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Preterm infant lung disease may be predictable

Tests of cells collected from the umbilical cord blood walls at birth can predict poor pulmonary outcomes or even death in extremely preterm infants, say researchers at the University of Alabama at Birmingham.

Explains Jegen Kandasamy MD, a neonatologist and assistant professor of pediatrics at the University of Alabama at Birmingham (UAB), "Now that we know there is useful information from cells we obtain from the umbilical cord, we could use their bioenergetics as a biomarker and for therapy approaches before bronchopulmonary dysplasia develops."

Bronchopulmonary dysplasia, or BPD, is a lung-function abnormality that affects one-fourth to one-half of extremely low birthweight premature infants, mostly those who need to be given prolonged oxygen therapy. This therapy creates reactive oxygen in the lung, and that stress along with some other contributors, can lead to chronic or life-threatening lung disease as it interferes with the still-developing maturation of the lung. Tiny lung saccules normally continue to develop throughout the last 14 weeks of a full-term gestation, and for another five weeks after birth.

The work is published in the American Journal of Respiratory and Critical Care Medicine.

"Every baby who is born extremely prematurely needs to have such lung injury minimized, or else they can go downhill pretty quickly."

Reyad A. Elbarbary PhD, Assistant Professor, Jegen Kandasamy MD, Neonatologist, Assistant Professor, Pediatrics, University of Alabama at Birmingham, Alabama, USA and corresponding author for the study.

Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen. In a biological context, ROS are formed as a natural byproduct of the normal metabolism of oxygen. They have important roles in cell signaling and cell stability.

Researchers collected blood endothelial cells from umbilical cords of 69 infants born at 26 weeks, on average, gestation. Average birthweight for these infants was 1.9 pounds; 34 survived without BPD, and 35 developed BPD. Of those 35, 24 survived with BPD and 11 died before their BPD status could be assessed at 36 weeks gestational age. These infants' umbilical vascular endothelial cells were grown in culture and tested for mitochondrial energy function and oxygen generation. Mitochondria are small organelles inside our cells that are often called the batteries of the cell as they generate most of a cell's ATP, a chemical form of energy. Oxidative stress can damage mitochondria, causing the release of dangerous reactive oxygen species.

Kandasamy and colleagues found that the endothelial cells of infants who developed BPD or died when compared to endothelial cells of infants who survived without developing BPD had significantly lower oxygen consumption rates, produced more superoxide after exposure to excess oxygen, and released more hydrogen peroxide after exposure to excess oxygen. Superoxide and hydrogen peroxide are two types of reactive oxygen species.

The changes in endothelial cells of the infants who developed BPD or who died, as well as increased damage to mitochondrial DNA and some other observed changes, indicated they had impaired vascular endothelial mitochondrial function. This impaired function is a potential biomarker for BPD susceptibility in preterm infants, and it could help modify therapeutic strategies to decrease the risk of poor lung outcomes in future preterm births.

The UAB researchers believe this is the first study to suggest that mitochondrial dysfunction in human-derived vascular endothelial cells are a strong predictor for BPD risk in premature infants.

"We are the first to study these cells from a baby's umbilical cord and compare their function to risk for diseases in the same baby."

Jegen Kandasamy MD, Neonatologist, Assistant Professor, Pediatrics, University of Alabama at Birmingham, Alabama, USA and corresponding author for the study.

Rationale: Vascular endothelial mitochondrial dysfunction contributes to the pathogenesis of several oxidant stress associated disorders. Oxidant stress is a major contributor to the pathogenesis of bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity that often leads to sequelae in adult survivors. Objectives: This study was conducted to identify whether differences in mitochondrial bioenergetic function and oxidant generation in HUVEC (human umbilical venous endothelial cells) obtained from extremely preterm infants were associated with risk for BPD or death before 36 weeks post-menstrual age. Methods: HUVEC oxygen consumption and superoxide and hydrogen peroxide generation were measured in 69 infants. Results: When compared to HUVECs from infants who survived without BPD, HUVEC obtained from infants who developed BPD or died had lower maximal OCR (mean SEM in pmol/min/30,000 cells, 107 8 vs. 235 22, p < 0.001), produced more superoxide after exposure to hyperoxia (mean SEM in MitoSox Red fluorescence units: 89807 16616 vs. 162706 25321, p < 0.05) and released more hydrogen peroxide (H2O2) into their supernatant after hyperoxia exposure (mean SEM in resorufin arbitrary fluorescence units, 1879 278 vs. 842 119, p < 0.001). Conclusions: Our results indicating that endothelial cells of premature infants who later develop BPD or die have impaired mitochondrial bioenergetic capacity and produce more oxidants at birth suggest that the vascular endothelial mitochondrial dysfunction seen at birth in these infants persists through their postnatal life and contributes to adverse pulmonary outcomes and increased early mortality.

Other authors: Nelida Olave , Scott W Ballinger , and Namasivayam Ambalavanan

Keywords: Bioenergetics Bronchopulmonary dysplasia Vascular endothelium Reactive oxygen species MtDNA

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May 26, 2017   Fetal Timeline   Maternal Timeline   News   News Archive   

Neonate with bronchopulmonary dysplasia receiving treatment in isolate(BPD).jpg

Bronchopulmonary dysplasia (BPD) or chronic lung disease (CLD) is the term given to
persisting lung symptoms that develop in a proportion fo usually very preterm babies
born before (<32 weeks) who are treated with oxygen and mechanical ventilation.
Image Credit: Euorpean Foundation for the care of newborn infants


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