Deborah L O'Connor1,2,3, Alex Kiss4,5, Christopher Tomlinson1,6,2,7, Nicole Bando1, Ann Bayliss8, Douglas M Campbell6,7,9, Alan Daneman10,11, Jane Francis1,2, Kirsten Kotsopoulos3, Prakesh S Shah7,3, Simone Vaz12, Brock Williams1, Sharon Unger6,7,3. 1. Translational Medicine Program and Divisions of Neonatology and Diagnostic Imaging, The Hospital for Sick Children, Toronto, Canada. 2. Departments of Nutritional Sciences, Pediatrics, and Medical Imaging, Sunnybrook Research Institute, University of Toronto, Toronto, Canada. 3. Department of Pediatrics, Sinai Health System, Toronto, Canada. 4. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada. 5. Evaluative and Clinical Sciences, Sunnybrook Research Institute, University of Toronto, Toronto, Canada. 6. Translational Medicine Program and Divisions of Neonatology, The Hospital for Sick Children, Toronto, Canada. 7. Departments of Pediatrics and Medical Imaging, Sunnybrook Research Institute, University of Toronto, Toronto, Canada. 8. Trillium Health Partners, Mississauga, Canada. 9. St. Michael's Hospital and Li Ka Shing Knowledge Institute, Toronto, Canada. 10. Translational Medicine Program and Divisions of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Canada. 11. Departments of Medical Imaging, Sunnybrook Research Institute, University of Toronto, Toronto, Canada. 12. Department of Pediatrics, William Osler Health System, Brampton, Canada.
Abstract
Background: Human milk-based fortifiers (HMBFs) are being adopted in neonatal care to enrich the nutrients in human milk for very low birth weight (VLBW) infants despite being costly and there being limited efficacy data. No randomized clinical trial has evaluated the use of HMBF compared with bovine milk-based fortifiers (BMBFs) in the absence of formula feeding. Objective: To determine if HMBF compared with BMBF for routine nutrient enrichment of human milk improves feeding tolerance, reduces morbidity, reduces fecal calprotectin (a measure of gut inflammation), and supports the growth of infants <1250 g. Design: In this blinded randomized clinical trial, infants born weighing <1250g were recruited from neonatal units in Ontario, Canada between August 2014 and November 2015. The infants were fed mother's milk and donor milk as required. Fortification commenced at 100 mL/kg per day of HMBF (0.81 kcal/mL) or BMBF (0.72 kcal/mL) and advanced at 140 mL/kg per day to 0.88 and 0.78 kcal/mL, respectively. The primary outcome was percentage of infants with a feeding interruption for ≥12 h or a >50% reduction in feeding volume. Secondary outcomes included a dichotomous mortality and morbidity index (i.e., affirmative for any one of death, late-onset sepsis, necrotizing enterocolitis, chronic lung disease, or severe retinopathy of prematurity), fecal calprotectin, and growth. Results: Of 232 eligible infants, 127 (54.7%) were randomized (n = 64 HMBF, n = 63 BMBF). Mean ±SD birth weight and gestational age of infants were 888 ± 201 g and 27.7 ± 2.5 wk, respectively. No statistically significant differences were identified in feeding interruptions [17/64 HMBF, 20/61 BMBF; unadjusted risk difference: -6.2% (95% CI: -22.2%, 9.8%)]. There was no statistically significant difference in the mortality and morbidity index (48.4% HMBF, 49.2% BMBF, adjusted P = 0.76), changes in fecal calprotectin, or growth z scores. Conclusions: Among infants born weighing <1250 g and exclusively fed human milk, the use of HMBF did not improve feeding tolerance or reduce mortality and morbidity compared with BMBF. This trial was registered at clinicaltrials.gov as NCT02137473.
RCT Entities:
Background: Human milk-based fortifiers (HMBFs) are being adopted in neonatal care to enrich the nutrients in human milk for very low birth weight (VLBW) infants despite being costly and there being limited efficacy data. No randomized clinical trial has evaluated the use of HMBF compared with bovine milk-based fortifiers (BMBFs) in the absence of formula feeding. Objective: To determine if HMBF compared with BMBF for routine nutrient enrichment of human milk improves feeding tolerance, reduces morbidity, reduces fecal calprotectin (a measure of gut inflammation), and supports the growth of infants <1250 g. Design: In this blinded randomized clinical trial, infants born weighing <1250 g were recruited from neonatal units in Ontario, Canada between August 2014 and November 2015. The infants were fed mother's milk and donor milk as required. Fortification commenced at 100 mL/kg per day of HMBF (0.81 kcal/mL) or BMBF (0.72 kcal/mL) and advanced at 140 mL/kg per day to 0.88 and 0.78 kcal/mL, respectively. The primary outcome was percentage of infants with a feeding interruption for ≥12 h or a >50% reduction in feeding volume. Secondary outcomes included a dichotomous mortality and morbidity index (i.e., affirmative for any one of death, late-onset sepsis, necrotizing enterocolitis, chronic lung disease, or severe retinopathy of prematurity), fecal calprotectin, and growth. Results: Of 232 eligible infants, 127 (54.7%) were randomized (n = 64 HMBF, n = 63 BMBF). Mean ± SD birth weight and gestational age of infants were 888 ± 201 g and 27.7 ± 2.5 wk, respectively. No statistically significant differences were identified in feeding interruptions [17/64 HMBF, 20/61 BMBF; unadjusted risk difference: -6.2% (95% CI: -22.2%, 9.8%)]. There was no statistically significant difference in the mortality and morbidity index (48.4% HMBF, 49.2% BMBF, adjusted P = 0.76), changes in fecal calprotectin, or growth z scores. Conclusions: Among infants born weighing <1250 g and exclusively fed human milk, the use of HMBF did not improve feeding tolerance or reduce mortality and morbidity compared with BMBF. This trial was registered at clinicaltrials.gov as NCT02137473.
Authors: Erynn M Bergner; Roman Shypailo; Chonnikant Visuthranukul; Joseph Hagan; Andrea R O'Donnell; Keli M Hawthorne; Steven A Abrams; Amy B Hair Journal: Breastfeed Med Date: 2020-04-16 Impact factor: 1.817
Authors: Mark Adams; Dirk Bassler; Brian A Darlow; Kei Lui; Brian Reichman; Stellan Hakansson; Mikael Norman; Shoo K Lee; Kjell K Helenius; Liisa Lehtonen; Laura San Feliciano; Maximo Vento; Marco Moroni; Marc Beltempo; Junmin Yang; Prakesh S Shah Journal: BMJ Open Date: 2019-10-14 Impact factor: 2.692