Fernandez-Gonzalez Sara María, Sucasas-Alonso Andrea, Balboa-Barreiro Vanesa, Rego-Perez Ignacio, Avila-Alvarez Alejandro
Neonatology Department, Complexo Hospitalario Universitario A Coruña (CHUAC), A Coruña, Spain.
Biostatistics and Epidemiology Unit, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), A Coruña, Spain.
Pediatr Res. 2025 Apr 17. doi: 10.1038/s41390-025-04052-7.
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.
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.
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]).
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.
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.
识别哪些早产儿发生支气管肺发育不良（BPD）/死亡的风险较高是新生儿学中的一项挑战。我们研究的目的是确定有BPD或死亡风险的极早产儿的线粒体单倍群，并定量循环游离线粒体DNA（ccf-mtDNA）水平，探讨这些变量与BPD/死亡发生之间的关系。
单中心前瞻性队列研究，纳入孕周≤32周（GA）且出生体重≤1500g的早产儿。测定临床变量、线粒体单倍群和ccf-mtDNA水平。随后，对BPD/死亡进行诊断和分期，并对各组进行比较。
该人群由107例新生儿组成（平均GA 28.73±2周；平均出生体重1121±332g）。共有44例患者（41.1%）出现BPD/死亡结局，在无BPD存活者（对照组）之间，单倍群分布和ccf-mtDNA水平无差异。与BPD/死亡独立相关的变量包括GA（p<0.001；OR=0.36[95%CI 0.23-0.5]）、出生体重（p<0.001；OR=0.99[95%CI 0.99-0.99]）、产房内最高吸氧浓度（p=0.001；OR=1.07[95%CI 1.03-1.12]）、机械通气时间（p=0.02；OR 1.02[95%CI 1.00-1.02]）和产后使用糖皮质激素（p<0.001；OR=47.12[95%CI=5.98-371.1]）。
这是第一项对有BPD/死亡风险的极早产儿的线粒体DNA单倍群和ccf-mtDNA进行特征分析的研究。所研究的线粒体变量均与BPD/死亡无关。需要进一步研究以阐明线粒体DNA在BPD中的作用。
尽管围产期护理取得了进展，但支气管肺发育不良仍然是与早产相关的最常见的慢性肺部疾病。早期预测BPD对于提高BPD发生率至关重要，但这仍然是新生儿病房面临的一项重大挑战。鉴于线粒体在炎症和氧化应激反应中起重要作用，我们旨在探讨线粒体单倍群、循环游离线粒体DNA水平与BPD之间的关系。这是在极早产儿中开展的第一项研究，旨在通过研究线粒体单倍群和ccf-mtDNA水平来发现一种新的BPD生物标志物。
