Melissa Spiel1, Saira Salahuddin2, Elizabeth Pernicone3, Zsuzsanna Zsengeller4, Alice Wang5, Anna M Modest1, S Ananth Karumanchi2, Jonathan L Hecht6. 1. Department of Obstetrics & Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA. 2. Department of Obstetrics & Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA. 3. Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA. 4. Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA; Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA. 5. Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA; Department of Medicine, Boston University School of Medicine, One Medical Center Place, Boston, MA 02118, USA. 6. Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA. Electronic address: jlhecht@BIDMC.harvard.edu.
Abstract
INTRODUCTION: Soluble 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. METHODS: Clinical and histologic data were compared between groups with high or low sFLT-1 expression determined by immunohistochemistry on archived placentas. RESULTS: Nineteen 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). DISCUSSION: Placental 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.
INTRODUCTION: Soluble 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. METHODS: Clinical and histologic data were compared between groups with high or low sFLT-1 expression determined by immunohistochemistry on archived placentas. RESULTS: Nineteen 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). DISCUSSION: Placental 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.
Authors: Anna M Modest; Louisa H Smith; Thomas L Toth; Ai-Ris Y Collier; Michele R Hacker Journal: Paediatr Perinat Epidemiol Date: 2022-01-04 Impact factor: 3.980
Authors: Carlo Rossi; Mark Lees; Vedanta Mehta; Tommi Heikura; John Martin; Ian Zachary; Rebecca Spencer; Donald M Peebles; Robert Shaw; Minna Karhinen; Seppo Yla-Herttuala; Anna L David Journal: Hum Gene Ther Date: 2020-11 Impact factor: 5.695