Mitochondrial DNA haplogroups and circulating cell-free mitochondrial DNA as biomarkers of bronchopulmonary dysplasia.

BACKGROUND

Recognizing which premature infants are at higher risk of developing BPD/death is a challenge in neonatology. The aims of our study are to identify mitochondrial haplogroups and quantify circulating cell-free mitochondrial DNA (ccf-mtDNA) levels in very preterm infants at risk of bronchopulmonary dysplasia (BPD) or death and explore the relationship between these variables and the development of BPD/death.

METHODS

Single-center prospective cohort study including preterm infants of ≤32 weeks gestational age (GA) and birth weight ≤1500 g. Clinical variables, mitochondrial haplogroups, and ccf-mtDNA levels were determined. Subsequently, diagnosis and staging of BPD/death were performed, and groups were compared.

RESULTS

The population consisted of 107 newborns (mean GA 28.73 ± 2 weeks; mean birth weight 1,121 ± 332 g). A total of 44 patients (41.1%) presented the outcome of BPD/death without differences in haplogroup distribution and ccf-mtDNA levels between those who survived without BPD (controls). Variables independently associated with BPD/death included GA (p < 0.001; OR = 0.36 [95%CI 0.23-0.5]), birth weight (p < 0.001; OR = 0.99 [95%CI 0.99-0.99]), maximum FiO in the delivery room (p = 0.001; OR = 1.07 [95%CI 1.03-1.12]), hours on mechanical ventilation (p = 0.02; OR 1.02 [95%CI 1.00-1.02]), and postnatal corticosteroids (p < 0.001; OR = 47.12 [95%CI = 5.98-371.1]).

CONCLUSION

This is the first study to characterize mtDNA haplogroups and ccf-mtDNA in very preterm infants at risk of BPD/death. None of the mitochondrial variables studied were associated with BPD/death. Further research is needed to elucidate the role of mtDNA in BPD.

IMPACT STATEMENT

Despite advances in perinatal care, bronchopulmonary dysplasia continues to be the most common chronic pulmonary morbidity associated with prematurity. Prediction of BPD in early stages is crucial to improve BPD rates, but this remains a major challenge in neonatal units. Given that mitochondria play an important role in the inflammatory and oxidative stress responses, we aimed to explore the relationship between mitochondrial haplogroups, circulating cell-free mitochondrial DNA levels, and BPD. This is the first work carried out in very preterm infants where mitochondrial haplogroups and the levels ccf-mtDNA are investigated with the intention of discovering a new biomarker for BPD.