This study aimed to explore the extent and impact of maternal dietary change for colic relief in a cohort of breastfeeding women.

A mixed-method non-sequential approach was devised, including a web-based survey (n = 66) and three semi-structured interviews.

Most women (70 %) changed their diet while breastfeeding a baby with colic and perceived a positive impact on their babies (63 %). The choice of foods eliminated was individual, based on a process of trial and error and on the perceived benefit to the baby. A sub-group of colicky babies, those with less intense colic symptoms, benefited significantly from the removal of cruciferous vegetables (p = 0.01) and were found to be 'less windy' (p = 0.10, ES0,20), a result trending towards statistical significance. Women felt unsupported while making changes to their diet. When dietary change brought relief to the baby, it turned into a coping tool for women facilitating extended breastfeeding.

Maternal dietary change can play a positive role in providing relief to breastfed babies with colic. Novel findings from this study revealed that different baby subtypes got relief from the elimination of different foods. This underscores the potential of personalised nutritional advice for colic relief in breastfed babies.

Background: This review investigates the impact of bioactive molecules produced by probiotics on child health, focusing on their roles in modulating gut microbiota, enhancing immune function, and supporting overall development. Key metabolites, including short-chain fatty acids (SCFAs), bacteriocins, exopolysaccharides (EPSs), vitamins, and gamma-aminobutyric acid (GABA), are highlighted for their ability to maintain gut health, regulate inflammation, and support neurodevelopment. Objectives: The aim of this review is to examine the mechanisms of action and clinical evidence supporting the use of probiotics and postbiotics in pediatric healthcare, with a focus on promoting optimal growth, development, and overall health in children. Methods: The review synthesizes findings from clinical studies that investigate the effects of probiotics and their metabolites on pediatric health. The focus is on specific probiotics and their ability to influence gut health, immune responses, and developmental outcomes. Results: Clinical studies demonstrate that specific probiotics and their metabolites can reduce gastrointestinal disorders, enhance immune responses, and decrease the incidence of allergies and respiratory infections in pediatric populations. Additionally, postbiotics-bioactive compounds from probiotic fermentation-offer promising benefits, such as improved gut barrier function, reduced inflammation, and enhanced nutrient absorption, while presenting fewer safety concerns compared to live probiotics. Conclusions: By examining the mechanisms of action and clinical evidence, this review underscores the potential of integrating probiotics and postbiotics into pediatric healthcare strategies to promote optimal growth, development, and overall health in children.

To systematically review evidence on the efficacy and safety of using a lactase supplementation for managing infant colic. The MEDLINE, EMBASE, and Cochrane Library databases were searched (up to September 2023) for randomized controlled trials (RCTs) comparing oral lactase supplementation with placebo or no intervention in infants younger than 6 months old with infant colic. The risk of bias was assessed using the revised version of the Cochrane risk-of-bias tool. Outcomes measured were selected according to a standardized core outcome set. Five RCTs involving a total of 391 infants were identified. Three RCTs reported reduced crying duration, but one showed effect only in a compliant group (40.4%, p = 0.0052). A meta-analysis of two RCTs found no difference in crying duration and fussing time during 1 week of lactase treatment compared with placebo (mean difference [MD] -17.66 min/day, 95% confidence interval [CI], -60.8 to 25.5; I2 = 68% and MD 2.75, 95% CI, -58.2 to 57.2; I2 = 80%, respectively). Other outcomes were assessed only in individual studies or not reported. The risk of bias was low in only one RCT, high in three, and raised some concerns in one. While individual trials have shown some promise, the overall evidence for the efficacy of lactase supplementation in treating infant colic remain inconclusive. Further well-designed RCTs are necessary to determine the effects of lactase on managing infant colic.

Infantile colic (IC) is c is a self-limiting functional gastrointestinal disorder (FGID) with a favorable natural history. Worldwide, IC has a significant impact on many newborns and their families. Although not an indication of an illness, its symptoms are wide and generic and may indicate a potentially serious underlying issue in a tiny percentage of newborns who may require a medical evaluation. The pathogenesis appears to be multifactorial implying a complex relationship between the infant and the environment. One of the most studied theories attributes a key role to the gut microbiota in the pathogenesis of IC. A variety of approaches have been suggested for the clinical management of IC, and several randomized controlled trials have been reported in the literature. Probiotics can change the host's microbiota and positively impact health. They may be able to restore balance and create a better intestinal microbiota landscape since there is mounting evidence that the gut microbial environment of colicky newborns differs from that of healthy infants. In this review, we revise the most commonly studied probiotics and mixtures to treat and prevent IC and the most recent recommendations.

Infant colic is a multifactorial syndrome for which various therapeutic strategies have been proposed. In this study, we evaluate the effectiveness of osteopathic manual therapy in treating symptoms related to infant colic.

A prospective, randomised, blinded clinical trial was conducted of patients diagnosed with infant colic. The treatment group were given osteopathic manual therapy, and their parents received two sessions of counselling. The control group received no such therapy, but their parents attended the same counselling sessions. The non-parametric Mann-Whitney U test was applied to determine whether there were significant differences between the groups for the numerical variables considered. For the qualitative variables, Fisher's exact test was used. The threshold assumed for statistical significance was 0.05.

