Pre-eclampsia affects 2 -3% of pregnancies in industrialized countries and up to 10% of all pregnancies in developing countries. Worldwide, pre-eclampsia is responsible for up to 500,000 maternal deaths per year. It is one of the major causes of maternal admissions to hospitals and is linked to 10 % stillbirths and 15 % preterm births. Predicting pre-eclampsia early would save lives and be an extremely valuable asset for obstetrics. There are multiple markers of pre-eclampsia, some can be identified very early in the pregnancy, while others cannot be measured until after the first trimester. The optimal timing for the evaluation of markers is being debated. Most markers are sensitive in the second trimester.
One of the primary risk factors for pre-eclampsia is a history of previous pre-eclampsia. Other risk factors include: body mass index of at least 35 kg/m2, pre-gestational diabetes, multiple pregnancies, and age of 40 and above. Pre-eclampsia is also more prevalent in women with black ethnicity.
Some biochemical markers that appear to be important pre-eclampsia indicators include: first-trimester pregnancy-associated plasma protein A (PAPP-A), second-trimester nonconjugated estriol, alpha-fetoprotein and beta-human chorionic gonadotropin (hCG). Placental protein-13 (PP13) has also been evaluated for the prediction of pre-eclampsia in the first trimester. Another group of analytes that have been tested are the angiogenic factors: placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), vascular endothelial growth factor and soluble endoglin (sEng).
Alone, many of these early markers have limited diagnostic performance but combining markers and evaluating the ratio of one compound to the other e.g. PlGF/sEng, in addition to measuring changes between the first and second trimester, has shown better predictability.
Uterine artery Doppler evaluation has shown acceptable diagnostic performance for pre-eclampsia. The approach of first trimester determination of biochemical markers followed by second trimester uterine artery Doppler has also been evaluated in several studies from the same group. Sequential first trimester measurement of inhibin A, activin A or ADAM-12 (a metalloprotease) followed by second trimester Doppler evaluation showed a detection rate for pre-eclampsia of about 65%.
While the pre-eclampsia remains a difficult condition to predict, combining current tests, especially for women with other risk factors may offer the best way forward.
Insights and Conclusion
The authors of the current study provide several important insights and conclusions:
1. Pre-eclampsia is an important health problem with a recognizable latent stage.
2. No single test predicts this condition with sufficient accuracy to be clinically useful.
3. Combining several tests into multi-parametric models can result in the early identification of a vast majority of cases bound to develop early pre-eclampsia.
Bottom line, more research is needed.