Prematurity More Accurately Predicted by Advances in Proteomic Technology

Abnormal proteins in amniotic fluid that signal a higher risk of delivering prematurely are being detected with increasing accuracy by Yale School of Medicine researchers who presented their work in two abstracts at the Society for Maternal-Fetal Medicine Conference February 8 in San Francisco.

In both studies, the researchers demonstrated that women with abnormal proteomic profiles (MR scores) are more likely to have inflammation and infection. The researchers previously developed the novel MR scoring method to discriminate healthy from diseased women in whom preterm delivery is impending and the health of the fetus is in danger. MR scoring relies on identification of a group of proteins that serve as biomarkers characteristic to women who will deliver preterm.

A normal MR score is 0 and a score of 3-4 is indicative of infection. The proteins detected are human neutrophil defensin 1, human neutrophil defensin 2, calgranulin C and calgranulin A.

About 50 percent of women who deliver prematurely have evidence of inflammation in the amniotic fluid. While there are many proteins in the amniotic fluid, not all are biomarkers with diagnostic significance.

The research team analyzed and generated MR scores for amniotic fluid taken from 123 women admitted to the Labor and Birth Unit or the prenatal units at Yale-New Haven Hospital. They found a direct relationship between the degree of amniotic fluid inflammation as indicated by the MR score, and the severity of infection in the placenta and umbilical cord.

“Our data suggest that at the time of amniocentesis and prior to delivery of the fetus, clinicians can be reassured by the absence of inflammation in a patient with an MR score of ‘0.’ Or they can initiate aggressive therapy immediately following delivery when there is an MR score of 3 or 4,” said first author on the abstracts Irina Buhimschi, M.D., assistant professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine.

Buhimschi said that neonates born to women with an MR score of 3-4 had an increased incidence of infection. They also found that calgranulin C most accurately predicted inflammatory cell infiltration of the umbilical cord, and calgranulin A reflected more advanced inflammation, which is predictive of early-onset neonatal infection.

“Early recognition, diagnosis and treatment of neonatal infection are important aspects of the current clinical practice,” said Buhimschi. “Therefore, prospective randomized studies to determine the appropriate treatment of newborns based on the MR score are highly desirable.”

Abstract Titles:

1. “Proteomic Analysis of the Human Amniotic Fluid (AF) to predict histological chorioamnionitis (HCA) in Utero.”

2. “Proteomics analysis of Amniotic Fluid. A Novel Methodology
to Provide Insight into The Mechanisms of Idiopathic Preterm Birth.”

Authors on Abstract #1 included Christian Pettker, Lissa Magliore, Stephen Thung, Guomao Zhao, Carolyn Salafia and Catalin Buhimschi.

Authors on Abstract #2 included Victor Rosenberg, Sonya Abdel-Razeq, Stephen Thung and Catalin Buhimschi.

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Karen N. Peart: karen.peart@yale.edu, 203-432-1326