Abstract
Bronchopulmonary dysplasia (BPD) and poor neurodevelopmental outcome after preterm
birth are closely associated. However, mechanistic links are uncertain. We are exploring
the hypothesis that decreased circulating insulin-like growth factor (IGF)-1 after
preterm birth due to the abrupt end of supply by the placenta impairs growth during
critical windows of development in most organs, including the lung and brain. Throughout
gestation, the fetus uses glycolysis as its main source of energy. Metabolism is mainly
stopped at pyruvate, which serves as a “metabolic crossroad”, allowing for the production
of amino acids and other “building blocks” for new cells. Metabolic pathways are differentially
regulated in the nucleus and the cytoplasm. The ratio between pyruvate dehydrogenase
(PDH) and pyruvate dehydrogenase kinase (PDK) determines the biochemical activity
which irreversibly metabolizes pyruvate to acetyl-co-A. Metabolites in the nucleus
modulate epigenetic remodeling, an essential mechanism of normal growth and maturation
during development. IGF-1 has been shown to contribute significantly to the development
of virtually all organs, especially related to the regulation of microvascular growth,
based on extensive studies of the brain, retina, lung, and intestine. With a preterm
birth, the abrupt withdrawal of the placental supply of IGF-1 and its local production
directly affects metabolism and microvascular development, which may contribute to
a high risk for organ maldevelopment and injury after birth. We speculate that reduced
bioavailability of IGF-1 is a possible link between lung and brain development disruption
and increases susceptibility for major pulmonary and neurocognitive morbidities in
preterm babies.
Key Points
-
Metabolic changes inherent to prterm birth may cause epigenetic changes which cause
“dysmaturational” development.
-
IGF-1 may be the potential link between BPD and brain development.
-
The ratio between pyruvate dehydrogenase and pyruvate dehydrogenase kinase determines
the biochemical activity.
Keywords
development of the microvasculature - IGF1 expression - preterm birth
