Assoc. Prof. Dr. Doğan Köse Oxidative Stress and DNA Damage Profile in Cord Blood of Vitamin B₁₂-Deficient Newborns
B₁₂ Deficiency, Oxidative Stress and Neonatal DNA Damage
Abstract
Background: Vitamin B₁₂ is an essential micronutrient that plays a critical role in DNA synthesis, methylation, and cellular energy metabolism. Its deficiency during the intrauterine period has been associated with increased oxidative stress and DNA damage, which may have lasting effects on the newborn. 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative DNA damage, is widely used to evaluate these processes. However, the effects of vitamin B₁₂ deficiency on such biomarkers at birth remain insufficiently investigated.
Methods: This single-center, prospective case-control study included 48 term newborns with vitamin B₁₂ deficiency and 40 healthy controls matched for gestational age. Vitamin B₁₂, total oxidant status, total antioxidant status, oxidative stress index, and 8-hydroxy-2'-deoxyguanosine were measured from umbilical cord venous blood obtained immediately after delivery. Oxidant and antioxidant levels were determined using colorimetric methods, and oxidative DNA damage was assessed by enzyme-linked immunosorbent assay. Group comparisons were made using appropriate statistical tests, with significance set at p<0.05.
Results: Vitamin B₁₂ levels were significantly lower in the patient group. Levels of 8-hydroxy-2'-deoxyguanosine, total oxidant status, and oxidative stress index were significantly higher, whereas total antioxidant status showed no significant difference between groups.
Conclusions: Term newborns with vitamin B₁₂ deficiency exhibited increased oxidative stress and measurable oxidative DNA damage at birth. The unchanged total antioxidant status may reflect the immature antioxidant defense system in the neonatal period. Biomarker evaluation at delivery could assist in early identification and intervention for infants at risk of complications associated with intrauterine vitamin B₁₂ deficiency.
References
2. La Colla A, Cámara CA, Campisano S, Chisari AN. Mitochondrial dysfunction and epigenetics underlying the link between early-life nutrition and non-alcoholic fatty liver disease. Nutr Res Rev. 2023; 36: 281-94. https://pubmed.ncbi.nlm.nih.gov/35067233/
3. Finkelstein JL, Layden AJ, Stover PJ. Vitamin B-12 and perinatal health. Adv Nutr. 2015; 6: 552-63. https://pubmed.ncbi.nlm.nih.gov/26374177/
4. Wirthensohn M, Wehrli S, Ljungblad UW, Huemer M. Biochemical, nutritional, and clinical parameters of vitamin B12 deficiency in infants: a systematic review and analysis of 292 cases published between 1962 and 2022. Nutrients. 2023; 15: 4960. https://www.mdpi.com/2072-6643/15/23/4960
5. Tat L, Cannizzaro N, Schaaf Z, Racherla S, Bottiglieri T, Green R, et al. Prenatal folic acid and vitamin B12 imbalance alter neuronal morphology and synaptic density in the mouse neocortex. Commun Biol. 2023; 6: 1133. https://pubmed.ncbi.nlm.nih.gov/37938221/
6. O’Leary F, Samman S. Vitamin B12 in health and disease. Nutrients. 2010; 2: 299-316. https://pubmed.ncbi.nlm.nih.gov/22254022/
7. van de Lagemaat EE, de Groot LCPGM, van den Heuvel EGHM. Vitamin B12 in relation to oxidative stress: a systematic review. Nutrients. 2019; 11: 482. https://pubmed.ncbi.nlm.nih.gov/30823595/
8. Cadet J, Wagner JR. DNA base damage by reactive oxygen species, oxidizing agents, and UV radiation. Cold Spring Harb Perspect Biol. 2013; 5: a012559. https://pubmed.ncbi.nlm.nih.gov/23378590/
9. Tain YL, Hsu CN. Perinatal oxidative stress and kidney health: bridging the gap between animal models and clinical reality. Antioxidants (Basel). 2022; 12: 13. https://pubmed.ncbi.nlm.nih.gov/36670875/
10. Siddiqua TJ, Akhtar E, Haq MA, Shahab-Ferdows S, Hampel D, Islam S, et al. Effects of vitamin B12 supplementation on oxidative stress markers and pro-inflammatory cytokines during pregnancy and postpartum among Bangladeshi mother-child pairs. BMC Nutr. 2024; 10: 3. https://pubmed.ncbi.nlm.nih.gov/38172996/
11. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005; 38: 1103-11. https://pubmed.ncbi.nlm.nih.gov/16214125/
12. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004; 37: 112-19. https://pubmed.ncbi.nlm.nih.gov/14725941/
13. Cayman Chemical. DNA/RNA oxidative damage (high sensitivity) ELISA kit – item no. 589320 [Internet]. Ann Arbor (MI): Cayman Chemical; [cited 2025 Aug 2]. https://www.caymanchem.com/product/589320.
