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

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.