Serum Inhibin A And Angiogenic Factor Levels In Pregnancies With Previous Preeclampsia And/or Chronic Hypertension: Are They Useful Markers For Prediction Of Subsequent Preeclampsia?

Objective: Our objective was to determine whether measurement of placenta growth factor (PLGF), inhibin A, or soluble fms-like tyrosine kinase-1 (sFlt-1) at 2 times during pregnancy would usefully predict subsequent preeclampsia (PE) in women at high risk. Study Design: We analyzed serum obtained at enrollment (120/7 to 196/7 weeks) and follow-up (24-28 weeks) from 704 patients with previous PE and/or chronic hypertension (CHTN) enrolled in a randomized trial for the prevention of PE. Logistic regression analysis assessed the association of log-transformed markers with subsequent PE; receiver operating characteristic analysis assessed predictive value. Results: One hundred four developed preeclampsia: 27 at 37 weeks or longer and 77 at less than 37 weeks (9 at less than 27 weeks). None of the markers was associated with PE at 37 weeks or longer. Significant associations were observed between PE at less than 37 weeks and reduced PLGF levels at baseline (P = .022) and follow-up (P < .0001) and elevated inhibin A (P < .0001) and sFlt-1 (P = .0002) levels at follow-up; at 75% specificity, sensitivities ranged from 38% to 52%. Using changes in markers from baseline to follow-up, sensitivities were 52-55%. Associations were observed between baseline markers and PE less than 27 weeks (P ≤ .0004 for all); sensitivities were 67-89%, but positive predictive values (PPVs) were only 3.4-4.5%. Conclusion: Inhibin A and circulating angiogenic factors levels obtained at 120/7 to 196/7 weeks have significant associations with onset of PE at less than 27 weeks, as do levels obtained at 24-28 weeks with onset of PE at less than 37 weeks. However, because the corresponding sensitivities and/or PPVs were low, these markers might not be clinically useful to predict PE in women with previous PE and/or CHTN. © 2008 Mosby, Inc. All rights reserved.1993268.e1268.e9Sibai, B.M., Diagnosis and management of gestational hypertension and preeclampsia (2003) Obstet Gynecol, 102, pp. 181-192Poston, L., Briley, A.L., Seed, P.T., Kelly, F.J., Shennan, A.H., Vitamins in preeclampsia (VIP) trial consortium. Vitamin C and vitamin E in pregnant women at risk for preeclampsia (VIP trial): randomized placebo-controlled trial (2006) Lancet, 367, pp. 1145-1154Spinnato, J.P., Friere, S., e Silva, J.L.P., Antioxidant therapy to prevent preeclampsia: A randomized controlled trial (2007) Obstet Gynecol, 110, pp. 1311-1318Conde-Agudelo, A., Villar, J., Lindheimer, M., World Health Organization systematic review of screening tests for preeclampsia (2004) Obstet Gynecol, 104, pp. 1367-1391Flario, P., Reis, F.M., Pezzani, I., Luisi, S., Severi, F.M., Petraglia, F., The addition of activin A and inhibin A measurement to uterine artery Doppler velocimetry to improve early prediction pre-eclampsia (2003) Ultrasound Obstet Gynecol, 21, pp. 165-169Spencer, K., Yu, C.K.H., Savvidou, N., Papageorghiou, A.T., Nicolaides, K.H., Prediction of pre-eclampsia by uterine artery Doppler ultrasonography and maternal serum pregnancy-associated plasma protein-A, free B-human chorionic gonadotropin, activin A and inhibin A at 22+0 to 24+6 weeks' gestation (2006) Ultrasound Obstet Gynecol, 27, pp. 658-663Chaiworapongsa, T., Romero, R., Espinoza, J., Evidence supporting a role for blockade of the vascular endothelial growth factor system in the pathophysiology of preeclampsia (2004) Am J Obstet Gynecol, 190, pp. 1541-1550Levine, F.J., Maynard, S.E., Qian, C., Circulating angiogenic factors and the risk of preeclampsia (2004) N Engl J Med, 350, pp. 672-683Levine, R.J., Lam, C., Qian, C., Soluble endoglin and other circulating angiogenic factors in preeclampsia (2006) N Engl J Med, 355, pp. 992-1005Widmer, M., Villar, J., Benigni, A., Mapping the theory of preeclampsia and the role of angiogenic factors: A systemic review (2007) Obstet Gynecol, 109, pp. 168-180Wathen, K.A., Tuutti, E., Stenman, U.H., Maternal serum-soluble vascular endothelia growth factor receptor-1 in early pregnancy ending in preeclampsia or intrauterine growth retardation (2006) J Clin Endocrinol Metab, 91, pp. 180-184Vatten, L.J., Eskild, A., Nilsen, T.I.L., Changes in circulating level of angiogenic factors from the first to second trimester as predictors of preeclampsia (2007) Am J Obstet Gynecol, 196, p. 239. , e1-6Smith, G.C.S., Crossley, J.A., Aitken, D.A., Circulating angiogenic factors in early pregnancy and the risk of preeclampsia, intrauterine growth restriction, spontaneous preterm birth, and stillbirth (2007) Obstet Gynecol, 109, pp. 1316-1324Espinoza, J., Romero, R., Nien, J.K., Identification of patients at risk for early onset and/or severe preeclampsia with the use of uterine artery Doppler velocimetry and placental growth factor (2007) Am J Obstet Gynecol, 196, p. 326. , e1-13Stepan, H., Unversucht, A., Wessel, N., Faber, R., Predictive value of maternal angiogenic factors in second trimester pregnancies with abnormal uterine perfusion (2007) Hypertension, 49, pp. 818-824Rana, S., Karumanchi, A., Levine, R.J., Sequential changes in antiangiogenic factors in early pregnancy and risk of developing preeclampsia (2007) Hypertension, 50, pp. 137-142Unal, E.R., Robinson, C.J., Johnson, D.D., Chang, E.Y., Second-trimester angiogenic factors as biomarkers for future-onset preeclampsia (2007) Am J Obstet Gynecol, 197, p. 211. , e1-4Moore Simas, T.A., Crawford, S.L., Solitro, M.J., Angiogenic factors for the prediction of preeclampsia in high-risk women (2007) Am J Obstet Gynecol, 197, p. 244. , e1-8Hosmer, D.W., Lemeshow, S., (2000) Applied logistic regression. 2nd ed, , John Wiley & Sons, New York (NY)Ruttimann, U.E., Statistical approaches to development and validation of predictive instruments (1994) Crit Care Clin, 10, pp. 19-3