Competing Risks Model in Early Screening for Preeclampsia by Biophysical and Biochemical Markers

Objective: To develop models for prediction of preeclampsia (PE) based on maternal characteristics, biophysical and biochemical markers at 11–13 weeks’ gestation in which the gestation at the time of delivery for PE is treated as a continuous variable. Methods: This was a screening study of singleton pregnancies at 11–13 weeks including 1,426 (2.4%) that subsequently developed PE and 57,458 that were unaffected by PE. We developed a survival time model for the time of delivery for PE in which Bayes’ theorem was used to combine the prior information from maternal characteristics with uterine artery pulsatility index (PI), mean arterial pressure (MAP), serum pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PLGF) multiple of the median (MoM) values. Results: In pregnancies with PE, there was a linear correlation between MoM values of uterine artery PI, MAP, PAPP-A and PLGF with gestational age at delivery and therefore the deviation from normal was greater for early than late PE for all four biomarkers. Screening by maternal characteristics, biophysical and biochemical markers detected 96% of cases of PE requiring delivery before 34 weeks and 54% of all cases of PE at a fixed false-positive rate of 10%. Conclusions: A new model has been developed for effective first-trimester screening for PE.

[1]  D. Wright,et al.  First‐trimester combined screening for trisomy 21 at 7–14 weeks' gestation , 2010, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[2]  J. Fleming,et al.  A CRITICAL EVALUATION OF SONAR “CROWN‐RUMP LENGTH” MEASUREMENTS , 1975, British journal of obstetrics and gynaecology.

[3]  D. Wright,et al.  Maternal Serum Placental Growth Factor in Prospective Screening for Aneuploidies at 8–13 Weeks’ Gestation , 2012, Fetal Diagnosis and Therapy.

[4]  François Audibert,et al.  Prevention of Preeclampsia and Intrauterine Growth Restriction With Aspirin Started in Early Pregnancy: A Meta-Analysis , 2010, Obstetrics and gynecology.

[5]  K. Nicolaides,et al.  Protocol for Measurement of Mean Arterial Pressure at 11-13 Weeks' Gestation , 2012, Fetal Diagnosis and Therapy.

[6]  J. Kalbfleisch,et al.  The Statistical Analysis of Failure Time Data , 1980 .

[7]  D. Wright,et al.  A Competing Risks Model in Early Screening for Preeclampsia , 2012, Fetal Diagnosis and Therapy.

[8]  K. Nicolaides,et al.  Maternal serum placental protein 13 at 11–13 weeks of gestation in preeclampsia , 2009, Prenatal diagnosis.

[9]  K. Nicolaides,et al.  Maternal serum placental growth factor at 11 + 0 to 13 + 6 weeks of gestation in the prediction of pre‐eclampsia , 2008, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[10]  Argyro Syngelaki,et al.  Prediction of early, intermediate and late pre‐eclampsia from maternal factors, biophysical and biochemical markers at 11–13 weeks , 2011, Prenatal diagnosis.

[11]  Lelia Duley,et al.  The global impact of pre-eclampsia and eclampsia. , 2009, Seminars in perinatology.

[12]  K. Nicolaides,et al.  Maternal plasma pentraxin 3 at 11 to 13 weeks of gestation in hypertensive disorders of pregnancy , 2009, Prenatal diagnosis.

[13]  J. Spencer-Jones,et al.  Make every mother and child count. , 2005, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[14]  F. Chantraine,et al.  Maternal plasma soluble endoglin at 11–13 weeks' gestation in pre‐eclampsia , 2010, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[15]  John D. Kalbfleisch,et al.  The Statistical Analysis of Failure Data , 1986, IEEE Transactions on Reliability.

[16]  Yves Giguère,et al.  Early Administration of Low-Dose Aspirin for the Prevention of Severe and Mild Preeclampsia: A Systematic Review and Meta-Analysis , 2012, American Journal of Perinatology.

[17]  Peter E. Hilsenrath,et al.  The World Health Report 2000 , 2002 .

[18]  Jean-Marie Moutquin,et al.  The Classification and Diagnosis of the Hypertensive Disorders of Pregnancy: Statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP) , 2001, Hypertension in pregnancy.

[19]  K. Nicolaides,et al.  Birthweight with Gestation and Maternal Characteristics in Live Births and Stillbirths , 2012, Fetal Diagnosis and Therapy.

[20]  K. Nicolaides,et al.  Maternal Plasma P-selectin at 11 to 13 Weeks of Gestation in Hypertensive Disorders of Pregnancy , 2011, Hypertension in pregnancy.

[21]  K. Nicolaides,et al.  Maternal plasma inhibin A at 11–13 weeks of gestation in hypertensive disorders of pregnancy , 2009, Prenatal diagnosis.

[22]  M. Tuuli,et al.  First‐trimester assessment of placenta function and the prediction of preeclampsia and intrauterine growth restriction , 2010, Prenatal diagnosis.

[23]  Cemach Confidential Enquiry into Maternal and Child Health , 2005 .

[24]  K. Kagan,et al.  Screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency, fetal heart rate, free beta-hCG and pregnancy-associated plasma protein-A. , 2008, Human reproduction.

[25]  B. Cohen,et al.  Abnormal placentation, angiogenic factors, and the pathogenesis of preeclampsia. , 2010, Obstetrics and gynecology clinics of North America.

[26]  K. Nicolaides,et al.  Uterine artery Doppler at 11 + 0 to 13 + 6 weeks in the prediction of pre‐eclampsia , 2007, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[27]  Kypros H Nicolaides,et al.  First-Trimester Prediction of Hypertensive Disorders in Pregnancy , 2009, Hypertension.

[28]  K. Nicolaides,et al.  Maternal Serum Activin A at 11–13 Weeks of Gestation in Hypertensive Disorders of Pregnancy , 2009, Fetal Diagnosis and Therapy.

[29]  K. Nicolaides Turning the Pyramid of Prenatal Care , 2011, Fetal Diagnosis and Therapy.

[30]  L. Shulman First-trimester maternal serum pregnancy-associated plasma protein-A and pre-eclampsia , 2009 .