Studies undertaken with α-lactalbumin-enriched formulae never addressed infants with colic. This study evaluated the nutritional adequacy, the gastrointestinal tolerance and the effect on colic of an α-lactalbumin-enriched and probiotic-supplemented formula. A double-blind, placebo-controlled study enrolled 66 healthy infants with colic, aged 3 weeks to 3 months, fed during 1 month with the either experimental formula (EF, Modilac Digest 1) or control formula (CF) and evaluated for efficacy and safety parameters at days 15 and 30. Weight and height gains were identical in the two groups and complied with standards (1023.4±360.4 g (EF) and 1047.4±372.1 g (CF), NS; 4.2±1.4 cm (EF) and 4.3±1.9 cm (CF), NS). No differences were found between groups for crying duration. ‘Feeding-related’ gastrointestinal side effects were significantly lower with EF than with CF (P=0.011). An α-lactalbumin-enriched and probiotic-supplemented formula guaranteed good weight and length gains to infants with colic and seemed to provide good gastrointestinal tolerance.
Several achievements of infant formulae (IF) tend to mimic some beneficial effects of human milk (HM). Enrichment in α-lactalbumin, the HM-dominant whey protein, allows improving the aminogram while reducing the total protein content (Heine et al., 1996; Lien et al., 2004). Also, the bifidogenic effect of HM, probably linked to soluble fibres (Coppa et al., 2004), lends support to a supplementation in probiotics or prebiotics.
Studies conducted with α-lactalbumin-enriched formulae (Lien et al., 2004; Davis et al., 2008) never addressed infants with colic, a disease partially related to IF nutritional composition, due to the potential role, among others, of food allergy and immaturity of gut function (Savino, 2007; Cohen-Silver and Ratnapalan, 2009). This study evaluated the nutritional adequacy, the gastrointestinal (GI) tolerance and the effect on colic of an α-lactalbumin-enriched and probiotic-supplemented IF, in infants with colic.
Subjects and methods
A prospective, multi-centre, randomized, double-blind, placebo-controlled study compared two IF, during 1 month, in colicky formula-fed children. The experimental formula (EF, Modilac Digest 1) was α-lactalbumin enriched and probiotics supplemented (Lactobacillus rhamnosus, Bifidobacterium infantis), reduced in protein and lactose content, and thickened with corn starch. The control formula (CF) was not enriched in α-lactalbumin, had a higher quantity of proteins and lactose, and neither probiotics nor starch (Table 1). Both IF were provided by Sodilac, France. The protocol was approved by the local ethical committee (CCPPRB, Cochin, Paris), with written informed consent from both parents and monitored by a contract research organisation. Comparing the crying duration (χ2-test, statistical significance 5%) implied analysing at least 28 infants in each group, that is, with a 10% loss estimation, enrolling a total of 64 infants.
Infants had to be born at term, aged 3 weeks to 3 months, weaned, with normal growth and with more than 3 weeks of crying periods, at least 3 h per day, 3 days per week (Wessel et al., 1954), with or without abdominal distension, gas and regurgitation. The study formula was introduced 1 day after enrolment. Periods of crying, irritability and agitation without crying, peaceful alertness, peaceful eating, sucking (thumb or pacifier) and sleep were recorded during the day preceding the first intake of the study formula and for the 3 days preceding the visit at days 15 and 30, using a time diary filled up by parents with colours corresponding to the different situations. ‘Irritable and agitated’ relates to a wincing and squirming infant drawing his legs up on his stomach. Regurgitations, flatulence/gas and vomiting were recorded on the same diary.
The tolerance population included all infants who received the study formula at least once and the intent-to-treat (ITT) population the same children if also evaluated at day 15. Per-protocol (PP) infants had no major protocol deviation. Efficacy parameters were analysed on the ITT and PP populations and safety parameters on the tolerance population.
