The Clinical Utility of the Congo-Red Dot Test for Diagnosis and Early Prediction of Preeclampsia During Pregnancy
The Clinical Utility of the Congo-Red Dot Test for Diagnosis and Early Prediction of Preeclampsia During Pregnancy
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.
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.
Inclusion Criteria:

 -  Pregnant women evaluated for the onset of clinical symptoms of preeclampsia in the
 Labor and Delivery Unit of The Ohio State Wexner Medical Center.

 Exclusion Criteria:

 -  Non-english speaking

 -  Men

 -  Prisoners

 -  Those unable to provide consent for themselves