title: Direct and rapid mass spectral fingerprinting of maternal urine for the detection of Down syndrome pregnancy.
abstract: BACKGROUND
  The established methods of antenatal screening for Down syndrome are based on immunoassay for a panel of maternal serum biomarkers together with ultrasound measures. Recently, genetic analysis of maternal plasma cell free (cf) DNA has begun to be used but has a number of limitations including excessive turn-around time and cost. We aimed to develop an alternative method based on urinalysis that is simple, affordable and accurate.
  
  
  METHODS
  101 maternal urine samples sampled at 12-17 weeks gestation were taken from an archival collection of 2567 spot urines collected from women attending a prenatal screening clinic. 18 pregnancies in this set subsequently proved to be Down pregnancies. Samples were either neat urine or diluted between 10 to 1000 fold in dH2O and subjected to matrix assisted laser desorption ionization (MALDI), time of flight (ToF) mass spectrometry (MS). Data profiles were examined in the region 6,000 to 14,000 m/z. Spectral data was normalised and quantitative characteristics of the profile were compared between Down and controls.
  
  
  RESULTS
  In Down cases there were additional spectral profile peaks at 11,000-12,000 m/z and a corresponding reduction in intensity at 6,000-8,000 m/z. The ratio of the normalised values at these two ranges completely separated the 8 Down syndrome from the 39 controls at 12-14 weeks. Discrimination was poorer at 15-17 weeks where 3 of the 10 Down syndrome cases had values within the normal range.
  
  
  CONCLUSIONS
  Direct MALDI ToF mass spectral profiling of maternal urinary has the potential for an affordable, simple, accurate and rapid alternative to current Down syndrome screening protocols.
authors: MAP Diagnostics Ltd, The BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AX UK.
authors: Ray K
authors: RK
authors: Iles
authors: MAP Diagnostics Ltd, The BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AX UK ; Middlesex University, Hendon, London, UK.
authors: Maryam E
authors: ME
authors: Shahpari
authors: Columbia University Medical Center, New York, USA.
authors: Howard
authors: H
authors: Cuckle
authors: MAP Diagnostics Ltd, The BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AX UK ; Middlesex University, Hendon, London, UK.
authors: Stephen A
authors: SA
authors: Butler
keywords: Down syndrome; MALDI ToF MS; NIPT; Urinalysis