Leona Poon

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.

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.

Maternal risk factors for hypertensive disorders in pregnancy: a multivariate approach

The study aimed to develop prediction algorithms for hypertensive disorders based on multivariate analysis of factors from the maternal history and compare the estimated performance of such algorithms in the prediction of early preeclampsia (PE), late-PE and gestational hypertension (GH) with that recommended by the National Institute for Clinical Excellence (NICE). Logistic regression analysis was used to determine which of the maternal characteristics and history had significant contribution in predicting early-PE, late-PE and GH. There were 37 cases with early-PE, 128 with late-PE, 140 with GH and 8061 cases that were unaffected by PE or GH. Predictors of early-PE were Black race, chronic hypertension, prior PE and use of ovulation drugs. Predictors of late-PE and GH were increased maternal age and body mass index, and family history or history of PE. Additionally, late-PE was more common in Black, Indian and Pakistani women. The detection rates of early-PE, late-PE and GH in screening by maternal factors were 37.0, 28.9 and 20.7%, respectively, for a 5% false positive rate. Screening as suggested by NICE would have resulted in a false positive rate of 64.1% with detection rates of 89.2, 93.0 and 85.0% for early-PE, late-PE and GH, respectively. Meaningful screening for hypertensive disorders in pregnancy by maternal history necessitates the use of algorithms derived by logistic regression analysis.

First‐trimester maternal serum pregnancy‐associated plasma protein‐A and pre‐eclampsia

To examine the relationship between low maternal serum pregnancy‐associated plasma protein‐A (PAPP‐A) and uterine artery pulsatility index (UtA‐PI) at 11 + 0 to 13 + 6 weeks with subsequent development of pre‐eclampsia (PE).

Meta‐analysis of second‐trimester markers for trisomy 21

To summarize by meta‐analysis the accumulated data on the screening performance of second‐trimester sonographic markers for fetal trisomy 21.

Combined screening for preeclampsia and small for gestational age at 11-13 weeks.

Objective: To combine a specific algorithm for small for gestational age (SGA) without preeclampsia (PE) and another algorithm for PE in the prediction of SGA and PE. Methods: This was a screening study of singleton pregnancies at 11–13 weeks including 1,426 (2.3%) that subsequently developed PE, 3,168 (5.1%) that delivered SGA neonates and 57,458 that were unaffected by PE and SGA. We developed a prediction algorithm for SGA requiring delivery before 37 weeks’ gestation (preterm-SGA) from maternal characteristics, uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein-A and placental growth factor multiple of the median values. We then examined the performance of this algorithm individually and in combination with a previously reported algorithm for early-PE in the prediction of SGA and PE. Results: When screen positivity was defined by risk cutoff of 1:200 using the algorithm for early-PE and the risk cutoff of 1:150 using the algorithm for preterm-SGA, the false positive rate was 10.9% and the detection rates of early-PE, late-PE, preterm-SGA and term-SGA were 95.3, 45.6, 55.5 and 44.3%, respectively. Conclusions: Effective first-trimester screening for early-PE and preterm-SGA can be provided by the combined use of the specific algorithms.

Fetal Fraction in Maternal Plasma Cell-Free DNA at 11-13 Weeks' Gestation: Effect of Maternal and Fetal Factors

Objective: It was the aim of this study to examine the possible effects of maternal and fetal characteristics on the fetal fraction in maternal plasma cell-free DNA (cfDNA) at 11–13 weeks’ gestation. Methods: In a nested case-control study, cfDNA was extracted from maternal plasma obtained before chorionic villous sampling from 300 euploid, 50 trisomy 21 and 50 trisomy 18 pregnancies at 11–13 weeks’ gestation. Chromosome-selective sequencing of maternal cfDNA non-polymorphic and polymorphic loci, where fetal alleles differ from maternal alleles, was used to determine the proportion of DNA which is of fetal origin. Multivariate regression analysis was used to determine which of the factors amongst maternal weight, racial origin, smoking status, plasma storage time, serum pregnancy-associated plasma protein (PAPP)-A and free β-subunit of human chorionic gonadotropin (β-hCG), fetal crown-rump length, nuchal translucency thickness, gender and karyotype were significant predictors of the fetal fraction. Results: Significant independent prediction of fetal fraction was provided by maternal weight, serum PAPP-A and serum free β-hCG multiples of the median, but not by other maternal characteristics, fetal karyotype, crown-rump length or nuchal translucency thickness. Fetal fraction increased with serum metabolite levels and decreased with maternal weight. Conclusions: The fetal fraction in maternal plasma cfDNA increases with serum PAPP-A and free β-hCG and decreases with maternal weight.

Hypertensive disorders in pregnancy: screening by uterine artery Doppler imaging and blood pressure at 11-13 weeks

To examine the performance of screening for hypertensive disorders in pregnancy at 11–13 weeks by a combination of the maternal history, uterine artery Doppler imaging and blood pressure.

Hypertensive disorders in pregnancy: combined screening by uterine artery Doppler, blood pressure and serum PAPP‐A at 11–13 weeks

To explore if the addition of pregnancy‐associated plasma protein‐A (PAPP‐A) to maternal factors and biophysical markers yields a significant improvement in the detection of hypertensive disorders before the clinical onset of disease.

A Competing Risks Model in Early Screening for Preeclampsia

Objective: It was the aim of this study to develop models for the prediction of preeclampsia (PE) based on maternal characteristics and biophysical markers at 11–13 weeks’ gestation in which 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%) cases that subsequently developed PE and 57,458 cases 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 the uterine artery pulsatility index (PI) and the mean arterial pressure (MAP), using multiple of the median values. Results: The risk for PE increased with maternal age, weight, Afro-Caribbean and South Asian racial origin, previous pregnancy with PE, conception by in vitro fertilization and a medical history of chronic hypertension, type 2 diabetes mellitus as well as systemic lupus erythematosus or antiphospholipid syndrome. In pregnancies with PE, there was an inverse correlation between multiple of the median values of the uterine artery PI and MAP with gestational age at delivery. Screening by maternal characteristics, uterine artery PI and MAP detected 90% of PE cases requiring delivery before 34 weeks and 57% of all PE cases at a fixed false-positive rate of 10%. Conclusions: A new model has been developed for effective first-trimester screening for PE.