Parenteral nutrition as a risk factor for bronchopulmonary dysplasia: its role and possible mechanisms in infants less than 29 weeks gestation
Bibliographic record
Abstract
One of the most devastating prematurity complications is bronchopulmonary dysplasia (BPD). BPD etiology is multifactorial and one major factor is early oxidative stress due to high oxygen exposure. The relationship between non-radical oxidative stress (redox stress) caused by the peroxides contaminating the parenteral nutrition (PN) and BPD is less studied. Studies applying complete photoprotection of PN, which can decrease the peroxide contamination of PN by half, decreased BPD by 25-30%. A correlation between the redox potential on day 7 of life and BPD severity was demonstrated in preterm infants. Hypothesis and objectives: Hypothesis: Peroxides contaminating PN lead to prolonged redox stress and contribute to the development of BPD. This effect is due to deficient detoxification of peroxides. Objectives: - To study the post PN redox stress duration and its impact on BPD in relation to other oxidants (O2, infection, blood transfusion) - To test if the deficient peroxides’ detoxification is related to glutathione deficiency - To evaluate first week urinary ascorbylperoxide concentration as a BPD biomarker Patients and methods: One hundred sixteen infants < 29 weeks of gestation were followed until 36 weeks postmenstrual age (PMA). Fifty-one families gave consent for urine and blood samples. The first objective was achieved by measuring total blood reduced (GSH) and disulfide (GSSG) glutathione at 36 weeks PMA using capillary electrophoresis to calculate the redox potential using Nernst equation. For the second objective, total plasma glutathione, red blood cell glutathione reductase (GR) and peroxidase (GPx) activities were measured on day 7 of life. The third objective was achieved by measuring ascorbylperoxide (AscOOH) in the urine on days 3, 5 and 7 of life. Chi-square, t-student, ANOVA, linear regression and repeated measure ANOVA were used as appropriate; p< 0.05 was significant. Results: PN duration > 14 days was associated with more oxidized redox potential (-193±5 versus -203±2 mV) and more BPD (89% versus 24%). FiO2 ≥ 25% on day 7 of life was also associated with a more oxidized redox potential (-191±2 versus -198 ±2 mV) and more BPD (90% versus 45%). The effects of PN and FiO2 on redox potential and BPD were additive. In logistic regression model, each 1% increase in FiO2 and each day increase on PN resulted in an increase in the OR for BPD by1.57 (1.09 - 2.28) and 1.17 (1.03 - 1.33) respectively. Compared to normal values, total plasma glutathione concentration was low (1.02, 0.49-1.76 µmol/l: median, 25th –75th percentiles) whereas GPx and GR activities were sufficient. Urinary AscOOH increased overtime (p=0.001) and was higher in infants who later developed BPD or death (p=0.037). Conclusion: Early O2 and peroxides contaminating PN have additive effects associated with prolonged oxidative stress and increased BPD. Extremely preterm infants have low glutathione level that limits their capacity to detoxify peroxides. Higher first week urinary AscOOH levels are associated with increased BPD or death. Judicious use of oxygen decreasing the duration or developing a safer formulation of PN and GSH replacement therapy should be investigated as strategies to decrease BPD in extremely preterm infants.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".