Newborn DNA methylation age differentiates long-term weight trajectory: The Boston Birth Cohort

Background: Gestational age (GEAA) estimated by newborn DNA methylation (GAmAge) is associated with maternal prenatal exposures and immediate birth outcomes. However, the association of GAmAge with long-term overweight or obesity (OWO) trajectories is yet to be determined. Methods: GAmAge was calculated for 831 children from a US predominantly urban, low-income, multi-ethnic birth cohort using Illumina EPIC array and cord-blood DNA samples. Repeated anthropometric measurements aligned with pediatric primary care schedule allowed us to calculate body-mass-index percentiles (BMIPCT) at specific age and to define long-term weight trajectories from birth to 18 years. Results: Four BMIPCT trajectory groups described the long-term weight trajectories: stable (consistent OWO: early OWO; constant normal weight: NW) or non-stable (OWO by year 1 of follow-up: late OWO; OWO by year 6 of follow-up: NW to very late OWO) BMIPCT. were used GAmAge was a predictor of long-term obesity, differentiating between group with consistently high BMIPCT and group with normal BMIPCT patterns and groups with late OWO development. Such differentiation can be observed in the age periods of birth to 1year, 3years, 6years, 10years, and 14years (p<0.05 for all; multivariate models adjusted for GEAA, maternal smoking, delivery method, and childs sex). Birth weight was a mediator for the GAmAge effect on OWO status for specific groups at multiple age periods. Conclusions: GAmAge is associated with BMI trajectories from birth to age 18 years, independent of GEAA and birth weight. If further confirmed, GAmAge may serve as an early biomarker for future OWO risk. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funding Support The Boston Birth Cohort (the parent study) was supported in part by the National Institutes of Health (NIH) grants (2R01HD041702, R01HD098232, R01ES031272, R21AI154233, R01ES031521, and U01 ES034983); and the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) (UT7MC45949). Dr. Yaskolka Meir is supported by the Council for Higher Education- Zuckerman support program for outstanding postdoctoral female researchers. This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by any funding agencies. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Written informed consent was obtained from all the study mothers. Institutional Review Boards of the Boston Medical Center and the Johns Hopkins Bloomberg School of Public Health approved the study. The study is also registered on ClinicalTrials.gov ([NCT03228875][1]). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data availability statement The data, data dictionary, and analytical programs for this manuscript are not currently available to the public. However, they can be made available upon reasonable request and after the review and approval of the institutional review board. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03228875&atom=%2Fmedrxiv%2Fearly%2F2023%2F11%2F03%2F2023.11.02.23297965.atom