Overexpression of microRNAs miR-25-3p, miR-185-5p and miR-132-3p in Late Onset Fetal Growth Restriction, Validation of Results and Study of the Biochemical Pathways Involved

In a prospective study, 48 fetuses were evaluated with Doppler ultrasound after 34 weeks and classified, according to the cerebroplacental ratio (CPR) and estimated fetal weight (EFW), into fetuses with normal growth and fetuses with late-onset fetal growth restriction (LO-FGR). Overexpression of miRNAs from neonatal cord blood belonging to LO-FGR fetuses, was validated by real-time PCR. In addition, functional characterization of overexpressed miRNAs was performed by analyzing overrepresented pathways, gene ontologies, and prioritization of synergistically working miRNAs. Three miRNAs: miR-25-3p, miR-185-5p and miR-132-3p, were significantly overexpressed in cord blood of LO-FGR fetuses. Pathway and gene ontology analysis revealed over-representation of certain molecular pathways associated with cardiac development and neuron death. In addition, prioritization of synergistically working miRNAs highlighted the importance of miR-185-5p and miR-25-3p in cholesterol efflux and starvation responses associated with LO-FGR phenotypes. Evaluation of miR-25-3p; miR-132-3p and miR-185-5p might serve as molecular biomarkers for the diagnosis and management of LO-FGR; improving the understanding of its influence on adult disease.

Download Full-text

Risk stratification for early-onset fetal growth restriction in women with abnormal serum biomarkers: a retrospective cohort study

Scientific Reports ◽

10.1038/s41598-020-78631-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

L. Ormesher ◽

L. Warrander ◽

Y. Liu ◽

S. Thomas ◽

L. Simcox ◽

...

Keyword(s):

Fetal Growth ◽

Fetal Growth Restriction ◽

Early Onset ◽

Late Onset ◽

Area Under The Curve ◽

Maternal Serum ◽

Serum Biomarkers ◽

Growth Restriction ◽

Aneuploidy Screening ◽

Internal Validation

AbstractAbnormal maternal serum biomarkers (AMSB), identified through the aneuploidy screening programme, are frequent incidental findings in pregnancy. They are associated with fetal growth restriction (FGR), but previous studies have not examined whether this association is with early-onset (< 34 weeks) or late-onset (> 34 weeks) FGR; as a result there is no consensus on management. The aims of this study were to determine the prevalence and phenotype of FGR in women with AMSB and test the predictive value of placental sonographic screening to predict early-onset FGR. 1196 pregnant women with AMSB underwent a 21–24 week “placental screen” comprising fetal and placental size, and uterine artery Doppler. Multivariable regression was used to calculate a predictive model for early-onset FGR (birthweight centile < 3rd/< 10th with absent umbilical end-diastolic flow, < 34 weeks). FGR prevalence was high (10.3%), however early-onset FGR was uncommon (2.3%). Placental screening effectively identified early-onset (area under the curve (AUC) 0.93, 95% confidence interval (CI) 0.87–1.00), but not late-onset FGR (AUC 0.70, 95% CI 0.64–0.75). Internal validation demonstrated robust performance for detection/exclusion of early-onset FGR. In this cohort, utilisation of our proposed algorithm with targeted fetal growth and Doppler surveillance, compared with universal comprehensive surveillance would have avoided 1044 scans, potentiating significant cost-saving for maternity services.

Download Full-text

Physiopathology of late-onset fetal growth restriction

Minerva Obstetrics and Gynecology ◽

10.23736/s2724-606x.21.04771-7 ◽

2021 ◽

Vol 73 (4) ◽

Author(s):

Edward ARAUJO JÚNIOR ◽

Ana C. ZAMARIAN ◽

Ana C. CAETANO ◽

Alberto B. PEIXOTO ◽

Luciano M. NARDOZZA

Keyword(s):

Fetal Growth ◽

Fetal Growth Restriction ◽

Late Onset ◽

Growth Restriction

Download Full-text

miR-16-5p, miR-103-3p, and miR-27b-3p as Early Peripheral Biomarkers of Fetal Growth Restriction

Frontiers in Pediatrics ◽

10.3389/fped.2021.611112 ◽

2021 ◽

Vol 9 ◽

Author(s):

Salvatore Tagliaferri ◽

Pasquale Cepparulo ◽

Antonio Vinciguerra ◽

Marta Campanile ◽

Giuseppina Esposito ◽

...

Keyword(s):

Fetal Growth ◽

Gestational Age ◽

Fetal Growth Restriction ◽

Late Onset ◽

Maternal Blood ◽

Growth Restriction ◽

Therapeutic Interventions ◽

Control Group ◽

Fetal Hypoxia ◽

Blood Samples

Current tests available to diagnose fetal hypoxia in-utero lack sensitivity thus failing to identify many fetuses at risk. Emerging evidence suggests that microRNAs derived from the placenta circulate in the maternal blood during pregnancy and may be used as non-invasive biomarkers for pregnancy complications. With the intent to identify putative markers of fetal growth restriction (FGR) and new therapeutic druggable targets, we examined, in maternal blood samples, the expression of a group of microRNAs, known to be regulated by hypoxia. The expression of microRNAs was evaluated in maternal plasma samples collected from (1) women carrying a preterm FGR fetus (FGR group) or (2) women with an appropriately grown fetus matched at the same gestational age (Control group). To discriminate between early- and late-onset FGR, the study population was divided into two subgroups according to the gestational age at delivery. Four microRNAs were identified as possible candidates for the diagnosis of FGR: miR-16-5p, miR-103-3p, miR-107-3p, and miR-27b-3p. All four selected miRNAs, measured by RT-PCR, resulted upregulated in FGR blood samples before the 32nd week of gestation. By contrast, miRNA103-3p and miRNA107-3p, analyzed between the 32nd and 37th week of gestation, showed lower expression in the FGR group compared to aged matched controls. Our results showed that measurement of miRNAs in maternal blood may form the basis for a future diagnostic test to determine the degree of fetal hypoxia in FGR, thus allowing the start of appropriate therapeutic interventions to alleviate the burden of this disease.

Download Full-text