Francesco Savino

Lactobacillus reuteri (American Type Culture Collection Strain 55730) Versus Simethicone in the Treatment of Infantile Colic: A Prospective Randomized Study

OBJECTIVE. The goal was to test the hypothesis that oral administration of Lactobacillus reuteri in a prospective randomized study would improve symptoms of infantile colic. METHODS. Ninety breastfed colicky infants were assigned randomly to receive either the probiotic L reuteri (108 live bacteria per day) or simethicone (60 mg/day) each day for 28 days. The mothers avoided cows milk in their diet. Parents monitored daily crying times and adverse effects by using a questionnaire. RESULTS. Eighty-three infants completed the trial: 41 in the probiotic group and 42 in the simethicone group. The infants were similar regarding gestational age, birth weight, gender, and crying time at baseline. Daily median crying times in the probiotic and simethicone groups were 159 minutes/day and 177 minutes/day, respectively, on the seventh day and 51 minutes/day and 145 minutes/day on the 28th day. On day 28, 39 patients (95%) were responders in the probiotic group and 3 patients (7%) were responders in the simethicone group. No adverse effects were reported. CONCLUSIONS. In our cohort, L reuteri improved colicky symptoms in breastfed infants within 1 week of treatment, compared with simethicone, which suggests that probiotics may have a role in the treatment of infantile colic.

Lactobacillus reuteri DSM 17938 in Infantile Colic: A Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVE: To test the efficacy of Lactobacillus reuteri on infantile colic and to evaluate its relationship to the gut microbiota. STUDY DESIGN: Fifty exclusively breastfed colicky infants, diagnosed according to modified Wessels criteria, were randomly assigned to receive either L reuteri DSM 17 938 (108 colony-forming units) or placebo daily for 21 days. Parental questionnaires monitored daily crying time and adverse effects. Stool samples were collected for microbiologic analysis. RESULTS: Forty-six infants (L reuteri group: 25; placebo group: 21) completed the trial. Daily crying times in minutes/day (median [interquartile range]) were 370 (120) vs 300 (150) (P = .127) on day 0 and 35.0 (85) vs 90.0 (148) (P = .022) on day 21, in the L reuteri and placebo groups, respectively. Responders (50% reduction in crying time from baseline) were significantly higher in the L reuteri group versus placebo group on days 7 (20 vs 8; P = .006), 14 (24 vs 13; P = .007), and 21 (24 vs 15; P = .036). During the study, there was a significant increase in fecal lactobacilli (P = .002) and a reduction in fecal Escherichia coli and ammonia in the L reuteri group only (P = .001). There were no differences in weight gain, stooling frequency, or incidence of constipation or regurgitation between groups, and no adverse events related to the supplementation were observed. CONCLUSION: L. reuteri DSM 17 938 at a dose of 108 colony-forming units per day in early breastfed infants improved symptoms of infantile colic and was well tolerated and safe. Gut microbiota changes induced by the probiotic could be involved in the observed clinical improvement.

Intestinal microflora in breastfed colicky and non-colicky infants

Background: Infantile colics are a common problem in the first months of life. During this period, a process of intestinal colonization rapidly occurs. A difference in the gut microflora could play an important role in the pathogenesis of colics, changing the metabolism of carbohydrates and fatty acids. Actually, in the literature, only few data have been collected about this topic. In this study, we evaluated intestinal microflora in breastfed colicky and non‐colicky infants. Methods: Seventy‐one breastfed infants, aged 3.2 ± 0.6 wk, free from episodes of gastroenteritis and without previous assumption of antibiotic and probiotic drugs, were enrolled in the study. They were divided into two groups: colicky (42 cases) and non‐colicky (29 cases), according to Wessels criteria. Stool samples were collected, diluted and cultured on several selective media to detect lactobacilli, clostridia, Gram‐negative anaerobes and Enterobacteriaceae. Statistical analysis was performed using Students t‐test, χ2 test and a non‐parametric test (Mann‐Whitney U‐test). Results: Differences in gut microflora were found among colicky and non‐colicky infants: colicky infants were less frequently colonized by Lactobacillus spp., and more frequently by anaerobic Gram‐negative bacteria.

