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Compromised respiratory function in postnatal lambs after placental insufficiency and intrauterine growth restriction
B J Joyce1, S Louey, M G Davey
1Fetal and Neonatal Research Group, Department of Physiology, Monash University, Victoria 3800, Australia. belinda.joyce@med.monash.edu.au
Insights
Intrauterine growth restriction (IUGR) in fetal sheep significantly impairs postnatal lung function and development. This study reveals lasting respiratory deficits in IUGR lambs, highlighting the impact of placental insufficiency on lung health.
Area of Science:
- Perinatal Medicine
- Respiratory Physiology
- Developmental Biology
Background:
- Low birth weight is linked to long-term respiratory issues.
- Mechanisms connecting intrauterine growth restriction (IUGR) to impaired lung function are unclear.
Purpose of the Study:
- To investigate the impact of IUGR on postnatal respiratory function in a sheep model.
- To understand how placental insufficiency affects fetal development and subsequent lung health.
Main Methods:
- IUGR induced via umbilico-placental embolization in late-gestation sheep.
- Chronic catheterization for monitoring fetal hypoxemia and hypoglycemia.
- Postnatal respiratory function assessment for 8 weeks, including gas exchange, lung volumes, and mechanics.
Main Results:
- IUGR lambs showed reduced birth weight, persistent hypoxemia, and hypercapnia.
- Decreased pulmonary diffusing capacity, smaller lung volumes (functional residual capacity, total lung capacity).
- Reduced static lung compliance and increased chest wall compliance; lower pulmonary DNA and protein concentrations.
Conclusions:
- Placental insufficiency leading to IUGR causes lasting lung and chest wall alterations.
- These alterations result in persistent respiratory function impairments in early postnatal life.
- Findings provide insights into mechanisms linking low birth weight to respiratory problems.
Abstract:
Epidemiologic studies have shown persistent effects of low birth weight on respiratory function and lung health, but underlying mechanisms are not understood. Our aim was to determine the effects of intrauterine growth restriction (IUGR), a major cause of low birth weight, on postnatal respiratory function. IUGR was induced by umbilico-placental embolization during late gestation in chronically catheterized sheep. Umbilico-placental embolization was performed between 120 d of gestation and term ( approximately 146 d) during which fetuses were hypoxemic and hypoglycemic relative to controls. Umbilico-placental embolization led to a 48% reduction in birth weight compared with controls, and throughout the postnatal study period IUGR lambs (n = 8) remained lighter than controls (n = 8). Respiratory function was repeatedly studied in lambs for 8 wk after birth; during this period, IUGR lambs were mildly hypoxemic and tended to be hypercapnic compared with controls. In IUGR lambs, relative to controls, O(2) consumption (mL/min/kg) and minute ventilation (mL/kg) were increased and pulmonary diffusing capacity (adjusted for functional residual capacity) was decreased. Functional residual capacity, measured by helium dilution, and total lung capacity (measured at 30 cm H(2)O) were smaller in IUGR lambs than in controls. When adjusted for functional residual capacity, static lung compliance was reduced and chest wall compliance was increased in IUGR lambs. At 8 wk, pulmonary DNA and protein concentrations were decreased in IUGR lambs relative to controls. We conclude that restriction of fetal growth by placental insufficiency induces alterations in the lungs and chest wall that result in persistent impairments in respiratory function during early postnatal life.