Pre-eclampsia
Role of placental function testing
Prognosis following a pregnancy with pre-eclampsia
What is Pre-Eclampsia?
Pre-eclampsia is a complication of pregnancy characterized by hypertension (elevated blood pressure) and proteinuria (protein in the urine). The disease most commonly occurs in near-term pregnancies. Up to 10% of cases result in premature delivery of the baby (see reference).
Pre-eclampsia is a potentially serious complication of pregnancy that resolves post-partum following delivery of the placenta. Prompt diagnosis and appropriate management, including premature delivery where necessary to avert maternal risks of hypertension almost always results in maternal recovery (see reference).
Classification of the hypertensive disorders of pregnancy:
- Gestational hypertension: characterized by hypertension developing after 20 weeks' and no other complications (including no proteinuria).
- Pre-eclampsia: development of hypertension and proteinuria after 20 weeks' gestation in a woman with previously normal blood pressure
- Chronic hypertension: characterized by hypertension before 20 weeks' that exists for at least 12 weeks after delivery
- Superimposed pre-eclampsia – chronic hypertension before 20 weeks' that either increases or is accompanied by proteinuria as pregnancy progresses.
- HELLP syndrome – (Hemolysis, Elevated Liver enzymes, Low Platelets) – this represents any form of pre-eclampsia with abnormal blood tests demonstrating low platelets and/or abnormal liver enzymes.
- Severe pre-eclampsia refers to pregnancies with pre-eclampsia that have very high blood pressure or proteinuria, or have additional complications, including IUGR and/or HELLP syndrome.
The classification of the different forms of hypertension varies between professional bodies due to the heterogenous nature of the pathophysiology and thus lack of a precise diagnostic test for pre-eclampsia.
What Causes Pre-Eclampsia?
Broadly speaking, the disease may be caused by maternal factors, placental pathology, or both (in varying combinations). These are as follows:
Maternal factors
- Strong family history of cardiovascular disease
- Advanced maternal age
- Obesity
- Pre-existing medical conditions
- Previous pregnancy affected by pre-eclampsia
- Maternal immune system rejection of the placenta
Placental factors
- Insufficient maternal blood flow to the placenta
- Abnormal development of the placental villi (see Placenta 101 for more information)
- New partner for pregnancy
- Use of IVF technology
Diagnosis of Pre-Eclampsia
Symptoms and Signs
- High blood pressure (hypertension) that was previously normal. Blood pressure over 140/90 mm Hg on two or more occasions suggests pre-eclampsia.
- Excess protein in urine (proteinuria) – this is determined by a dipstick test
- Excessive swelling of lower limbs and/or hands (edema)
- Severe headaches
- Changes in vision (including blurry vision, sudden loss of sight, light sensitivity, sparks and eye pain)
- Nausea or vomiting, pain in the upper right abdomen under the ribs where the liver is located
- Dizziness
- Rapid weight gain (typically exceeding 2 lbs or 0.9 kg per week)
Tests
- Blood tests
- Low platelet count (<150x109/mL)
- Abnormal liver function (e.g. AST>40)
- Elevated uric acid (>10x gestational age in weeks: a uric acid level of 330umol/L at 29 weeks gestation is elevated)
- Ultrasound: observations indicating IUGR (see IUGR for more information)
Risk factors
The International SCOPE consortium recently evaluated an array of potential risk factors (and protective factors) for pre-eclampsia.
