December 1, 2010 (Denver, Colorado) — A simple measurement of key proteins in spot urine samples can detect preeclampsia in women during the early stages of pregnancy, according to research presented here at Renal Week 2010: American Society of Nephrology 43rd Annual Meeting.
Researchers in the United Kingdom report that an analysis of urine samples obtained before 20 weeks of gestation from 145 pregnant women who either did or did not develop preeclampsia allowed them to identify 5 protein peaks that predicted preeclampsia with 92% accuracy.
The clinical signs of preeclampsia typically do not appear until later in pregnancy, but the researchers theorized that because abnormal placentation or placental insufficiency is central to the pathogenesis of preeclampsia, and placentation is complete by 18 weeks of gestation, changes in the urinary protein profile early in pregnancy might predict the development of the disease.
"Given that proteinuria is a key diagnostic and prognostic factor in preeclampsia, the renal morphological changes occur early in the disease, and the initiation of this process begins 4 to 5 months before the clinical manifestations," explained Matt Hall, MBChB, from the Leicester General Hospital and the University of Leicester, in the United Kingdom, who was lead author of the study.
"We hypothesized that there could be a unique fingerprint early in pregnancy that would be predictive of disease development."
The prospective longitudinal study involved pregnant women who were recruited before 20 weeks of gestation from a high-risk obstetric outpatient clinic. Urine samples were taken and analyzed the same day with surface enhanced laser desorption/ionization time-of-flight mass spectrometry.
After delivery, patients were categorized as having had preeclampsia or a normal pregnancy, defined by International Society for the Study of Hypertension in Pregnancy 2001 criteria.
A spectral analysis of the urine samples of preeclampsia and nonpreeclampsia pregnancies taken before 20 weeks of gestation was performed with an artificial neural network algorithm and multivariate nonlinear regression. A random sampling of 50 test datasets validated the model.
The results identified a panel of 5 peaks that predicted preeclampsia with 92% accuracy; the test datasets showed a sensitivity of 87% and a specificity of 82%.
"We've identified the urine protein fingerprint of pregnancy that is capable of predicting the subsequent development of preeclampsia with high accuracy," Dr. Hall said. "Validation of this model and characterization of this peptide peak are believed to assemble an accurate predictive model for preeclampsia."
Preeclampsia is a leading cause of maternal and fetal morbidity and mortality, affecting up to 5% of pregnancies worldwide.
Numerous biomarkers have been investigated to try to detect the condition early, most notably soluble FMS-like tyrosine kinase and soluble endoglin — peptides that are produced by the placenta. The identification of a urinary proteomic fingerprint could help with diagnosis, said Arlene Chapman, MD, professor of medicine at Emory School of Medicine in Atlanta, Georgia.
"Preeclampsia can be sort of a diagnostic dilemma that really results from the placenta not growing properly at different stages in the pregnancy," she said. "There are different compounds released into the maternal circulation that may end up being an early footprint for detecting the condition."
"There are several biomarkers that have had some success in validation to identify the clinical scenario before it occurs, so it's interesting to see a unique proteomic footprint that might provide an early detector for this condition as well."
Earlier detection could allow for improved care for the mother and child, she added.
"Women typically don't go to their doctor more than once a month in early pregnancy, and sometimes less than that if they're doing well, so this could allow for closer monitoring of their blood pressure, for instance, and patients could be placed on blood pressure medication sooner rather than later, if necessary.
"Clinicians could also monitor [women] to identify proteinuria earlier. All of those things suggest better protection for the mom and the baby," Dr. Chapman said. "They will need to spend some time validating this in prospective populations to see if it can actually detect the development of preeclampsia, but I think this is exciting."
The study was supported by an unrestricted grant from Baxter Healthcare and University Hospitals Leicester National Health Service Trust Charitable Funds. Dr. Hall and Dr. Chapman have disclosed no relevant financial relationships.
Renal Week 2010: American Society of Nephrology 43rd Annual Meeting. Abstract FC223. Presented November 19, 2010.
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