TY - JOUR
T1 - A prospective cohort study of the value of maternal plasma concentrations of angiogenic and anti-angiogenic factors in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia Prediction of preeclampsia J. P. Kusanovic et al.
AU - Kusanovic, Juan Pedro
AU - Romero, Roberto
AU - Chaiworapongsa, Tinnakorn
AU - Erez, Offer
AU - Mittal, Pooja
AU - Vaisbuch, Edi
AU - Mazaki-Tovi, Shali
AU - Gotsch, Francesca
AU - Edwin, Samuel S.
AU - Gomez, Ricardo
AU - Yeo, Lami
AU - Conde-Agudelo, Agustin
AU - Hassan, Sonia S.
N1 - Funding Information:
This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National In-
PY - 2009/11/1
Y1 - 2009/11/1
N2 - Objective.Changes in the maternal plasma concentrations of angiogenic (placental growth factor PlGF and vascular endothelial growth factor (VEGF)) and anti-angiogenic factors (sEng and vascular endothelial growth factor receptor-1 (sVEGFR-1)) precede the clinical presentation of preeclampsia. This study was conducted to examine the role of maternal plasma PlGF, sEng, and sVEGFR-1 concentrations in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia. Methods. This longitudinal cohort study included 1622 consecutive singleton pregnant women. Plasma samples were obtained in early pregnancy (6-15 weeks) and midtrimester (20-25 weeks). Maternal plasma PlGF, sEng, and sVEGFR-1 concentrations were determined using sensitive and specific immunoassays. The primary outcome was the development of preeclampsia. Secondary outcomes included term, preterm, and early-onset preeclampsia. Receiving operating characteristic curves, sensitivity, specificity, positive and negative likelihood ratios, and multivariable logistic regression were applied. A p-value of <0.05 was considered significant. Results. (1) The prevalence of preeclampsia, term, preterm, (<37 weeks) and early-onset preeclampsia (<34 weeks) was 3.8 (62/1622), 2.5 (40/1622), 1.4 (22/1622) and 0.6% (9/1622), respectively; (2) Higher likelihood ratios were provided by ratios of midtrimester plasma concentrations of PlGF, sEng, and sVEGFR-1 than single analytes; (3) Individual angiogenic and anti-angiogenic factors did not perform well in the identification of preeclampsia as a whole; in particular, they perform poorly in the prediction of term preeclampsia; (4) In contrast, a combination of these analytes such as the PlGFsEng ratio, its delta and slope had the best predictive performance with a sensitivity of 100, a specificity of 98-99%, and likelihood ratios for a positive test of 57.6, 55.6 and 89.6, respectively, for predicting early-onset preeclampsia. Conclusions. (1) The PlGFsEng ratio and its delta and slope had an excellent predictive performance for the prediction of early-onset preeclampsia, with very high likelihood ratios for a positive test result and very low likelihood ratios for a negative test result; and (2) Although the positive likelihood ratios are high and the positive predictive values low, the number of patients needed to be closely followed is 4:1 for the PlGF/sEng ratio and 3:1 for the slope of PlGFsEng.
AB - Objective.Changes in the maternal plasma concentrations of angiogenic (placental growth factor PlGF and vascular endothelial growth factor (VEGF)) and anti-angiogenic factors (sEng and vascular endothelial growth factor receptor-1 (sVEGFR-1)) precede the clinical presentation of preeclampsia. This study was conducted to examine the role of maternal plasma PlGF, sEng, and sVEGFR-1 concentrations in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia. Methods. This longitudinal cohort study included 1622 consecutive singleton pregnant women. Plasma samples were obtained in early pregnancy (6-15 weeks) and midtrimester (20-25 weeks). Maternal plasma PlGF, sEng, and sVEGFR-1 concentrations were determined using sensitive and specific immunoassays. The primary outcome was the development of preeclampsia. Secondary outcomes included term, preterm, and early-onset preeclampsia. Receiving operating characteristic curves, sensitivity, specificity, positive and negative likelihood ratios, and multivariable logistic regression were applied. A p-value of <0.05 was considered significant. Results. (1) The prevalence of preeclampsia, term, preterm, (<37 weeks) and early-onset preeclampsia (<34 weeks) was 3.8 (62/1622), 2.5 (40/1622), 1.4 (22/1622) and 0.6% (9/1622), respectively; (2) Higher likelihood ratios were provided by ratios of midtrimester plasma concentrations of PlGF, sEng, and sVEGFR-1 than single analytes; (3) Individual angiogenic and anti-angiogenic factors did not perform well in the identification of preeclampsia as a whole; in particular, they perform poorly in the prediction of term preeclampsia; (4) In contrast, a combination of these analytes such as the PlGFsEng ratio, its delta and slope had the best predictive performance with a sensitivity of 100, a specificity of 98-99%, and likelihood ratios for a positive test of 57.6, 55.6 and 89.6, respectively, for predicting early-onset preeclampsia. Conclusions. (1) The PlGFsEng ratio and its delta and slope had an excellent predictive performance for the prediction of early-onset preeclampsia, with very high likelihood ratios for a positive test result and very low likelihood ratios for a negative test result; and (2) Although the positive likelihood ratios are high and the positive predictive values low, the number of patients needed to be closely followed is 4:1 for the PlGF/sEng ratio and 3:1 for the slope of PlGFsEng.
KW - Angiogenic factors
KW - Anti-angiogenic state
KW - Cohort study
KW - Early-onset preeclampsia
KW - PlGF
KW - Placental growth factor
KW - Prediction
KW - SEng
KW - SFlt-1
KW - SVEGFR-1
KW - Soluble Endoglin
KW - Uterine artery Doppler velocimetry
KW - Vascular endothelial growth factor
UR - http://www.scopus.com/inward/record.url?scp=70350320956&partnerID=8YFLogxK
U2 - 10.3109/14767050902994754
DO - 10.3109/14767050902994754
M3 - Article
AN - SCOPUS:70350320956
SN - 1476-7058
VL - 22
SP - 1021
EP - 1038
JO - Journal of Maternal-Fetal and Neonatal Medicine
JF - Journal of Maternal-Fetal and Neonatal Medicine
IS - 11
ER -