14. Friso S, Choi SW. Gene-nutrient interactions in one-carbon metabolism. Curr Drug Metab. 2005; 6: 37-46. https://pubmed.ncbi.nlm.nih.gov/15720206/
15. Valavanidis A, Vlachogianni T, Fiotakis K. 8-hydroxy-2′-deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2009; 27: 120-39. https://pubmed.ncbi.nlm.nih.gov/19412858/
16. Shigenaga MK, Ames BN. Assays for 8-hydroxy-2′-deoxyguanosine: a biomarker of in vivo oxidative DNA damage. Free Radic Biol Med. 1991; 10: 211-16. https://pubmed.ncbi.nlm.nih.gov/1650737/
17. Elkabany ZA, El-Farrash RA, Shinkar DM, Ismail EA, Nada AS, Farag AS, et al. Oxidative stress markers in neonatal respiratory distress syndrome: advanced oxidation protein products and 8-hydroxy-2-deoxyguanosine in relation to disease severity. Pediatr Res. 2020; 87: 74-80. https://pubmed.ncbi.nlm.nih.gov/31216566/
18. Shoji H, Ikeda N, Hosozawa M, Ohkawa N, Matsunaga N, Suganuma H, et al. Oxidative stress early in infancy and neurodevelopmental outcome in very low-birthweight infants. Pediatr Int. 2014; 56: 709-13. https://pubmed.ncbi.nlm.nih.gov/24617865/
19. Fırat CK, Ozkan BN, Güler EM. Beneficial effects of vitamin B₁₂ treatment in pediatric patients diagnosed with vitamin B₁₂ deficiency regarding total-native thiol, oxidative stress, and mononuclear leukocyte DNA damage. Free Radic Res. 2022; 56: 631-39. https://pubmed.ncbi.nlm.nih.gov/36571212/
20. Lembo C, Buonocore G, Perrone S. Oxidative stress in preterm newborns. Antioxidants (Basel). 2021; 10: 1672. https://pubmed.ncbi.nlm.nih.gov/34829543/
21. Güney T, Alişik M, Akinci S, Neşelioğlu S, Dilek İ, Erel O. Evaluation of oxidant and antioxidant status in patients with vitamin B12 deficiency. Turk J Med Sci. 2015; 45: 1280-84. https://pubmed.ncbi.nlm.nih.gov/26775383/
22. Sukumar N, Rafnsson SB, Kandala NB, Bhopal R, Yajnik CS, Saravanan P. Prevalence of vitamin B-12 insufficiency during pregnancy and its effect on offspring birth weight: a systematic review and meta-analysis. Am J Clin Nutr. 2016; 103: 1232-51. https://pubmed.ncbi.nlm.nih.gov/27076577/
23. Rogne T, Tielemans MJ, Chong MF-F, Yajnik CS, Krishnaveni GV, Poston L, et al. Associations of maternal vitamin B12 concentration in pregnancy with the risks of preterm birth and low birth weight: a systematic review and meta-analysis of individual participant data. Am J Epidemiol. 2017; 185: 212-23. https://pubmed.ncbi.nlm.nih.gov/28108470/
24. Roy S, Kale A, Dangat K, Sable P, Kulkarni A, Joshi S. Maternal micronutrients (folic acid and vitamin B₁₂) and omega-3 fatty acids: implications for neurodevelopmental risk in the rat offspring. Brain Dev. 2012; 34: 64-71. https://pubmed.ncbi.nlm.nih.gov/21300490/
25. McCullough LE, Miller EE, Mendez MA, Murtha AP, Murphy SK, Hoyo C. Maternal B vitamins: effects on offspring weight and DNA methylation at genomically imprinted domains. Clin Epigenetics. 2016; 8: 8. https://pubmed.ncbi.nlm.nih.gov/26807160/
26. Monasso GS, Hoang TT, Mancano G, Fernández-Barrés S, Dou J, Jaddoe VWV, et al. A meta-analysis of epigenome-wide association studies on pregnancy vitamin B12 concentrations and offspring DNA methylation. Epigenetics. 2023; 18: 2202835. https://pubmed.ncbi.nlm.nih.gov/37093107/
27. Díaz-García H, Vilchis-Gil J, García-Roca P, Klünder-Klünder M, Gómez-López J, Granados-Riverón JT, et al. Dietary and antioxidant vitamins limit the DNA damage mediated by oxidative stress in the mother–newborn binomial. Life (Basel). 2022; 12: 1012. https://pubmed.ncbi.nlm.nih.gov/35888100/
28. Guo Q, Jin Y, Chen X, Ye X, Shen X, Lin M, et al. NF-κB in biology and targeted therapy: new insights and translational implications. Signal Transduct Target Ther. 2024; 9: 53. https://pubmed.ncbi.nlm.nih.gov/38433280/
29. Ali AAH, Mohamed FHA, Hago S, Elgali IFES, Mohammed HES, Mirghani RG. The neurological sequelae of vitamin B12 deficiency: a systematic review and randomized controlled trial. Cureus. 2025; 17: e83668. https://pubmed.ncbi.nlm.nih.gov/40486314/
Copyright (c) 2025 Doğan Köse, Mahmut Demir
This work is licensed under a Creative Commons Attribution 4.0 International License.
The published articles will be distributed under the Creative Commons Attribution 4.0 International License (CC BY). It is allowed to copy and redistribute the material in any medium or format, and remix, transform, and build upon it for any purpose, even commercially, as long as appropriate credit is given to the original author(s), a link to the license is provided and it is indicated if changes were made. Users are required to provide full bibliographic description of the original publication (authors, article title, journal title, volume, issue, pages), as well as its DOI code. In electronic publishing, users are also required to link the content with both the original article published in Journal of Medical Biochemistry and the licence used.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.