Placenta | Pre-eclampsia

Pre-eclampsia is a pregnancy complication characterized by new-onset maternal hypertension and protein in the urine. This section outlines risk factors associated with pre-eclampsia, as well as its causes, management and other useful information.

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Overview

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 and 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).

Pre-eclampsia is one of the hypertensive disorders of pregnancy. The collection of hypertensive disorders can be classified as follows:

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 heterogeneous nature of the pathophysiology and, thus, lack of a precise diagnostic test for pre-eclampsia.

Causes

Broadly speaking, the disease may be caused by maternal factors, placental pathology, or both (in varying combinations).

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
Prompt diagnosis and management is essential to minimize the risk to the mother and baby.

Risk Factors

The International SCOPE consortium recently evaluated an array of potential risk factors (and protective factors) for pre-eclampsia (see abstract).

Factors that increase the risk of developing pre-eclampsia

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)
Advanced maternal age (>35 years)
High maternal body mass index (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

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)

Diagnosis

Several tools are available to physicians in order to help diagnose pre-eclampsia in a pregnant woman.

Symptoms and Signs

High blood pressure (hypertension) that was previously normal (blood pressure over 140/90 mmHg on two or more occasions)
Excess protein in the urine (proteinuria) 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 (<150×10⁹/mL)
Abnormal liver function (e.g. AST>40)
Elevated uric acid (>10 times for gestational age in weeks: a uric acid level of 330umol/L at 29 weeks gestation is elevated)

Ultrasound scans

The ultrasound scans are used to monitor baby’s wellbeing and be on the lookout for signs of IUGR (see IUGR for more information).

Management

The definitive cure for pre-eclampsia in near term pregnancies is delivery of the placenta, necessitating the 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 (<32 weeks’ gestation), premature delivery may compromise the baby’s health. In this scenario, the health care team would try to safely prolong the pregnancy using the following interventions:

Enhanced surveillance of the mother;
Anti-hypertensive medication: 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, in case 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 doctor 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 by Dr. Toal, published in the American Journal of Obstetrics and Gynecology, April 2007).

Prognosis

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. Among the women with persistent hypertension after delivery, most of them likely have had undiagnosed chronic hypertension prior to pregnancy. A small proportion of women have underlying kidney disease. Therefore, persistently-hypertensive women require medical investigations into the underlying causes of their blood pressure problems.

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 Caesarean 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 test done more than 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 (see article). 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, the most common of which is obesity, as described above. 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 over 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.