A total of 42 babies were assigned to each group. Those in the experimental group presented less severe infant colic with a trend towards statistical significance after the first session (p = 0.09). In sucking, excretion, eructation and gas there were no significant differences between the groups. Crying was a statistically significant dimension both after the first intervention (p = 0.03) and two weeks after (p = 0.04). Regurgitation values were significantly lower in the experimental group during the three weeks of follow-up (p = 0.05). Values for sleep were lower in the experimental group, but the differences were not statistically significant. In both groups, colic severity decreased over time, with no side effects.

Treatment with osteopathic manual therapy alleviates the symptoms of infant colic and could be recommended for this purpose from the onset of the condition.

Probiotics, defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, are widely used despite uncertainty regarding their efficacy and discordant recommendations about their use. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Special Interest Group on Gut Microbiota and Modifications provides updated recommendations for the use of probiotics for the management of selected pediatric gastrointestinal disorders.

All systematic reviews and/or meta-analyses, as well as subsequently published randomized controlled trials (RCTs) (until December 2021), that compared the use of probiotics in all delivery vehicles and formulations, at any dose, with no probiotic (ie, placebo or no treatment), were eligible for inclusion. The recommendations were formulated only if at least 2 RCTs on a similar well-defined probiotic strain were available. The modified Delphi process was used to establish consensus on the recommendations.

Recommendations for the use of specific probiotic strains were made for the management of acute gastroenteritis, prevention of antibiotic-associated diarrhea, nosocomial diarrhea and necrotizing enterocolitis, management of Helicobacter pylori infection, and management of functional abdominal pain disorders and infant colic.

Despite evidence to support the use of specific probiotics in some clinical situations, further studies confirming the effect(s) and defining the type, dose, and timing of probiotics are still often required. The use of probiotics with no documented health benefits should be discouraged.

Infantile colic (IC) or fussing and crying behavior of unknown cause, affects up to 20% of the infant population and is one of the major reasons for parents to seek medical advice. Therapeutic options are limited and the key component for IC management is parental support. Fennel-based herbal treatments were shown to significantly reduce crying time. The current study was designed to evaluate the parent perception of effectiveness of a fennel-based commercially-available herbal treatment for IC (BabyCalm, Hisunit Ltd., Israel) using a retrospective online survey.

This was a real-world observational, case-control retrospective study. Parents of babies with IC symptoms, who either used the herbal product for their baby or did not use any product were invited to participate in an online survey during August-December 2019. The primary outcome was the perceived level of treatment success and symptom improvement.

1218 parents of IC babies (48% females, 90% up to 3 months of age, 58% exclusively breast-fed) responded to the survey of whom 771 used the treatment. Significantly fewer IC-related symptoms were reported by parents who used the product compared to those that did not. Parents perceived the treatment as successful in 65% of the cases, reporting meaningful improvements within 30 min for 69%-79% of the symptoms.

The majority of parents perceived the herbal treatment as effective in rapid symptom reduction suggesting that this may provide a satisfactory solution for IC in the community.

With the development of human genome sequencing and techniques such as intestinal microbial culture and fecal microbial transplantation, newly discovered microorganisms have been isolated, cultured, and researched. Consequently, many beneficial probiotics have emerged as next-generation probiotics (NGPs). Currently, "safety," "individualized treatment," and "internal interaction within the flora" are requirements of a potential NGPs. Furthermore, in the complex ecosystem of humans and microbes, it is challenging to identify the relationship between specific strains, specific flora, and hosts to warrant a therapeutic intervention in case of a disease. Thus, this review focuses on the progress made in NGPs and human health research by elucidating the limitations of traditional probiotics; summarizing the functions and strengths of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides fragilis, Eubacterium hallii, and Roseburia spp. as NGPs; and determining the role of their intervention in treatment of certain diseases. Finally, we aim to provide a reference for developing new probiotics in the future.

Recent studies have highlighted the positive impact of high sn-2 formulas on gastrointestinal (GI) tolerance. We assessed the GI tolerance, acceptability, and safety of high sn-2 infant formula among non-breastfed healthy term infants in the Gulf countries. A multicenter observational study was conducted on 227 healthy-term infants who were prescribed high sn-2 palmitate infant formula and received a minimum of two formula feedings per day for the past two weeks prior to the study's initiation. The number of stools per day decreased significantly from a median of four (interquartile range [IQR] = 4) at baseline to 3.0 (2) stools per day at the end of follow-up (p = 0.015). The percentage of stool amount changed significantly, where 61.2% and 33.7% of the infants had an amount of 25-50% of the diaper and >50% of the diaper, respectively (p < 0.001) at the end of the follow-up. Similarly, the percentage of hard stool decreased significantly from 17.4% at baseline to 0.4% of the population at week 12 (p < 0.00). The prevalence of colic and abdominal distention declined from 21.4% and 39.9% at baseline to 2.9% and 9.4% at week 12, respectively (p < 0.05). The same decline was observed in abdominal distension and regurgitation score (p < 0.05).

