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Type: Journal article
Title: Association of vascular endothelial growth factor +936 C/T single-nucleotide polymorphism with pregnancies complicated by small-for-gestational-age babies
Author: Andraweera, P.
Dekker, G.
Thompson, S.
Nowak, R.
Zhang, V.
McCowan, L.
North, R.
Roberts, C.
Citation: JAMA Pediatrics, 2011; 165(12):1123-1130
Publisher: Amer Medical Assoc
Issue Date: 2011
ISSN: 1072-4710
Statement of
Prabha H. Andraweera, Gustaaf A. Dekker, Steven D. Thompson, Rachael C. Nowak, Jamie V. Zhang, Lesley M. E. McCowan, Robyn A. North, Claire T. Roberts
Abstract: Objectives: 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. Design: Multicenter prospective cohort study. Settings Adelaide, Australia, and Auckland, New Zealand. Participants: A total of 3234 nulliparous pregnant women, their partners, and their infants. Main Outcome Measures: 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). Conclusion: 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.
Keywords: Umbilical Arteries
Pregnancy Complications
Vascular Endothelial Growth Factor C
RNA, Messenger
Ultrasonography, Doppler
Ultrasonography, Prenatal
Logistic Models
Risk Factors
Chi-Square Distribution
Case-Control Studies
Prospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Pregnancy Trimester, First
Polymorphism, Single Nucleotide
Infant, Newborn
Infant, Small for Gestational Age
New Zealand
Uterine Artery
Rights: ©2011 American Medical Association. All rights reserved.
DOI: 10.1001/archpediatrics.2011.796
Grant ID: WO/2009/108073
Appears in Collections:Aurora harvest
Obstetrics and Gynaecology publications

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