ASPRE study opened a new era in the treatment of pre-eclampsia, one of the most severe gestational diseases

Pre-eclampsia¹ is an essential cause of morbility and death of the mother, fetus and newborn.  The risk is even higher when the disease is severe and starts at the early stage of pregnancy and might cause the need of preterm birth (before week 37). The problem is also actual in Estonia. 272 women got sick with pre-eclampsia in Estonia in 2016².

 

In modern obstetric care one of the greatest challenges is the detection of pregnant with high risk of pre-eclampsia and application of necessary measures to favour the placentation and decrease the occurrence rate of the disease.

 

During the last thirty years one key topic examined in obstetric care has been the prophylactic use of low-dose aspirin to prevent pre-eclampsia.

The meta-analysis of studies indicated that the use of low-dose aspirin in case of high risk pregnancies resulted only in 10% decrease in cases of pre-eclampsia³. At the same time in case of most studies aspirin was taken after the 16th gestation week with less than 100 mg a day.

 

However, the other meta-analysis⁴ indicated that when starting with use of aspirin before week 16 the rate of occurrence of pre-eclampsia has decreased by half. At the same time the use of aspirin after week 16 had no considerable effect. Also, the efficiency of aspirin depended on the dosage, by decreasing the rate of occurrence of pre-eclampsia in case of higher dose than 100 mg a day.

 

The first objective of ASPRE study⁵ was to explain whether the screening of the first trimester based on the maternal biophysical markers, anamnesis, markers received during ultrasound scan, biochemical markers of mother’s blood, can be recognized in at least 75% of cases as to the pregnant developing pre-eclampsia before gestation week 37.

 

The other objective of ASPRE study was to explain whether the prophylactic use of optimum dose of aspirin during the first gestation week to the women with higher risk of developing pre-eclampsia ending with pre-term birth can decrease the sickening by at least 50%.

 

ASPRE study is up to now the biggest prospective randomized placebo control screening carried out to examine the effect of prophylactic use of aspirin by the women with high risk of pre-eclampsia.

 

ASPRE study was carried out from June 2015 up to April 2016 under the leadership of the English professor Kypros Nicolaides and the Chinese professor Liona Poon. The screening was financed by the European Union and Fetal Medicine Foundation. The data on 26941 pregnant from England, Belgium, Italy, Spain, Greece and Israel were used in the screening.

 

 

Screening protocol

 

The cornerstone of ASPRE study was also the pre-eclampsia risk calculation programme developed by Fetal Medicine Foundation used in Loote Ultrahelikeskus based on maternal biophysical markers, anamnesis, markers received at the ultrasound scan and maternal blood biophysical markers. As a result of screening 1776 pregnant belonged to the high risk group.

 

 

150 mg aspirin was given to half of the women of high risk group at night up to gestation week 36 and placebo medicine was given to the other half of women of high risk group which did not include active substance.

 

 

Results of the study

 

The combined screening programme of the first trimester recognizes 76.7% cases of the pregnant who develop pre-eclampsia before gestation week 37 by 9.2% false positive results (138/180) and in 43.1% cases of pregnant (194/450) who developed pre-eclampsia after gestation week 37⁶.

 

The pre-term pre-eclampsia developed in aspirin group by 1.6% of pregnant (13/798) and by 4.3% of pregnant (35/822) in placebo group.

 

The agreement of patients with treatment was good: 79.9% of patients took at least 85% of the prescribed medicines.

 

ASPRE study proved:

 

When starting the prophylactic use of aspirin during the first trimester by the women belonging to the high risk group of pre-eclampsia decreased the occurrence of this severe disease before gestation week 34 by 82% and before gestation week 37 by 62%.

 

At the same time the prophylactics with aspirin did not prevent late pre-eclampsia developing after gestation week 37 by decreasing the occurrence rate of the given disease only by 5%.

 

The aspirin prophylactics by the pregnant having hypertension did not prevent the occurrence of pre-eclampsia.