Probiotic Lactobacillus reuteri DSM 17938 (LR 17938) is beneficial to infants with colic. To understand its mechanism of action, we assessed ultrasonic vocalizations (USV) and brain pain/stress genes in newborn mice exposed to maternal separation stress.

Pups were exposed to unpredictable maternal separation (MSU or SEP) or MSU combined with unpredictable maternal stress (MSU + MSUS or S + S), from postnatal days 5 to 14. USV calls and pain/stress/neuroinflammation-related genes in the brain were analyzed.

We defined 10 different neonatal call patterns, none of which increased after MSU. Stress reduced overall USV calls. Orally feeding LR 17938 also did not change USV calls after MSU. However, LR 17938 markedly increased vocalizations in mice allowed to stay with their dams. Even though LR 17938 did not change MSU-related calls, LR 17938 modulated brain genes related to stress and pain. Up-regulated genes following LR 17938 treatment were opioid peptides, kappa-opioid receptor 1 genes, and CD200, important in anti-inflammatory signaling. LR 17938 down-regulated CCR2 transcripts, a chemokine receptor, in the stressed neonatal brain.

USV calls in newborn mice are interpreted as "physiological calls" instead of "cries." Feeding LR 17938 after MSU did not change USV calls but modulated cerebral genes favoring pain and stress reduction and anti-inflammatory signaling.

We defined mouse ultrasonic vocalization (USV) call patterns in this study, which will be important in guiding future studies in other mouse strains. Newborn mice with maternal separation stress have reduced USVs, compared to newborn mice without stress, indicating USV calls may represent "physiological calling" instead of "crying." Oral feeding of probiotic Lactobacillus reuteri DSM 17938 raised the number of calls when newborn mice continued to suckle on their dams, but not when mice were under stress. The probiotic bacteria had a dampening effect on monocyte activation and on epinephrine and glutamate-related stress gene expression in the mouse brain.

AMSTAR-2 is a 16-item assessment tool to check the quality of a systematic review and establish whether the most important elements are reported. ROBIS is another assessment tool which was designed to evaluate the level of bias present within a systematic review. Our objective was to compare, contrast and establish both inter-rater reliability and usability of both tools as part of two overviews of systematic reviews. Strictly speaking, one tool assesses methodological quality (AMSTAR-2) and the other assesses risk of bias (ROBIS), but there is considerable overlap between the tools in terms of the signalling questions.

Three reviewers independently assessed 31 systematic reviews using both tools. The inter-rater reliability of all sub-sections using each instrument (AMSTAR-2 and ROBIS) was calculated using Gwet's agreement coefficient (AC1 for unweighted analysis and AC2 for weighted analysis).

Thirty-one systematic reviews were included. For AMSTAR-2, the median agreement for all questions was 0.61. Eight of the 16 AMSTAR-2 questions had substantial agreement or higher (> 0.61). For ROBIS, the median agreement for all questions was also 0.61. Eleven of the 24 ROBIS questions had substantial agreement or higher.

ROBIS is an effective tool for assessing risk of bias in systematic reviews and AMSTAR-2 is an effective tool at assessing quality. The median agreement between raters for both tools was identical (0.61). Reviews that included a meta-analysis were easier to rate with ROBIS; however, further developmental work could improve its use in reviews without a formal synthesis. AMSTAR-2 was more straightforward to use; however, more response options would be beneficial.

The potential benefit of the administration of probiotics in children has been studied in many settings globally. Probiotics products contain viable micro-organisms that confer a health benefit on the host. Beneficial effects of selected probiotic strains for the management or prevention of selected pediatric conditions have been demonstrated. The purpose of this paper is to provide an overview of current available evidence on the efficacy of specific probiotics in selected conditions to guide pediatricians in decision-making on the therapeutic or prophylactic use of probiotic strains in children. Evidence to support the use of certain probiotics in selected pediatric conditions is often available. In addition, the administration of probiotics is associated with a low risk of adverse events and is generally well tolerated. The best documented efficacy of certain probiotics is for treatment of infectious gastroenteritis, and prevention of antibiotic-associated, Clostridioides difficile-associated and nosocomial diarrhea. Unfortunately, due to study heterogeneity and in some cases high risk of bias in published studies, a broad consensus is lacking for specific probiotic strains, doses and treatment regimens for some pediatric indications. The current available evidence thus limits the systematic administration of probiotics. The most recent meta-analyses and reviews highlight the need for more well-designed, properly powered, strain-specific and dedicated-dose response studies.

The aim of this review was to evaluate the evidence for interventions for infantile colic.

This was a systematic review based on a literature search in December 2017 for articles published during 2007-2017 about preventive and treatment interventions for infantile colic in infants. The review included original randomised controlled trials (RCTs) and meta-analyses with at least 20 infants in each study group that were assessed according to GRADE criteria.

The review found moderately strong evidence that administration of Lactobacillus reuteri DSM 17938 shortened the crying duration, with positive evidence from three out of four national contexts. There were four RCTs of acupuncture, all with no or minimal effect on crying duration. All studies reviewed with a follow-up until or beyond three months of age show a quite steep decline over time in crying duration in both treatment and control groups.

