Bronchopulmonary Dysplasia, Infant, Newborn, Disease, Infant, Premature, Diseases, Lung Diseases, Parenteral Nutrition, Pathologic Processes, Respiratory Tract Disease
Conditions
Keywords
Photo-protection of Multivitamins, Oxidative Stress, Ascorbyl peroxide, Urine peroxides
Brief summary
The purpose of this study is to examine if a new and simple method involving complete photo-protection of multivitamins only (since sampling through infusion) will result in a significant reduction of peroxide contamination of parenteral nutrition compared to standard method of parenteral nutrition preparation and infusion in extremely preterm infants.
Detailed description
Hypothesis and Objectives: The investigators propose, in this pilot study, a new and simple method involving complete photo-protection of multivitamins (MV) only (since sampling through infusion) and they hypothesize that this method will be readily applicable and will result in a significant reduction of peroxide contamination of parenteral nutrition (PN) compared to standard care of PN preparation and infusion method. In Vitro Results Using This Proposed Photo-Protection Method: This method has reduced the quantity of infused peroxides (as equivalent H2O2). When adding the generated peroxides over 5 hours (5 samples: at times 0, 30 minutes, 1, 3 and 5 hours), the total peroxides were 1270± 47 micromolar (μM) without photo-protection vs. 710±16 μM with this method, leading to 45% reduction of peroxides (data presented as a poster presentation in the Pediatric academic societies meeting , 2018, Poster number 2874.625). This reduction is comparable to the previously reported in vitro data for the whole PN complete photo-protection that reported 50% reduction of peroxides. Specific objective of this pilot study: To examine if this new and simple method will be feasible in clinical practice and will result in a significant reduction of urinary peroxide concentration when compared to standard PN compounding and infusion technique. Innovation: The investigators' team's long experience in this field permitted the identification of the interaction between light and MV (specifically riboflavin) that leads to doubling the amount of peroxides contaminating the PN. The complexity of complete photo-protection encountered by the team to conduct small uni-center studies and the incapacity to introduce the complete photo-protection in daily clinical practice led the team to create this simple intervention that will address the problem at its origin in a practical way. All trials, including complete PN photo-protection, faced the complexity of keeping MV away from light while needing to prepare the PN admixture under the light of a sterile hood. Added to this was the complexity of completely covering the PN bag while compounding the admixture. Light exposure may also occur during the transportation of the PN from the hospital pharmacy to the neonatal unit (even with special attention to the bottom of the bag and the area around the tubing being well covered). The proposed intervention will eliminate all these complex procedures by directly sampling the MV in a photo-protected syringe, transporting it in this syringe, and directly infusing the MV into the photo-protected intravenous lines through its infusion into the patient.
Interventions
OTHERPhoto-protection
The MV solution is delivered from producing companies in amber vials. The MV will be sampled by the pharmacy technician in a syringe that is photo-protected with a white label indicating the subject study name, protocol number and the infusion rate. The MV will be transported to the unit in the same photo-protected syringe. In the neonatal unit, this syringe will be installed in the pump and connected to photo-protected extension duration.
OTHERStandard Care
This group will receive the standard practice of PN compounding in the pharmacy followed by infusion in standard infusion kit available in Sainte-Justine's Hospital.
Sponsors
St. Justine's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
The primary outcome is the concentration of peroxides in the urine. The urine samples will not indicate the arm of the study.
