Format

Send to

Choose Destination
Am J Obstet Gynecol. 2016 Apr;214(4):521.e1-521.e8. doi: 10.1016/j.ajog.2016.01.191. Epub 2016 Feb 12.

Identifying late-onset fetal growth restriction by measuring circulating placental RNA in the maternal blood at 28 weeks' gestation.

Author information

1
Translational Obstetrics Group, Department of Obstetrics and Gynecology, University of Melbourne, Mercy Hospital for Women, Melbourne, Australia. Electronic address: clarew@unimelb.edu.au.
2
Department of Obstetrics and Gynecology, University of Melbourne, Royal Women's Hospital, Parkville, Australia.
3
Translational Obstetrics Group, Department of Obstetrics and Gynecology, University of Melbourne, Mercy Hospital for Women, Melbourne, Australia.
4
Hudson Institute of Medical Research, Monash Health, Clayton, Australia.

Abstract

BACKGROUND:

Late-onset fetal growth restriction (FGR) is often undetected prior to birth, which puts the fetus at increased risk of adverse perinatal outcomes including stillbirth.

OBJECTIVE:

Measuring RNA circulating in the maternal blood may provide a noninvasive insight into placental function. We examined whether measuring RNA in the maternal blood at 26-30 weeks' gestation can identify pregnancies at risk of late-onset FGR. We focused on RNA highly expressed in placenta, which we termed "placental-specific genes."

STUDY DESIGN:

This was a case-control study nested within a prospective cohort of 600 women recruited at 26-30 weeks' gestation. The circulating placental transcriptome in maternal blood was compared between women with late-onset FGR (<5th centile at >36+6 weeks) and gestation-matched well-grown controls (20-95th centile) using microarray (n = 12). TaqMan low-density arrays, reverse transcription-polymerase chain reaction (PCR), and digital PCR were used to validate the microarray findings (FGR n = 40, controls n = 80).

RESULTS:

Forty women developed late-onset FGR (birthweight 2574 ± 338 g, 2nd centile) and were matched to 80 well-grown controls (birthweight 3415 ± 339 g, 53rd centile, P < .05). Operative delivery and neonatal admission were higher in the FGR cohort (45% vs 23%, P < .05). Messenger RNA coding 137 placental-specific genes was detected in the maternal blood and 37 were differentially expressed in late-onset FGR. Seven were significantly dysregulated with PCR validation (P < .05). Activating transcription factor-3 messenger RNA transcripts were the most promising single biomarker at 26-30 weeks: they were increased in fetuses destined to be born FGR at term (2.1-fold vs well grown at term, P < .001) and correlated with the severity of FGR. Combining biomarkers improved prediction of severe late-onset FGR (area under the curve, 0.88; 95% CI 0.80-0.97). A multimarker gene expression score had a sensitivity of 79%, a specificity of 88%, and a positive likelihood ratio of 6.2 for subsequent delivery of a baby <3rd centile at term.

CONCLUSION:

A unique placental transcriptome is detectable in maternal blood at 26-30 weeks' gestation in pregnancies destined to develop late-onset FGR. Circulating placental RNA may therefore be a promising noninvasive test to identify pregnancies at risk of developing FGR at term.

KEYWORDS:

activating transcription factor-3; circulating RNA; fetal growth restriction

PMID:
26880734
DOI:
10.1016/j.ajog.2016.01.191
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center