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Chandak GR, Silver MJ, Saffari A, et al. Protocol for the EMPHASIS study; epigenetic mechanisms linking maternal pre-conceptional nutrition and children's health in India and Sub-Saharan Africa. BMC Nutr. 2017;3doi: 10.1186/s40795-017-0200-0.
Chandak, G. R., Silver, M. J., Saffari, A., Lillycrop, K. A., Shrestha, S., Sahariah, S. A., Di Gravio, C., Goldberg, G., Tomar, A. S., Betts, M., Sajjadi, S., Acolatse, L., James, P., Issarapu, P., Kumaran, K., Potdar, R. D., Prentice, A. M., & Fall, C. H. (2017). Protocol for the EMPHASIS study; epigenetic mechanisms linking maternal pre-conceptional nutrition and children's health in India and Sub-Saharan Africa. BMC nutrition, 3. https://doi.org/10.1186/s40795-017-0200-0
Chandak, Giriraj R, et al. "Protocol for the EMPHASIS study; epigenetic mechanisms linking maternal pre-conceptional nutrition and children's health in India and Sub-Saharan Africa." BMC nutrition vol. 3 (2017). doi: https://doi.org/10.1186/s40795-017-0200-0
Chandak GR, Silver MJ, Saffari A, Lillycrop KA, Shrestha S, Sahariah SA, Di Gravio C, Goldberg G, Tomar AS, Betts M, Sajjadi S, Acolatse L, James P, Issarapu P, Kumaran K, Potdar RD, Prentice AM, Fall CH. Protocol for the EMPHASIS study; epigenetic mechanisms linking maternal pre-conceptional nutrition and children's health in India and Sub-Saharan Africa. BMC Nutr. 2017 Oct 30;3. doi: 10.1186/s40795-017-0200-0. PMID: 30820326; PMCID: PMC6390934.
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BMC Nutr. 2017 Oct 30;3. doi: 10.1186/s40795-017-0200-0.

Protocol for the EMPHASIS study; epigenetic mechanisms linking maternal pre-conceptional nutrition and children's health in India and Sub-Saharan Africa.

BMC nutrition

Giriraj R Chandak, Matt J Silver, Ayden Saffari, Karen A Lillycrop, Smeeta Shrestha, Sirazul Amin Sahariah, Chiara Di Gravio, Gail Goldberg, Ashutosh Singh Tomar, Modupeh Betts, Sara Sajjadi, Lena Acolatse, Philip James, Prachand Issarapu, Kalyanaraman Kumaran, Ramesh D Potdar, Andrew M Prentice, Caroline Hd Fall

Affiliations

  1. CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
  2. MRC Unit The Gambia and MRC International Nutrition Group, London School of Hygiene and Tropical Medicine, UK.
  3. MRC Unit, The Gambia and MRC International Nutrition Group, London School of Hygiene and Tropical Medicine, UK.
  4. University of Southampton, UK.
  5. Centre for the Study of Social Change, Mumbai, India.
  6. MRC Lifecourse Epidemiology Unit, University of Southampton, UK.
  7. MRC Elsie Widdowson Laboratory, Cambridge, UK.
  8. MRC Unit The Gambia.
  9. MRC Lifecourse Epidemiology Unit, University of Southampton, UK and CSI Holdsworth memorial Hospital, Mysore, India.

PMID: 30820326 PMCID: PMC6390934 DOI: 10.1186/s40795-017-0200-0

Abstract

BACKGROUND: Animal studies have shown that nutritional exposures during pregnancy can modify epigenetic marks regulating fetal development and susceptibility to later disease, providing a plausible mechanism to explain the developmental origins of health and disease. Human observational studies have shown that maternal peri-conceptional diet predicts DNA methylation in offspring. However, a causal pathway from maternal diet, through changes in DNA methylation, to later health outcomes has yet to be established. The EMPHASIS study (Epigenetic Mechanisms linking Pre-conceptional nutrition and Health Assessed in India and Sub-Saharan Africa, ISRCTN14266771) will investigate epigenetically mediated links between peri-conceptional nutrition and health-related outcomes in children whose mothers participated in two randomized controlled trials of micronutrient supplementation before and during pregnancy.

METHODS: The original trials were the Mumbai Maternal Nutrition Project (MMNP, ISRCTN62811278) in which Indian women were offered a daily snack made from micronutrient-rich foods or low-micronutrient foods (controls), and the Peri-conceptional Multiple Micronutrient Supplementation Trial (PMMST, ISRCTN13687662) in rural Gambia, in which women were offered a daily multiple micronutrient (UNIMMAP) tablet or placebo. In the EMPHASIS study, DNA methylation will be analysed in the children of these women (~1,100 children aged 5-7 y in MMNP and 298 children aged 7-9 y in PMMST). Cohort-specific and cross-cohort effects will be explored. Differences in DNA methylation between allocation groups will be identified using the Illumina Infinium MethylationEPIC array, and by pyrosequencing top hits and selected candidate loci. Associations will be analysed between DNA methylation and health-related phenotypic outcomes, including size at birth, and children's post-natal growth, body composition, skeletal development, cardio-metabolic risk markers (blood pressure, serum lipids, plasma glucose and insulin) and cognitive function. Pathways analysis will be used to test for enrichment of nutrition-sensitive loci in biological pathways. Causal mechanisms for nutrition-methylation-phenotype associations will be explored using Mendelian Randomization. Associations between methylation unrelated to supplementation and phenotypes will also be analysed.

