Increased mitochondrial oxygen consumption in adult survivors of preterm birth

Abstract

Background: Premature birth affects roughly 10% of live births and is associated with long-term increased risk for multiple comorbidities. Though many comorbidities are associated with increased oxidative stress, the potential late impact of extreme premature birth on mitochondrial function has not previously been assessed. We hypothesized that mitochondrial function would be impaired in adult survivors of premature birth. Methods: Mitochondrial function in peripheral blood mononuclear cells from young adults born moderately to extremely preterm was measured using a Seahorse XF Analyzer at baseline and in response to acute oxidative stress, and compared to age-matched term-born adults. Adult pulmonary function was also obtained. Results: Young adults born preterm (average gestational age 29 weeks) had increased mitochondrial oxygen consumption at baseline, particularly with respect to basal and non-ATP linked respiration. Maximal and spare capacity were also higher, even in response to acute oxidative stress. Lung function was lower in adults born preterm, and the degree of airflow obstruction correlated only modestly with mitochondrial function. Conclusion: In conclusion, adults born preterm have higher basal and non-ATP linked mitochondrial respiration. Similar mitochondrial profiles have previously been documented in diabetics, and may support the increased risk for cardiometabolic disease in adults born preterm.

Effects of Pre-Term Birth on the Cardio-Respiratory Responses to Hypoxic Exercise in Children

“…Pre-term children also displayed a lower peak V E and heart rate. Regarding baseline characteristics, in accordance with previous research [3,16,17], the pre-term participants in this study demonstrated a reduced peak expiratory flow rate and relative forced expiratory volume in the first second of exhalation than the full-term control group.…”

RETRACTED ARTICLE: The Effect of Preterm Birth on Maximal Aerobic Exercise Capacity and Lung Function in Healthy Adults: A Systematic Review and Meta-analysis

“…Specifically, mitochondrial density and function may play a role, in particular during exercise. Studies have postulated that impaired alveolar and cerebral white matter development in infants born prematurely may be linked to mitochondrial dysfunction [50], and that adults born preterm may have a (paradoxically) increased mitochondrial O 2 consumption [51]. As similarly increased O 2 consumption has been reported in diabetic patients, these data indicate a negative metabolic development that could be associated with an increased risk of disease.…”

Cardiac Left Ventricle Mitochondrial Dysfunction After Neonatal Exposure to Hyperoxia: Relevance for Cardiomyopathy After Preterm Birth

“… 51 In adults born preterm, mitochondrial oxygen consumption patterns in circulating peripheral blood mononuclear cells were similar to those reported for individuals diagnosed with metabolic diseases, such as type II diabetes. 52 These studies support the concept that preterm birth impacts cellular energetic metabolism in several tissues. To translate our experimental findings to a clinical context, we measured circulating levels of humanin, a peptide encoded by mtDNA and considered mitoprotective and cytoprotective.…”