title: Association of vascular endothelial growth factor +936 C/T single-nucleotide polymorphism with pregnancies complicated by small-for-gestational-age babies.
abstract: OBJECTIVE
  To examine whether single-nucleotide polymorphisms (SNPs) in VEGFA (-2578 C/A and +936 C/T) associate with small-for-gestational-age (SGA) pregnancies and to identify their effects on first-trimester placental VEGFA expression.
  
  
  METHODS
  Multicenter prospective cohort study.
  
  
  METHODS
  Adelaide, Australia, and Auckland, New Zealand.
  
  
  METHODS
  A total of 3234 nulliparous pregnant women, their partners, and their infants.
  
  
  METHODS
  The SNPs in the parent-infant trios and first-trimester placentae (n = 74) were genotyped. Placental VEGFA messenger RNA expression was determined by quantitative reverse transcription-polymerase chain reaction. Small for gestational age was defined as a birth weight less than the 10th customized birth weight percentile adjusted for maternal height, weight, parity, and ethnicity and for gestational age at delivery and infant sex. Uterine and umbilical artery Doppler was performed at 20 weeks' gestation, and resistance indices greater than the 90th percentile were considered abnormal.
  
  
  RESULTS
  Of 2123 pregnancies, 1176 (55.4%) were uncomplicated and 216 (10.2%) had SGA infants. Neonatal VEGFA +936 C/T SNP associates with SGA (adjusted odds ratio [aOR], 1.6; 95% CI, 1.0-2.3), SGA with abnormal Doppler findings (aOR, 3.5; 95% CI, 1.8-7.1), lower birth weight (P = .006), customized birth weight percentile (P = .049), and abnormal uterine artery Doppler findings (OR, 2.5; 95% CI, 1.2-5.4). Maternal VEGFA +936 C/T associates with abnormal umbilical artery Doppler findings (OR, 1.5; 95% CI, 1.1-2.2). VEGFA +936 CT+TT first-trimester placentae have 36% lower VEGFA messenger RNA expression compared with CC (P = .045).
  
  
  CONCLUSIONS
  Neonatal VEGFA +936 C/T associates with SGA, and the association is stronger for SGA with abnormal uterine or umbilical artery Doppler findings. The SNP also associates with reduced first-trimester placental VEGFA expression, suggesting that it may have a role in the pathogenesis of SGA. Trial Registration clinicaltrials.gov Identifier: ACTRN12607000551493.
authors.affiliation: Discipline of Obstetrics and Gynaecology, Research Centre for Reproductive Health, University of Adelaide, Adelaide, Australia.
authors.forename: Prabha H
authors.initials: PH
authors.lastname: Andraweera
authors.forename: Gustaaf A
authors.initials: GA
authors.lastname: Dekker
authors.forename: Steven D
authors.initials: SD
authors.lastname: Thompson
authors.forename: Rachael C
authors.initials: RC
authors.lastname: Nowak
authors.forename: Jamie V
authors.initials: JV
authors.lastname: Zhang
authors.forename: Lesley M E
authors.initials: LM
authors.lastname: McCowan
authors.forename: Robyn A
authors.initials: RA
authors.lastname: North
authors.forename: Claire T
authors.initials: CT
authors.lastname: Roberts
mesh_terms: D000328:Adult; D001315:Australia; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D016015:Logistic Models; D009520:New Zealand; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000000981:diagnostic imaging; D011247:Pregnancy; D011248:Pregnancy Complications / Q000000981:diagnostic imaging; D011261:Pregnancy Trimester, First; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D018608:Ultrasonography, Doppler; D016216:Ultrasonography, Prenatal; D014469:Umbilical Arteries / Q000000981:diagnostic imaging*; D055988:Uterine Artery / Q000000981:diagnostic imaging*; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D042582:Vascular Endothelial Growth Factor C