First-Trimester Maternal Serum Levels of sFLT1, PGF and ADMA Predict Preeclampsia

Abstract

BACKGROUND: Placental growth factor (PGF), soluble fms-like tyrosine kinase 1 (sFLT1) and asymmetric dimethylarginine (ADMA) are involved in the pathogenesis of preeclampsia. Abnormal maternal sFLT1, PGF and ADMA levels are detectable weeks before the onset of preeclampsia. OBJECTIVE: To investigate sFLT1, PGF and ADMA in the first trimester of pregnancy as predictors of preeclampsia. METHODS: In this prospective nested case-control study, 740 pregnant women enrolled at 12-16 weeks of gestation and followed up until 6 weeks after delivery at the Shanghai First Maternity and Infant Health Hospital of Tongji University between January 2010 and December 2012. Forty-four women developed preeclampsia. Urinary proteins were measured using 24-hour collection or dipsticks. sFLT1, PGF and ADMA were measured by ELISA in the first trimester. Pulsatility index (PI) was measured by Doppler ultrasound in the second trimester. RESULTS: First-trimester serum sFLT1 and ADMA levels of women who developed preeclampsia were significantly higher compared with women with normal pregnancies (sFLT1: 0.321 ± 0.023 vs. 0.308 ± 0.019 ng/ml, P = 0.001; ADMA: 0.86 ± 0.16 vs. 0.68 ± 0.20 μM, P < 0.001). First-trimester serum PGF levels of women who developed preeclampsia were significantly lower than in women with normal pregnancies (115.72 ± 32.55 vs. 217.30 ± 74.48 pg/ml, P < 0.001). Multiple logistic regression and receiver-operating characteristic curves identified first-trimester PGF and ADMA to be sensitive and selective predictors of preeclampsia (area under the curve [AUC]: 0.902), as well as second-trimester uterine artery pulse index (AUC: 0.836). CONCLUSION: In the first trimester, maternal serum sFLT1, PGF and ADMA levels, as well as second-trimester uterine artery PI, could predict preeclampsia.