suggest that the prenatal development of the brain-stem or respiratory chemoreceptors may be affected by intra-uterine factors associated with IUGR, such as foetal hypoxaemia or hypoglycaemia. It is also possible that the structure of respiratory muscles and, hence, their ability to maintain a high level of ventilation may be affected by IUGR. 4. Recently, we studied the influence of IUGR on foetal lung development, in particular its effects on foetal lung liquid, a major determinant of lung growth, as well as alveolar structure and pulmonary surfactant. Lung liquid secretion and volume, in relation to bodyweight, were unaffected; however, there was evidence of structural and functional immaturity in the lungs. In foetuses exposed to IUGR, the air-blood barrier was thicker and, after birth, the diffusing capacity of the lungs for carbon monoxide was lower. In contrast, surfactant protein gene expression was enhanced, particularly in foetuses with high levels of circulating cortisol. 5. Further studies are needed to characterize the effects of specific types of prenatal compromise on postnatal control of ventilation and lung function, to determine mechanisms underlying these effects and to determine the capacity for postnatal recovery.

Original languageEnglish (US)
Pages (from-to)114-119
Number of pages6
JournalClinical and Experimental Pharmacology and Physiology
Volume27
Issue number1-2
DOIs
StatePublished - Jan 2000
Externally publishedYes

Fingerprint

Respiration
Parturition
Lung
Growth
Hypercapnia
Ventilation
Fetus
Blood-Air Barrier
Placental Insufficiency
Lung Volume Measurements
Pulmonary Surfactants
Respiratory Muscles
Aptitude
Wakefulness
Carbon Monoxide
Fetal Development
Hypoglycemia
Surface-Active Agents
Brain Stem
Hydrocortisone

Keywords

  • Hypoxaemia
  • Intra-uterine growth restriction
  • Lung function
  • Lung structure

ASJC Scopus subject areas

  • Physiology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Effects of intra-uterine growth restriction on the control of breathing and lung development after birth. / Harding, R.; Tester, M. L.; Moss, T. J.; Davey, M. G.; Louey, Samantha; Joyce, B.; Hooper, S. B.; Maritz, G.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 27, No. 1-2, 01.2000, p. 114-119.

Research output: Contribution to journalArticle

Harding, R. ; Tester, M. L. ; Moss, T. J. ; Davey, M. G. ; Louey, Samantha ; Joyce, B. ; Hooper, S. B. ; Maritz, G. / Effects of intra-uterine growth restriction on the control of breathing and lung development after birth. In: Clinical and Experimental Pharmacology and Physiology. 2000 ; Vol. 27, No. 1-2. pp. 114-119.
@article{8639f945bcc74d94a0e951bcaa62e68a,
title = "Effects of intra-uterine growth restriction on the control of breathing and lung development after birth",
abstract = "1. Low birthweight is now recognized as an important risk factor for early postnatal respiratory illness and it is becoming evident that low birthweight can increase the risk for airway dysfunction in children and adults. Our studies have been aimed at determining how low birthweight, resulting from intra-uterine growth restriction (IUGR), affects the control of breathing and the structural and functional development of the lung. 2. We have measured ventilatory responsiveness to progressive hypoxia and progressive hypercapnia during the first weeks after birth in postnatal lambs in which IUGR was induced by chronic placental insufficiency. It was found that the postnatal increase in ventilatory sensitivity to hypoxia observed in control lambs was diminished in low birthweight lambs; in contrast, the sensitivity to hypercapnia was not affected. In other studies, we found that IUGR caused by maternal anaemia led to elevated CO2 levels during sleep and wakefulness. 3. Our findings suggest that the prenatal development of the brain-stem or respiratory chemoreceptors may be affected by intra-uterine factors associated with IUGR, such as foetal hypoxaemia or hypoglycaemia. It is also possible that the structure of respiratory muscles and, hence, their ability to maintain a high level of ventilation may be affected by IUGR. 4. Recently, we studied the influence of IUGR on foetal lung development, in particular its effects on foetal lung liquid, a major determinant of lung growth, as well as alveolar structure and pulmonary surfactant. Lung liquid secretion and volume, in relation to bodyweight, were unaffected; however, there was evidence of structural and functional immaturity in the lungs. In foetuses exposed to IUGR, the air-blood barrier was thicker and, after birth, the diffusing capacity of the lungs for carbon monoxide was lower. In contrast, surfactant protein gene expression was enhanced, particularly in foetuses with high levels of circulating cortisol. 5. Further studies are needed to characterize the effects of specific types of prenatal compromise on postnatal control of ventilation and lung function, to determine mechanisms underlying these effects and to determine the capacity for postnatal recovery.",
keywords = "Hypoxaemia, Intra-uterine growth restriction, Lung function, Lung structure",
author = "R. Harding and Tester, {M. L.} and Moss, {T. J.} and Davey, {M. G.} and Samantha Louey and B. Joyce and Hooper, {S. B.} and G. Maritz",
year = "2000",
month = "1",
doi = "10.1046/j.1440-1681.2000.03191.x",
language = "English (US)",
volume = "27",
pages = "114--119",
journal = "Clinical and Experimental Pharmacology and Physiology",
issn = "0305-1870",
publisher = "Wiley-Blackwell",
number = "1-2",

}

TY - JOUR

T1 - Effects of intra-uterine growth restriction on the control of breathing and lung development after birth

AU - Harding, R.

