title: Quantifying mRNA coding growth genes in the maternal circulation to detect fetal growth restriction.
abstract: OBJECTIVE
  To examine whether mRNA circulating in maternal blood coding genes regulating fetal growth are differentially expressed in (1) severe preterm fetal growth restriction (FGR) and (2) at 28 weeks' gestation in pregnancies destined to develop FGR at term.
  
  
  METHODS
  mRNA coding growth genes were measured in 2 independent cohorts. The first was women diagnosed with severe preterm FGR (<34 weeks' gestation; n = 20) and gestation matched controls (n = 15), where the mRNA was measured in both maternal blood and placenta. The second cohort was a prospective longitudinal study (n = 52) of women whom had serial ultrasound assessments of fetal growth. mRNA coding growth genes in maternal blood were measured at 28 and 36 weeks in pregnancies with declining growth trajectories (ending up with term FGR; n = 10 among the 52 recruited) and controls who maintained normal growth trajectory (n = 15).
  
  
  RESULTS
  In women with severe preterm FGR, there was increased expression of placental growth hormone (6.3-fold), insulin-like growth factors (IGF1, 3.4-fold; IGF2, 5.0-fold), IGF receptors (2.1-fold) and IGF binding proteins (3.0-fold), and reduced expression of ADAM12 (0.5-fold) in maternal blood (and similar trends in placenta) compared with controls (P < .05). Notably, at 28 weeks' gestation there was increased IGF2 (3.9-fold), placental growth hormone (2.7-fold), and IGF BP2 (2.1-fold) expression in maternal blood in women destined to develop FGR at term (P < .05).
  
  
  CONCLUSIONS
  Measuring mRNA coding growth genes in maternal blood may detect unsuspected severe preterm FGR already present in utero, and predict term FGR when measured at 28 weeks' gestation.
authors.affiliation: Translational Obstetrics Group, Department of Obstetrics and Gynecology, Mercy Hospital for Women, Heidelberg, VIC, Australia.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Whitehead
authors.forename: Susan P
authors.initials: SP
authors.lastname: Walker
authors.forename: Sonali
authors.initials: S
authors.lastname: Mendis
authors.forename: Martha
authors.initials: M
authors.lastname: Lappas
authors.forename: Stephen
authors.initials: S
authors.lastname: Tong
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D000072199:ADAM12 Protein; D000328:Adult; D005260:Female; D047109:Fetal Development; D005317:Fetal Growth Retardation / Q000175:diagnosis*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D011247:Pregnancy / Q000097:blood*; D012333:RNA, Messenger / Q000097:blood*; D017451:Receptors, Somatomedin / Q000235:genetics; D013002:Somatomedins / Q000235:genetics
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D013002:Somatomedins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human
keywords: biomarker; fetal growth restriction; free RNA; maternal circulation; placenta