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Title: | Identifying late-onset fetal growth restriction by measuring circulating placental RNA in the maternal blood at 28 weeks' gestation. | Authors: | Fuller P.J.;Tong S.;Kaitu'u-Lino T.J.;Tuohey L.;Vickers D.K.;Whitehead C.L.;McNamara H.;Walker S.P.;Alexiadis M.;Hastie R.;Hannan N.J. | Institution: | (Whitehead, Walker, Vickers, Hannan, Hastie, Tuohey, Kaitu'u-Lino, Tong) Translational Obstetrics Group, Department of Obstetrics and Gynecology, University of Melbourne, Mercy Hospital for Women, Melbourne, Australia (McNamara) Department of Obstetrics and Gynecology, University of Melbourne, Royal Women's Hospital, Parkville, Australia (Alexiadis, Fuller) Hudson Institute of Medical Research, Monash Health, Clayton, Australia | Issue Date: | 7-Apr-2016 | Copyright year: | 2016 | Publisher: | Mosby Inc. (E-mail: customerservice@mosby.com) | Place of publication: | United States | Publication information: | American Journal of Obstetrics and Gynecology. 214 (4) (pp e1-521), 2016. Date of Publication: 01 Apr 2016. | Journal: | American Journal of Obstetrics and Gynecology | 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.Copyright © 2016 Elsevier Inc. All rights reserved. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1016/j.ajog.2016.01.191 | PubMed URL: | 26880734 [http://www.ncbi.nlm.nih.gov/pubmed/?term=26880734] | ISSN: | 0002-9378 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/39944 | Type: | Article | Subjects: | adrenomedullin/ec [Endogenous Compound] kisspeptin/ec [Endogenous Compound] messenger RNA/ec [Endogenous Compound] placental growth factor/ec [Endogenous Compound] protein/ec [Endogenous Compound] *RNA/ec [Endogenous Compound] somatomedin C/ec [Endogenous Compound] tachykinin/ec [Endogenous Compound] transcriptome/ec [Endogenous Compound] unclassified drug kisspeptin 1/ec [Endogenous Compound] syncytin/ec [Endogenous Compound] tachykinin 3/ec [Endogenous Compound] microarray analysis article case control study cohort analysis controlled study disease severity female fetus gene control gene expression *gestational age human *intrauterine growth retardation/di [Diagnosis] major clinical study *maternal blood outcome assessment *placenta placenta function priority journal prospective study protein expression reverse transcription polymerase chain reaction *RNA analysis activating transcription factor 3/ec [Endogenous Compound] human *intrauterine growth retardation / *diagnosis major clinical study *maternal blood microarray analysis outcome assessment *placenta placenta function priority journal prospective study case control study reverse transcription polymerase chain reaction *RNA analysis Article protein expression cohort analysis controlled study disease severity female fetus gene control gene expression *gestational age |
Type of Clinical Study or Trial: | Observational study (cohort, case-control, cross sectional or survey) |
Appears in Collections: | Articles |
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