Enteral Zinc to Improve Growth in Infants at Risk for Bronchopulmonary Dysplasia

Study Overview
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Brief Summary
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Multiple factors contribute to growth failure in infants with BPD, including poor nutrient stores, inadequate intake, increased losses, and increased needs. Furthermore, compared to infants without BPD, those with BPD have increased resting metabolic rates and energy expenditure. Growth deficits manifest as lower weight, length, and head circumference, as well as changes in body composition. These deficits precede the development of BPD and persist post-discharge. While similar rates of growth are observed in very low birth weight infants with and without BPD once receiving equal calories, catch up growth does not occur in the BPD group. Thus, early growth deficits remained uncompensated. After iron, zinc is the most metabolically active trace element in the human body. It has a critical role in growth, through its actions on growth hormone, IGF-1, IGFBP-3, and bone metabolism. Prematurity is a risk factor for zinc deficiency, as 60% of zinc accretion occurs in the third trimester. Impaired intake and absorption or excess excretion can further increase this risk. Finally, periods of rapid growth, as seen in preterm infants, increase the need for zinc. Biochemically, zinc deficiency is defined by a serum zinc level less than 55mcg/dl. However, while zinc depletion is associated with deficiency, the opposite may not be true. For example, in starving patients, clinical symptoms of zinc deficiency occur during re-feeding, suggesting overall requirements are related to needs, regardless of overall zinc status. This may be the case in preterm infants, who may have a subclinical deficiency despite serum zinc level. Thus, zinc deficiency should be considered in infants with poor growth despite receiving adequate protein and calories. The objective of this study is to determine whether enteral zinc supplementation leads to improved growth in infants at risk for bronchopulmonary dysplasia (BPD). The investigator's hypothesis is that enteral zinc supplementation in very preterm infants at high risk for BPD will significantly improve growth compared to standard of care.

Official Title
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Enteral Zinc to Improve Growth in Infants at Risk for Bronchopulmonary Dysplasia

Conditions
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Infant,Premature, Bronchopulmonary Dysplasia, Growth Failure

Intervention / Treatment
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* Dietary Supplement: Zinc Acetate
* Other: No supplemental zinc


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 23 0/7 to 29 6/7 weeks GA Birth weight 501 to 1000g, inclusive 14 to 28 days of life, inclusive 14 day BPD risk score ≥ 50% for death or moderate-severe BPD, calculated using the algorithm on the Neonatal Research Network website (https://neonatal.rti.org/index.cfm?fuseaction=BPDCalculator.start).- Exclusion Criteria: Major congenital and/or chromosomal anomalies Inability to reach 80ml/kg/day enteral feeds by 28 days of life

Ages Eligible for Study
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Minimum Age: 14 Days
Maximum Age: 28 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Infants will be stratified by gestational age (23-24 wks, 25-26 wks, 27-29 wks) and then are randomized to receive supplemental oral zinc acetate or no zinc acetate.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Zinc plus standard of care<br>Infants will receive daily doses of zinc at 2mg/kg from enrollment through 35 6/7 weeks corrected gestational age. | Dietary Supplement: Zinc Acetate<br>* Zinc Acetate given with elemental zinc dose of 2mg/kg given orally only daily through 35 6/7 weeks corrected gestational age<br>|
| Placebo Comparator: Standard of care only<br>Infants will not receive any doses of zinc through 35 6/7 weeks corrected gestational age | Other: No supplemental zinc<br>* Infants will receive standard of care, which is currently no supplemental zinc<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth rate for weight (g/kg/day) from birth to 36+0 weeks corrected gestational age (CGA) | Average daily changes in weight from birth to 36+0 CGA will be calculated and compared between both arms. | Birth to 36+0 weeks corrected gestational age | 
| Growth rate for weight (g/kg/day) from birth to 40+0 weeks CGA | Average daily changes in weight from birth to 40+0 CGA (or discharge, whichever happens first) will be calculated and compared between both arms. | Birth to 40+0 weeks corrected gestational age | 
| Growth rate for length (cm/week) from birth to 36+0 weeks CGA | Average weekly changes in length from birth to 36+0 weeks CGA will be calculated and compared between both arms. | Birth to 36+0 weeks corrected gestational age | 
| Growth rate for length (cm/week) from birth to 40+0 weeks CGA | Average weekly changes in length from birth to 40+0 weeks (or discharge, whichever happens first) CGA will be calculated and compared between both arms. | Birth to 40+0 weeks corrected gestational age | 
| Growth rate for head circumference (cm/week) from birth to 36+0 weeks CGA | Average weekly changes in head circumference from birth to 36+0 weeks CGA will be calculated and compared between both arms. | Birth to 36+0 weeks corrected gestational age | 
| Growth rate for head circumference (cm/week) from birth to 40+0 weeks CGA | Average weekly changes in head circumference from birth to 40+0 weeks CGA (or discharge, whichever happens first) will be calculated and compared between both arms. | Birth to 40+0 weeks corrected gestational age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure changes in serum insulin-like growth factor 1 (IGF-1) | Differences in baseline, 28 days after study intervention initiation, and 36 weeks CGA will be compared between both arms | Study day 0 to 36 weeks corrected gestational age | 
| Measure changes in serum insulin-like growth factor binding protein 3 (IGFBP-3) | Differences in baseline, 28 days after study intervention initiation, and 36 weeks CGA will be compared between both arms | Study day 0 to 36 weeks corrected gestational age | 
| Measure rates of severe BPD diagnoses at 36+0 weeks CGA | Infants will be screened per the NICHD 2001 criteria for severe BPD at 36+0 weeks CGA and these rates will be compared between the two arms. | 36+0 weeks corrected gestational age | 
| Measure changes in bone quality per tibial ultrasound | Differences in baseline, 28 days after study intervention initiation, and 36 weeks CGA will be compared between both arms | Study day 0 to 36 weeks corrected gestational age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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zinc