Cord blood biomarkers of vascular endothelial growth (VEGF and sFlt-1) and postnatal growth: a preterm birth cohort study.
BACKGROUND
Preterm infants are at risk for postnatal growth failure (PGF). Identification of biomarkers that are associated with neonatal growth may help reduce PGF and associated long-term morbidity.


OBJECTIVE
To investigate the associations between cord blood vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1) with birth weight (BW) and postnatal growth in premature infants.


METHODS
From an ongoing birth cohort, 123 premature infants from 23 to 36 weeks gestational age (GA) were studied. Cord blood plasma VEGF and sFlt-1 were measured via enzyme-linked immunoassay. Growth parameters and nutritional information were evaluated. Multivariate logistic regression models were constructed to evaluate the associations of VEGF and sFlt-1 on PGF, defined as weight <10th percentile at 36 weeks corrected age or discharge.


RESULTS
VEGF was positively correlated, and sFlt-1 was negatively correlated with BW and BW-for-GA percentiles. Higher cord blood VEGF levels were associated with reduced risk of PGF (OR=0.7; 95% CI=0.5-0.9), while higher sFlt-1 levels appeared to increase the risk of PGF (OR=1.6; 95% CI=1.1-2.4). The above biomarker associations were attenuated after adjustment for maternal preeclampsia, fetal growth restriction and related neonatal characteristics, and when taking into account placental vascular pathologies. Longitudinal growth patterns by mean weight and length percentiles were consistently lower among infants with low VEGF/sFlt-1 ratios.


CONCLUSIONS
Our data support that intrauterine regulation of angiogenesis is an important mechanism of fetal and postnatal growth. Cord blood VEGF and sFlt-1 are useful in elucidating how intrauterine processes may have long-standing effects on developing premature infants.
Department of Pediatrics, Division of Neonatology, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA. Electronic address: smbv@me.com.
Stephannie Baehl
SB
Voller
Department of Pediatrics, Division of Neonatology, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
Susanne
S
Chock
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Linda M
LM
Ernst
Department of Obstetrics and Gynecology, Divisions of Maternal Fetal Medicine and Reproductive Biology Research, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Emily
E
Su
Mary Ann and J. Milburn Smith Child Health Research Program, Ann & Robert H. Lurie Children's Hospital of Chicago Research Center, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Xin
X
Liu
Department of Pediatrics, Division of Neonatology, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
Kathryn N
KN
Farrow
Department of Pediatrics, Division of Neonatology, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
Karen K
KK
Mestan
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001724:Birth Weight; D004730:Endothelium, Vascular / Q000254:growth & development; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D006130:Growth Disorders / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood / Q000254:growth & development*; D008297:Male; D018919:Neovascularization, Physiologic; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
Birth weight; Cord blood; Fetal growth restriction; Fetal origins; Postnatal growth; Preterm infants; Vascular endothelial growth factor (VEGF)