Eligibility
Sex/Gender
ALL
Age
1 Minutes to 2 Days
Healthy volunteers
No
Inclusion criteria
* Infants \< 28 weeks of gestational age * Obtaining parental consent before the start of the first PN prescribed by the attending physician
Exclusion criteria
* Significant congenital malformations * Infant is currently enrolled in another trial -unless approval of trial research team- * Parent inability to comprehend and consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in urine peroxides concentration | Baseline, 48 hours post-parenteral nutrition and on day 7 of life | From each urine sample, an aliquot (0.2 ml) will be used for creatinin measurement whereas another (0.5 ml) will be used for peroxide determination using the ferrous oxidation/xylenol orange technique. H2O2 will serve for the standard curve. The results will be expressed as μmol equ H2O2/mg creatinine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Whole blood glutathione redox potential | On day 7 of life | Whole blood levels of glutathione (GSH) and glutathione disulfide (GSSG) will be measured by capillary electrophoresis as previously described by the investigators' team, using 0.5 ml of blood. The whole blood redox potential (mV) will be calculated, using the Nernst equation. |
| Serum inflammatory cytokines: Interleukin 1 alpha (IL-1alpha) and beta (IL-1beta), Interleukin 6 (IL-6), Interleukin 8 (IL-8), Interleukin (IL-10), Tumor Necrosis Factor alpha (TNF-alpha), Vascular Endothelial Growth Factor (VEGF) | On day 7 of life | Multiplex assay (Luminex R&D systems), using 0.1 ml of blood |
| Serum inflammatory cytokines: IL-1alpha, IL-1beta, IL-6, IL-8, IL-10, TNF-alpha, VEGF | At 36 weeks Post-Menstrual Age | Multiplex assay (Luminex R&D systems), using 0.1 ml of blood |
| Clinical outcome - Incidence of Bronchopulmonary dysplasia (BPD) and BPD severity (Mild, moderate, sever) | At 36 weeks Post-Menstrual Age | According to the National Institute of Child Health and Human Development (NICHD) criteria (Jobe Alan H.,2001) |
| Clinical outcome - Mortality rate | At 36 weeks Post-Menstrual Age | Death before 36 weeks post menstrual age |
| Clinical outcome - length of mechanical ventilation (invasive, non-invasive) | From birth to discharge home, an average of 4 months | Total number of days on mechanical ventilation (both invasive and non invasive respiratory support) |
| Clinical outcome - length of supplemental oxygen (in days) | From birth to discharge home, an average of 4 months | Total number of days on Nasal cannula O2 supplements |
| Clinical outcome - Incidence and stage of necrotizing enterocolitis (According to Bell's classification) | From birth to discharge home, an average of 4 months | Necrotizing enterocolitis stages as defind by Bell stage II or higher. The incidence in the two arms will be reported and compared |
| Urinary ascorbylperoxide (AscOOH) | On day 7 of life | Urine AscOOH concentration will be determined using Mass spectrometry. |
| Clinical outcome - Incidence of significant liver cholestasis (defined as two or more consecutive conjugated bilirubin values ≥ 34 μmol/L) | From birth to discharge home, an average of 4 months | Cholestasis is defined as two or more consecutive conjugated bilirubin values ≥ 34 μmol/L. The incidence of cholestasis in each arm will be reported and compared. |
| Clinical outcome - Incidence and stage of Retinopathy Of Prematurity (ROP) (highest stage) | From birth to discharge home, an average of 4 months | The incidence of ROP stage II and higher as defined by the National Eye Institute will be reported and compared. |
| Clinical outcome - Incidence of significant Patent Ductus Arteriosus (PDA) | From birth to discharge home, an average of 4 months | PDA requiring medical or surgical treatment according to the treating neonatologist will be reported and compared. |
| Clinical outcome - infant anthropometry: weight | At 36 weeks Post-Menstrual Age | Weight in grams |
| Clinical outcome - infant anthropometry: length | At 36 weeks Post-Menstrual Age | Length in centimeters |
| Clinical outcome - infant anthropometry: head circumference | At 36 weeks Post-Menstrual Age | Head circumference in centimeters |
| Clinical outcome - length of hospital stay (in days) | From birth to discharge home, an average of 4 months | Total number of days till discharge home |
| Clinical outcome - Incidence and grade of intraventricular hemorrhage (IVH), according to Papille criteria | From birth to discharge home, an average of 4 months | Any intraventricular hemorrhage (IVH), IVH grade III and IV in each arm will be reported and compared. |
Countries
Canada
Outcome results
None listed