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

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.

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.

Infants will receive daily doses of zinc at 2mg/kg from enrollment through 35 6/7 weeks corrected gestational age.

Zinc Acetate given with elemental zinc dose of 2mg/kg given orally only daily through 35 6/7 weeks corrected gestational age

Average daily changes in weight from birth to 36+0 CGA will be calculated and compared between both arms.

Average daily changes in weight from birth to 40+0 CGA (or discharge, whichever happens first) will be calculated and compared between both arms.

Average weekly changes in length from birth to 36+0 weeks CGA will be calculated and compared between both arms.

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.

Average weekly changes in head circumference from birth to 36+0 weeks CGA will be calculated and compared between both arms.

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.

Differences in baseline, 28 days after study intervention initiation, and 36 weeks CGA will be compared between both arms

Differences in baseline, 28 days after study intervention initiation, and 36 weeks CGA will be compared between both arms

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.

Differences in baseline, 28 days after study intervention initiation, and 36 weeks CGA will be compared between both arms

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

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.

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.