title: Applicability of a high-throughput shotgun plasma protein screening approach in understanding maternal biological pathways relevant to infant birth weight outcome.
abstract: There are reports linking maternal nutritional status, smoking and environmental chemical exposures to adverse pregnancy outcomes. However, biological bases for association between some of these factors and birth outcomes are yet to be established. The objective of this preliminary work is to test the capability of a new high-throughput shotgun plasma proteomic screening in identifying maternal changes relevant to pregnancy outcome. A subset of third trimester plasma samples (N=12) associated with normal and low-birth weight infants were fractionated, tryptic-digested and analyzed for global proteomic changes using a MALDI-TOF-TOF-MS methodology. Mass spectral data were mined for candidate biomarkers using bioinformatic and statistical tools. Maternal plasma profiles of cytokines (e.g. IL8, TNF-α), chemokines (e.g. MCP-1) and cardiovascular endpoints (e.g. ET-1, MMP-9) were analyzed by a targeted approach using multiplex protein array and HPLC-Fluorescence methods. Target and global plasma proteomic markers were used to identify protein interaction networks and maternal biological pathways relevant to low infant birth weight. Our results exhibited the potential to discriminate specific maternal physiologies relevant to risk of adverse birth outcomes. This proteomic approach can be valuable in understanding the impacts of maternal factors such as environmental contaminant exposures and nutrition on birth outcomes in future work.
  
  
  CONCLUSIONS
  We demonstrate here the fitness of mass spectrometry-based shot-gun proteomics for surveillance of biological changes in mothers, and for adverse pathway analysis in combination with target biomarker information. This approach has potential for enabling early detection of mothers at risk for low infant birth weight and preterm birth, and thus early intervention for mitigation and prevention of adverse pregnancy outcomes. This article is part of a Special Issue entitled: Can Proteomics Fill the Gap Between Genomics and Phenotypes?
authors.affiliation: Analytical Biochemistry and Proteomics Laboratory, Mechanistic Studies Division, Health Canada, Ottawa, ON, K1A 0K9, Canada. Electronic address: premkumari.kumarathasan@hc-sc.gc.ca.
authors.forename: P
authors.initials: P
authors.lastname: Kumarathasan
authors.affiliation: Inhalation Toxicology Laboratory, Hazard Identification Division, Health Canada, Ottawa, ON, K1A 0K9, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Vincent
authors.affiliation: Analytical Biochemistry and Proteomics Laboratory, Mechanistic Studies Division, Health Canada, Ottawa, ON, K1A 0K9, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Das
authors.affiliation: Analytical Biochemistry and Proteomics Laboratory, Mechanistic Studies Division, Health Canada, Ottawa, ON, K1A 0K9, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Mohottalage
authors.affiliation: Analytical Biochemistry and Proteomics Laboratory, Mechanistic Studies Division, Health Canada, Ottawa, ON, K1A 0K9, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Blais
authors.affiliation: Analytical Biochemistry and Proteomics Laboratory, Mechanistic Studies Division, Health Canada, Ottawa, ON, K1A 0K9, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Blank
authors.affiliation: Inhalation Toxicology Laboratory, Hazard Identification Division, Health Canada, Ottawa, ON, K1A 0K9, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Karthikeyan
authors.affiliation: Inhalation Toxicology Laboratory, Hazard Identification Division, Health Canada, Ottawa, ON, K1A 0K9, Canada.
authors.forename: N Q
authors.initials: NQ
authors.lastname: Vuong
authors.affiliation: Population Studies Division, Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON, K1A 0K9, Canada.
authors.forename: T E
authors.initials: TE
authors.lastname: Arbuckle
authors.affiliation: St-Justine Hospital, Montreal, QC, H3T 1C5, Canada.
authors.forename: W D
authors.initials: WD
authors.lastname: Fraser
mesh_terms: D001724:Birth Weight; D005260:Female; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D011247:Pregnancy; D011256:Pregnancy Outcome; D011263:Pregnancy Trimester, Third; D040901:Proteomics / Q000379:methods*; D012307:Risk Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
keywords: Biomarkers; Birth weight; Mass spectrometry; Shot-gun proteomic