Maternal serum soluble fms-like tyrosine kinase-1–to–placental growth factor ratio distinguishes growth-restricted from non–growth-restricted small-for-gestational-age fetuses

BACKGROUND: Fetal growth restriction secondary to chronic placental insufficiency is a major cause of perinatal morbidity and mortality. A significant proportion of fetuses with fetal growth restriction are small for gestational age, defined as a birthweight of ≤10th percentile. However, not all small-for-gestational-age fetuses are growth restricted. Some are constitutionally small and otherwise healthy. It is important to distinguish between small-for-gestational-age fetuses with and without fetal growth restriction to ensure appropriate interventions in small-for-gestational-age fetuses with fetal growth restriction and to minimize unnecessary interventions in healthy small-for-gestational-age fetuses. The maternal serum ratio of soluble fms-like tyrosine kinase-1 and placental growth factor is an indicator of placental insufficiency in the latter half of pregnancy. As such, the soluble fms-like tyrosine kinase-1–to–placental growth factor ratio may be a clinically useful tool to distinguish between small-for-gestational-age fetuses with and without fetal growth restriction. OBJECTIVE: This study aimed to determine whether the soluble fms-like tyrosine kinase-1–to–placental growth factor ratio can distinguish between small-for-gestational-age fetuses with and without fetal growth restriction with a birthweight of ≤10th percentile. STUDY DESIGN: A retrospective audit of 233 singleton pregnancies delivering an infant with a birthweight of ≤10th percentile corrected for gestational age with an antenatal maternal serum soluble fms-like tyrosine kinase-1–to–placental growth factor result was performed. Fetal growth restriction was defined as a birthweight of ≤10th percentile with an umbilical artery pulsatility index of >95th percentile, fetal middle cerebral artery pulsatility index of <5th percentile, amniotic fluid index of <6 cm, and/or cerebroplacental ratio of <1st percentile. The soluble fms-like tyrosine kinase-1–to–placental growth factor ratios before delivery between fetuses with and without fetal growth restriction (121 [fetal growth restriction] vs 112 [no fetal growth restriction]) were compared. The Student t test and Fisher exact test were used to compare cases and controls. The Mann-Whitney U test, linear regression analysis, and Spearman correlation coefficient (Rho) were used to examine associations between the soluble fms-like tyrosine kinase-1–to–placental growth factor ratio and fetal outcomes to determine whether the soluble fms-like tyrosine kinase-1–to–placental growth factor ratio served as a prognostic marker of fetal growth restriction severity. RESULTS: The mean soluble fms-like tyrosine kinase-1–to–placental growth factor ratio was increased in fetal growth restriction cases compared with non–fetal growth restriction controls (234.3±25.0 vs 67.4±7.7, respectively; P