How to effectively manage Pre-eclampsia during whole pregnancy?

Pre-eclampsia is a multisystem, life-threatening pregnancy related disorder, with an incidence reaching 2-8% of pregnancies¹. It is usually defined by the new onset of hypertension and proteinuria, before the 20th week of gestation. This disease may lead to severe short-term complications (HELLP-syndrome, eclampsia), as well as to long-term complications (increased risk for cardiac and other complications later in life).

Although the cause of pre-eclampsia remains unclear, an imbalance of the angiogenic factors Placental Growth Factor (PlGF) and soluble FMS-like Tyrosine Kinase (sFlt-1) seems to induce endothelium dysfunction and therefore may initiate the disease.

Pre-eclampsia can be classified as early-onset pre-eclampsia² (clinical onset of disease <34 weeks of gestation; Rapid progression, multiple complications), or as late-onset pre-eclampsia² (clinical onset of disease >37 weeks of gestation; Impact on fetus less severe).

Regarding the early-onset pre-eclampsia, it is nowadays possible to predict it and take the necessary measures to reduce its incidence.

Results from the ASPRE Study^3,4 showed that women at risk to develop the disease may benefit from low-dose aspirin (75-150 mg/day) intake. If prevention with aspirin starts prior to the 16th week of gestation, incidence of pre-eclampsia may be reduced by 50-90%.

To identify women at risk, first trimester pre-eclampsia screening must be performed, using a combination of maternal risk factors, multiple biophysical and biochemical measurements.

Pre-eclampsia screening performance achieves a detection rate >90% at a false positive rate of 10%⁵.

Risk assessment for fetal trisomies and maternal pre-eclampsia can be performed at the same time, using the same blood draw.

What about women who could not benefit from a pre-eclampsia screening at first trimester of pregnancy?

Here, making a clear diagnosis is key. Later on in pregnancy, 10% of pregnant women show unspecific signs and symptoms of pre-eclampsia and only one fifth of them is actually developing pre-eclampsia⁶.As assessment of blood pressure and proteinuria alone offer a poor sensitivity and specificity in predicting pre-eclampsia^{7, 8}, the diagnostic standard can significantly improve by adding sFlt-1 and PlGF serum measurement.

Indeed, as separation of curves of healthy vs pre-eclamptic pregnancy is already showing from week 8, PlGF is a perfect biomarker for first trimester pre-eclampsia screening as well as pre-eclampsia diagnosis >20 weeks. Differences in sFlt-1 levels are starting to show after week 20, which makes sFlt-1 the perfect partner for PlGF in the diagnosis of pre-eclampsia > week 20.

Women with hypertension due to pre-eclampsia have a significantly higher sFlt-1/PlGF ratio than women with any other form of hypertensive disorder. Therefore, the sFlt-1/PlGF ratio improves pre-eclampsia diagnosis and clearly helps differentiating between pre-eclampsia and other forms of hypertensive disorders⁹.

Women with any subsequent adverse outcome due to pre-eclampsia have a significantly higher sFlt-1/PlGF ratio than women with no complications^{10, 11}. Therefore, sFlt-1/PlGF ratio enables short-term prognosis in pre-eclamptic women. It also improves preparation time for delivery if needed^{10, 11} and outbalancing of maternal risk vs fetal prematurity.

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References:

1. The World Health Report 2005; p62
2. Akolekar R et al. Prenat Diagn 2011; 31: 66-74
3. Bujold E et al. J Obstet Gynaecol 2010; 116: 402-14
4. Park et al. Ultrasound Obstet Gynecol 2015; 46(4): 419-23
5. Poon LCY et al. Hypertension 2009; 53: 812-818
6. Milne et al. BMJ 2009; 339: b3129
7. Verlohren et al.Clin Sci 2012; 122(2): 43-52
8. Zhang et al. Obstet Gyneol 2001; 97: 261-7
9. Verlohren et al. Am J Obstet Gynecol 2010; 202: 161.e1-11
10. Rana et al. Circulation 2012; 125 (7): 911-9
11. Salahuddin et al. Hypert Pregn 2016; 35(3): 330-45