An elevated maternal plasma, but not amniotic fluid, soluble fms-like tyrosine kinase-1 (sFlt-1) at the time of mid-trimester genetic amniocentesis is a risk factor for preeclampsia.
OBJECTIVE
The purpose of this study was to determine if an elevated concentration of soluble fms-like tyrosine kinase-1(sFlt-1) in maternal plasma and amniotic fluid is a risk factor for the subsequent development of preeclampsia.


METHODS
A case-control study was conducted to compare mid-trimester concentrations of maternal plasma and amniotic fluid sFlt-1 in patients who developed preeclampsia with those who did not. The study included 32 cases with preeclampsia (18 cases: severe preeclampsia) and 128 matched controls with normal outcomes. Patients with an abnormal fetal karyotype or major anomaly, multiple pregnancies, chronic hypertension, diabetes, and renal disease were excluded. Soluble Flt-1 concentration was measured by specific immunoassay. Nonparametric techniques were used for statistical analysis.


RESULTS
1) The median maternal plasma, but not amniotic fluid, sFlt-1 concentration in patients who developed preeclampsia was significantly higher than in the control cases (maternal plasma: median 730 pg/mL, range 60-3375 pg/mL vs median 441 pg/mL, range 58-1959 pg/mL, P < .05; amniotic fluid: median 10,504 pg/mL, range 5253-38,023 pg/mL vs median 10,236 pg/mL, range 4326-87,684 pg/mL, P = .65). 2) The median plasma concentration of sFlt-1 was higher in cases of severe preeclampsia than in those with mild preeclampsia without reaching statistical significance (median 762 pg/mL, range 261-3309 pg/mL vs median 334 pg/mL, range 60-3375 pg/mL; P = .07). However, there was no significant difference in the median amniotic fluid sFlt-1 concentrations between patients with severe preeclampsia and those with mild preeclampsia (P = .45). 3) An elevated maternal plasma sFlt-1 concentration (higher than 700 pg/mL) is a risk factor for the development of preeclampsia (OR 3.9, 95% CI 1.7-8.6) and severe preeclampsia (OR 7.4, 95% CI 2.5-22.1) after genetic amniocentesis. 4) The median interval from amniocentesis to the diagnosis of preeclampsia in patients with maternal plasma sFlt-1 concentrations higher than 700 pg/mL was 117 days (range 19-154 days).


CONCLUSIONS
An elevated concentration of sFlt-1 in maternal plasma at the time of mid-trimester amniocentesis is a risk factor for the subsequent development of preeclampsia.
Park
Chan-Wook
CW
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
Park
Joong Shin
JS
Shim
Soon-Sup
SS
Jun
Jong Kwan
JK
Yoon
Bo Hyun
BH
Romero
Roberto
R
D000328:Adult; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000737:chemistry*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000097:blood* / Q000453:epidemiology; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011506:Proteins / Q000032:analysis*; D012307:Risk Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis* / Q000097:blood
D011506:Proteins; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1