Quantifying circulating hypoxia-induced RNA transcripts in maternal blood to determine in uterofetal hypoxic status

Whitehead, Clare; Teh, Wan Tinn; Walker, Susan P.; Leung, Cheryl; Mendis, Sonali; Larmour, Luke; Tong, Stephen

doi:10.1186/1741-7015-11-256

Cited by 30 publications

(24 citation statements)

References 30 publications

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“…We performed an in‐silico approach to screen for placental‐specific cpRNA using online microarray repositories to identify genes expressed in placental tissue at far greater levels than in other human tissues, including non‐pregnant whole blood. We confirmed their presence in maternal and fetal blood and demonstrated a close correlation between their expression in the placenta and the maternal blood in both healthy and complicated pregnancies [preeclampsia, fetal growth restriction (FGR) and intrapartum hypoxia] . This suggests that measuring cpRNAs might reflect the placental transcriptome and measuring cpRNAs may be a novel avenue to perform non‐invasive studies to derive further insights into placental function while the pregnancy continues .…”

Section: Introductionsupporting

confidence: 56%

Measuring circulating placental RNAs to non-invasively assess the placental transcriptome and to predict pregnancy complications

2016

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Circulating nucleic acids have revolutionized prenatal diagnosis in the last decade, allowing non-invasive screening for single gene or chromosomal defects using a single sample of maternal blood. In addition to DNAs, RNAs from the placenta are released into the maternal blood from early in pregnancy and may reflect changes in gene expression occurring within the placenta. Measuring circulating RNA may therefore provide insights into the placental transcriptome without the need for invasive testing. Combined with advances in next-generation sequencing and molecular analyses, it may be possible to measure circulating RNA to improve our understanding of placental pathology and develop novel non-invasive biomarkers for pregnancy complications and monitoring high-risk pregnancies. This review summarizes the current technologies available and the studies that have measured circulating placental RNA to predict and/or monitor pregnancies complicated by preeclampsia, fetal growth restriction, preterm birth, early pregnancy complications, invasive placentation and twin-twin transfusion syndrome. Prospective cohort studies are now required to validate these findings to determine the clinical applicability of measuring circulating placental RNA to develop novel biomarkers for a wide spectrum of pregnancy complications.

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Section: Introductionsupporting

confidence: 56%

Measuring circulating placental RNAs to non-invasively assess the placental transcriptome and to predict pregnancy complications

2016

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“…Whitehead et al 56 have reported mRNAcoding placental specific genes in maternal blood are differentially regulated in pregnancies complicated by severe preterm FGR. In a separate report, mRNAcoding fetal growth genes was found to be altered in the maternal blood at both 28 weeks and 36 weeks among women carrying a fetus destined to be growth restricted at birth.…”

Section: Downstream Evidence Of Placental Insufficiencymentioning

confidence: 99%

Shining light in dark corners: Diagnosis and management of late‐onset fetal growth restriction

MacDonald

McCarthy

Walker

2015

Aust NZ J Obst Gynaeco

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Fetal growth restriction (FGR) is the single biggest risk factor for stillbirth. In the absence of any effective treatment for fetal growth restriction, the mainstay of management is close surveillance and timely delivery. While such statements are almost self-evident, the daily clinical challenge of late-onset fetal growth restriction remains; the competing priorities of minimising stillbirth risk, while avoiding excessive obstetric intervention and the neonatal sequelae of iatrogenic preterm birth. This dilemma is made harder because the tools for late-onset FGR diagnosis and surveillance compare poorly to those used in early-onset FGR; screening tests in early pregnancy have limited predictive value; most cases escape clinical detection, a phenomenon set to worsen given the obesity epidemic; there is a failure of consensus on the definition of small for gestational age, and ancillary tools, such as umbilical artery Doppler--of value in identification of preterm FGR--are less useful in the late-preterm period and at term. Most importantly, the problem is common; 96% of all births occur after 32 weeks. This means a poor noise/signal ratio of any test or management algorithm will inevitably have large clinical consequences. Into such a dark corner, we cast some light; a summary on diagnostic criteria, new developments to improve the diagnosis of late-onset FGR and a suggested approach to management.

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“…Importantly, they appear to be correlated with the degree of fetal hypoxia [8]. Using microarray, we showed that there was global upregulation of hypoxiainduced mRNAs in maternal blood in women bearing fetuses that were hypoxic.…”

mentioning

confidence: 85%

“…We found this gene hypoxia score tightly correlated with the degree of fetal hypoxia in two cohorts: acute fetal hypoxia caused by labor and chronic hypoxia in preterm severe FGR fetuses. Excitingly, the gene hypoxia score appeared to be more precise in determining the degree of fetal hypoxia than the current gold-standard antenatal test, measuring umbilical artery Doppler waveforms using ultrasound [8].…”

mentioning

confidence: 97%

Measuring hypoxia-induced RNA in maternal blood: a new way to identify critically hypoxic fetusesin utero?

Whitehead

Tong

2014

Expert Review of Molecular Diagnostics

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Quantifying circulating hypoxia-induced RNA transcripts in maternal blood to determine in uterofetal hypoxic status

Cited by 30 publications

References 30 publications

Measuring circulating placental RNAs to non-invasively assess the placental transcriptome and to predict pregnancy complications

Measuring circulating placental RNAs to non-invasively assess the placental transcriptome and to predict pregnancy complications

Shining light in dark corners: Diagnosis and management of late‐onset fetal growth restriction

Measuring hypoxia-induced RNA in maternal blood: a new way to identify critically hypoxic fetusesin utero?

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