The Maternal Nutrition And Offspringís Epigenome (MANOE) Study: A Prospective, Monocentric, Observational Study

Sara PAUWELS, KU Leuven, Belgium
HUYBRECHTS I. 3 , DEVLIEGER R. 4,5 , KOPPEN G. 2 , GODDERIS L. 1,6

1 KU Leuven, Department of Public Health and Primary Care, Environment and Health, Kapucijnenvoer 35 blok D box 7001, 3000 Leuven, Belgium
2 Flemish Institute of Technological Research (VITO), Unit Environmental Risk and Health, Vlasmeer 7, 2400 Mol, Belgium
3 International Agency for Research on Cancer, Dietary Exposure Assessment Group, 150 Cours Albert Thomas, 69372 Lyon CEDEX 08, France
4 KU Leuven, Department of Development and Regeneration, Leuven, Belgium
5 University Hospitals of Leuven, Department of Obstetrics and Gynecology, University Hospitals of Leuven, Belgium
6 IDEWE, External Service for Prevention and Protection at Work, Interleuvenlaan 58, 3001 Heverlee, Belgium

Introduction: Epigenetic modifications, e.g. DNA methylation, have the ability to change the susceptibility to metabolic diseases like obesity. DNA methylation can change during a life course due to environmental exposures like diet.
 
Aim: To determine the effects of dietary intake of methyl-group donors (methionine, folate, betaine and choline) during pregnancy on the DNA methylation pattern of mother and child. In addition, the association between the DNA methylation pattern of the mother and child on body composition/weight gain of the infant during the first year will be studied.
 
Methods: We have recruited 175 and 105 expectant mothers and fathers respectively, who are followed up in UZ Leuven. A novel food-frequency questionnaire was developed and validated to categorize women in groups according to their methyl-group intake. Women are asked to fill out a 7-day estimated dietary record to have information about macro- and micronutrient intake. Body composition is followed up by means of the bio-electrical impedance method. Blood samples are collected at standard ultrasounds during pregnancy and after delivery until 1 year postpartum. After delivery, cord blood is taken and mouth epithelial cells are obtained from the infants (6 and 12 months). Samples are analyzed for global DNA (de)methylation by liquid chromatography–mass spectrometry and specific target genes involved in DNA (de)methylation and genes linked with obesity/adiposity/metabolisation by pyrosequencing.
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Results: Our results show that the intake of methyl-groups is stable, except for a decrease in folate and folic acid intake. Global DNA methylation analysis shows that maternal global DNA (hydroxy)methylation changes significantly over pregnancy, with a significant decrease at 12 weeks and 30 weeks of pregnancy, and at delivery.
 
Discussion: With this study we will gain insight on the effect of maternal nutrition on offspring DNA methylation and potentially identify DNA methylation biomarkers at birth that can mediate problems with metabolism/obesity.