The Role of Angiogenic and Antiangiogenic Factors in the Second Trimester in the Prediction of Preeclampsia in Pregnant Women With Type 1 Diabetes
- Valerie A. Holmes, PHD1⇑,
- Ian S. Young, MD1,
- Christopher C. Patterson, PHD1,
- Michael J.A. Maresh, MD2,
- Donald W.M. Pearson, MD3,
- James D. Walker, MD4,
- David R. McCance, MD5,
- for the Diabetes and Preeclampsia Intervention Trial (DAPIT) Study Group
- 1Centre for Public Health, School of Medicine, Dentistry, and Biomedical Sciences, Queen’s University Belfast, Belfast, United Kingdom
- 2Department of Obstetrics, St. Mary’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
- 3Department of Diabetes, Aberdeen Royal Infirmary, Aberdeen, United Kingdom
- 4Department of Diabetes, St. John’s Hospital at Howden, West Lothian, United Kingdom
- 5Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, United Kingdom
- Corresponding author: Valerie Holmes, .
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.
RESEARCH DESIGN AND 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.
- Received April 22, 2013.
- Accepted May 31, 2013.
- © 2013 by the American Diabetes Association.
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