Lactobacillus reuteri DSM 17938 is a promising treatment for infantile colic with moderately strong evidence in this review, but studies in more populations are needed. Acupuncture is not an effective treatment for infantile colic. Systematic support strategies to parents with infantile colic are important knowledge gaps.

We aimed to compare the efficacy of a partially hydrolysed formula (pHF) with reduced lactose content and Lactobacillus reuteri DSM 17938 (L. reuteri) with a standard formula in infant colic (IC).

We performed a double blind, parallel-group randomized active-controlled. Inclusion criteria were: exclusively formula fed, full term infants, aged <4 months, diagnosis of IC. All the enrolled infants were randomized to receive either pHF with reduced lactose content and L. reuteri (Group A) or standard formula (Group B). The treatment duration was 4 weeks and children were followed-up to 8 weeks. The primary outcome was the mean infant crying duration at 28 days.

Two-hundred-forty-one children were randomized to the treatments' group (Group A = 124; Group B = 117). Mean daily crying time at 28th day was significantly lower in Group B when compared to Group A [104.7 (87-122.4) versus 146.4 min (129.2-163.7), treatment effect -41.8 (95% C.I.: -66.5 to -17.1), p = 0.001]. No significant adverse event was reported in both groups.

Standard formula showed a lower overall crying time respect to the intervention formula (ClinicalTrials.govNCT02813772).

To conduct a systematic review of systematic reviews and national guidelines to assess the effectiveness of four treatment approaches (manual therapy, probiotics, proton pump inhibitors and simethicone) on colic symptoms including infant crying time, sleep distress and adverse events.

We searched PubMed, Embase, Cochrane and Mantis for studies published between 2009 and 2019. Inclusion criteria were systematic reviews and guidelines that used evidence and expert panel opinion. Three reviewers independently selected articles by title, abstract and full paper review. Data were extracted by one reviewer and checked by a second. Selected studies were assessed for quality using modified standardised checklists by two authors. Meta-analysed data for our outcomes of interest were extracted and narrative conclusions were assessed.

Thirty-two studies were selected. High-level evidence showed that probiotics were most effective for reducing crying time in breastfed infants (range -25 min to -65 min over 24 hours). Manual therapies had moderate to low-quality evidence showing reduced crying time (range -33 min to -76 min per 24 hours). Simethicone had moderate to low evidence showing no benefit or negative effect. One meta-analysis did not support the use of proton pump inhibitors for reducing crying time and fussing. Three national guidelines unanimously recommended the use of education, parental reassurance, advice and guidance and clinical evaluation of mother and baby. Consensus on other advice and treatments did not exist.

The strongest evidence for the treatment of colic was probiotics for breastfed infants, followed by weaker but favourable evidence for manual therapy indicated by crying time. Both forms of treatment carried a low risk of serious adverse events. The guidance reviewed did not reflect these findings.

CRD42019139074.

Infantile colic has an effect on both infants and their parents, who become exhausted and concerned as they attempt to comfort their child. Common approaches have focused upon physical treatments to reduce symptoms, with inconclusive evidence as to their effectiveness. An alternative approach seeks to provide training, support and psychological interventions for parents. This approach is known as parent training programmes. Programmes can include soothing techniques, advice on feeding or normalisation material in any form. The teaching format can vary including face-to-face courses, online learning, printed materials, home visits and remote support and counselling. Here, we aim to collate the evidence on the effectiveness of these interventions and examine their effectiveness at reducing infantile colic symptoms and parental anxiety levels, and their safety.

1. To evaluate the effectiveness and safety of parent training programmes for managing colic in infants under four months of age. 2. To identify the educational content and attributes of such published programmes.

In June 2019 we searched CENTRAL, MEDLINE, Embase, 13 other databases and two trials registers. We also handsearched conference abstracts, inspected the references of included studies and contacted leaders in the field for more trials.

Randomised controlled trials (RCTs) and quasi-RCTs investigating the effectiveness of any form of parental training programmes, alone or in combination, versus another intervention(s) or control, on infantile colic.

Two authors independently selected studies for inclusion, extracted data, and assessed the risk of bias within the included studies. We used Review Manager 5 to analyse the data. We assessed the certainty of the evidence using GRADE methodology.

