Circulating angiogenic factors in early pregnancy and the risk of preeclampsia, intrauterine growth restriction, spontaneous preterm birth, and stillbirth.
OBJECTIVE
To estimate the relationship between maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in early pregnancy with the risk of subsequent adverse outcome.


METHODS
A nested, case-control study was performed within a prospective cohort study of Down syndrome screening. Maternal serum levels of sFlt-1 and PlGF at 10-14 weeks of gestation were compared between 939 women with complicated pregnancies and 937 controls. Associations were quantified as the odds ratio for a one decile increase in the corrected level of the analyte.


RESULTS
Higher levels of sFlt-1 were not associated with the risk of preeclampsia but were associated with a reduced risk of delivery of a small for gestational age infant (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.88-0.96), extreme (24-32 weeks) spontaneous preterm birth (OR 0.90, 95% CI 0.83-0.99), moderate (33-36 weeks) spontaneous preterm birth (OR 0.93, 95% CI 0.88-0.98), and stillbirth associated with abruption or growth restriction (OR 0.77, 95% CI 0.61-0.95). Higher levels of PlGF were associated with a reduced risk of preeclampsia (OR 0.95, 95% CI 0.90-0.99) and delivery of a small for gestational age infant (OR 0.95, 95% CI 0.91-0.99). Associations were minimally affected by adjustment for maternal characteristics.


CONCLUSIONS
Higher early pregnancy levels of sFlt-1 and PlGF were associated with a decreased risk of adverse perinatal outcome.
Smith
Gordon C S
GC
Department of Obstetrics and Gynaecology, Cambridge University, Cambridge, United Kingdom. gcss2@cam.ac.uk
Crossley
Jennifer A
JA
Aitken
David A
DA
Jenkins
Nicola
N
Lyall
Fiona
F
Cameron
Alan D
AD
Connor
J Michael
JM
Dobbie
Richard
R
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D005317:Fetal Growth Retardation / Q000453:epidemiology*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007236:Infant, Small for Gestational Age; D016017:Odds Ratio; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000453:epidemiology*; D011247:Pregnancy / Q000097:blood; D011256:Pregnancy Outcome; D011257:Pregnancy Proteins / Q000097:blood*; D011261:Pregnancy Trimester, First / Q000097:blood; D047928:Premature Birth / Q000453:epidemiology*; D011446:Prospective Studies; D012307:Risk Factors; D050497:Stillbirth / Q000453:epidemiology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1