Urinary and Serum Angiogenic Markers in Women With Preexisting Diabetes During Pregnancy and Their Role in Preeclampsia Prediction

Abstract

OBJECTIVE To determine the correlation between urinary and serum placental growth factor (PlGF) and investigate the predictive value as pregnancy progresses of urinary PlGF compared with serum PlGF, soluble fms-like tyrosine kinase 1 (sFLT-1), and the sFLT-1–to–PlGF ratio for the outcome of preeclampsia in women with preexisting diabetes. RESEARCH DESIGN AND METHODS A multicenter prospective cohort study was conducted of 158 women with preexisting insulin-requiring diabetes (41 with type 1 and 117 with type 2). Urinary PlGF and serum PlGF, sFLT-1, and the sFLT-1–to–PlGF ratio were assessed four times (14, 24, 30, and 36 weeks’ gestation), and the association with the outcome of preeclampsia was investigated. RESULTS A correlation between urinary and serum PlGF was demonstrated from 24 weeks’ gestation onward (P < 0.001). At all time points, those who developed preeclampsia had lower serum PlGF levels (P < 0.05), and receiver operating characteristic curves demonstrated that serum PlGF in this cohort performed better than the serum sFLT-1–to–PlGF ratio as a predictive test for preeclampsia. Preconception HbA1c ≥6.5% (48 mmol/mol) was an important discriminative predictor for preeclampsia (P = 0.01). CONCLUSIONS This study prospectively describes the longitudinal changes in urinary PlGF alongside serum angiogenic markers throughout pregnancy in women with preexisting diabetes. We demonstrate correlation between urinary and serum PlGF and that in women with preexisting diabetes in pregnancy, serum PlGF is a better predictor of preeclampsia than the sFLT-1–to–PlGF ratio.