Reduction of crying episodes owing to infantile colic: a randomized controlled study on the efficacy of a new infant formula

Objectives:The aim of this study was to evaluate the efficacy on crying episodes owing to infantile colic of a new infant formula containing partially hydrolysed whey proteins, prebiotic oligosaccharides (OS), with a high β-palmitic acid content.Design:Prospective randomized controlled study.Setting:Italy.Subjects:Two hundred and sixty-seven formula-fed infants, aged less than 4 months, with infantile colic, were randomized to receive either the new infant formula (study treatment (ST)) or a standard formula and simethicone (6 mg/kg twice a day) (control treatment (CT)). A questionnaire was given to parents to evaluate for 14 days the daily number of colic episodes and crying time.Results:Out of the 199 infants who completed the study, 96 were treated with the new formula and 103 were not treated. Infants receiving the new formula had a significant decrease in colic episodes after 1 week (2.47±1.94 at day 7 vs 5.99±1.84 at the study entry) compared to infants receiving the CT (3.72±1.98 at day 7 vs 5.41±1.88 at the study entry) (P<0.0001). Also at day 14, the crying episodes were significantly different between the two groups of infants (1.76±1.60 in ST vs 3.32±2.06 in CT) (P<0.0001).Conclusions:The use of a partially hydrolysed formula supplemented with fructo- and galacto-OS induces a reduction of crying episodes in infants with colic after 7 and 14 days when compared with a standard formula and simethicone.Sponsorship:The study was supported by funds from Numico, Italy.

Molecular identification of coliform bacteria from colicky breastfed infants

Objective:  To determine the presence of intestinal coliform bacteria in colicky vs healthy infants.

Ghrelin, leptin and IGF-I levels in breast-fed and formula-fed infants in the first years of life.

Aim: To establish ghrelin, leptin and IGF‐I serum levels in breastfed (BF) and formula‐fed (FF) infants during the first period of life. Methods: A cross‐sectional study was conducted on fasting blood venous samples obtained from exclusively BF (n=106) and FF (n=100) infants to measure total ghrelin (RIA test), leptin (RIA test) and IGF‐I (chemiluminescence). Anthropometrical measurements of weight, length and cranial circumference were performed. Results: During the first 4 mo of life, FF infants compared to BF ones showed higher ghrelin levels (2654.86 vs 2132.96 pg/ml; p<0.032), higher IGF‐I levels (3.73 vs 3.15 ng/ml; p=0.00) and lower leptin levels (0.68 vs 1.16 ng/ml; p<0.04). Leptin values were higher in females than in males (0.80 vs 0.47 ng/ml; p<0.03), while no gender‐related difference was found for ghrelin and IGF‐I. No differences were found in anthropometrical measurements comparing the two groups of infants. A multiple regression analysis showed an inverse correlation between ghrelin and leptin values (p<0.04) and between IGF‐I and leptin levels (p=0.00).

Leptin levels in breast‐fed and formula‐fed infants

Aim: Leptin, a hormone that regulates food intake and energy metabolism, is present in breast milk and thus may be involved in body composition differences between breastfed and formula‐fed infants. The aim of this study was to evaluate whether diet and gender affect plasma leptin concentration in breastfed and formula‐fed infants during the first months of life. Methods: Anthropometric and bioelectrical impedance measurements [total body water (TBW) calculated with the Fjeld equation] were made and venous blood plasma samples were analysed for leptin concentration in healthy, exclusively breastfed or formula‐fed Italian infants in the first year of life. Infants were subdivided in two ways: three groups (periods) in relation to age, and five groups in relation to weight. Results: The average serum concentration of leptin was 7.35 ng ml‐1. Serum leptin values were higher in breastfed than in formula‐fed infants. Breastfed infants in group 1 had a statistically higher serum leptin concentration (2500–3749 g). There were no significant differences in anthropometric measurements, body mass index or skinfold thickness between breastfed and formula‐fed infants. In the periods I and II, breastfed infants had a significantly higher TBW than formula‐fed infants. Males had a significantly higher TBW than females in periods I and II. Breastfed infants in group 2 (3750–4999 g) had a significantly higher TBW than formula‐fed infants.

454 Pyrosequencing Analysis on Faecal Samples from a Randomized DBPC Trial of Colicky Infants Treated with Lactobacillus reuteri DSM 17938

Objective To analyze the global microbial composition, using large-scale DNA sequencing of 16 S rRNA genes, in faecal samples from colicky infants given L. reuteri DSM 17938 or placebo. Methods Twenty-nine colicky infants (age 10–60 days) were enrolled and randomly assigned to receive either Lactobacillus reuteri (108 cfu) or a placebo once daily for 21 days. Responders were defined as subjects with a decrease of 50% in daily crying time at day 21 compared with the starting point. The microbiota of faecal samples from day 1 and 21 were analyzed using 454 pyrosequencing. The primers: Bakt_341F and Bakt_805R, complemented with 454 adapters and sample specific barcodes were used for PCR amplification of the 16 S rRNA genes. The structure of the data was explored by using permutational multivariate analysis of variance and effects of different variables were visualized with ordination analysis. Results The infants’ faecal microbiota were composed of Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes as the four main phyla. The composition of the microbiota in infants with colic had very high inter-individual variability with Firmicutes/Bacteroidetes ratios varying from 4000 to 0.025. On an individual basis, the microbiota was, however, relatively stable over time. Treatment with L. reuteri DSM 17938 did not change the global composition of the microbiota, but when comparing responders with non-responders the group responders had an increased relative abundance of the phyla Bacteroidetes and genus Bacteroides at day 21 compared with day 0. Furthermore, the phyla composition of the infants at day 21 could be divided into three enterotype groups, dominated by Firmicutes, Bacteroidetes, and Actinobacteria, respectively. Conclusion L. reuteri DSM 17938 did not affect the global composition of the microbiota. However, the increase of Bacteroidetes in the responder infants indicated that a decrease in colicky symptoms was linked to changes of the microbiota. Trial Registration ClinicalTrials.gov NCT00893711

