Epigenetic signature of very low birth weight in young adult life

Epigenetic signature of very low birth weight in young adult life

Pediatric Research

10.1038/s41390-024-03354-6

https://doi.org/10.1038/s41390-024-03354-6

Juho Kuula, Darina Czamara, Helena Hauta-alus, Jari Lahti, Petteri Hovi, Maija E. Miettinen, Justiina Ronkainen, Johan G. Eriksson, Sture Andersson, Marjo-Riitta Jarvelin, Sylvain Sebert, Katri Räikkönen, Elisabeth B. Binder, Eero Kajantie

Genetics and Molecular Biology

19 June 2024

Kuula, J., Czamara, D., Hauta-alus, H., Lahti, J., Hovi, P., Miettinen, M. E., Ronkainen, J., Eriksson, J. G., Andersson, S., Järvelin, M.-R., Sebert, S., Räikkönen, K., Binder, E. B., & Kajantie, E. (2024). Epigenetic signature of very low birth weight in young adult life. Pediatric Research, 97(1), 229–238. https://doi.org/10.1038/s41390-024-03354-6

Abstract Background Globally, one in ten babies is born preterm (<37 weeks), and 1–2% preterm at very low birth weight (VLBW, <1500 g). As adults, they are at increased risk for a plethora of health conditions, e.g., cardiometabolic disease, which may partly be mediated by epigenetic regulation. We compared blood DNA methylation between young adults born at VLBW and controls. Methods 157 subjects born at VLBW and 161 controls born at term, from the Helsinki Study of Very Low Birth Weight Adults, were assessed for peripheral venous blood DNA methylation levels at mean age of 22 years. Significant CpG-sites (5’—C—phosphate—G—3’) were meta-analyzed against continuous birth weight in four independent cohorts (pooled n = 2235) with cohort mean ages varying from 0 to 31 years. Results In the discovery cohort, 66 CpG-sites were differentially methylated between VLBW adults and controls. Top hits were located in HIF3A, EBF4, and an intergenic region nearest to GLI2 (distance 57,533 bp). Five CpG-sites, all in proximity to GLI2, were hypermethylated in VLBW and associated with lower birth weight in the meta-analysis. Conclusion We identified differentially methylated CpG-sites suggesting an epigenetic signature of preterm birth at VLBW present in adult life. Impact Being born preterm at very low birth weight has major implications for later health and chronic disease risk factors. The mechanism linking preterm birth to later outcomes remains unknown. Our cohort study of 157 very low birth weight adults and 161 controls found 66 differentially methylated sites at mean age of 22 years. Our findings suggest an epigenetic mark of preterm birth present in adulthood, which opens up opportunities for mechanistic studies.

Attribution 4.0 International (CC BY 4.0)

This study was supported by the following institutions: the Doctoral Programme in Clinical Research, University of Helsinki; the Finnish Foundation for Pediatric Research; Finska Läkaresällskapet; the Juho Vainio Foundation; the Paulo Foundation; the Päivikki and Sakari Sohlberg Foundation; the Jalmari and Rauha Ahokas Foundation; the Novo Nordisk Foundation; the Signe and Ane Gyllenberg Foundation; the Sigrid Jusélius Foundation; and the Yrjö Jahnsson Foundation. The PREDO Study has been funded by the Academy of Finland (J.L.:311617 and 269925, K.R.: 1312670, 128789, 1287891, 1324596), Era Net Neuron, EVO (a special state subsidy for health science research), University of Helsinki Research Funds, the Signe and Ane Gyllenberg Foundation, the Emil Aaltonen Foundation, the Finnish Medical Foundation, the Jane and Aatos Erkko Foundation, the Novo Nordisk Foundation, the Päivikki, and Sakari Sohlberg Foundation, the Sigrid Juselius Foundation granted to members of the Predo study board. Methylation assays were funded by the Academy of Finland (269925). GLAKU cohort has been supported by the Academy of Finland, Hope and Optimism Initiative, the Signe and Ane Gyllenberg Foundation, the Emil Aaltonen Foundation, the Foundation for Pediatric Research, the Foundation for Cardiovascular Research, the Juho Vainio Foundation, the Sigrid Jusélius Foundation, the Yrjö Jahnsson Foundation, and the University of Helsinki Research Funds. NFBC1986 was funded by EU QLG1-CT-2000-01643 (EUROBLCS) Grant no. E51560, NorFA Grant no. 731, 20056, 30167, USA/NIH 2000 G DF682 Grant no. 50945. NFBC1966 31 yr follow-up received financial support from University of Oulu Grant no. 65354, Oulu University Hospital Grant no. 2/97, 8/97, Ministry of Health and Social Affairs Grant no. 23/251/97, 160/97, 190/97, National Institute for Health and Welfare, Helsinki Grant no. 54121, Regional Institute of Occupational Health, Oulu, Finland Grant no. 50621, 54231. J.R., M.R.J and S.S. were supported by European Union’s Horizon 2020 research and innovation program under grant agreements No 874739 (LongITools), 733206 (LifeCycle) and 633595 (DynaHEALTH) and Academy of Finland under grant agreement No 285547 (EGEA). NFBC1966 (31 years study) received financial support from University of Oulu Grant No. 65354, Oulu University Hospital Grant No. 2/97, 8/97, Ministry of Health and Social Affairs Grant No. 23/251/97, 160/97, 190/97, National Public Health Institute, Helsinki Grant No. 54121, Regional Institute of Occupational Health, Oulu, Finland Grant No. 50621, 54231, NHLBI Grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01), NIH/NIMH (5R01MH63706:02). NFBC1966 (46 years study) received financial support from University of Oulu Grant No. 24000692, Oulu University Hospital Grant No. 24301140, ERDF European Regional Development Fund Grant No. 539/2010 A31592. Open Access funding provided by Finnish Institute for Health and Welfare.

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