WP 1-1 Biochemical phenotyping of umbilical cord blood

Biochemical phenotyping of umbilical cord blood to identify risks of obese pregnancies (PEACHES mother-child cohort)

gyne 9:22-24 Mediengruppe Oberfranken - Fachverlage GmbH & Co. KG: Phenotyping of cord blood

Maternal milieu factors can influence the metabolic regulation and function of the offspring during critical stages of fetal development ("fetal metabolic programming"), which can have far-reaching consequences for the long-term health of the offspring. Relevant prenatal risk factors for childhood overweight include excessive gestational weight gain, smoking during pregnancy and gestational diabetes, and among those, maternal pre-conceptional obesity appears to confer the strongest risk.

Research questions:

  1. What are the mechanisms and metabolic pathways underlying the relationship between nutritionally-related determinants and adverse offspring outcomes?
  2. Which are the maternal obese pregnancy phenotypes that confer the highest metabolic risk on offspring health?

Analyses will use previously collected data and biosamples from the prospective PEACHES (Programming of Enhanced Adiposity Risk in CHildhood - Early Screening) mother-child cohort, which was jointly initiated by the Research Group "Molecular Nutrition", Dr. von Hauner Children's Hospital, LMU München (Prof. Regina Ensenauer) and the obstetric departments of the LMU München and the TU München in 2010. This unique cohort of obese mothers and their children (and normal weight mother-child pairs) provides detailed information on all relevant prenatal risk factors of childhood overweight including pre-conceptional maternal BMI, gestational weight gain, gestational diabetes, smoking during pregnancy and assessment of the maternal nutritional status for all trimesters of pregnancy. Outcome parameters comprise annual child anthropometric data. Data on potential postnatal confounding factors, such as parental BMI and socioeconomic status, are available. In this project we will quantify about 300 metabolites in cord blood of obese and normal weight pregnant women of the PEACHES cohort (n = 600) via metabolite profiling (LC-MS/MS, GC-MS) at the Chair of Nutritional Physiology of the TU München. Metabolite data will be biostatistically analyzed, interpreted and validated. Cord blood metabolite patterns will be defined with regard to their potential to predict a high childhood weight status at age 2 to 4 years. Involved metabolic pathways will be experimentally validated. Associations of cord blood metabolite profiles and known pregnancy risk categories (e.g. excessive weight gain) will be examined and a "Pregnancy Risk Score" will be deduced.

Objective:

Aim of the project is the early identification of "high risk" obese pregnant women susceptible to conferring fetal metabolic risks as a prerequisite for targeting preventive nutritional strategies during pregnancy. We aim to
1.) deduce "risk markers" for childhood overweight in umbilical cord blood of offspring prenatally exposed to maternal overnutrition and
2.) develop a "pregnancy risk score" predictive of metabolic dysregulation at birth that is associated with offspring overweight.

Coordinating investigator

Prof. Dr. Regina Ensenauer

Ludwig-Maximilians-Universität München
Dr. von Haunersches Kinderspital, Molekulare Ernährung und
Heinrich-Heine-Universität Düsseldorf

Phone:+49 (89) 4400 57967
Email: regina.ensenauer[at]med.uni-muenchen.de  

Co-Investigator

Sarah Perschbacher

Ludwig-Maximilian-Universität München
Dr. von Haunersches Kinderspital, Molekulare Ernährung

Phone:+49 (89) 4400 57967
Email: sarah.perschbacher[at]med.uni-muenchen.de

Cooperation partner

Prof. Dr. Hannelore Daniel

Technische Universität München
Lehrstuhl für Ernährungsphysiologie

Phone:+49 (8161) 71 3400
Email: hannelore.daniel[at]tum.de

PEACHES-mother-child cohort

Project-specific own publications, e.g.

  • Dahlhoff M, et al., ENSENAUER R. Peri-conceptional obesogenic exposure induces sex-specific programming of disease susceptibilities in adult mouse offspring. Biochim Biophys Acta (2014) 1842(2): 304-317.
  • ENSENAUER R, et al. In situ assay of fatty acid beta-oxidation by metabolite profiling following permeabilization of cell membranes. J Lipid Res (2012) 53(5): 1012-1020.
  • Krug S, et al., DANIEL H. The dynamic range of the human metabolome revealed by challenges. FASEB Journal (2012) 26: 2607-2619.
  • Skurk T, et al., DANIEL H. New metabolic interdependencies revealed by plasma metabolite profiling after two dietary challenges. Metabolomics (2011) 7: 388-399.
  • Rubio-Aliaga I, et al., DANIEL H. Metabolomics of prolonged fasting in humans reveals new catabolic markers. Metabolomics (2011) 7: 375-387.

Own current/previous projects, e.g.

  • EU Joint Programming Initiative “A Healthy Diet for a Healthy Life”, DEDIPAC (Ensenauer, BMBF)
  • Nachwuchsforschergruppe Molekulare Ernährung „Amino acids and nutrient-sensing“ (Ensenauer, BMBF)
  • Kompetenznetzwerk Adipositas „Perinatal Prevention of Obesity Development (PEPO): contribution of prenatal influences“ (Ensenauer, BMBF)
  • Gesund.Leben.Bayern „Bavarian Early Risk Survey“ (Ensenauer, Bayerisches Staatsministerium für Umwelt und Gesundheit)
  • NutriTech “Comprehensive plasma metabolomic phenotyping in the framework of human challenge experiments and a lifestyle-intervention” (Daniel, EU)
  • Food4me “An integrated analysis of opportunities and challenges for personalized nutrition” (Daniel, EU)