Clinical trial NCT03532555: Enteral Zinc to Improve Growth in Infants at Risk for Bronchopulmonary Dysplasia
Official title: Enteral Zinc to Improve Growth in Infants at Risk for Bronchopulmonary Dysplasia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Infant,Premature
Bronchopulmonary Dysplasia
Growth Failure
Keywords: zinc
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: Intermountain Research and Medical Foundation
First posted: 2018-05-22
Enrollment: 37
Sex: ALL
Minimum age (years): 14
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. 23 0/7 to 29 6/7 weeks GA
2. Birth weight 501 to 1000g, inclusive
3. 14 to 28 days of life, inclusive
4. 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:

1. Major congenital and/or chromosomal anomalies
2. Inability to reach 80ml/kg/day enteral feeds by 28 days of life

Primary outcomes:
measure: Growth rate for weight (g/kg/day) from birth to 36+0 weeks corrected gestational age (CGA)
timeFrame: Birth to 36+0 weeks corrected gestational age
measure: Growth rate for weight (g/kg/day) from birth to 40+0 weeks CGA
timeFrame: Birth to 40+0 weeks corrected gestational age
measure: Growth rate for length (cm/week) from birth to 36+0 weeks CGA
timeFrame: Birth to 36+0 weeks corrected gestational age
measure: Growth rate for length (cm/week) from birth to 40+0 weeks CGA
timeFrame: Birth to 40+0 weeks corrected gestational age
measure: Growth rate for head circumference (cm/week) from birth to 36+0 weeks CGA
timeFrame: Birth to 36+0 weeks corrected gestational age
measure: Growth rate for head circumference (cm/week) from birth to 40+0 weeks CGA
timeFrame: Birth to 40+0 weeks corrected gestational age
Secondary outcomes:
measure: Measure changes in serum insulin-like growth factor 1 (IGF-1)
timeFrame: Study day 0 to 36 weeks corrected gestational age
measure: Measure changes in serum insulin-like growth factor binding protein 3 (IGFBP-3)
timeFrame: Study day 0 to 36 weeks corrected gestational age
measure: Measure rates of severe BPD diagnoses at 36+0 weeks CGA
timeFrame: 36+0 weeks corrected gestational age
measure: Measure changes in bone quality per tibial ultrasound
timeFrame: Study day 0 to 36 weeks corrected gestational age
Other outcomes:
Locations:
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
Study officials:
affiliation: University of Utah
name: Bradley Yoder, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Staub E, Evers K, Askie LM. Enteral zinc supplementation for prevention of morbidity and mortality in preterm neonates. Cochrane Database Syst Rev. 2021 Mar 12;3(3):CD012797. doi: 10.1002/14651858.CD012797.pub2.
citation: Vazquez-Gomis R, Bosch-Gimenez V, Juste-Ruiz M, Vazquez-Gomis C, Izquierdo-Fos I, Pastor-Rosado J. Zinc concentration in preterm newborns at term age, a prospective observational study. BMJ Paediatr Open. 2019 Sep 13;3(1):e000527. doi: 10.1136/bmjpo-2019-000527. eCollection 2019.