Second Trimester Maternal Urine for the Diagnosis of Trisomy 21 and Prediction of Poor Pregnancy Outcomes

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• 作者：S铆lvia O. Diaz ; Ant贸nio S. Barros ; Brian J. Goodfellow ; Iola F. Duarte ; Eul谩lia Galhano ; Cristina Pita ; Maria do C茅u Almeida ; Isabel M. Carreira ; Ana M. Gil
• 刊名：Journal of Proteome Research
• 出版年：2013
• 出版时间：June 7, 2013
• 年：2013
• 卷：12
• 期：6
• 页码：2946-2957
• 全文大小：647K
• 年卷期：v.12,no.6(June 7, 2013)
• ISSN：1535-3907

文摘

Given the recognized lack of prenatal clinical methods for the early diagnosis of preterm delivery, intrauterine growth restriction, preeclampsia and gestational diabetes mellitus, and the continuing need for optimized diagnosis methods for specific chromosomal disorders (e.g., trisomy 21) and fetal malformations, this work sought specific metabolic signatures of these conditions in second trimester maternal urine, using ¹H Nuclear Magnetic Resonance (¹H NMR) metabolomics. Several variable importance to the projection (VIP)- and b-coefficient-based variable selection methods were tested, both individually and through their intersection, and the resulting data sets were analyzed by partial least-squares discriminant analysis (PLS-DA) and submitted to Monte Carlo cross validation (MCCV) and permutation tests to evaluate model predictive power. The NMR data subsets produced significantly improved PLS-DA models for all conditions except for pre-premature rupture of membranes. Specific urinary metabolic signatures were unveiled for central nervous system malformations, trisomy 21, preterm delivery, gestational diabetes, intrauterine growth restriction and preeclampsia, and biochemical interpretations were proposed. This work demonstrated, for the first time, the value of maternal urine profiling as a complementary means of prenatal diagnostics and early prediction of several poor pregnancy outcomes.

Keywords:

maternal urine; fetal malformations; trisomy 21; gestational diabetes; preterm; intrauterine growth restriction; preeclampsia; NMR; metabolomics; variable selection