Predicting and Preventing Pre-eclampsia
Pre-eclampsia: a global health issue
2019 FIGO releases Guidelines to combat pre-eclampsia, and calls for all women to receive first-trimester screening.
Pre-eclampsia is predictable and preventable with early antenatal care and comprehensive screening practices in the first trimester.
76,000 women and 500,000 babies die each year from hypertension and pre-eclampsia during pregnancy, making this disorder one of the leading causes of maternal and perinatal morbidity and mortality globally.
Pre-eclampsia affects 2-8% of pregnancies.
The life expectancy of women who develop preterm pre-eclampsia, requiring delivery at <37 weeks, is reduced on an average by 10 years. More women are entering pregnancy with risk factors that make them vulnerable to this complication because of economic and nutrition transition, and the consequent changing lifestyle and demographics.
Addressing hypertension and pre-eclampsia is a critical dimension in reducing maternal and perinatal risks, and preventing long term non-communicable diseases (NCD). Hypertension and pre-eclampsia is fast becoming a priority global health issue given its significant adverse contribution to maternal and newborn child health and the global NCD epidemic.
What is pre-eclampsia?
Pre-eclampsia is a complication of pregnancy marked by high blood pressure and presence of protein in the urine (proteinuria). In the absence of proteinuria, the finding of maternal organ dysfunction is sufficient to make the diagnosis of pre-eclampsia.
Pre-eclampsia develops as a result of abnormal blood flow to and within the placenta, which in turn can cause growth-restriction or preterm birth of the child. When left untreated, pre- eclampsia can lead to eclampsia, a serious condition that can endanger the mother's life.
In one third of the cases the condition leads to delivery at <37 weeks' gestation (preterm pre-eclampsia) and in two thirds delivery occurs at ≥37 weeks (term pre-eclampsia).
How can pre-eclampsia affect you and the baby?
There is evidence that pre-eclampsia also leads to long term health problems. Women who develop pre-eclampsia have twice the risk of cardiovascular disease (CVD) at some stage in their life. It is not known whether pre-eclampsia causes vascular damage that ultimately leads to CVD or whether women prone to CVD are stressed by pregnancy to develop pre-eclampsia.
Children born to pre-eclamptic mothers have twice the risk of cerebral palsy; this increased risk being mediated through premature birth, growth-restriction or both. Offspring exposed to pre-eclampsia also have higher blood pressure and body mass index, compared to those born after normal pregnancy, and have increased risk of CVD and diabetes in adult life.
Classification of pre-eclampsia:
1. Early (<34 weeks) pre-eclampsia
2. Preterm (<37 weeks) pre-eclampsia
3. Late onset ( ≥34+0 weeks) of pre-eclampsia
4. Term pre-eclampsia (≥ 37 weeks)
Early and preterm pre-eclampsia - placental origin
While the direct cause of pre-eclampsia is unknown, researchers agree that if pre- eclampsia requires delivery before 37 weeks, there is a high chance that poor placentation is the underlying cause of the disease.
Early onset pre-eclampsia is associated with preterm birth and fetal growth restriction, with prematurity accounting for most pre-eclampsia-related healthcare costs. If HELLP syndrome (hemolysis, elevated liver enzymes, low plateles) or eclampsia occurs, intensive care is probable.
Term pre-eclampsia
New evidence suggests that in term pre-eclampsia (with delivery after 37 weeks) the resulting condition is more closely related to cardiac and metabolic dysfunction in the mother rather than poor placentation. In fact, term pre-eclampsia has been hypothesized to be a completely different pregnancy complication to early and preterm pre-eclampsia.
Pre-eclampsia is predictable and preventable with early antenatal care and comprehensive screening practices in the first trimester.
The quest to effectively predict PE in the first trimester of pregnancy is fueled by the desire to identify women who are at high risk of developing PE, so that necessary measures can be initiated early enough to improve placentation and thus prevent or at least reduce the frequency of its occurrence. Furthermore, identification of an "at risk" group will allow tailored prenatal surveillance to anticipate and recognize the onset of the clinical syndrome and manage it promptly.
Are you at risk?
It is well established that a number of maternal risk factors are associated with the development of PE.
