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Pediatrics

Exploring mitochondrial heteroplasmy in neonates: implications for growth patterns and overweight in the first years of life

Abstract

Background

Mitochondrial heteroplasmy reflects genetic diversity within individuals due to the presence of varying mitochondrial DNA (mtDNA) sequences, possibly affecting mitochondrial function and energy production in cells. Rapid growth during early childhood is a critical development with long-term implications for health and well-being. In this study, we investigated if cord blood mtDNA heteroplasmy is associated with rapid growth at 6 and 12 months and overweight in childhood at 4–6 years.

Methods

This study included 200 mother-child pairs of the ENVIRONAGE birth cohort. Whole mitochondrial genome sequencing was performed to determine mtDNA heteroplasmy levels (in variant allele frequency; VAF) in cord blood. Rapid growth was defined for each child as the difference between WHO-SD scores of predicted weight at either 6 or 12 months and birth weight. Logistic regression models were used to determine the association of mitochondrial heteroplasmy with rapid growth and childhood overweight. Determinants of relevant cord blood mitochondrial heteroplasmies were identified using multiple linear regression models.

Results

One % increase in VAF of cord blood MT-D-Loop16362T > C heteroplasmy was associated with rapid growth at 6 months (OR = 1.03; 95% CI: 1.01–1.05; p = 0.001) and 12 months (OR = 1.02; 95% CI: 1.00–1.03; p = 0.02). Furthermore, this variant was associated with childhood overweight at 4–6 years (OR = 1.01; 95% CI 1.00–1.02; p = 0.05). Additionally, rapid growth at 6 months (OR = 3.00; 95% CI: 1.49–6.14; p = 0.002) and 12 months (OR = 4.05; 95% CI: 2.06–8.49; p < 0.001) was also associated with childhood overweight at 4–6 years. Furthermore, we identified maternal age, pre-pregnancy BMI, maternal education, parity, and gestational age as determinants of cord blood MT-D-Loop16362T > C heteroplasmy.

Conclusions

Our findings, based on mitochondrial DNA genotyping, offer insights into the molecular machinery leading to rapid growth in early life, potentially explaining a working mechanism of the development toward childhood overweight.

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Fig. 1: Volcano plot for the association between cord blood mitochondrial heteroplasmy and rapid growth at 6 (black) and 12 months (red).

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Data availability

The data used in this study are not publicly available because they contain information that could compromise research participant privacy but are available within General Data Protection Regulation restrictions from the corresponding author upon reasonable request.

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Acknowledgements

The ENVIRONAGE birth cohort is supported by the Methusalem Fund, the Research Foundation Flanders (FWO, grant numbers 1516112N, G.0873.11.N.10), and Kom op Tegen Kanker. CC was financially supported by the Special Research Fund of Hasselt University (grant number BOF22PD04) and Fund Orcadia (grant number 2022-E2210890-228297), managed by the King Baudouin Foundation. FWO financially supported RA (grant number 1296523N) and DSM (grant number 12X9623N). The authors are extremely grateful to the participating women and neonates, as well as the staff of the maternity ward, midwives, and the staff of the clinical laboratory of East-Limburg Hospital in Genk.

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Contributions

Charlotte Cosemans: conceptualization, methodology, formal analysis, investigation, writing—original draft, writing—review & editing, visualization. Rossella Alfano: data curation, writing—review & editing. Hanne Sleurs: investigation, writing—review & editing. Dries S. Martens: investigation, writing—review & editing. Tim S. Nawrot: conceptualization, funding acquisition, writing—review & editing, supervision. Michelle Plusquin: conceptualization, writing—review & editing, supervision.

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Correspondence to Michelle Plusquin.

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Cosemans, C., Alfano, R., Sleurs, H. et al. Exploring mitochondrial heteroplasmy in neonates: implications for growth patterns and overweight in the first years of life. Int J Obes (2024). https://doi.org/10.1038/s41366-024-01537-z

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