CONCLUSION: The study will increase understanding of the epigenetic mechanisms underpinning the long-term impact of maternal nutrition on offspring health. It will potentially lead to better nutritional interventions for mothers preparing for pregnancy, and to identification of early life biomarkers of later disease risk.

Keywords: Body composition; Bone density; Children; Cognitive function; DNA methylation; Developmental origins of health and disease (DOHaD); Epigenetics; Growth; Non-communicable disease (NCD) risk markers; Pre- and peri-conceptional nutrition

Conflict of interest statement

Competing interests  The authors declare that they have no competing interests.

References

  1. Dev Neuropsychol. 2001;20(1):331-54 - PubMed
  2. J Nutr. 2005 Jun;135(6):1382-6 - PubMed
  3. J Clin Endocrinol Metab. 2006 Aug;91(8):2994-3001 - PubMed
  4. Annu Rev Nutr. 2007;27:363-88 - PubMed
  5. Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17046-9 - PubMed
  6. Diabetes Care. 2009 Feb;32(2):335-41 - PubMed
  7. PLoS One. 2009 Nov 16;4(11):e7845 - PubMed
  8. Annu Rev Nutr. 2010 Aug 21;30:315-39 - PubMed
  9. PLoS Genet. 2010 May 13;6(5):e1000952 - PubMed
  10. PLoS Genet. 2010 Dec 23;6(12):e1001252 - PubMed
  11. Diabetes. 2011 May;60(5):1528-34 - PubMed
  12. Epigenetics. 2011 Jul;6(7):928-36 - PubMed
  13. Calcif Tissue Int. 2012 Feb;90(2):120-7 - PubMed
  14. FASEB J. 2012 May;26(5):1782-90 - PubMed
  15. Hum Mol Genet. 2012 May 1;21(9):2086-101 - PubMed
  16. J Pediatr. 2012 Jul;161(1):31-9 - PubMed
  17. Int J Epidemiol. 2012 Feb;41(1):161-76 - PubMed
  18. Lancet. 2013 Aug 3;382(9890):427-451 - PubMed
  19. Lancet. 2013 Aug 3;382(9890):452-477 - PubMed
  20. J Bone Miner Res. 2014 Mar;29(3):600-7 - PubMed
  21. Diabetes. 2014 Jul;63(7):2528-37 - PubMed
  22. Genome Res. 2014 Jul;24(7):1064-74 - PubMed
  23. Nat Commun. 2014 Apr 29;5:3746 - PubMed
  24. Epigenetics. 2014 Aug;9(8):1120-30 - PubMed
  25. Lancet. 2014 Sep 6;384(9946):857-68 - PubMed
  26. PLoS Genet. 2014 Sep 18;10(9):e1004663 - PubMed
  27. Am J Clin Nutr. 2014 Nov;100(5):1257-68 - PubMed
  28. Int J Epidemiol. 2015 Aug;44(4):1263-76 - PubMed
  29. Genome Biol. 2015 Jun 11;16:118 - PubMed
  30. J Child Psychol Psychiatry. 2016 Feb;57(2):152-60 - PubMed
  31. Int J Epidemiol. 2017 Apr 1;46(2):e13 - PubMed
  32. Am J Clin Nutr. 2015 Dec;102(6):1450-9 - PubMed
  33. Epigenomics. 2015;7(8):1239-43 - PubMed
  34. Genome Biol. 2016 Mar 31;17:61 - PubMed
  35. Obesity (Silver Spring). 2016 May;24(5):1018-26 - PubMed
  36. Lancet. 2016 Apr 9;387(10027):1513-30 - PubMed
  37. Biol Psychiatry. 2016 Nov 15;80(10):765-774 - PubMed
  38. J Nutr. 2016 Jul;146(7):1453S-60S - PubMed
  39. Int J Epidemiol. 2016 Jun;45(3):908-15 - PubMed
  40. Cell Metab. 2016 Sep 13;24(3):502-509 - PubMed
  41. Lancet. 2017 Jan 7;389(10064):91-102 - PubMed
  42. Lancet. 2017 Jan 7;389(10064):37-55 - PubMed
  43. Genes (Basel). 2016 Nov 24;7(12): - PubMed
  44. Matern Child Nutr. 2018 Jan;14(1): - PubMed
  45. EBioMedicine. 2017 May;19:60-72 - PubMed
  46. Diabet Med. 1994 Apr;11(3):286-92 - PubMed
  47. Lancet. 1993 Apr 10;341(8850):938-41 - PubMed
  48. Nature. 1997 Jul 31;388(6641):434 - PubMed

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