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Circulating Angiogenic Factors in Early Pregnancy and the Risk of Preeclampsia, Intrauterine Growth Restriction, Spontaneous Preterm Birth, and Stillbirth

From the ¹Department of Obstetrics and Gynaecology, Cambridge University, Cambridge, United Kingdom; ²Institute of Medical Genetics, Yorkhill NHS Trust, Glasgow, United Kingdom; ³Department of Fetal Medicine, the Queen Mother's Hospital, Glasgow, United Kingdom; and ⁴Information and Statistics Division, Common Services Agency, Edinburgh, United Kingdom.

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.

CONCLUSION: Higher early pregnancy levels of sFlt-1 and PlGF were associated with a decreased risk of adverse perinatal outcome.

LEVEL OF EVIDENCE: II

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