Subscribe to RSS
Progression of Enteral Feeding Volumes in Extremely Low Birth Weight Infants in the “Connection Trial”Funding This study was financed by Infant Bacterial Therapeutics Inc.
Objective Investigate daily feeding volumes and their association with clinical variables in the early postnatal care of premature infants of the “Connection Trial.”
Study Design A total of 641 infants of 510 to 1,000-g birth weight (BW, mean: 847 g) and mean 27 weeks' gestational age at birth (GA) were analyzed for total daily enteral (TDE) feeding volumes of 10, 20, 40, 80, and 120 mL/kg/d and their association with 24 clinical variables. Uni- and multivariable Cox regression models were used to calculate hazard ratios (HR) with 95% confidence intervals as a measure of the chance of reaching each of the TDE volumes.
Results Daily feeding volumes were highly variable and the median advancement from 10 to 120 mL/kg/d was 11 mL/kg/d. Univariable analyses showed the lowest chance (HR, 0.22–0.81) of reaching the TDE volumes for gastrointestinal (GI) serious adverse events (SAEs), GI perforation, GI obstruction, and necrotizing enterocolitis, as well as respiratory SAEs, persistent ductus arteriosus, and hypotension. Each GA week, 100-g BW, and point in 5-minute Apgar score at birth associated with 8 to 20% increased chance of reaching the TDE volumes. Multivariable analyses showed independent effects for BW, GA, Apgar score, GI SAEs, abdominal symptoms/signs, respiratory SAEs, days on antibiotics, and hypotension.
Conclusion This observational analysis demonstrates the variable and cautious progression of enteral feedings in contemporary extremely low BW infants and the extent to which clinical variables associate with this progression.
Total feedings of 10 and 120 mL/kg/d were reached at median 4 and 14 day of age, respectively, and at a daily increase of 11 mL/kg.
Each incremental GA week, 100-g BW, and point in 5-minute Apgar score associated with 8 to 20% increased chance of reaching enteral feedings of 10 to 120 mL/kg/d.
Progression of enteral feeding associated with several clinical events and was slower than advocated in common feeding protocols.
Keywordspremature infants - enteral feeding - feeding progression - feeding volumes - adverse clinical events
Received: 03 March 2023
Accepted: 01 August 2023
Article published online:
08 September 2023
© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
- 1 Wittwer A, Hascoët J-M. Impact of introducing a standardized nutrition protocol on very premature infants' growth and morbidity. PLoS One 2020; 15 (05) e0232659
- 2 Bakker L, Jackson B, Miles A. Oral-feeding guidelines for preterm neonates in the NICU: a scoping review. J Perinatol 2021; 41 (01) 140-149
- 3 Thoene M, Anderson-Berry A. Early enteral nutrition in preterm infants: a narrative review of the nutritional, metabolic and developmental benefits. Nutrients 2021; 13 (07) 2289-2304
- 4 Hay WW. Optimizing nutrition of the preterm infant. Zhongguo Dang Dai Er Ke Za Zhi 2017; 19 (01) 1-21
- 5 Oddie SJ, Young L, McGuire W. Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev 2021; 8 (08) CD001241
- 6 Young L, Oddie SJ, McGuire W. Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev 2022; 1 (01) CD001970
- 7 Aceti A, Gori D, Barone G. et al. Probiotics and time to achieve full enteral feeding in human milk-fed and formula-fed preterm infants: systematic review and meta-analysis. Nutrients 2016; 8 (08) 471
- 8 Kreissl A, Sauerzapf E, Repa A. et al. Starting enteral nutrition with preterm single donor milk instead of formula affects time to full enteral feeding in very low birthweight infants. Acta Paediatr 2017; 106 (09) 1460-1467
- 9 Dorling J, Hewer O, Hurd M. et al. Two speeds of increasing milk feeds for very preterm or very low-birthweight infants: the SIFT RCT. Health Technol Assess 2020; 24 (18) 1-94
