scholarly journals Placenta-specific Slc38a2/SNAT2 knockdown causes fetal growth restriction in mice.

2021 ◽  
Author(s):  
Owen Vaughan ◽  
Katarzyna Maksym ◽  
Elena Silva ◽  
Kenneth Barentsen ◽  
Russel V Anthony ◽  
...  
Keyword(s):  
Amino Acid ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Late Onset ◽  
Specific Treatment ◽  
Later Life ◽  
Growth Restriction ◽  
Amino Acid Transport System ◽  
Mortality And Morbidity ◽  
Appropriate For Gestational Age

Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease.  No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2/SNAT2 deficiency in the development of restricted fetal growth, hypothesizing that placenta-specific Slc38a2 knockdown causes fetal growth restriction in mice. Using lentiviral transduction of blastocysts with a small hairpin RNA, we achieved 59% knockdown of placental Slc38a2, without altering fetal Slc38a2 expression. Placenta-specific Slc38a2 knockdown reduced near-term fetal and placental weight, fetal viability, trophoblast plasma membrane SNAT2 protein abundance, and both absolute and weight-specific placental uptake of the amino acid transport System A tracer, 14C-methylaminoisobutyric acid. We also measured human placental SLC38A2 gene expression in a well-defined term clinical cohort and found that SLC38A2 expression was decreased in late-onset, but not early-onset FGR, compared to appropriate for gestational age control placentas. The results demonstrate that low placental Slc38a2/SNAT2 causes fetal growth restriction and could be a target for clinical therapies for late-onset FGR.

scholarly journals Diagnosis and Management of Fetal Growth Restriction

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Jacqueline E. A. K. Bamfo ◽  
Anthony O. Odibo
Keyword(s):  
Metabolic Syndrome ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Clinical Management ◽  
Later Life ◽  
Growth Restriction ◽  
Surveillance Program ◽  
Mortality And Morbidity ◽  
Diagnosis And Management ◽  
Biophysical Profile

Fetal growth restriction (FGR) remains a leading contributor to perinatal mortality and morbidity and metabolic syndrome in later life. Recent advances in ultrasound and Doppler have elucidated several mechanisms in the evolution of the disease. However, consistent classification and characterization regarding the severity of FGR is lacking. There is no cure, and management is reliant on a structured antenatal surveillance program with timely intervention. Hitherto, the time to deliver is an enigma. In this paper, the challenges in the diagnosis and management of FGR are discussed. The biophysical profile, Doppler, biochemical and molecular technologies that may refine management are reviewed. Finally, a model pathway for the clinical management of pregnancies complicated by FGR is presented.

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

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.

Physiopathology of late-onset fetal growth restriction

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

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

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.

scholarly journals Early‐onset fetal growth restriction: A systematic review on mortality and morbidity

2019 ◽  
Vol 99 (2) ◽  
pp. 153-166 ◽  
Author(s):  
Anouk Pels ◽  
Irene M. Beune ◽  
Aleid G. van Wassenaer‐Leemhuis ◽  
Jacqueline Limpens ◽  
Wessel Ganzevoort
Keyword(s):  
Systematic Review ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Early Onset ◽  
Growth Restriction ◽  
Mortality And Morbidity
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