Pre-eclampsia, also known as “toxaemia of pregnancy”, is a complication of pregnancy characterized by the development of elevated blood pressure and high protein levels in the urine. It affects about two out of 100 pregnant women. Pre-eclampsia usually occurs beyond 20 weeks of pregnancy. One of the main features of pre-eclampsia is a reduced blood flow from the mother to the placenta, resulting in an insufficient supply of oxygen and nutrients to the baby. The condition may be associated with severe short- and long-term effects for both, mother and her baby.
• Multisystem, life-threatening pregnancy-related disorder
• Incidence: In India between 8-10% of pregnancies
• Definition: New onset of hypertension and proteinuria at >20 weeks of gestation
• Short-term complications: HELPP-syndrome, eclampsia
• Long-term complications: Increased risk of cardiac and other complications later in life
Cause: The cause of pre-eclampsia is unknown, but the placenta has been identified as is the central organ in pathogenesis.
Clinical onset of disease <34 weeks of gestation
Rapid progression, multiple complications
Clinical onset of disease >37 weeks of gestation
Impact on fetus less severe
Intervention with low dose aspirin
• Use of low dose aspirin can reduce incidence of pre-eclampsia by 50-90%
• Low dose aspirin: 75-150 mg/day
• Start of aspirin therapy: <16 weeks of gestation
1.Early pre-eclampsia screening & benefits (weeks 11-13 6 Days)(FMF Approved)
• Early identification of women at risk for pre-eclampsia allows for timely intervention with low dose aspirin (<16 weeks) to significantly reduce the incidence of pre-eclampsia
• Early screening allows for closer monitoring of high-risk patients for optimal patient care. A meta-analysis has shown that the application of low- dose aspirin (<150 mg/day) started before week 16 of gestation caused a significant reduction in pre-eclampsia and intrauterine fetal growth restriction (IUGR) compared to controls, while aspirin started after 16 weeks of gestation did not. Recent prospective studies proved the efficacy of low-dose aspirin in reducing pre-eclampsia. Women identified at high risk for pre-eclampsia after first-trimester screening either received low-dose aspirin or nothing. In the aspirin group, the prevalence of pre-eclampsia was reduced by 90%
Biomarkers used for screening the first trimester:
2. Free Beta HCG
1.Sequential application of a multimarker algorithm followed by determination of treatable risk factors in screen-positive women is the optimal approach for first-trimester pre-eclampsia prediction and identification of women that may benefit from targeted metabolic or cardiovascular treatment.
2.The majority of pregnancies that develop HELLP syndrome can be predicted in the first trimester.
3.Combination of maternal factors and biomarkers provides effective first-trimester screening for preterm-pre-eclampsia.
4.A study demonstrated 96.6% diagnostic accuracy of the multi-variable screening test to predict the risk of PE in the first trimester. The negative predictive value (>98%) reinforces the utility of cost-effective noninvasive screening test for the early detection of PE.
5.First-trimester prediction rules using parameters currently available at first-trimester screening identify a significant proportion of women with subsequent pre-eclampsia.
6.In the overall PE model, UtA PI turned out to be statistically significant but did not improve the detection rate.
7.First TMP screening for pre-eclampsia also improves the detection of trisomy 21. PIGF levels are reduced in Trisomy 21.
2.Diagnosis of Pre-eclampsia in the 2nd TMP(FMF Approved)
Usually, the gold standard for a diagnosis of pre-eclampsia is an assessment of BP and proteinuria. This has a relatively low specificity and sensitivity.
The rate of detection can be improved by the following:
In patients with pre-eclampsia sFlt-1 levels are significantly increased while PlGF levels are significantly decreased compared to normals.The sFlt-1/PlGF ratio is a useful tool as an aid to confirm the diagnosis of pre-Eclampsia.
Screening by biophysical and biochemical testing at 30-33 weeks could identify most pregnancies developing PE and requiring delivery within the subsequent 4 weeks.
The sFlt-1/PlGF ratio improves the predictive value of Doppler ultrasound alone
The sFlt-1/PlGF ratio is useful in the differential diagnosis of hypertensive pregnancy-related disorders. The sFlt-1/PlGF ratio is useful in predicting the development of an adverse outcome in women with diagnosed pre-eclampsia
1.The additive value of an increased ratio for diagnosing PE is limited since most patients with clinical PE also have a positive ratio. However, an elevated ratio is superior to the clinical diagnosis of PE for predicting an adverse pregnancy outcome. Furthermore, irrespective of clinical PE, a low ratio is inversely correlated with prolongation of pregnancy.
2. A sFlt-1: PlGF ratio of 38 or lower can be used to predict the short-term absence of pre-eclampsia in women in whom the syndrome is suspected clinically.
3.Measurement of angiogenic factors improves the specificity of an abnormal UtADV for prediction of PE. Compared with the prediction of PE an abnormal sFLT-1/PlGF ratio revealed higher sensitivity for prediction of induced delivery at <34 0 weeks. The NPV of 97% will help to reassure most patients with an abnormal UtADV and a normal sFLT-1/PlGF ratio.
4.Fetal growth restriction is characterized by elevated maternal sFlt-1/PlGF ratio,reaching values as high as those observed in pre-eclampsia or HELLP.
5.The sFlt-1/PlGF ratio can identify pathologic pregnancy outcomes such as IUGR and PE before clinical diagnosis.
6.Repeated measurements are necessary to assess the dynamics of serum values.
7. The time-dependent slope of the sFlt-1/PlGF ratio is predictive for future pregnancy outcome and risk of developing pre-eclampsia.
8.In women with suspected pre-eclampsia presenting at <34 weeks, circulating sFlt1/PlGF ratio predicts adverse outcomes occurring within 2 weeks.
9.The accuracy of this test is substantially better than that of current approaches and may be useful in risk stratification and management.
10.Measurement of circulating angiogenic proteins for the diagnosis and prediction of pre-eclampsia is still at an early stage but is rapidly evolving.
Algorithm for First TMP screening and diagnosis of pre-eclampsia.
TAKE HOME POINTS FROM THIS ALGORITHM
- 1st TMP screening for pre-eclampsia at 11-13( 6d) weeks is advisable for prediction, especially of early-onset pre-eclampsia. This has 3 markers instead of the usual dual marker test. In addition to Free Beta HCG and PAPP-A, PlGF is done which improves the detection of Trisomy 21 by 3%
- The sFlt1/PlGF ratio is to be done after the 20th week for the diagnosis of pre-eclampsia. It can also predict the severity of pre-eclampsia and can guide a further course of therapy i.e early delivery.
- The sFlt-1: PlGF ratio of 38 or lower can be used to predict the short-term absence of pre-eclampsia in women in whom the syndrome is suspected clinically.
- Using the ratio after 24 weeks can also predict adverse outcomes of pregnancy and fetal IUGR.
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This test requires specific data to be inputted into a software which is FMF approved.