First-Trimester Prediction of Hypertensive Disorders in Pregnancy

This study aimed to establish a method of screening for pregnancy hypertension by a combination of maternal variables, including mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein-A, and placental growth factor in early pregnancy. The base-cohort population constituted of 7797 singleton pregnancies, including 34 case subjects who developed preeclampsia (PE) requiring delivery before 34 weeks (early PE) and 123 with late PE, 136 with gestational hypertension, and 7504 cases subjects (96.3%) who were unaffected by PE or gestational hypertension. Maternal history, uterine artery pulsatility index, mean arterial pressure, and pregnancy-associated plasma protein-A were recorded in all of the cases in the base cohort, but placental growth factor was measured only in the case-control population of 209 cases who developed hypertensive disorders and 418 controls. In each case the measured mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein-A, and placental growth factor were converted to a multiple of the expected median (MoM) after correction for maternal characteristics found to affect the measurements in the unaffected group. Early PE and late PE were associated with increased mean arterial pressure (1.15 MoM and 1.08 MoM) and uterine artery pulsatility index (1.53 MoM and 1.23 MoM) and decreased pregnancy-associated plasma protein-A (0.53 MoM and 0.93 MoM) and placental growth factor (0.61 MoM and 0.83 MoM). Logistic regression analysis was used to derive algorithms for the prediction of hypertensive disorders. It was estimated that, with the algorithm for early PE, 93.1%, 35.7%, and 18.3% of early PE, late PE, and gestational hypertension, respectively, could be detected with a 5% false-positive rate and that 1 in 5 pregnancies classified as being screen positive would develop pregnancy hypertension. This method of screening is far superior to the traditional approach, which relies entirely on maternal history.

[1]  F. Dunn,et al.  Borderline Hypertension and Obesity: Two Prehypertensive States with Elevated Cardiac Output , 1982, Circulation.

[2]  L. Giudice,et al.  Role of the IGF system in trophoblast invasion and pre-eclampsia. , 1999, Human reproduction.

[3]  Arya M. Sharma Mediastinal fat, insulin resistance, and hypertension. , 2004, Hypertension.

[4]  C. O'Herlihy,et al.  Maternal central hemodynamics in hypertensive disorders of pregnancy. , 1999, Obstetrics and gynecology.

[5]  L. Bowyer The Confidential Enquiry into Maternal and Child Health (CEMACH). Saving Mothers’ Lives: reviewing maternal deaths to make motherhood safer 2003–2005. The Seventh Report of the Confidential Enquiries into Maternal Deaths in the UK , 2008 .

[6]  Malcolm Higgs,et al.  A Framework for Action , 1988 .

[7]  Asif Ahmed,et al.  Elevated Placental Soluble Vascular Endothelial Growth Factor Receptor-1 Inhibits Angiogenesis in Preeclampsia , 2004, Circulation research.

[8]  M. Egbor,et al.  Maternal medicine: Morphometric placental villous and vascular abnormalities in early‐ and late‐onset pre‐eclampsia with and without fetal growth restriction , 2006, BJOG : an international journal of obstetrics and gynaecology.

[9]  A. Weindling,et al.  The confidential enquiry into maternal and child health (CEMACH) , 2003, Archives of disease in childhood.

[10]  R. T. Lie,et al.  Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study. , 2001, BMJ : British Medical Journal.

[11]  T. Libermann,et al.  Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. , 2003, The Journal of clinical investigation.

[12]  T. Benedetti,et al.  Maternal Hemodynamics in Normal and Preeclamptic Pregnancies: A Longitudinal Study , 1990, Obstetrics and gynecology.

[13]  J R Yates,et al.  The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[14]  K. Nicolaides,et al.  Maternal cardiac function and uterine artery Doppler at 11–14 weeks in the prediction of pre‐eclampsia in nulliparous women , 2008, BJOG : an international journal of obstetrics and gynaecology.

[15]  G. Nicocia,et al.  Adiponectin and insulin resistance in early‐ and late‐onset pre‐eclampsia , 2006, BJOG : an international journal of obstetrics and gynaecology.

[16]  L. Magee,et al.  Subclassification of Preeclampsia , 2003, Hypertension in pregnancy.