Our search found 6064 records from which we selected 20 for full-text review. From these, we identified seven studies with 1187 participants that met our inclusion criteria. All of the studies included infants under the age of four months suffering from infantile colic. Four studies were conducted in the USA, one in Canada, one in the Netherlands and one in Iran. Four studies stated their funding sources, which included national research institutes, foundations and nutritional companies. Five studies assessed parent training versus a control group that received reassurance or routine care; and of these, one study was three-armed and also examined the effectiveness of using a specialised baby seat. One study examined parent training programmes against a milk-exclusion diet and one study assessed a parent training programme versus the same parent training programme plus swaddling. The duration of the interventions varied, with the shortest being six days and the longest being three months. Generally, most studies had low participant numbers and were at high risk of bias, prone to selection bias, performance bias, and the placebo effect. We could not complete the planned qualitative analysis (objective 2) due to lack of data in study reports and no further information being supplied by authors on request. Instead, we completed a descriptive content analysis with the limited information available. The parent training interventions were found to focus on one or a combination of the following: soothing techniques for crying infants (six studies); general care advice, including sleep (four studies); feeding advice (two studies); stress reduction and empathic programme for parents (two studies); and positive play interaction advice (one study). One study taught 'kangaroo care', a specific form of skin-to-skin cuddling. The control groups consisted of reassurance (two studies), advice to rock the infant in the crib (one study), or no intervention (two studies). Parent training versus control We conducted a meta-analysis using data from three studies (157 infants) that assessed the primary outcome of 'crying time at completion of study period'. Parent training was more effective than control: mean difference (MD) -113.58 m/d, 95% confidence interval (CI) -144.19 m/d to -82.96 m/d; low-certainty evidence (downgraded due to imprecision and some concerns with risk of bias). Parent training versus specialised baby seat One study (38 participants) found no difference in mean crying time at completion between the parent training group and the specialised baby seat group, but did not report specific figures. Parent training versus a milk-exclusion/soy milk formula One study (20 participants) comparing parent training with a milk-exclusion/soy milk formula found crying time at completion of the study to be 2.03 hours versus 1.08 hours, respectively. Parent training versus parent training plus swaddling One study (398 participants) comparing parental training with the same intervention plus training on how to swaddle an infant did not report separate data for each group. No adverse effects were reported, but these were not explicitly reported in any study.

There is limited evidence on the effectiveness and safety of parent training programmes for managing infantile colic. Despite a single meta-analysis showing that parent training may reduce crying times for infants, compared to control, the certainty of the evidence was low. Evidence for other comparisons was sparse. We were unable to identify comprehensively the educational content and attributes of the included programmes due to a lack of information in study reports. Further RCTs are needed: they should define interventions clearly to ensure replicability, address all appropriate outcome measures, and minimise risk of bias in order to assess definitively the role of parent training programmes in managing infantile colic.

Infantile colic is a distressing condition characterised by excessive crying in the first few months of life. The aim of this research was to update the synthesis of evidence of complementary and alternative medicine (CAM) research literature on infantile colic and establish what evidence is currently available.

Medline, Embase and AMED (via Ovid), Web of Science and Central via Cochrane library were searched from their inception to September 2018. Google Scholar and OpenGrey were searched for grey literature and PROSPERO for ongoing reviews. Published systematic reviews that included randomised controlled trials (RCTs) of infants aged up to 1 year, diagnosed with infantile colic using standard diagnostic criteria, were eligible. Reviews of RCTs that assessed the effectiveness of any individual CAM therapy were included. Three reviewers were involved in data extraction and quality assessment using the AMSTAR-2 scale and risk of bias using the ROBIS tool.

Sixteen systematic reviews were identified. Probiotics, fennel extract and spinal manipulation show promise to alleviate symptoms of colic, although some concerns remain. Acupuncture and soy are currently not recommended. The majority of the reviews were assessed as having high or unclear risk of bias and low confidence in the findings.

There is clearly a need for larger and more methodologically sound RCTs to be conducted on the effectiveness of some CAM therapies for IC. Particular focus on probiotics in non-breastfed infants is pertinent.

PROSPERO: CRD42018092966.

There is growing evidence encouraging the use of probiotics in many conditions in children. However, given the wide number of probiotics available and contradictory data in the literature, the health-care provider is often faced with uncertainness about whether or not to use probiotics and which one(s) to choose. We here review current hypotheses regarding the efficacy and safety of probiotics and evaluate the available data on the use of probiotics in most common diseases in children. Considering that probiotics have strain-specific effects, we will focus on individual probiotic strains rather than on probiotics in general.

Strain-specific efficacy was clearly demonstrated with Lactobacillus rhamnosus GG and Saccharomyces boulardii I-745 in the treatment of acute infectious diarrhea, Lactobacillus reuteri DSM 17938 in infantile colics, Lactobacillus rhamnosus GG, and VSL#3 in irritable bowel syndrome. In addition, encouraging results are seen for use of probiotics in necrotizing enterocolitis, food allergy, and nonalcoholic fatty liver disease. However, the data available for constipation are to be considered somewhat equivocal.

The clinical relevance of these findings indicates that healthcare providers need to take strain-specificity and disease specificity of probiotics into consideration when recommending probiotic for their patients.

Infantile colic is a common benign disease occurring in early infancy that may have a great impact on family life. In the present study, the effectiveness and safety of the complex homeopathic medicine Enterokind was compared with Simethicone for treating infantile colic.

Current data were drawn from a prospective, multicenter, randomized, open-label, controlled clinical trial that was conducted in 2009 in 3 Russian outpatient clinics. Children received either Enterokind (Chamomilla D6, Cina D6, Colocynthis D6, Lac defloratum D6 and Magnesium chloratum D6) or Simethicone. Data from infants ≤ 6 months with infantile colic are presented here.

The main outcomes assessments were the change of total complaints score (maximum 17 points) and total objective symptoms score (maximum 22 points) after 10 days of treatment.

