Abstract
Spontaneous preterm birth (PTB) complicates about 12% of pregnancies worldwide, remaining the main cause of neonatal morbidity and mortality. Spontaneous preterm birth PTBs is often caused by microbial-induced preterm labor, mediated by an inflammatory process threatening both maternal and newborn health. In search for novel predictive biomarkers of PTB and preterm prelabor rupture of the membranes (pPROM), and to improve understanding of infection related PTB, we performed an untargeted mass spectrometry discovery study on 51 bioptic mid zone amnion samples from premature babies. A total of 6352 proteins were identified. Bioinformatics analyses revealed a ranked core of 159 proteins maximizing the discrimination between the selected clinical stratification groups allowing to distinguish conditions of absent (FIR 0) from maximal Fetal Inflammatory Response (FIR 3) stratified in function of Maternal Inflammatory Response (MIR) grade. Matrix metallopeptidase-9 (MMP-9) was the top differentially expressed protein. Gene Ontology enrichment analysis of the core proteins showed significant changes in the biological pathways associated to inflammation and regulation of immune and infection response. Data suggest that the conditions determining PTB would be a transversal event, secondary to the maternal inflammatory response causing a breakdown in fetal-maternal tolerance, with fetal inflammation being more severe than maternal one. We also highlight matrix metallopeptidase-9 as a potential predictive biomarker of PTB that can be assayed in the maternal serum, for future investigation.
Highlights
Spontaneous preterm birth (PTB) complicates about 12% of pregnancies worldwide, remaining the main cause of neonatal morbidity and mortality
maternal inflammatory response (MIR) is the inflammatory response of the p lacenta[16], histological subclinical (HCA), that extends into the chorion, amnion or decidua
The weighted gene co-expression network analysis (WGCNA) clusters in a module the proteins sharing the same co-expression profile, that are deemed to be in a functional relationship with each other[22]
Summary
Spontaneous preterm birth (PTB) complicates about 12% of pregnancies worldwide, remaining the main cause of neonatal morbidity and mortality. Spontaneous preterm birth PTBs is often caused by microbial-induced preterm labor, mediated by an inflammatory process threatening both maternal and newborn health. PTB is caused by diverse pathologic processes, among which decidual vascular disease or premature senescence; decline in progesterone action; uterine overdistension and microbial-induced inflammation[2]. The latter is the only one associated to spontaneous preterm delivery, one in three preterm infants has a subclinical intra-amniotic infection[2]. FIR is an inflammation infiltrating the chorionic plate, umbilical cord (funisitis) and fetal blood vessels (vasculitis of chorioamniotic vessels, vasculitis of umbilical vein and artery) and associated with poor neonatal outcomes including low birth weight, and s epsis[17,18,19]. Ultrasound measurement of cervical length at 20–24 weeks of gestation has been utilized[20], these methods have low-detection and high false-positive r ates[21]
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