[17]  C. Oxvig,et al.  Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta. , 1994, Laboratory investigation; a journal of technical methods and pathology.

[18]  H. Tournaye,et al.  No differences in outcome after intracytoplasmic sperm injection with fresh or with frozen-thawed epididymal spermatozoa. , 1999, Human reproduction.

[19]  G. Saade,et al.  Predictors of neonatal outcome in women with severe preeclampsia or eclampsia between 24 and 33 weeks' gestation. , 2000, American journal of obstetrics and gynecology.

[20]  P Wicker,et al.  Framework for action. , 1992, The British journal of theatre nursing : NATNews : the official journal of the National Association of Theatre Nurses.

[21]  Maternal Cardiac Output Between 11 and 13 Weeks of Gestation in the Prediction of Preeclampsia and Small for Gestational Age , 2008, Obstetrics and gynecology.

[22]  R. J. Harman,et al.  National Institute for clinical excellence preoperative tests: Is the consensus hard to get?: 1AP3-9 , 2007 .

[23]  R. Pijnenborg,et al.  Placental bed spiral arteries in the hypertensive disorders of pregnancy , 1991, British journal of obstetrics and gynaecology.

[24]  K. Nicolaides,et al.  Maternal serum placental growth factor at 11–13 weeks in chromosomally abnormal pregnancies , 2009, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

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

[26]  B. Sibai,et al.  The frequency and severity of placental findings in women with preeclampsia are gestational age dependent. , 2003, American journal of obstetrics and gynecology.

[27]  Kypros H Nicolaides,et al.  An integrated model for the prediction of preeclampsia using maternal factors and uterine artery Doppler velocimetry in unselected low-risk women. , 2005, American journal of obstetrics and gynecology.

[28]  K. Lim,et al.  Circulating angiogenic factors and the risk of preeclampsia. , 2004, The New England journal of medicine.

[29]  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.

[30]  K. Kagan,et al.  Screening for trisomy 21 by maternal age, fetal nuchal translucency thickness, free beta‐human chorionic gonadotropin and pregnancy‐associated plasma protein‐A , 2008, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[31]  D. Wright,et al.  First‐trimester screening for trisomy 21 by free beta‐human chorionic gonadotropin and pregnancy‐associated plasma protein‐A: impact of maternal and pregnancy characteristics , 2008, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[32]  N. Wessel,et al.  Predictive Value of Maternal Angiogenic Factors in Second Trimester Pregnancies With Abnormal Uterine Perfusion , 2007, Hypertension.

[33]  K. Nicolaides,et al.  UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10–14 weeks of gestation , 1998, The Lancet.

[34]  B V Howard,et al.  Relations of Stroke Volume and Cardiac Output to Body Composition: The Strong Heart Study , 2001, Circulation.

[35]  K. Kagan,et al.  First-Trimester Screening for Trisomy 21 by Free Beta-Human Chorionic Gonadotropin and Pregnancy-Associated Plasma Protein-A : Impact of Maternal and Pregnancy Characteristics , 2008 .

[36]  Cemach Saving mothers' lives: reviewing maternal deaths to make motherhood safer - 2003-2005 , 2007 .

[37]  C. Labarrere,et al.  Inadequate maternal vascular response to placentation in pregnancies complicated by preeclampsia and by small‐for‐gestational‐age infants , 1987, British journal of obstetrics and gynaecology.

[38]  K. Nicolaides,et al.  Mean Arterial Pressure at 11+0 to 13+6 Weeks in the Prediction of Preeclampsia , 2008, Hypertension.

[39]  Kirsten Duckitt,et al.  Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies , 2005, BMJ : British Medical Journal.

[40]  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.

[41]  S. Cicero,et al.  Uterine artery Doppler at 11–14 weeks of gestation in chromosomally abnormal fetuses , 2001, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[42]  T. Khong,et al.  Inadequate maternal vascular response to placentation in pregnancies complicated by pre‐eclampsia and by small‐for‐gestational age infants , 1986 .

[43]  I. Macgillivray,et al.  The classification and definition of the hypertensive disorders of pregnancy. , 1988, American journal of obstetrics and gynecology.