Factors that increase the risk of developing pre-eclampsia include:
- A history of pre-eclampsia in your immediate family or in a previous pregnancy
- First pregnancy (the highest risk for developing pre-eclampsia is during a mother’s first pregnancy)
- New partner (pregnancy with a new partner can increase the risk)
- Age >35 (risk increases with age)
- Weight (risk increases with BMI)
- Multi-fetal pregnancies (pre-eclampsia is more common in pregnancies with twins, triplets or more)
- Medical history – certain medical conditions increase the risk of developing pre-eclampsia, including:
- Pre-existing diabetes
- Chronic hypertension
- Chronic (long-standing) kidney disease
- Auto-immune disease (SLE/lupus)
- Tendency to blood clotting (thrombophilia)
- Personal history of low birth weight
- Vaginal bleeding (>5 days) in the first trimester
- Chronic hypertension
- Substance abuse (some forms)
Factors that decrease the risk of pre-eclampsia include:
- A healthy diet and lifestyle (high fruit intake)
- One miscarriage (pregnancy loss <10 weeks gestation) with the same partner
- >12 months to conceive
- Subsequent pregnancy with same partner 1-3 years after the first pregnancy
- Smoking (5+/day)
Management of Pre-Eclampsia
The definitive cure for pre-eclampsia in near term pregnancies is delivery of the baby. For most women, this means induction of labour (IOL) and is preferable to no intervention, since the disease otherwise progresses (see reference). However, when pre-eclampsia presents before term (especially before 32 weeks gestation), premature delivery may compromise the baby's health. In this scenario, we would try to safely prolong the pregnancy as follows:
- Enhanced surveillance of the mother
- Anti-hypertensives: drugs given (mostly by mouth) to lower blood pressure to an acceptable level until delivery
- Corticosteroids: two maternal intra-muscular injections 24 hours apart. The corticosteroids cross the placenta to stimulate the developing baby's lungs to mature faster, incase premature birth has to occur (due to severe pre-eclampsia or IUGR). Corticosteroids can also temporarily (for up to 7 days) improve maternal liver tests and increase maternal platelet count in order to prolong an otherwise extremely premature pregnancy
- Admission to hospital with bed rest may be necessary as a safety measure in severe pre-eclampsia (to provide 24 hour nursing and immediate MD assistance)
- Inpatient care of women with severe pre-eclampsia includes enhanced fetal monitoring (Doppler ultrasound and additional biophysical profile tests and daily non-stress tests) as well as serial maternal blood pressure monitoring and daily blood and urine tests
Role of Placental Function Testing in Pre-Eclampsia
The more rare early-onset type of pre-eclampsia, presenting <34 weeks', is much more likely to have a placental pathology component than the milder form occurring near term. A program of screening for placental insufficiency (using IPS blood tests, uterine artery Doppler, and placental morphology ultrasounds; see Placental Function Testing) can identify women at most risk.
Conversely, amongst women with clinical risk factors (described above), the likelihood of developing pre-eclampsia if these tests are all normal is 1/5 (20%) of the underlying risk (see abstract, article by Dr Toal, published in the American Journal of Obstetrics and Gynecology, April 2007).
What is the Prognosis Following a Pregnancy With Severe Pre-Eclampsia?
Mother's health
Provided the pre-eclampsia is managed well (effective control of blood pressure and proactive decision-making around delivery), the risk of serious complications is very low.
Most women discharged home on blood pressure medications will be able to discontinue them within 4 weeks. Most women with persistent hypertension had undiagnosed chronic hypertension prior to pregnancy. A small proportion have underlying kidney disease. Therefore, persistently-hypertensive women require medical investigations.
Women who have had a diagnosis of severe pre-eclampsia should receive counseling after delivery to address the following topics:
- Appropriate birth control
- Review and address potentially modifiable risk factors (the most common is obesity)
- Implications of Cesarean section delivery (if required)
- Emotional support if infant is born premature, or if other risk factors are present (personal or family history of depression or anxiety)
Women who have developed severe pre-eclampsia with a strong family history of cardiovascular disease should have an ECG and fasting blood lipids done >6 months after delivery and review their potentially modifiable cardiovascular risk factors with their family doctor or specialist in internal medicine.
Baby's health
Most babies born to pre-eclamptic women are healthy. The majority of babies admitted prematurely to a special care baby unit (level 2 care) at 32-37 weeks' will have no ongoing concerns. Progressively earlier delivery, especially with co-existent IUGR, has attendant risk of developmental delay, though the risks are small if the period of hospitalization was uncomplicated.
Recent research links birth with pre-eclampsia to later (adult) cardiovascular disease. Therefore, blood pressure measurement is prudent during school-age. However, the benefits of a healthy lifestyle, including balanced diet, sport activities, and avoidance of obesity, likely override any negative risks.
Future pregnancies
All women who have had a pregnancy complicated by pre-eclampsia should review their potentially-modifiable risk factors, as described above (the most common of which is obesity).
For women who desire a future pregnancy, the risk of pre-eclampsia 1-3 years later is small. The exceptions are women who had very severe/early disease, who are now >35 years of age, are obese, or have ongoing medical problems. Such women are likely to benefit from pre-pregnancy counseling.
The risk in all future pregnancies is likely to be reduced by:
- Waiting 12 months before becoming pregnant again
- Taking pre-conceptual multivitamins
- Completion of relevant maternal tests before attempting conception
- Addressing modifiable risk factors, commonly weight loss