Data from 125 infants ≤ 6 months with infantile colic were analyzed. The differences in total complaints and objective symptoms scores between baseline and day 10, estimated from the ANCOVA model, were found to be highly significant (p < 0.0001; ITT) in favor of Enterokind, both for complaints (Δ=-2.38; 95% confidence interval (CI): [-2.87; -1.89]) and for objective symptoms (Δ=-2.07; 95% CI: [-2.65; -1.49]). 1 adverse event (AE), vomiting, occurred under Enterokind and was rated to be unlikely related to it; 4 AEs occurred under Simethicone. All AEs were non-serious.

The current study indicates that Enterokind is an effective and safe homeopathic treatment for functional intestinal colic in infants ≤ 6 months.

The gastrointestinal microbiome is a hot topic in clinical research. Beneficial effects of selected probiotics in the prevention of gastrointestinal disorders are mainly restricted to acute gastroenteritis, antibiotic-associated diarrhoea, infantile colic, and necrotising enterocolitis. However, no broad consensus exists to recommend the use of probiotics in the prevention of these conditions, mainly because of the different design of the studies done so far, resulting in little evidence for specific strains, dosages, and indications. More well designed studies are needed before recommendations can be proposed. At this stage, the evidence is insufficient to recommend the routine use of probiotics in infants and children for the prevention of gastrointestinal disorders.

Functional gastrointestinal disorders (FGIDs) such as infantile colic, constipation and colic occur in almost half of the infants. The aim of this paper is to provide a critical and updated review on the management of FGIDs and their impact on the health of the infant and family to health care physicians. Guidelines and expert recommendations were reviewed. FGIDs are a frequent cause of parental concern, impairment in quality of life of infants and relatives, and impose a financial burden to families, health care, and insurance. Therefore, primary management of the FGIDs should be focused on improving the infants' symptoms and quality of life of the family. If more than parental reassurance is needed, available evidence recommends nutritional advice as it is an effective strategy and most of the time devoid of adverse effects. The role of healthcare providers in reassuring parents and proposing the correct behavior and nutritional intervention by avoiding inappropriate use of medication, is essential in the management of FGIDs.

The importance of gut microbiota in gastrointestinal (GI) physiology was well described, but our ability to study gut microbial ecosystems in their entirety was limited by culture-based methods prior to the sequencing revolution. The advent of high-throughput sequencing opened new avenues, allowing us to study gut microbial communities as an aggregate, independent of our ability to culture individual microbes. Early studies focused on association of changes in gut microbiota with different disease states, which was necessary to identify a potential role for microbes and generate novel hypotheses. Over the past few years the field has moved beyond associations to better understand the mechanistic implications of the microbiome in the pathophysiology of complex diseases. This movement also has resulted in a shift in our focus toward therapeutic strategies, which rely on better understanding the mediators of gut microbiota-host cross-talk. It is not surprising the gut microbiome has been implicated in the pathogenesis of functional gastrointestinal disorders given its role in modulating physiological processes such as immune development, GI motility and secretion, epithelial barrier integrity, and brain-gut communication. In this review, we focus on the current state of knowledge and future directions in microbiome research as it pertains to functional gastrointestinal disorders. We summarize the factors that help shape the gut microbiome in human beings. We discuss data from animal models and human studies to highlight existing paradigms regarding the mechanisms underlying microbiota-mediated alterations in physiological processes and their relevance in human interventions. While translation of microbiome science is still in its infancy, the outlook is optimistic and we are advancing in the right direction toward precise mechanism-based microbiota therapies.

To dissect potential confounding effects of breast milk and formula feeding on crying + fussing, fecal calprotectin, and gut microbiota in babies with colic. We hypothesized that infant colic is associated with gut inflammation linked to intestinal dysbiosis.

A nested case-control design of 3 of our studies was used to analyze clinical and laboratory data at presentation, comparing babies with colic with controls. All investigators other than the biostatistician were blinded during data analysis. Subjects were recruited based on their age and crying + fussy time. We screened 65 infants, 37 with colic, as defined by Barr diary (crying + fussing time >3 hours daily), who were compared with 28 noncolicky infants.

Fecal calprotectin was elevated in babies with colic. For each mode of infant feeding (breast milk, formula, or breast + formula), infants' fecal calprotectin was higher in babies with colic. Infants with colic had similar levels of fecal alpha diversity (richness) when compared with controls, and alpha diversity was lower in breast-fed babies. Beta diversity at the phylum level revealed significant differences in microbial population. A phylum difference resulted from reduced Actinobacteria (95% of which are Bifidobacilli) in babies with colic. Species significantly associated with colic were Acinetobacter and Lactobacillus iners.

Colic is linked with gut inflammation (as determined by fecal calprotectin) and dysbiosis, independent of mode of feeding, with fewer Bifidobacilli.

Clinicaltrials.gov: NCT01279265 and NCT01849991.

Infant colic is a characteristic group of behaviors seen in young infants. The most prominent feature is prolonged crying. Additional characteristics, including clenching of the fists and flexion of the hips, have led to the suggestion that these behaviors are related to abdominal discomfort. In this article, we show emerging evidence to support the concept that infant colic could represent gut inflammation and microbial dysbiosis that impacts brain function and even brain development.

