2 research outputs found
Screening for preeclampsia
Background: Preeclampsia (PE) affects 2-3% of all pregnancies and is a major
cause of maternal and perinatal morbidity and mortality. It is thought to occur due to
abnormal placentation characterised by poor trophoblastic invasion resulting in
oxidative stress and release of factors that promote endothelial dysfunction and
inflammation. The current approach of screening for PE is to identify risk factors from
maternal demographic characteristics and medical history. In the United Kingdom,
the National Institute for Health and Clinical Excellence (NICE) has issued guidelines
recommending that women should be considered to be at high risk of developing PE
if they have any 1 high-risk factor or any 2 moderate-risk factors. With this approach,
defined by NICE, at a screen positive rate of 11%, the detection rate (DR) for total
PE is 35%. Such a screening approach has two main limitations. Firstly, it does not
provide individualised, patient specific results and secondly, it does not allow the
integration of biomarkers for improving the performance of the screening test.
However, the integration of such biomarkers is essential in achieving an effective
screening strategy for PE.
Objectives: The aims of the papers included in this thesis are firstly, to identify and
quantify the effects of variables from maternal characteristics and medical history on
specific biochemical markers, secondly to present a model for standardising
biochemical marker measurements in all three trimesters of pregnancy into multiples
of the normal median (MoM) values, thirdly to summarize the distribution of MoM
values in pregnancies with normal outcomes and those that subsequently develop
PE and fourthly, to examine the potential improvement in performance of screening
for PE at 30-34 weeks’ gestation by maternal factors alone with the addition of
biophysical and biochemical markers.
Methods: The data for this thesis were derived from prospective screening of
women with singleton pregnancies attending for three routine hospital visits at 12, 22
and 32 or 36 weeks’ gestation. We have recorded a series of maternal
characteristics and history, measured the maternal weight and height as well as the
uterine artery pulsatility index (UTPI), mean arterial pressure (MAP), serum
concentration of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1
(sFLIT-1). The pregnancy outcomes were obtained from the hospital maternity
records or the general medical practitioners of the women. Bayes theorem was used to combine the a priori risk from maternal factors with various combinations of
biomarker MoM values. The potential value of biophysical and biochemical markers
in improving the performance in screening for PE were evaluated.
Results: Firstly, in pregnancies that developed PE, serum PlGF is decreased, while
sFLIT-1, MAP and UTPI were increased, secondly, the separation in MoM values
from normal is greater with earlier than later gestational age at which delivery for PE
is necessary and thirdly, the slope of the regression lines of PlGF MoM with
gestational age at delivery in pregnancies that develop PE increases with gestational
age at screening. Combined screening at 30-34 weeks’ gestation by maternal
factors, MAP, UTPI, PlGF, and sFLIT-1 predicted 98% (95% confidence interval, 88-
100%) of preterm PE and 49% (95% confidence interval, 42-57%) of term PE, at a
false positive rate of 5%.
Conclusions: This thesis has demonstrated that biophysical and biochemical
markers increase significantly the performance of screening for PE and as a result
the timing and content of clinical visits can be defined by the patient-specific risk of
developing the disease. The vast majority of women would be screened low risk and
these can follow the routine antenatal care, whereas those few who are high risk
could be directed to a more specialized pathway, where early therapeutic
interventions prophylactically may lead to the prevention of the disease and close
follow-up will reduce the adverse consequences of PE