Endotypes of Prematurity and Phenotypes of Bronchopulmonary Dysplasia: Toward Personalized Neonatology

Abstract

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is increasingly recognized as the consequence of a pathological reparative response of the developing lung to both antenatal and postnatal injury. According to this view, the pathogenesis of BPD is multifactorial and heterogeneous with different patterns of antenatal stress (endotypes) that combine with varying postnatal insults and might distinctively damage the development of airways, lung parenchyma, interstitium, lymphatic system, and pulmonary vasculature. This results in different clinical phenotypes of BPD. There is no clear consensus on which are the endotypes of prematurity but the combination of clinical information with placental and bacteriological data enables the identification of two main pathways leading to birth before 32 weeks of gestation: (1) infection/inflammation and (2) dysfunctional placentation. Regarding BPD phenotypes, the following have been proposed: parenchymal, peripheral airway, central airway, interstitial, congestive, vascular, and mixed phenotype. In line with the approach of personalized medicine, endotyping prematurity and phenotyping BPD will facilitate the design of more targeted therapeutic and prognostic approaches.

Pulmonary Magnetic Resonance Imaging Replaces Bedside Imaging in Diagnosing Pneumonia in Infants

“…It is located by the tracking machine following a set of guidelines; they were turned into pictures. [ 22 ], which is gradually being characterized as the result of the growing lung's defective tissue repair mechanism to both antenatal and postpartum damage. Various prenatal stressing forms interact with various prenatal impairments to produce a diverse and complex pathology, which may specifically harm the formation of the respiratory system, lung illness, cracks, and capillary systems.…”

Aberrant methylation of Serpine1 mediates lung injury in neonatal mice prenatally exposed to intrauterine inflammation

“…Previous findings and our study suggest a possible role for IUI in inducing fetal and infant lung injury. BPD occurs owing to abnormal repair responses to prenatal and postnatal lung injury [ 35 ]. In this study, hematoxylin and eosin staining revealed abnormal lung morphology in neonatal mice with IUI, including fewer alveoli and simple alveolarization.…”

Association between endotypes of prematurity and pharmacological closure of patent ductus arteriosus: A systematic review and meta-analysis

“…As mentioned in the introduction, the different endotypes of prematurity are not only the trigger for preterm birth but also induce a different pathophysiological environment for the development of fetal organs and systems. Thus, the infectious-inflammatory endotype is characterized by the development of a systemic inflammatory response with elevated cytokine levels (21, 23, 24). In turn, the placental dysfunction endotype is characterized by chronic hypoxia and imbalance of pro- and anti-angiogenic factors (21-24).…”

“…In addition, preterm infants born due to HDP tend to have higher gestational ages than those born due to chorioamnionitis (22). This leads to higher clinical stability and lower incidence of respiratory complications (22, 23). Finally, exposure to HDP does not induce the inflammatory response that is induced by chorioamnionitis.…”

“…Our meta-analysis further supports the growing evidence that not all preterm infants are identical even if they are of the same gestational age. Therefore, one size fits all is no longer an appropriate approach to perinatal medicine (23, 80-82). Personalized medicine requires an adequate characterization of endotypes and clinical phenotypes so that each infant can receive the therapeutic approach best suited to his or her individual characteristics.…”