CC BY-NC-ND 4.0 · Am J Perinatol
DOI: 10.1055/s-0043-1774314
Original Article

Progression of Enteral Feeding Volumes in Extremely Low Birth Weight Infants in the “Connection Trial”

Josef Neu
1   Department of Pediatrics, University of Florida Health Shands Children's Hospital, Gainesville, Florida
Patricia Ashley
2   Department of Pediatrics, Duke University, Durham, North Carolina
Vikas Chowdhary
3   Department of Pediatrics, Arkansas Children's Hospital, Little Rock, Arkansas
Andrea Lampland
4   Department of Neonatology, Children's Minnesota St. Paul Clinic, Saint Paul, Minnesota
Peter Porcelli
5   Department of Pediatrics, Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, North Carolina
Robert Rothstein
6   Department of Pediatrics, Baystate Children's Hospital, Springfield, Massachusetts
Boriana Slancheva
7   Department of Neonatology, Medical University of Sofia, Sofia, Bulgaria
Anders Kronström
8   Infant Bacterial Therapeutics Inc., Stockholm, Sweden
Jonas Rastad
8   Infant Bacterial Therapeutics Inc., Stockholm, Sweden
Staffan Strömberg
8   Infant Bacterial Therapeutics Inc., Stockholm, Sweden
Marcus Thuresson
8   Infant Bacterial Therapeutics Inc., Stockholm, Sweden
The Connection Study Group › Author Affiliations
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.

Key Points

  • 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.

Publication History

Received: 03 March 2023

Accepted: 01 August 2023

Article published online:
08 September 2023

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