- Maternal age
- Parity
- Previous history of preeclampsia
- Pregnancy interval
- Assisted reproduction
- Family history of PE
- Obesity
- Race and ethnicity
- Comorbities
- Hyperglycemia in pregnancy (pre- pregnancy type 1 and type 2 diabetes mellitus, overt diabetes in pregnancy, and gestational diabetes requiring insulin treatment)
- Pre- existing chronic hypertension
- Renal disease
- Autoimmune diseases such as systemic lupus erythematosus (SLE) and antiphospholipidsyndrome (APS).
When should you be screened for pre-eclampsia?
Combined pre-eclampsia screening
Combined pre-eclampsia screening, developed by the Fetal Medicine Foundation, allows estimation of individual, patient specific risk for developing pre- eclampsia later in pregnancy.
When should combined pre-eclampsia screening be performed?
The optimal time for the combined screening is at 11-13 weeks' gestation.
Who should the pre-eclampsia screening be offered to?
All pregnant women should be assessed early in their pregnancy and, as part of this assessment, preventing the subsequent development of pre-eclampsia should be regarded as a major objective. All women should have access to screening, even if there are no maternal risk factors or history of pre-eclampsia.
Pre-eclampsia screening markers
- Biochemical markers-placental growth factor (PlGF) and pregnancy associated plasma protein-A (PAPP-A),
- Biophysical markers-mean arterial blood pressure (MAP) and the mean uterine artery pulsatility index (UTPI) between 11 weeks and 13+6 weeks' gestation
In early pregnancy values for biochemical markers (PIGF, PAPP-A) are reduced and values for biophysical markers (MAP, UTPI) are elevated, indicating increased risk of pre-eclampsia.
Combined pre-eclampsia screening program
The combined pre-eclampsia screening program is made up of four simple steps that require short training and minimal additional investment in equipment.
1. Record medical history, measure weight and height.
2. Take blood sample for measuring PlGF 1-2-3TM (+/- PAPP-A)
3. Measure blood pressure 2 times from both arms simultaneously with validated automated BP devices.
4. Measure uterine artery Doppler pulsatility index by transabdominal ultrasound (FMF acreditaion is necessary).
What does the test tell you?
The test tells you whether you are high risk or low risk. High risk women will benefit from aspirin treatment.
If you are at low risk, you are unlikely to develop pre-eclampsia later in your pregnancy. You will continue to receive normal prenatal monitoring and counseling.
Combined pre-eclampsia screening at 11-13+6 weeks
Low risk Increased risk
Normal prenatal care Aspirin at 12-36 weeks
How can you reduce the risk of pre-eclampsia?
The ASPRE study (Aspirin vs placebo in the prevention of preterm pre-eclampsia) has successfully shown that the use of aspirin treatment for screen positive pregnant women dramatically reduces the risk of preterm pre- eclampsia if administration of the optimal dosage of aspirin is started during the first trimester of pregnancy.
Dose 150 mg
The significant reduction in the rate of preterm pre-eclampsia is achieved using 150 mg of aspirin/night.
When Bed time
Aspirin taken at the end of the day is more effective in reducing the rate of pre-eclampsia than if taken in the morning or afternoon.
Starting at ~12 weeks
Screen positive women benefit from aspirin treatment that is started early. In practice, the starting time of the treatment is around 12 weeks, right after the results of the screening test are available. To be effective, the aspirin treatment must be started at the latest at 16 weeks.
Finishing at 36 weeks
Women should continue to take aspirin up to 36 weeks of gestation.
What is known about the safety of aspirin?
The safety data on aspirin are reassuring. There is no evidence that aspirin increases vaginal spotting. It is suggested that aspirin at a daily dose of ≥100 mg initiated at ≤16 weeks may also decrease the risk of adverse events other than pre-eclampsia (placental abruption or antepartum hemorrhage).
Conclusion
With regard to pre-eclampsia, we are stepping into a new era in terms of how the disease is predicted and managed. The ASPRE study has now given definitive evidence that the best way to reduce the rate of preterm pre-eclampsia (with delivery before 37 weeks' gestation) is through early prediction and prevention by low-dose aspirin. A significant 62% reduction in the rate of preterm pre-eclampsia amongst women who would otherwise develop the condition is great news for women at risk and their families.
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Combined pre-eclampsia screening with the PIGF 1-2-3 TM Assay. Doctor's booklet