Bronchopulmonary Dysplasia and Impaired Neurodevelopment-What May Be the Missing Link?

Boris W. Kramer, Victoria Niklas, Steven Abman

Research output: Contribution to journalReview articlepeer-review

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)S14-S17
Number of pages4
JournalAmerican Journal of Perinatology
Volume39
Issue number3
Early online date1 Nov 2022
DOIs
Publication statusPublished - Dec 2022

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