Elvira Isganaitis, MD, MPH, pediatric endocrinologist, Joslin Diabetes Center; assistant professor of pediatrics, Harvard Medical School
What is the background for this study?
Response: The concept that a mother’s nutrition prior to and during pregnancy is important for health outcomes in the offspring is now well accepted. For example, women intending to get pregnant must take prenatal vitamins, and are encouraged to attain a healthy weight before conception. However, much less is known about how a father’s nutritional status may influence childhood health outcomes. Based on studies in animals, exposure to undernutrition, high-fat diet, or stressful experiences in fathers can result in increased risk of obesity and diabetes in the offspring. These effects are mediated in part by epigenetic mechanisms (i.e. changes in gene expression due to differences in DNA methylation, histones, or other non-genetic mechanisms).
What are the main findings?
Response: In this study, we examined whether father’s weight status (body mass index) at the time of conception was associated with epigenetic marks and weight status in the offspring. We found that father’s BMI was associated with infant birth weight and with DNA methylation at several genetic loci in the offspring. Importantly, these associations remained significant after adjusting for multiple potential confounders such as maternal BMI, age, pregnancy complications, socioeconomic factors, smoking, etc.
What should readers take away from your report?
“The health of both parents (not just the mother) may influence childhood health outcomes.”
Response: The health of both parents (not just the mother) may influence childhood health outcomes. Our data add to the emerging body of evidence pointing to effects of paternal risk factors on pediatric health. For example, there are data linking increasing paternal age to risk of autism, and several studies have shown that paternal type 1 diabetes increases risk of childhood diabetes to a greater extent than maternal type 1 diabetes.
What recommendations do you have for future research as a result of this work?
Response: As these data were based on a population cohort in the Boston area (Project Viva), it will be important to verify whether these associations are reproduced in other populations.
An exciting possibility that is raised by these data is that preconception interventions in fathers could provide a novel approach to improve health outcomes in the next generation.
Is there anything else you would like to add?
Response: This type of research is only possible through collaborations. Co-authors included: Nudrat Noor, PhD1,2; Andres Cardenas, PhD, MPH3,4; Sheryl L. Rifas-Shiman, MPH3; Hui Pan, PhD5; Jonathan M. Dreyfuss, PhD5; Emily Oken, MD, MPH3,6; Marie-France Hivert, MD3; Tamarra James-Todd, PhD1,2; Mary-Elizabeth Patti, MD5,7
1Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
2Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
3Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts
4Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley
5Research Division, Joslin Diabetes Center, Boston, Massachusetts
6Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
7Department of Medicine, Harvard Medical School, Boston, Massachusetts
8Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
Funding/Support: This work was conducted with support from Harvard Catalyst: The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award UL 1TR002541) and financial contributions from Harvard University and its affiliated academic healthcare centers. This study was funded by National Institutes of Health grants R01 HD034568 and UH3 OD023286 (funding for Project Viva), R21 HD091974 (Drs Isganaitis and Patti), P30 DK036836 (to Joslin Diabetes Center, Diabetes Research Center Award), R01 DK105193 (Dr Patti), P30 ES000002 (Dr James-Todd), and T32 ES007069 (Dr Noor). Grants R01 HL111108 and R01 NR013945 from the National Institutes of Health funded the DNA methylation analyses.
Conflict of Interest Disclosures: Ms Rifas-Shiman reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Oken reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Patti reported receiving grants from the National Institutes of Health, research grants from Xeris and Dexcom, personal fees from Fractyl, Eiger Pharmaceuticals, and Avolynt, and research supplies from Insulet during the conduct of the study, all outside the submitted work. Dr Isganaitis reported receiving grants from the National Institute of Child Health and Human Development, the National Institute of Diabetes and Digestive and Kidney Diseases, and AstraZeneca during the conduct of the study. No other disclosures were reported.
Noor N, Cardenas A, Rifas-Shiman SL, et al. Association of Periconception Paternal Body Mass Index With Persistent Changes in DNA Methylation of Offspring in Childhood. JAMA Netw Oen. 2019;2(12):e1916777. doi:https://doi.org/10.1001/jamanetworkopen.2019.16777