Cell-Free DNA (cfDNA) Fetal Fraction in Early- and Late-Onset Fetal Growth Restriction

AbstractObjectiveTo investigate the possible predictive value of fetal fraction in the cell-free DNA (cfDNA) test in pregnancies with early- and late-onset fetal growth restriction (FGR).MethodsThis retrospective study comprised 247 women who were screened using the cfDNA test for aneuploidies during the first or second trimester and had deliveries at our institution from January 2016 to December 2019. The fetal fractions of women with early- (n = 14) and late-onset (n = 83) FGR and those with uncomplicated pregnancies (n = 150) were compared.ResultsThe median fetal fractions for the early-onset FGR, late-onset FGR, and control groups were 5.7 [interquartile range (IQR) 2.65], 7 (IQR 5), and 7.35 (IQR 3.65), respectively. The fetal fractions were significantly lower in the early-onset FGR group than in the late-onset FGR and control groups (P = 0.047 and P = 0.037, respectively). There was no difference in fetal fractions between the late-onset FGR and control groups (P = 1.00).ConclusionAs a placenta-related disease, early-onset FGR had lower fetal fractions in the cfDNA test than uncomplicated pregnancies. For clinical use, lower fetal fractions can contribute as a biomarker for screening asymptomatic women for possible placenta-related diseases, such as early-onset FGR. However, more studies are needed to define the “lower” limit.

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Cell-free DNA Screening Following Severe Fetal Growth Restriction Leading to Diagnosis of Maternal Mosaic Turner Syndrome (45,X/46,XX)

European Journal of Obstetrics & Gynecology and Reproductive Biology ◽

10.1016/j.ejogrb.2021.06.017 ◽

2021 ◽

Author(s):

David M. Sherer ◽

Vicky Hsieh ◽

Mila Kheyman ◽

Alexandra M. Dryer ◽

Mudar Dalloul

Keyword(s):

Turner Syndrome ◽

Fetal Growth ◽

Fetal Growth Restriction ◽

Growth Restriction ◽

Cell Free Dna ◽

Free Dna

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Maternal total cell-free DNA in preeclampsia and fetal growth restriction: Evidence of differences in maternal response to abnormal implantation

PLoS ONE ◽

10.1371/journal.pone.0200360 ◽

2018 ◽

Vol 13 (7) ◽

pp. e0200360 ◽

Cited By ~ 13

Author(s):

Tal Rafaeli-Yehudai ◽

Majdi Imterat ◽

Amos Douvdevani ◽

Dan Tirosh ◽

Neta Benshalom-Tirosh ◽

...

Keyword(s):

Fetal Growth ◽

Fetal Growth Restriction ◽

Total Cell ◽

Growth Restriction ◽

Maternal Response ◽

Cell Free Dna ◽

Free Dna

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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.

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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

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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.

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