Long-Term Safety and Efficacy of Prebiotic Enriched Infant Formula—A Randomized Controlled Trial Neumer, Franka Campoy Folgoso, Cristina Inulin Oligofructose Prebiotic Infant formula Safety Efficacy Infection The clinical study was part of the EARNEST project (EARly Nutrition programminglong term follow up of Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research), an EU-funded integrated project within the 6th Framework Programme (FOOD-CT-2005-007036). Within this project, Laboratorios Ordesa, Barcelona, Spain and BENEO-Orafti, Tienen, Belgium contributed to the overall funding of the SYNERGY-1 study. The following are available online at https://www.mdpi.com/article/10 .3390/nu13041276/s1, Table S1: Study formula characteristics, Table S2: Primer selection for qPCR, Table S3: Growth-related variables of infants following the consumption of either prebiotic vs. control formula at the following time points: age of 2, 4, 6, 9 and 12 months, Table S4: Amount of formula ingested following the consumption of either prebiotic vs. control formula at the following time points: age of 2, 4, 6, 9 and 12 months, Table S5: Number of infections until 12 months of age, Table S6: Digestive symptoms of the infants by feeding group and study time. The study was performed following the Helsinki declaration and the guidelines for the ethical conduct of medical research involving children. The study protocol was approved by the Ethical Committees of all participating hospitals and the CEIC Fundacio Sant Joan de Déu (Central Ethical Committee Spain, approval No: 2008). Written informed consent was obtained from the parents or guardians of the infants This study was financed in part by the Commission of the European Communities, within FP6 (contract 007036), as it was part of the Early Nutrition Programming [EARNEST] project. The present study aims to evaluate the effects of an infant formula supplemented with a mixture of prebiotic short and long chain inulin-type oligosaccharides on health outcomes, safety and tolerance, as well as on fecal microbiota composition during the first year of life. In a prospective, multicenter, randomized, double-blind study, n = 160 healthy term infants under 4 months of age were randomized to receive either an infant formula enriched with 0.8 g/dL of Orafti(R)Synergy1 or an unsupplemented control formula until the age of 12 months. Growth, fever (>38 degrees C) and infections were regularly followed up by a pediatrician. Digestive symptoms, stool consistency as well as crying and sleeping patterns were recorded during one week each study month. Fecal microbiota and immunological biomarkers were determined from a subgroup of infants after 2, 6 and 12 months of life. The intention to treat (ITT) population consisted of n = 149 infants. Both formulae were well tolerated. Mean duration of infections was significantly lower in the prebiotic fed infants (p < 0.05). The prebiotic group showed higher Bifidobacterium counts at month 6 (p = 0.006), and higher proportions of Bifidobacterium in relation to total bacteria at month 2 and 6 (p = 0.042 and p = 0.013, respectively). Stools of infants receiving the prebiotic formula were softer (p < 0.05). Orafti(R)Synergy1 tended to beneficially impact total daily amount of crying (p = 0.0594). Supplementation with inulin-type prebiotic oligosaccharides during the first year of life beneficially modulates the infant gut microbiota towards higher Bifidobacterium levels at the first 6 months of life, and is associated with reduced duration of infections. 2021-05-07T10:57:22Z 2021-05-07T10:57:22Z 2021-04-13 info:eu-repo/semantics/article Neumer, F.; Urraca, O.; Alonso, J.; Palencia, J.; Varea, V.; Theis, S.; Rodriguez-Palmero, M.; Moreno-Muñoz, J.A.; Guarner, F.; Veereman, G.; et al. Long-Term Safety and Efficacy of Prebiotic Enriched Infant Formula—A Randomized Controlled Trial. Nutrients 2021, 13, 1276. [https://doi.org/10.3390/nu13041276] http://hdl.handle.net/10481/68389 10.3390/nu13041276 eng info:eu-repo/grantAgreement/EC/FP6/007036 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España MDPI