Randomised controlled trial demonstrates that fermented infant formula with short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides reduces the incidence of infantile colic

Abstract

Aim: We examined the effects on gastrointestinal (GI) tolerance of a novel infant formula that combined specific fermented formula (FERM) with short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS), with a 9:1 ratio and concentration of 0.8 g/100 mL.

Methods: This prospective, double-blind, randomised, controlled trial comprised 432 healthy, term infants aged 0-28 days whose parents decided to not start, or discontinued, breastfeeding. Infant formula with scGOS/lcFOS+50%FERM, scGOS/lcFOS+15%FERM, 50%FERM and scGOS/lcFOS were tested. Parents completed standardised seven-day diaries on GI symptoms, crying, sleeping and stool characteristics each month until the infants were 17 weeks.

Results: All the formulas were well tolerated. At four weeks, the overall incidence of infantile colic was significantly lower (8%) with scGOS/lcFOS+50%FERM than scGOS/lcFOS (20%, p = 0.034) or 50%FERM (20%, p = 0.036). Longitudinal modelling showed that scGOS/lcFOS+50%FERM-fed infants also displayed a persistently lower daily crying duration and showed a consistent stool-softening effect than infants who received formula without scGOS/lcFOS.

Conclusion: The combination of fermented formula with scGOS/lcFOS was well tolerated and showed a lower overall crying time, a lower incidence of infantile colic and a stool-softening effect in healthy term infants. These findings suggest for the first time that a specific infant formula has a preventive effect on infantile colic in formula-fed infants.

Keywords: Fermented formula; Gastrointestinal tolerance; Infant formula; Infantile colic; Prebiotic.

Figure 1

(A) Study visits were conducted at four, eight, 13 and 17 weeks after birth. At four weeks, this visit may have been combined with the screening/baseline visit, depending on the age at inclusion. (B) Randomisation, dropouts and study completers. From the 432 randomised infants, one infant with hypothyroidism was excluded from the intention to treat population (n = 431), which constitutes the primary analysis set for GI and tolerance parameters.

Figure 2

Stool parameters. A mean value was calculated per infant and week from the parental diaries for (A) frequency, (B) consistency (watery = 1, soft, pudding like = 2, soft, formed = 3, dry formed = 4 or dry, hard pellets = 5). (*p ≤ 0.05, **p < 0.001; Wilcoxon rank‐sum test).

Figure 3

Crying and infantile colic. (A) mean number of crying episodes per day, (B) incidence of infantile colic according to adapted Rome III criteria (≥3 hours of crying per day, for at least three days during one week) given as the percentage of infants that fulfilled these criteria. (*p ≤ 0.05, crying episodes calculated using Wilcoxon rank‐sum test; infantile colic calculated at four and eight weeks using the chi‐square test and 13 and 17 weeks with the Wilcoxon rank‐sum test). (C) Longitudinal modelling of average crying duration per infant in hours per day. There was no statistically significant difference in the median crying duration at baseline.

Figure 4

Incidence of gastrointestinal symptoms in infants with and without infantile colic. For example, at four weeks of age, infants with infantile colic had a 4.9 (1.4–16.7) higher chance of also having constipation than infants without colic. OR = odds ratio, CI = confidence interval; **p < 0.001, *p < 0.01, n.a. = not applicable; p values relate to difference in incidence – Fisher's exact test was used for all symptoms except flatulence and diarrhoea at four and eight weeks, and arching of the back at eight weeks, where the chi‐square test was used.