Perinatal Nutritional and Metabolic Pathways: Early Origins of Chronic Lung Diseases

Abstract

Lung development is not completed at birth, but expands beyond infancy, rendering the lung highly susceptible to injury. Exposure to various influences during a critical window of organ growth can interfere with the finely-tuned process of development and induce pathological processes with aberrant alveolarization and long-term structural and functional sequelae. This concept of developmental origins of chronic disease has been coined as perinatal programming. Some adverse perinatal factors, including prematurity along with respiratory support, are well-recognized to induce bronchopulmonary dysplasia (BPD), a neonatal chronic lung disease that is characterized by arrest of alveolar and microvascular formation as well as lung matrix remodeling. While the pathogenesis of various experimental models focus on oxygen toxicity, mechanical ventilation and inflammation, the role of nutrition before and after birth remain poorly investigated. There is accumulating clinical and experimental evidence that intrauterine growth restriction (IUGR) as a consequence of limited nutritive supply due to placental insufficiency or maternal malnutrition is a major risk factor for BPD and impaired lung function later in life. In contrast, a surplus of nutrition with perinatal maternal obesity, accelerated postnatal weight gain and early childhood obesity is associated with wheezing and adverse clinical course of chronic lung diseases, such as asthma. While the link between perinatal nutrition and lung health has been described, the underlying mechanisms remain poorly understood. There are initial data showing that inflammatory and nutrient sensing processes are involved in programming of alveolarization, pulmonary angiogenesis, and composition of extracellular matrix. Here, we provide a comprehensive overview of the current knowledge regarding the impact of perinatal metabolism and nutrition on the lung and beyond the cardiopulmonary system as well as possible mechanisms determining the individual susceptibility to CLD early in life. We aim to emphasize the importance of unraveling the mechanisms of perinatal metabolic programming to develop novel preventive and therapeutic avenues.

Machine learning for prediction of bronchopulmonary dysplasia-free survival among very preterm infants

“…The literature suggests a developmental origin of BPD [ 13 , 17 , 18 , 24 , 26 , 39 – 41 ]. In this study, we expanded on this concept to develop a machine learning BPD-free survival prediction model.…”

Maternal propionate supplementation ameliorates glucose and lipid metabolic disturbance in hypoxia-induced fetal growth restriction

“…26 There is accumulating clinical and experimental evidence that IUGR is a major risk factor for bronchopulmonary dysplasia. 6 In an isocyclic gestational protein restriction-induced IUGR model, propionate concentration was decreased by IUGR before weaning, whereas the concentrations of other SCFAs were decreased at day 40. 27 However, whether propionate performs a therapeutic effect on IUGR remains unknown.…”

“…1 Hypoxic stress in pregnancy is one of the most common conditions and occurs in various scenarios such as high-altitude pregnancy, maternal smoking, pulmonary diseases, preeclampsia, placental insufficiency, and others. 2,3 Antenatal maternal hypoxia has been shown to cause altered cardiac growth and neonatal vascular function, 4,5 pulmonary arterial dysfunction 6 and fetal growth restriction. 7 Fetal growth restriction or intrauterine growth retardation (IUGR) is one of the major complications of pregnancy and is one of the main leading causes of perinatal death.…”

Ventilation-Induced Lung Injury (VILI) in Neonates: Evidence-Based Concepts and Lung-Protective Strategies

“…Good nutrition is necessary for somatic growth and development [99]. Likewise, optimal nutrition is also necessary for lung development and repair [100][101][102][103], as well as defense against infection [42,104,105] and oxidative stress [106][107][108], which are all risk factors for VILI. Preterm infants are at risk of poor nutritional states due to the increased work of breathing, immature gastrointestinal function, fluid restriction, and exposure to medications such as steroids and diuretics [42,109,110].…”