Persistent, inconsolable crying in young infants is common, distressing but usually benign. This selective review examines perceptions and perceived origins of this phenomenon in babies where serious pathology has been excluded. Adult brains have evolved to become hypersensitive to infant cries. Babies respond to parental stress by crying more, thus setting up a vicious cycle. Most treatments appear to work largely through a placebo effect. The imperative for healthcare professionals is to reduce parental anxiety by offering reassurance and support.

The use of herbal products to treat irritable bowel syndrome (IBS), a disease that frequently affects the quality of life (QoL), is still under evaluation. This open pilot study assessed the efficacy of bio-optimized extracts of turmeric and essential fennel oil (Enterofytol®) in IBS patients.

A total of 211 patients (14% diarrhea-predominant, IBS-D; 24% constipation-predominant, IBS-C; 62% mixed, IBS-M) were enrolled by general practitioners and completed questionnaires measuring symptom severity and QoL before and after Enterofytol®, two capsules b.i.d. for one month, followed by two capsules q.d. for another month.

IBS severity index and QoL were inversely related. A significant reduction in the severity index and an improvement in QoL were evident following treatment in all IBS subgroups. IBS-D patients showed the worst clinical picture at entry, with the highest IBS severity index and the lowest QoL score, compared with IBS-C and IBS-M subtypes. IBS-D patients, however, also showed the most pronounced response to therapy, considering both scores. The improvement in the IBS severity index was independent of age and sex.

Results from this "real-life" study show that the combination of turmeric and essential fennel oil over two months improves both symptoms and QoL in IBS patients, irrespectively of age, sex, initial severity of symptoms and IBS-subtypes, suggesting a potential role for the natural treatment of IBS.

Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to impact the immune system, both in vivo and in vitro. This interaction is linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on mechanistic studies in animal models. Microbial⁻immune system crosstalk has been linked to: short-chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor. Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multiorgan inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis. Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes.

Few treatments for human diseases have received as much investigation in the past 20 years as probiotics. In 2017, English-language meta-analyses totaling 52 studies determined the effect of probiotics on conditions ranging from necrotizing enterocolitis and colic in infants to constipation, irritable bowel syndrome, and hepatic encephalopathy in adults. The strongest evidence in favor of probiotics lies in the prevention or treatment of 5 disorders: necrotizing enterocolitis, acute infectious diarrhea, acute respiratory tract infections, antibiotic-associated diarrhea, and infant colic. Probiotic mechanisms of action include the inhibition of bacterial adhesion; enhanced mucosal barrier function; modulation of the innate and adaptive immune systems (including induction of tolerogenic dendritic cells and regulatory T cells); secretion of bioactive metabolites; and regulation of the enteric and central nervous systems. Future research is needed to identify the optimal probiotic and dose for specific diseases, to address whether the addition of prebiotics (to form synbiotics) would enhance activity, and to determine if defined microbial communities would provide benefit exceeding that of single-species probiotics.

A newborn brings joy to the family. Crying belongs to the spectrum of normal behaviour of young infants. However, although it occurs in about 20% of all infants, unsoothable and persistent crying in young infants distresses the family, although it is usually benign. The aetiology of infantile colic remains unknown, although an unbalanced gastro-intestinal microbiome, increased intestinal permeability, and chronic inflammation are involved, as well as behavioural factors, including over- and under-stimulation. It is a challenge for healthcare professionals to decide when organic disease needs to be excluded. Parental stress is a reason for babies to cry more, inducing a vicious cycle. Therefore, parental reassurance with explanatory guidance is the cornerstone of management. The placebo effect is estimated to be as high as 50%. If an intervention is felt to be necessary to offer further support to the baby and family, it is important to choose the options for which there is some efficacy without adverse effects. There is evidence that some specific probiotic strains such as Lactobacillus reuteri DSM 19378, especially in breastfed infants, are effective. However, there are also promising data for some synbiotics and/or killed or tyndallized bacteria, as well as substances decreasing intestinal permeability. Formula management with extensive and/or partial hydrolysates may also bring relief. But, above all, offering parental support remains imperative.

Regurgitation, infantile colic and functional constipation are common functional gastrointestinal disorders (FGIDs) during infancy. Our aim was to carry out a concise review of the literature, evaluate the impact of these common FGIDs on infants and their families, and provide an overview of national and international guidelines and peer-reviewed expert recommendations on their management.

National and international guidelines and peer-reviewed expert recommendations on the management of regurgitation, infantile colic and functional constipation were examined and summarised.

Regurgitation, infantile colic and functional constipation cause frequent parental concerns, lead to heavy personal and economic costs for families and impose a financial burden on public healthcare systems. Guidelines emphasise that the first-line management of these common FGIDs should focus on parental education, reassurance and nutritional advice. Nutritional advice should stress the benefits of continuing breastfeeding, while special infant formulas may be considered for non-breastfed infants with common FGIDs. Drug treatment is seldom required, with the exception of functional constipation.

