Metabolomics of neonatal blood spots reveal distinct phenotypes of pediatric acute lymphoblastic leukemia and potential effects of early-life nutrition

Cancer Lett. 2019 Jun 28;452:71-78. doi: 10.1016/j.canlet.2019.03.007. Epub 2019 Mar 20.


Early-life exposures are believed to influence the incidence of pediatric acute lymphoblastic leukemia (ALL). Archived neonatal blood spots (NBS), collected within the first days of life, offer a means to investigate small molecules that reflect early-life exposures. Using untargeted metabolomics, we compared abundances of small-molecule features in extracts of NBS punches from 332 children that later developed ALL and 324 healthy controls. Subjects were stratified by early (1-5 y) and late (6-14 y) diagnosis. Mutually-exclusive sets of metabolic features - representing putative lipids and fatty acids - were associated with ALL, including 9 and 19 metabolites in the early- and late-diagnosis groups, respectively. In the late-diagnosis group, a prominent cluster of features with apparent 18:2 fatty-acid chains suggested that newborn exposure to the essential nutrient, linoleic acid, increased ALL risk. Interestingly, abundances of these putative 18:2 lipids were greater in infants who were fed formula rather than breast milk (colostrum) and increased with the mother's pre-pregnancy body mass index. These results suggest possible etiologic roles of newborn nutrition in late-diagnosis ALL.

Keywords: Breastfeeding; Lipids; Maternal BMI; Pre-B ALL; t(12;21) translocation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Age Factors
  • Biomarkers / blood
  • Bottle Feeding
  • Breast Feeding
  • California / epidemiology
  • Child
  • Child, Preschool
  • Dried Blood Spot Testing*
  • Energy Metabolism*
  • Female
  • Humans
  • Incidence
  • Infant
  • Infant Formula
  • Infant Nutritional Physiological Phenomena*
  • Infant, Newborn
  • Lipids / blood*
  • Male
  • Metabolomics*
  • Neonatal Screening / methods*
  • Nutritional Status*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / epidemiology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / prevention & control
  • Protective Factors
  • Risk Assessment
  • Risk Factors


  • Biomarkers
  • Lipids