 

 

Summary

 

Pre-eclampsia is an incurable disease causing pre-term birth to save the life of mother and/or fetus. At the same time pre-eclampsia starts by 0.5% of the pregnant before gestation week 34 when the child is still immature for birth.

 

The traditional pre-eclampsia screening has up to now been based on the anamnesis of pregnant women in Estonia as well as elsewhere in Europe. The given screening method has not been effective, by recognizing only 40 % of the pregnant with pre-term pre-eclampsia⁷. The treatment of pre-eclampsia has also been focused on the detection of disease in the second and third trimester of pregnancy and treatment of the women sick with pre-eclampsia ⁸ which often terminated with pre-term birth of immature child.

 

ASPRE study has conveyed a clear message that already at the beginning of the pregnancy, in the first trimester during gestation weeks 11- 13⁺⁶ OSCAR test enables to detect 76.7% of the pregnant who develop pre-eclampsia before the 37th gestation week with very high probability. If the women in the given risk group are treated with aspirin with the dosage of 150 mg, it is possible to avoid the pre-term pre-eclampsia by 62%.

 

This is long-awaited good news for the team of Loote Ultrahelikeskus who has offered OSCAR test to its patients already from the year 2011, the essential part of which is the assessment of risk of pre-eclampsia.

 

Comment

 

Dr. Marek Šois has successfully passed the theoretical training of Fetal Medicine Foundation and external audit to perform pre-eclampsia screening including ultrasound pictures. The doctor’s name has been entered to the list of audited ultrasound specialists to the website of Fetal Medicine Foundation.

 

• Loote Ultrahelikeskus offers the pre-eclampsia screening of the first trimester as the part of OSCAR test to specify these women of the risk group who could benefit from the prophylactics of low-dose aspirin.

 

• Loote Ultrahelikeskus provides pre-eclampsia screening also during the gestation weeks 20, 32 and 36 to duly detect these women with pre-eclampsia risk group whose intensive monitoring enables to duly diagnose the pre-eclampsia and thus decrease the complications of mother as well as fetus caused by pre-eclampsia.

 

Used literature

 

1. The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP.  Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 4 (2014) 97–104.
2. http://www.tai.ee/et/tegevused/registrid/meditsiiniline-sunniregister-ja-raseduskatkestusandmekogu/statistika
3. Askie LM, Duley L, Henderson-Smart DJ, Stewart LA. Antiplatelet agents for prevention of preeclampsia: a meta-analysis of individual patient data. Lancet 2007; 369: 1791-8.
4. Roberge S, Nicolaides KH, Demers S, Villa P, Bujold E. Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin: a meta-analysis. Ultrasound Obstet Gynecol 2013; 41: 491-9.
5. Rolnik DL, Wright D, Poon LC, O'Gorman N, Syngelaki A, de Paco Matallana C, Akolekar R, Cicero S, Janga D, Singh M, Molina FS, Persico N, Jani JC, Plasencia W, Papaioannou G, Tenenbaum-Gavish K, Meiri H, Gizurarson S, Maclagan K, Nicolaides KH. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med 2017 Jun 28. doi: 10.1056/NEJMoa1704559.
6. Rolnik DL, Wright D, Poon LC, O'Gorman N, Syngelaki A, de Paco Matallana C, Akolekar R, Cicero S, Janga D, Singh M, Molina FS, Persico N, Jani JC, Plasencia W, Papaioannou G, Tenenbaum-Gavish K, Meiri H, Gizurarson S, Maclagan K, Nicolaides KH. ASPRE trial: performance of screening for preterm pre-eclampsia. Ultrasound Obstet Gynecol 2017. DOI: 10.1002/uog.18816
7. National Collaborating Centre for Women’s and Children’s Health (UK). Hypertension in pregnancy: the management of hypertensive disorders during pregnancy. London: RCOG Press, 2010.
8. ENS pregnancy monitoring instruction.

 

Video of ASPRE study

 

 

 

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