Gastrointestinal Tolerance of Formula Supplemented with Oligosaccharides

Abstract

ObjectiveHuman milk oligosaccharides (HMOs) are the third largest solid component in mature human milk. The objective of this study was to evaluate gastrointestinal tolerance of infants fed infant formula supplemented with short‐chain fructooligosaccharides (scFOS) and 2‐fucosyllactose (2′FL).MethodsWe conducted a prospective, randomized, multi‐center, double‐blinded, controlled 3‐arm tolerance study in full term, singleton infants (birth weight ≥ 2490g) enrolled between 0 and 8 days of age. At enrollment, formula‐fed infants were randomized to one of two experimental milk‐based infant formulas with a caloric density of 643 kcal/L. Experimental Formula 1 (EF1) did not contain oligosaccharides (n=42) and Experimental Formula 2 (EF2) contained 2g/L scFOS and 0.2g/L 2′FL (n=46). The 2 formula groups were compared with a human milk‐fed (HM) reference group (n=43). Infants were exclusively fed formula or human milk from enrollment until 35 days of age. Data related to intake, stool patterns, anthropometrics and parental questionnaires were collected. The primary outcome was average mean rank stool consistency (MRSC) from Study Day 1 to Visit 3. MRSC was calculated from stool records (1=watery, 2=loose/mushy, 3=soft, 4=formed, 5=hard).ResultsThirty‐six (86%) subjects in the EF1 group, 41 (89%) in the EF2 group and 42 (98%) in the HM group completed the study. There were no differences among groups for gender, ethnicity, race, gestational age, birth weight or age at enrollment. Reported results are from the protocol evaluable analysis. From Study Day 1 to Visit 3, there were no differences in MRSC among the three feeding groups. MRSC was 2.37 ± 0.10, 2.15 ± 0.10 and 2.06 ± 0.08 for the EF1, EF2 and HM groups respectively. There were also no differences among groups for predominant stool consistency from Study Day 1 to Visit 3. The average number of stools per day for the HM group was significantly greater than EF1 (p<0.0001) and EF2 (p<0.0001) from Study Day 1 to Visit 3. At Visit 3, there were no differences between groups for average volume of study formula intake, number of study formula feedings per day, anthropometric data or percent feedings with spit‐up/vomit.ConclusionAn experimental formula containing 2′FL and scFOS was well tolerated in young infants as evidenced by stool consistency, formula intake, anthropometric data and percent feedings with spit‐up/vomit similar to that of infants fed formula without oligosaccharides or HM.Support or Funding InformationThis study was funded by Abbott Nutrition, Abbott Laboratories, Columbus, OH.

Clinical Studies on the Supplementation of Manufactured Human Milk Oligosaccharides: A Systematic Review

“…In the first group of studies, 2′-FL was added to infant formula alone [ 56 ] or in combination with other prebiotics such as GOS [ 40 ], fructooligosaccharides (FOS) [ 42 , 54 ], or a mixture of fermented GOS and FOS including 3′-GL [ 47 ]. It has also been combined with probiotic bacteria such as Bifidobacterium animalis ssp.…”

“…It was mostly assessed in terms of non-inferior weight gain per day in intervention groups compared to control formulas and breastfed groups throughout the intervention period. Other anthropometric parameters measured included length, head circumference, weight, body mass index, and interval gains, which were assessed either by comparison with reference groups or WHO child growth standards [ 39 , 40 , 42 , 43 , 44 , 46 , 47 , 49 , 50 , 51 , 52 , 54 , 57 , 58 , 59 ]. All studies reported age-appropriate growth following HMO supplementation and the absence of significant growth differences between intervention groups and controls ( Table 2 and Table 3 ).…”

“…No difference in intake between the formulas with and without HMOs [ 39 , 42 , 43 , 44 , 47 , 49 , 50 , 52 , 57 , 60 ]. Formulas with and without HMOs also invoked similar levels of flatulence [ 43 , 49 , 50 , 55 ], regurgitation [ 47 , 49 ], and vomiting associated with feeding [ 40 , 42 , 43 , 44 , 49 , 55 ]. There was also no effect on crying or fussiness [ 44 , 49 , 50 ].…”

“…Other studies involving infants did not find effects on stool characteristics. In these cases, a formula was supplemented with 0.2–1 g/L 2′-FL [ 40 , 42 , 44 , 47 , 50 , 56 ], or an EHF was supplemented with 1 g/L 2′-FL and 0.5 g/L LNnT [ 55 ]. Similarly, HMO supplements had no effect on stool consistency in preterm infants but reduced stool frequency after 1 week of full-enteral feeding [ 59 ].…”

“…Even so, exploratory indications for health benefits were evident from these studies, indicating the potential of HMO supplementation. Of note, not all infant studies measured changes in stool characteristics [ 40 , 42 , 44 , 47 , 50 , 55 , 56 , 59 ] nor infection incidence [ 47 , 49 , 50 , 54 , 59 ]. The diverse results may reflect the number of different HMOs tested and their relative and absolute doses.…”