HELLP Syndrome

Mamas on Bedrest: Urine Tests May Predict Pre-Eclampsia

December 6th, 2010

The Discovery

Recently, two different groups of researchers identified urine proteins that can detect pre-eclampsia in early pregnancy. Pre-Eclampsia affects 5% of all pregnancies worldwide and is a leading cause of maternal and fetal morbidity and mortality. Symptoms of pre-eclampsia (hypertension, proteinuria and edema) typically manifest late in pregnancy, but the protein markers which the researchers have identified are present by 18 weeks gestation. Researchers theorize that abnormal development and function of the placenta is the central cause of pre-eclampsia.  This abnormal development gives rise to certain proteins which can be found in maternal urine. The presence of these proteins can predict whether or not a woman is at risk for, or actually developing pre-eclampsia.

Congo Red Dot Urine Test

The first study was conducted by Irina Buhimschi, MD, Associated Professor in the Department of Obstetrics, Gynecology and Reproductive Sciences at Yale University and the data was presented in February 2010 at the Society for Maternal and Fetal Medicine 30th Annual Meeting: The Pregnancy Meeting.* Dr. Bahimschi and her colleagues sought to create and confirm the Congo Red Dot Test as a way to assess for pre-eclampsia. Their rationale was that pre-eclampsia is frequently diagnosed and often over treated in the United States, primarily due to litigation fears. Yet pre-eclampsia is often underdiagnosed and undertreated in developing countries due to the lack of diagnostic resources.  They chose to use the Congo Red Dot test as a screening test because the test is quick (results are available in 10-15 minutes) and the test does not require any technical equipment so it can be done anywhere. The results of the Congo tests are easy to determine and are based on the percentage of Congo Red Retained in target proteins. The researchers compared Congo Red Retained as a predictor of delivery for pre-eclampsia with two other tests, one for urine protein and another for the ratio of high soluble fms-like tyrosine kinase 1 t placental growth factor (sFlt1/PIGF). Dr. Buhimschi and her colleagues found:

  • 61% (211/347) of the subjects had an indicated delivery for pre-eclampsia, with the highest percentages in those with superimposed pre-eclampsia (100%), severe pre-eclampsia (99%), and mild pre-eclampsia (69%); in the control group, the rate was 4%.
  • CRR levels were higher in women with mild pre-eclampsia than in those with gestational hypertension, and were even higher in women with severe and superimposed pre-eclampsia.
  • 11% (4/35) of the asymptomatic women evaluated longitudinally with Congo Red Dot urine testing had preterm indications for delivery for pre-eclampsia and elevated CRR levels before they developed symptoms.
  • CRR levels more accurately predicted and indicated delivery for pre-eclampsia than the more intensive urine protein test (P < .001) and sFlt1/PlGF (P = 0.014).

Urine Test to Detect Pre-Eclampsia in Early Pregnancy

Matt Hall, MBChB, Leicester General Hospital and The University of Leicester in the United Kingdom reported that urine samples obtained before 20 weeks gestation allowed them to identify 5 protein peaks that predict pre-eclampsia with 92% accuracy,  87% sensitivity and 82% specificity for the proteins in question.

Urine samples were obtained from woman at 20 weeks gestation and analyzed the same day using surface enhanced laser desorption/ionization time-of-flight mass spectrometry. The results of the urine samples were compared with the pregnancy outcomes (those who had pre-eclampsia and those who did not) at birth. Pre-Eclampsia was defined by the International society for the Study of Hypertension in Pregnancy, 2001 criteria.

Hall and his colleagues also noted, as did Buhimschi, that because placental development is complete by 18 weeks gestation, urinary protein changes early in pregnancy as a result can be used to predict subsequent development of pre-eclampsia. The findings were presented at the Renal Week 2010: American Society of Nephrology 43rd Annual Meeting.**

Implications for Mamas on Bedrest

Pre-Eclampsia is one of the leading reasons that pregnant women are prescribed bed rest and carries with it significant morbidity and mortality for both mamas and babies. To date, pregnant women diagnosed with pre-eclampsia are prescribed bed rest and their blood pressure is monitored carefully. If their blood pressures remains high, they are often given Magnesium Sulfate to prevent the pre-eclampsia from progressing to eclampsia or HELLP (Hemolysis, Elevated Liver Enzymes, and Low Platelet Count) Syndrome. Magnesium Sulfate is also used to prevent women from developing hypertension induced seizures. While Magnesium Sulfate has been used for some 60 years for the treatment of pre-eclampsia, it has some pretty uncomfortable side effects.

  • Flushing
  • Nausea
  • Vomiting
  • Palpitations
  • Headache
  • General muscle weakness
  • Lethargy
  • Constipation

Magnesium Sulfate can cause these dangerous complications:

  • Cardiac arrest
  • Pulmonary edema (lungs fill with fluid; can be fatal)
  • Chest pain
  • Cardiac conduction defects
  • Low blood pressure
  • Low calcium
  • Increased urinary calcium
  • Visual disturbances
  • Decreased bone density
  • Respiratory depression (difficulty breathing)
  • Muscular hyperexcitability

Rare, Severe Complications

  • Profound muscular paralysis
  • Paralytic ileus (intestinal obstruction)

(NOTE: The side effects and complications of Magnesium Sulfate are intensified by kidney failure, a common complication of pre-eclampsia. Your obstetrician should monitor your kidney function carefully if you develop pre-eclampsia, and even more so if you are prescribed Magnesium Sulfate.)

If the urine tests  mentioned in the studies could be performed early in pregnancy to detect which women are in imminent danger of developing pre-eclampsia or who may already have the early stages of pre-eclampsia, the prevalence of pre-eclampsia could be significantly reduced. Women experiencing the horrible side effects of pre-eclampsia could be spared the discomfort of treatment and the risk to their lives and the risk to the lives of their babies. These tests could make pre-eclampsia and bed rest for pre-eclampsia a thing of the past-or at the very least, a rare occurrence.

Clearly more research is necessary in order to confirm these study findings. However, the implications of these studies is extremely exciting for mamas on bed rest. Each year thousands of women are prescribed bed rest as part of the treatment for pre-eclampsia, yet there is no documented proof that bed rest aids in the treatment of pre-eclampsia.  Additionally as it has been stated here, once a woman begins to exhibit the signs and symptoms of pre-eclampsia, she and her baby are already in danger. If tests could be made available to detect pre-eclampsia early or even before it even develops, thousands, maybe even millions of women and their babies could be spared the trauma of pre-eclampsia and the potentially life threatening treatments and consequences.

* From MedScape Medical News: Congo Red Dot Urine Test Can Predict, Diagnose Pre-Eclampsia.

**From MedScape Medical News: Urine Test Early in Pregnancy Can Predict Pre-Eclampsia.