Tolerance and safety evaluation in a large cohort of healthy infants fed an innovative prebiotic formula: a randomized controlled trial

Pasqua Piemontese, Maria L Giannì, Christian P Braegger, Gaetano Chirico, Christoph Grüber, Josef Riedler, Sertac Arslanoglu, Margriet van Stuijvenberg, Günther Boehm, Jürgen Jelinek, Paola Roggero, MIPS 1 Working Group, Pieter Sauer, Margriet van Stuijvenberg, Annemieke Eisses, Ulrich Wahn, Christoph Gruber, Juliane Wauer, Parasher Kirn, Madeleine Wust, Ingrid Lawnitzak, Marion Trentmann, Gabi Schulz, Eckard Hamelmann, Paola Roggero, Pasquina Piemontese, Anna Orsi, Valeria Puricelli, Fabio Mosca, Sertac Arslanoglu, Guido Moro, Silvia Rizzardi, Michela Coppola, Elisa Rigotti, Laura Tandoi, Christian Braegger, Michael Friedt, Rebecca Koller, Petra Martel, Sarah Nussbaumer, Daniela Rogler, Tamar Stricker, Josef Riedler, Margret Macheiner, Christine Tyma, Gaetano Chirico, Antonella Gasparoni, Elena Garzoli, Chiara Offer, Vania Spinoni, Graziella Iacono, Maria Stellini, Jürgen Jelinek, Bernd Stahl, Esther König, Anja Frings, Yvonne Zens, Anja Wittke, Stephanie Cremers, Janina Gerloff, Kathrin Friedrichs, Ayako Fischer, Bruno Gemma, Günther Boehm, Jan van der Mooren, Johan Garssen, Leon Knippels, Chryssanthi Kiriakidou, Joop Pfeil, Pasqua Piemontese, Maria L Giannì, Christian P Braegger, Gaetano Chirico, Christoph Grüber, Josef Riedler, Sertac Arslanoglu, Margriet van Stuijvenberg, Günther Boehm, Jürgen Jelinek, Paola Roggero, MIPS 1 Working Group, Pieter Sauer, Margriet van Stuijvenberg, Annemieke Eisses, Ulrich Wahn, Christoph Gruber, Juliane Wauer, Parasher Kirn, Madeleine Wust, Ingrid Lawnitzak, Marion Trentmann, Gabi Schulz, Eckard Hamelmann, Paola Roggero, Pasquina Piemontese, Anna Orsi, Valeria Puricelli, Fabio Mosca, Sertac Arslanoglu, Guido Moro, Silvia Rizzardi, Michela Coppola, Elisa Rigotti, Laura Tandoi, Christian Braegger, Michael Friedt, Rebecca Koller, Petra Martel, Sarah Nussbaumer, Daniela Rogler, Tamar Stricker, Josef Riedler, Margret Macheiner, Christine Tyma, Gaetano Chirico, Antonella Gasparoni, Elena Garzoli, Chiara Offer, Vania Spinoni, Graziella Iacono, Maria Stellini, Jürgen Jelinek, Bernd Stahl, Esther König, Anja Frings, Yvonne Zens, Anja Wittke, Stephanie Cremers, Janina Gerloff, Kathrin Friedrichs, Ayako Fischer, Bruno Gemma, Günther Boehm, Jan van der Mooren, Johan Garssen, Leon Knippels, Chryssanthi Kiriakidou, Joop Pfeil

Abstract

Background: the addition of oligosaccharides to infant formula has been shown to mimic some of the beneficial effects of human milk. The aim of the study was to assess the tolerance and safety of a formula containing an innovative mixture of oligosaccharides in early infancy.

Methodology/principal findings: this study was performed as a multi-center, randomized, double-blind, placebo-controlled trial including healthy term infants. Infants were recruited before the age of 8 weeks, either having started with formula feeding or being fully breast-fed (breastfeeding group). Formula-fed infants were randomized to feeding with a regular formula containing a mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides (prebiotic formula group) or regular formula without oligosaccharides (control formula group). Growth, tolerance and adverse events were assessed at 8, 16, 24 and 52 weeks of age. The prebiotic and control groups showed similar mean weight, length and head circumference, skin fold thicknesses, arm circumference gains and stool frequency at each study point. As far as the anthropometric parameters are concerned, the prebiotic group and the control group did not attain the values shown by the breastfeeding group at any study point. The skin fold thicknesses assessed in the breastfeeding group at 8 weeks were strikingly larger than those in formula fed infants, whereas at 52 weeks were strikingly smaller. The stool consistency in the prebiotic group was softer than in the control group at 8, 16 and 24 weeks (p<0.001) and closer to that of the breastfeeding group. There was no difference in the incidence of adverse events between the two formula groups.

Conclusions: our findings demonstrate the tolerability and the long term safety of a formula containing an innovative mixture of oligosaccharides in a large cohort of healthy infants.

Trial registration: drks-neu.uniklinik-freiburg.de DRKS 00000201.

Conflict of interest statement

Competing Interests: CG and GC receive research support from Danone. CB has consultant arrangements and receives research support from Danone. JR is on the advisory board for Numico and receives research support from MIPS. JJ and GB are employed by Danone Research - Centre for Specialised Nutrition. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. The rest of the authors have declared that they have no conflict of interest.

Figures

Figure 1. Trial profile.
Figure 1. Trial profile.
Figure 2. Mean (SE) subscapular skinfold thickness…
Figure 2. Mean (SE) subscapular skinfold thickness values.
P>0.05 for comparisons between PG and CG, resulting from repeated measures linear and logistic regression, using centre as a random effect PG = prebiotics group; CG = control group; BG = breastfeeding group.
Figure 3. Mean (SE) triceps skinfold thickness…
Figure 3. Mean (SE) triceps skinfold thickness values.
P>0.05 for comparisons between PG and CG, resulting from repeated measures linear and logistic regression, using centre as a random effect PG = prebiotics group; CG = control group; BG = breastfeeding group.
Figure 4. Stool consistency at each study…
Figure 4. Stool consistency at each study point.
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