AU - Tester, M. L.

AU - Moss, T. J.

AU - Davey, M. G.

AU - Louey, Samantha

AU - Joyce, B.

AU - Hooper, S. B.

AU - Maritz, G.

PY - 2000/1

Y1 - 2000/1

N2 - 1. Low birthweight is now recognized as an important risk factor for early postnatal respiratory illness and it is becoming evident that low birthweight can increase the risk for airway dysfunction in children and adults. Our studies have been aimed at determining how low birthweight, resulting from intra-uterine growth restriction (IUGR), affects the control of breathing and the structural and functional development of the lung. 2. We have measured ventilatory responsiveness to progressive hypoxia and progressive hypercapnia during the first weeks after birth in postnatal lambs in which IUGR was induced by chronic placental insufficiency. It was found that the postnatal increase in ventilatory sensitivity to hypoxia observed in control lambs was diminished in low birthweight lambs; in contrast, the sensitivity to hypercapnia was not affected. In other studies, we found that IUGR caused by maternal anaemia led to elevated CO2 levels during sleep and wakefulness. 3. Our findings suggest that the prenatal development of the brain-stem or respiratory chemoreceptors may be affected by intra-uterine factors associated with IUGR, such as foetal hypoxaemia or hypoglycaemia. It is also possible that the structure of respiratory muscles and, hence, their ability to maintain a high level of ventilation may be affected by IUGR. 4. Recently, we studied the influence of IUGR on foetal lung development, in particular its effects on foetal lung liquid, a major determinant of lung growth, as well as alveolar structure and pulmonary surfactant. Lung liquid secretion and volume, in relation to bodyweight, were unaffected; however, there was evidence of structural and functional immaturity in the lungs. In foetuses exposed to IUGR, the air-blood barrier was thicker and, after birth, the diffusing capacity of the lungs for carbon monoxide was lower. In contrast, surfactant protein gene expression was enhanced, particularly in foetuses with high levels of circulating cortisol. 5. Further studies are needed to characterize the effects of specific types of prenatal compromise on postnatal control of ventilation and lung function, to determine mechanisms underlying these effects and to determine the capacity for postnatal recovery.

AB - 1. Low birthweight is now recognized as an important risk factor for early postnatal respiratory illness and it is becoming evident that low birthweight can increase the risk for airway dysfunction in children and adults. Our studies have been aimed at determining how low birthweight, resulting from intra-uterine growth restriction (IUGR), affects the control of breathing and the structural and functional development of the lung. 2. We have measured ventilatory responsiveness to progressive hypoxia and progressive hypercapnia during the first weeks after birth in postnatal lambs in which IUGR was induced by chronic placental insufficiency. It was found that the postnatal increase in ventilatory sensitivity to hypoxia observed in control lambs was diminished in low birthweight lambs; in contrast, the sensitivity to hypercapnia was not affected. In other studies, we found that IUGR caused by maternal anaemia led to elevated CO2 levels during sleep and wakefulness. 3. Our findings suggest that the prenatal development of the brain-stem or respiratory chemoreceptors may be affected by intra-uterine factors associated with IUGR, such as foetal hypoxaemia or hypoglycaemia. It is also possible that the structure of respiratory muscles and, hence, their ability to maintain a high level of ventilation may be affected by IUGR. 4. Recently, we studied the influence of IUGR on foetal lung development, in particular its effects on foetal lung liquid, a major determinant of lung growth, as well as alveolar structure and pulmonary surfactant. Lung liquid secretion and volume, in relation to bodyweight, were unaffected; however, there was evidence of structural and functional immaturity in the lungs. In foetuses exposed to IUGR, the air-blood barrier was thicker and, after birth, the diffusing capacity of the lungs for carbon monoxide was lower. In contrast, surfactant protein gene expression was enhanced, particularly in foetuses with high levels of circulating cortisol. 5. Further studies are needed to characterize the effects of specific types of prenatal compromise on postnatal control of ventilation and lung function, to determine mechanisms underlying these effects and to determine the capacity for postnatal recovery.

KW - Hypoxaemia

KW - Intra-uterine growth restriction

KW - Lung function

KW - Lung structure

UR - http://www.scopus.com/inward/record.url?scp=0033951113&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033951113&partnerID=8YFLogxK

U2 - 10.1046/j.1440-1681.2000.03191.x

DO - 10.1046/j.1440-1681.2000.03191.x

M3 - Article

VL - 27

SP - 114

EP - 119

JO - Clinical and Experimental Pharmacology and Physiology

JF - Clinical and Experimental Pharmacology and Physiology

SN - 0305-1870

IS - 1-2

ER -