Angiogenic Factors in Maternal Circulation and the Risk of Severe Fetal Growth Restriction

Maternal angiogenic factors (placental growth factor, soluble fms-like tyrosine kinase 1 (Flt-1), and soluble endoglin) may be associated with fetal growth restriction, and the associations may differ according to stage of pregnancy. Among children born to pregnant women without preeclampsia in Norway between 1992 and 1994, 217 singletons with severe growth restriction (small for gestational age (SGA), < 2.5th percentile) were compared with 378 singleton controls. For each angiogenic factor, SGA risk was related to concentrations in maternal serum collected in the first 2 trimesters, by using women with a serum concentration in the middle third at both samplings as reference. A low placental growth factor (lowest third) at both samplings was associated with high risk of SGA (odds ratio = 3.8, 95% confidence interval: 1.6, 8.8). An increase from the lowest to the highest third of soluble Flt-1 was associated with high SGA risk (odds ratio = 6.2, 95% confidence interval: 2.4, 16.1). Women with high soluble endoglin (highest third) at the second sampling had approximately a 3.5-fold increased risk of SGA. Low maternal soluble Flt-1 in early pregnancy followed by a strong subsequent increase in soluble Flt-1 and soluble endoglin was associated with a particularly high risk of severe fetal growth restriction.