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IUGR pathogenetic mechanisms to identify an integrated biomarker profile predicting the risk for be born preterm SGA infant.

Progetto sottoposto a competizione per finanziamento in seno ai Progetti di Ricerca Scientifica di Alta Rilevanza Nazionale

Intrauterine growth restriction (IUGR) is a major complication of pregnancy that results in marked fetal, neonatal and long-term morbidity and mortality.

Reduced fetal growth is seen in about 10% of pregnancies. The spectrum of IUGR phenotype is pleiotropic and actual understanding of the multidimensional underpinnings of IUGR pregnancy lacks to provide an adequate picture of the overall condition of the affected fetuses. As a consequence, the decision to deliver a preterm IUGR fetus still remains one of the great challenges in medicine. Feto-placental hypoxaemia, oxidative stress (OS), inflammation, umbilical cord morphology and cell components including stem cells, have been described to be involved in IUGR pathogenesis.

This project aims to go in depth on pathogenetic mechanisms of IUGR allowing to setting up an integrated biomarkers panel to classify IUGR pregnancies into different sub-diagnostic categories and carefully identify fetuses who effectively would benefit of early intervention.

To this end we will perform a collaborative project combining the different skills of university laboratories with a well-recognized experience in the field. The expertise of each participant will be unified as in a jigsaw puzzle in which all dowels point out and unravel mechanisms of the heterogeneous pathogenesis of IUGR pregnancy.

Omics techniques (metabolomics, miRNA) will be used to investigate complex fetal response to an adverse intrauterine environment.

mRNA, OS biomarkers, and metabolomics will be analyzed in mothers and in cord blood, miRNAs, autophagy and ER stress, histological and immunohistochemical studies will be performed in umbilical cord.

This project has the potentiality to provide a better clarification of the role of intrauterine factors in pregnancy allowing to identify those babies diagnosed with IUGR that are more likely to have complications during pregnancy, during delivery and afterward, grading the risk on the knowledge of what caused the growth problem and how severe the growth restriction is. The identification and validation of new indices of complexity to be used in the clinical routine will reduce concerns and uncertainity about how and when to intervene  in case of IUGR diagnosis.

In conclusion, the better knowledge of IUGR pathology together with a new integrated panel of biomarkers profiles should allow to improve decision-making, to implement new treatment strategies, addressing the critical needs of pregnant women and their offspring. Ad hoc startup among  the universities involved in the project will take care of all the technological  potentialities including to develop one or more integrated diagnostic kits. It is reasonable that, if this project will contribute to reduce at least of 10% the incidence of low birth weight and low gestational age, thought better, personalized  management of IUGR pregnancies, it will reach the goal to effectively  reduce the financial and social enormous burden of IUGR pregnancies.

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