- 10 Mank E, Sáenz de Pipaón M, Lapillonne A. et al; FIT-04 Study Group. Efficacy and safety of enteral recombinant human insulin in preterm infants. A randomized clinical trial. JAMA Pediatr 2022; 176 (05) 452-460
- 11 Culpepper C, Hendrickson K, Marshall S, Benes J, Grover TR. Implementation of feeding guidelines hastens the time to initiation of enteral feeds and improves growth velocity in very low birth-weight infants. Adv Neonatal Care 2017; 17 (02) 139-145
- 12 Neu J, Del Moral T, Ferry J. et al. Clinical outcomes correlating to a one-day shift in sustained feeding tolerance in very low birth weight infants in the 'Connection Trial'. Br J Gastroenterol 2022; 4: 255-260
- 13 Guthrie SO, Neu J, Doctor B. et al. Association of clinical events to the time to a strict definition of sustained feeding tolerance in premature infants in the 'Connection Trial. Br J Gastroenterol. 2022; 4: 264-272
- 14 Juber BA, Boly TJ, Pitcher GJ, McElroy SJ. Routine administration of a multispecies probiotic containing Bifidobacterium and Lactobacillus to very low birth weight infants had no significant impact on the incidence of necrotizing enterocolitis. Front Pediatr 2021; 9: 757299
- 15 Lewis ZT, Shani G, Masarweh CF. et al. Validating bifidobacterial species and subspecies identity in commercial probiotic products. Pediatr Res 2016; 79 (03) 445-452
- 16 Poindexter B. Committee on fetus and newborn. Use of probiotics in preterm infants. Pediatrics 2021; 147: e202151485
- 17 Food and Drug Administration. Guidance Document E6, Good Clinical Practice. Docket no FDA-2018-D-0719
- 18 Akaike H. Information theory and an extension of the maximum likelihood principle. Breakthroughs in Statistics. 1992; 1: 610-624
- 19 Neu J. Necrotizing enterocolitis: The future. Neonatology 2020; 117 (02) 240-244
- 20 Athalye-Jape G, Rao S, Patole S. Lactobacillus reuteri DSM 17938 as a probiotic for preterm neonates: a strain-specific systematic review. JPEN J Parenter Enteral Nutr 2016; 40 (06) 783-794
- 21 Cui X, Shi Y, Gao S, Xue X, Fu J. Effects of Lactobacillus reuteri DSM 17938 in preterm infants: a double-blinded randomized controlled study. Ital J Pediatr 2019; 45 (01) 140
- 22 Morgan RL, Preidis GA, Kashyap PC, Weizman AV, Sadeghirad B. McMaster Probiotic, Prebiotic, and Synbiotic Work Group. Probiotics reduce mortality and morbidity in preterm, low-birth-weight infants: a systematic review and network meta-analysis of randomized trials. Gastroenterology 2020; 159 (02) 467-480
- 23 Weeks CL, Marino LV, Johnson MJ. A systematic review of the definitions and prevalence of feeding intolerance in preterm infants. Clin Nutr 2021; 40 (11) 5576-5586
- 24 Patton L, de la Cruz D, Neu J. Gastrointestinal and feeding issues for infants <25 weeks of gestation. Semin Perinatol 2022; 46 (01) 151546
- 25 Olaloye O, Swatski M, Konnikova L. Role of nutrition in prevention of neonatal spontaneous intestinal perforation and its complications: a systematic review. Nutrients 2020; 12 (05) 1347
- 26 Walsh V, Brown JVE, Copperthwaite BR, Oddie SJ, McGuire W. Early full enteral feeding for preterm or low birth weight infants. Cochrane Database Syst Rev 2020; 12 (12) CD013542
- 27 Abiramalatha T, Thanigainathan S, Ninan B. Routine monitoring of gastric residual for prevention of necrotising enterocolitis in preterm infants. Cochrane Database Syst Rev 2019; 7 (07) CD012937
- 28 Chee YY, Wong MS, Wong RM, Wong KY. Neonatal outcomes of preterm or very-low-birth-weight infants over a decade from Queen Mary Hospital, Hong Kong: comparison with the Vermont Oxford Network. Hong Kong Med J 2017; 23 (04) 381-386
- 29 Rysavy MA, Horbar JD, Bell EF. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and Vermont Oxford Network. Assessment of an updated neonatal research network extremely preterm birth outcome model in the Vermont Oxford Network. JAMA Pediatr 2020; 174 (05) e196294
- 30 Thoene MK, Lyden E, Anderson-Berry A. Improving nutrition outcomes for infants <1500 grams with a progressive, evidence-based enteral feeding protocol. Nutr Clin Pract 2018; 33 (05) 647-655