The Clinical Utility of the Congo-Red Dot Test for Diagnosis and Early Prediction of Preeclampsia During Pregnancy
Condition: Preeclampsia
MeSH terms: Pre-Eclampsia
Study type: Observational [Patient Registry]

Summary: 
      The aim of the study is to validate in a prospective fashion the value of the Congo-Red Dot
      (CRD) test for diagnosis of preeclampsia. The working hypothesis is that in pregnancies
      complicated by preeclampsia, will display urine congophilia and have a positive CRD test.
    

Detailed description: 
      Preeclampsia is a pregnancy-specific hypertensive disorder and a leading cause of maternal
      and perinatal morbidity and death worldwide. When left untreated, preeclampsia leads to
      seizures (eclampsia), stroke, hemorrhage, kidney and liver failure, and death. The World
      Health Organization (WHO) estimates that 99% of preeclampsia-related deaths occur in low- and
      mid-income countries. Although most cases of maternal death are preventable, it is estimated
      that ~63,000 women die annually due to preeclampsia alone.

      In developed countries, such as the U.S. and UK, development and implementation of clinical
      guidelines for diagnosis and management of preeclampsia has resulted in a dramatic decrease
      in maternal morbidity and mortality. Some of these measures include: a) blood pressure and
      dipstick proteinuria screening during each prenatal visits; b) extensive laboratory work-up
      to rule-out hemolysis, elevated liver enzymes, and thrombocytopenia (HELLP) syndrome; c)
      hospital admission for intensive clinical observation; d) use of magnesium sulfate and
      anti-hypertensive medication to prevent eclampsia and intracranial hemorrhage and e)
      medically indicated early delivery for strict clinical criteria of severity given that
      delivery is the only definitive cure for preeclampsia.

      It is well-recognized that the number of medically-indicated early deliveries in the U.S. and
      U.K. exceeds those necessary to prevent maternal death or morbidity related to preeclampsia.
      However, in the era of widespread use of antenatal corticosteroids and advances in neonatal
      intensive care, in developed countries, obstetricians lean more towards indicating delivery
      than they were three decades ago. At present in the U.S., preeclampsia is estimated to
      trigger 70% of medically indicated preterm births. Yet, implementation of the same guidelines
      is not feasible for low- or mid-income countries. In this scenario, the tendency is to
      prolong pregnancy at least until 34 weeks so that the likelihood of survival for the
      premature neonate is maximized. Recognizing this conundrum, increased emphasis has been
      placed on finding novel diagnostic and prognostic biomarkers that may help with
      identification of preeclamptic women in real need of medically-indicated deliveries as
      opposed to those whose pregnancy could be safely extended. That said, for low- and mid-income
      countries, such biomarkers have the potential to significantly help with current barriers in
      reducing maternal morbidity and deaths from severe preeclampsia. Because compliance with
      physician referral and transport to the hospital are significant issues in rural areas, the
      earlier the problem is identified, the better the outcome. Accurate identification of women
      whose pregnancies are at high risk for preeclampsia or eclampsia would result in timely
      referral to medical facilities where appropriate treatments (i.e magnesium sulfate or
      medically-indicated delivery) can be provided. Additionally, an accurate diagnostic test for
      preeclampsia implemented in a developing country will allow maternity units to run more cost
      effectively by avoiding unnecessary referrals, unnecessary admissions for 24h protein
      assessment. This will also reduce the number of admissions for labor induction, the number of
      inductions in general and indirectly the number of C-sections.

      Traditionally, the diagnosis of preeclampsia relies on presence of hypertension and
      proteinuria. Unfortunately, these signs are often non-specific and could be confounded by
      many co-morbidities including essential hypertension and chronic kidney disease. Spearheaded
      by proteomics research, our group identified that women with severe forms of preeclampsia
      excrete in their urine high amounts of unfolded or misfolded proteins. This phenomenon
      classifies preeclampsia as a protein conformational disorder similar to Alzheimer's and prion
      disease, yet particular to pregnancy. It logically followed that misfolded proteins in
      preeclampsia urine should exhibit congophilia (affinity for the azo-dye Congo Red). Congo Red
      was developed for textile industry in the 1800', but later found to have self-assembling
      properties and to selectively stain misfolded amyloid in brains of patients with Alzheimer's.
      Based on these premises, a simple urine diagnostic test [Congo Red Dot (CRD) Test] has been
      designed, developed and validated in our research laboratory.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        This study involves testing of urine specimens that originate from pregnant women (ages
        18-48) who are presenting for evaluation, following onset of clinical symptoms of
        preeclampsia. Preeclampsia is a pregnancy specific medical complication of pregnancy and
        thus selection of specimens only of pregnant women is necessary. The urine specimens from
        symptomatic women will be used for the testing of the diagnosis value of the CRD test.
      
Biospecimen description: 
      Urine specimens
    
Keywords: Urine congophilia