Placental soluble fms-like tyrosine kinase expression in small for gestational age infants and risk for adverse outcomes

Abstract

IntroductionSoluble fms-like tyrosine kinase 1 (sFLT-1) is an anti-angiogenic factor implicated in the pathogenesis of preterm preeclampsia. We evaluated sFLT-1 expression and placental pathology in pregnancies complicated by small for gestational age (SGA) infants (<10th percentile), without evidence of preeclampsia. MethodsClinical and histologic data were compared between groups with high or low sFLT-1 expression determined by immunohistochemistry on archived placentas. ResultsNineteen of 69 placentas showed high sFLT-1 expression. The high sFLT-1 group had higher predelivery median systolic blood pressure (BP); 140 (interquartile range (IQR) 133–152) vs. 126 (118–139) mm Hg (p = 0.003), and median diastolic BP; 87 (78–94) vs. 77.5 (71–86) mm Hg (p = 0.02). Abnormal umbilical Doppler abnormalities were more prevalent; 89.5% vs. 46% (p = 0.001). These pregnancies delivered earlier; 31.9 weeks (28.3–34.7 weeks) vs. 37.1 weeks (33.7–38.7 weeks) (p < 0.001), and infants had lower birthweight; 980 grams (520–1545 grams) vs. 2087.5 grams (1455–2340 grams) (p < 0.001). Placental-weight to fetal-weight ratios, a marker of vascular insufficiency, was increased in the high sFlt-1 group: 0.18 (0.14–0.28) vs 0.15 (0.13–0.18), p = 0.03. Placentas with high sFLT-1 showed more decidual vasculopathy; 42.1% vs. 10.0% (p = 0.005), infarction; 36.8% vs. 14.0% (p = 0.048), distal villous hypoplasia; 78.9% vs. 36.0% (p = 0.001), and fetal thrombotic vasculopathy; 47.4% vs. 16.0% (p = 0.01). DiscussionPlacental sFLT-1 expression is upregulated in approximately 28% of non-preeclamptic pregnancies complicated by SGA infants. These pregnancies showed increased placental vascular pathology, more umbilical Doppler abnormalities, and earlier delivery with lower birthweight. A subgroup of non-preeclamptic fetal growth restriction with upregulated sFlt-1 expression may share a common pathogenic pathway with preterm preeclampsia. This subgroup is worthy of additional study.