The role of angiogenic and antiangiogenic factors in the second trimester in the prediction of preeclampsia in pregnant women with type 1 diabetes.
OBJECTIVE
To assess the association between circulating angiogenic and antiangiogenic factors in the second trimester and risk of preeclampsia in women with type 1 diabetes.


METHODS
Maternal plasma concentrations of placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), and soluble endoglin (sEng) were available at 26 weeks of gestation in 540 women with type 1 diabetes enrolled in the Diabetes and Preeclampsia Intervention Trial.


RESULTS
Preeclampsia developed in 17% of pregnancies (n = 94). At 26 weeks of gestation, women in whom preeclampsia developed later had significantly lower PlGF (median [interquartile range]: 231 pg/mL [120-423] vs. 365 pg/mL [237-582]; P < 0.001), higher sFlt-1 (1,522 pg/mL [1,108-3,393] vs. 1,193 pg/mL [844-1,630] P < 0.001), and higher sEng (6.2 ng/mL [4.9-7.9] vs. 5.1 ng/mL[(4.3-6.2]; P < 0.001) compared with women who did not have preeclampsia. In addition, the ratio of PlGF to sEng was significantly lower (40 [17-71] vs. 71 [44-114]; P < 0.001) and the ratio of sFlt-1 to PlGF was significantly higher (6.3 [3.4-15.7] vs. 3.1 [1.8-5.8]; P < 0.001) in women who later developed preeclampsia. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to a logistic model containing established risk factors (area under the curve [AUC], 0.813) significantly improved the predictive value (AUC, 0.850 and 0.846, respectively; P < 0.01) and significantly improved reclassification according to the integrated discrimination improvement index (IDI) (IDI scores 0.086 and 0.065, respectively; P < 0.001).


CONCLUSIONS
These data suggest that angiogenic and antiangiogenic factors measured during the second trimester are predictive of preeclampsia in women with type 1 diabetes. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to established clinical risk factors significantly improves the prediction of preeclampsia in women with type 1 diabetes.
Corresponding author: Valerie A. Holmes, v.holmes@qub.ac.uk.
Valerie A
VA
Holmes
Ian S
IS
Young
Christopher C
CC
Patterson
Michael J A
MJ
Maresh
Donald W M
DW
Pearson
James D
JD
Walker
David R
DR
McCance
D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D006801:Humans; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011262:Pregnancy Trimester, Second / Q000097:blood*; D012307:Risk Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1