Minor feeding problems during the first months of life: effect of a partially hydrolysed milk formula containing fructo- and galacto-oligosaccharides.

Background: Colic, regurgitation and constipation are common feeding problems in formula‐fed infants that might benefit from dietary treatment. A formula containing fructo‐ and galacto‐oligosaccharides, partially hydrolysed proteins, low levels of lactose and palmitic acid in the β position and higher density has been tested to reduce the occurrence of these symptoms. The aim of this prospective study was to describe the effects of such a formula in infants with minor gastrointestinal disorders. Methods: An observational prospective trial involving practising Italian paediatricians was performed. Formula fed‐infants up to 90 d of age with minor gastrointestinal problems such as infantile colics and/or regurgitation and/or constipation were enrolled in the study from January 2001 to May 2001. The study was completed within 14 d of treatment. On days 1, 7 and 14 the infants were visited by the paediatricians. Parents were given a structured diary to record daily episodes of colic, regurgitation and type and number of stools. Results: Of the 932 infants enrolled, 604 completed the study. Of the 214 infants with colic, 169 (79%) demonstrated a reduction in frequency of colic from 4.1 ± 2.0 per day at the beginning of the study to 2.0 ± 1.8 at the end of the study (I.C. 95%: 1.72–2.39; p < 0.005). A reduction in the number of episodes of colic of 1.8 per day at the beginning of the study (I.C. 95%: 1.49–2.11; p < 0.05) was recorded between day 1 and day 7, and of 0.26 (I.C. 95%: 0.15–0.37; p < 0.05) between day 7 and day 14. Of the 201 infants with regurgitation problems, 141 (70%) demonstrated a reduction of frequency of the symptoms from 4.2 ± 2.0 per day at the beginningof the study to 2.1 ± 2.2 at the end of the study (I.C. 95%: 1.75–2.35; p < 0.005). A reduction of 1.87 in the number of regurgitation episodes was reported between day 1 and day 7 (I.C. 95%: 1.57–2.16; p < 0.05) and of 0.18 (I.C. 95%: 0.06–0.31; p < 0.05) between day 7 and day 14. Of the 232 infants with constipation, 147 (63%) demonstrated an increase in the daily number of stools of 0.42 (I.C. 95%: 0.5–0.3; p < 0.005). An increase in stool frequency of 0.41 (I.C. 95%: 0.51–0.23; p < 0.05) was reported between day 1 and day 7, and of 0.04 (I.C. 95%: 0.22–0.14; p= ns) between day 7 and day 14. Parents’evaluation of the formula was 7.9 ± 1.8 (score 0–10); 550 parents (91%) gave a positive judgement (score >6). The evaluation by the paediatricians of the improvement in symptoms after the treatment was 8.2 ± 1.5; 574 (95%) a positive effect (score >6).

New treatments for infant colic

Purpose of review Infantile colic is a common problem within the first 3 months of life and causes considerable distress for parents and paediatricians. Despite 40 years of research, its pathogenesis is incompletely understood and treatment remains an open issue. This review will describe recent studies that have examined different kinds of interventions. Recent findings Important advances in understanding the aetiopathogenesis of infantile colic have been recently proposed and opened new perspectives in its management. The composition of intestinal microbiota, specially an inadequate amount of lactobacilli and an increased concentration of coliforms, might influence the pathogenesis of infantile colic. The benefit of supplementation with Lactobacillus reuteri has been recently reported and experimental data showed the effect of probiotics may be related to the influence on gut motility and pain perception. Summary Infantile colic is a clinical entity with a wide range of clinical presentations and outcome. Firstly, paediatricians have to exclude other underlying diseases with a medical examination and prevent feeding disorders. Then, considering the favourable clinical course of the disturbance, well tolerated strategies should be adopted. The findings highlighted in this review may promote the implementation of new researches and treatments to reduce abdominal pain related to infantile colic.