From 66 infants enrolled, 30 EF and 32 CF remained in the tolerance population; 16 infants dropped out (10 EF and 6 CF, NS), mainly because of side effects (2 EF, 3 CF), therapeutic failure (2 EF, 2 CF), consent withdrawal (2 EF, 1 CF), non-attendance at follow-up visits (3 EF). The ITT population consisted of 25 EF and 28 CF and the PP population of 23 EF and 24 CF.
At enrolment, infants were aged 52.5 days (EF) and 50.3 days (CF), NS. Slight differences occurred at baseline between groups in body weight (g): 4991.3±663.3 (mean±s.d., EF) vs 4593.2±559.9 (CF), P=0.013, and body height (cm): 55.95±3.02 (EF) vs 54.20±3.45 (CF), P=0.039. Nevertheless, during the study, weight (g) and height (cm) gains were similar, 1023.4±360.4 (EF) and 1047.4±372.1 (CF), NS; 4.2±1.4 (EF) and 4.3±1.9 (CF), NS. No difference was observed with the corresponding WHO reference growth charts (WHO, 2004; data not shown).
The major criterion, that is, the number of infants presenting a reduction in daily crying duration higher than 25% between enrolment and day 15, did not differ between groups (ITT and PP). Nevertheless, irritability and agitation without crying decreased more with EF (53.2 min), compared to CF (21.1 min) (−39.8 vs −13.6%, P=0.036; PP) between enrolment and the day preceding day 15. Also, the crying duration decreased with time in both groups (P=0.003), with a significant increase of parents' satisfaction related to improvement of GI symptoms (P<0.001).
Side effects, that is, any event temporally associated with the consumption of the study formula, were labelled by the investigators either ‘any causality’ or ‘feeding related’. GI side effects did not differ between groups but ‘feeding-related’ GI side effects were significantly lower with EF (Figure 1).
This EF, slightly reduced in protein content and enriched in α-lactalbumin, guaranteed appropriate weight and height gains in this population of infants with colic, confirming the nutritional adequacy of the protein profile (Lien et al., 2004; Davis et al., 2008).
The study failed to show any reduction in colic. This may be due to a lack of superiority of the EF, to a limited number of infants, to a flaw in the system used to measure colic or to an underestimation of the time effect as time improved significantly the symptoms in both groups.
Gastrointestinal side effects were less frequent with EF. The effect of α-lactalbumin on GI side effects first came up in the trial by Lien et al. (2004) and was confirmed by Davis et al. (2008). This study confirms the beneficial effect in a population of children with colic. Noteworthy, the formula also contained probiotics, for which a potential contribution to a better GI tolerance may be considered (Savino et al., 2007): infants with colic were successfully handled with formulae containing, among others, prebiotic oligosaccharides (Savino et al., 2006) or Lactobacillus reuteri (Savino et al., 2007).
In conclusion, an α-lactalbumin-enriched and probiotic-supplemented formula proved to be adequate for infants with colic in terms of growth and of reduction in GI side effects.
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This work was financially supported by Sodilac, France. We thank the Ordesa Group for providing scientific support. The protocol was carried out by the following general paediatricians: Dr N Belaroussi Maamri, Dr F Gressin-Cohen, Dr C Grillon, Dr S Hadji, Dr N Kalach, Dr B Pacault, Dr C Rizk, Dr A Locquet and Dr K Ara.
Honoraria were granted to Professor C Dupont for coordination of the study and to all investigators, including Dr N Belaroussi, Dr F Gressin-Cohen, Dr C Grillon, Dr S Hadji, Dr N Kalach, Dr B Pacault, Dr C Rizk, Dr A Locquet and Dr K Ara.
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Dupont, C., Rivero, M., Grillon, C. et al. α-Lactalbumin-enriched and probiotic-supplemented infant formula in infants with colic: growth and gastrointestinal tolerance. Eur J Clin Nutr 64, 765–767 (2010). https://doi.org/10.1038/ejcn.2010.81
- infant formula
- protein composition