By providing complete and updated parental education, reassurance and nutritional advice, healthcare professionals can optimise the management of FGIDs and related symptoms and reduce the inappropriate use of medication or dietary interventions.

Infantile colic is a common pediatric problem. The cause of infantile colic remains unclear. Treatment options are limited. Evidence suggests that probiotics might offer some benefit. The aim of the study was to systematically assess the effectiveness of probiotics supplementation in the management of infantile colic.

MEDLINE and the Cochrane Library were searched up to April 2016 for randomized controlled trials (RCTs) evaluating the efficacy of probiotics (any well-defined strain) compared with placebo for the management of infantile colic. The outcome measures of interest were treatment success and the duration of crying at the end of the intervention.

Seven RCTs (471 participants) were included. Compared with placebo the administration of Lactobacillus reuteri DSM 17938 at a daily dose of 108 CFU was associated with the treatment success (relative risk = 1.67, 95% CI: 1.10-2.81, number needed to treat 5, 95% CI: 4-8) and reduced crying times at the end of the intervention (mean difference: -49 min, 95% CI: -66 to -33); however, the effect was mainly seen in exclusively breastfed infants. Other probiotics (single or in combinations) were studied in single trials only.

Some probiotics, primarily L. reuteri DSM 17938, may be considered for the management of infantile colic. Data on other probiotics are limited.

Infant colic is a commonly reported phenomenon of excessive crying in infancy with an enigmatic and distressing character. Despite its frequent occurrence, little agreement has been reached on the definition, pathogenesis or the optimal management strategy for infant colic. This Review aims to delineate the definitional entanglement with the Rome IV criteria, which were published in 2016, as the leading, most recent diagnostic criteria. Moreover, neurogenic, gastrointestinal, microbial and psychosocial factors that might contribute to the pathophysiology of infant colic are explored. This Review underlines that a comprehensive medical history and physical examination in the absence of alarm symptoms serve as guidance for the clinician to a positive diagnosis. It also highlights that an important aspect of the management of infant colic is parental education and reassurance. Management strategies, including behavioural, dietary, pharmacological and alternative interventions, are also discussed. Owing to a lack of large, high-quality randomized controlled trials, none of these therapies are strongly recommended. Finally, the behavioural and somatic sequelae of infant colic into childhood are summarized.

Lactobacillus reuteri DSM17938 has shown promise in managing colic, but conflicting study results have prevented a consensus on whether it is truly effective.

Through an individual participant data meta-analysis, we sought to definitively determine if L reuteri DSM17938 effectively reduces crying and/or fussing time in infants with colic and whether effects vary by feeding type.

We searched online databases (PubMed, Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, the Database of Abstracts of Reviews of Effects, and Cochrane), e-abstracts, and clinical trial registries.

These were double-blind randomized controlled trials (published by June 2017) of L reuteri DSM17398 versus a placebo, delivered orally to infants with colic, with outcomes of infant crying and/or fussing duration and treatment success at 21 days.

We collected individual participant raw data from included studies modeled simultaneously in multilevel generalized linear mixed-effects regression models.

Four double-blind trials involving 345 infants with colic (174 probiotic and 171 placebo) were included. The probiotic group averaged less crying and/or fussing time than the placebo group at all time points (day 21 adjusted mean difference in change from baseline [minutes] -25.4 [95% confidence interval (CI): -47.3 to -3.5]). The probiotic group was almost twice as likely as the placebo group to experience treatment success at all time points (day 21 adjusted incidence ratio 1.7 [95% CI: 1.4 to 2.2]). Intervention effects were dramatic in breastfed infants (number needed to treat for day 21 success 2.6 [95% CI: 2.0 to 3.6]) but were insignificant in formula-fed infants.

There were insufficient data to make conclusions for formula-fed infants with colic.

L reuteri DSM17938 is effective and can be recommended for breastfed infants with colic. Its role in formula-fed infants with colic needs further research.

To evaluate crying time, retinoid-related orphan receptor-γ (RORγ) and forkhead box P3 (FOXP3) messenger RNA levels (transcription factors that can modulate T cell responses to gut microbes), and to investigate gut microbiota and fecal calprotectin in infants treated with Lactobacillus reuteri for infantile colic.

A double-blind, placebo-controlled randomized trial was conducted in primary care in Torino from August 1, 2015 to September 30, 2016. Patients suffering from infantile colic were randomly assigned to receive daily oral L reuteri (1 × 10⁸ colony forming unit) or placebo for 1 month. Daily crying times were recorded in a structured diary. FOXP3 and RORγ messenger RNA in the peripheral blood was assessed with real-time TaqMan reverse transcription polymerase chain reaction. Gut microbiota and fecal calprotectin were evaluated.

After infants with colic were supplemented with L reuteri DSM 17938 for 30 days, crying times were significantly shorter among infants with colic in the probiotic group compared with infants in the placebo group (74.67 ± 25.04 [IQR = 79] minutes /day vs 147.85 [IQR = 135] minutes /day [P = .001]). The FOXP3 concentration increased significantly (P = .009), resulting in decreased RORγ/FOXP3 ratios: 0.61 (IQR = 0.60) at day 0 and 0.48 (IQR = 0.28) at day 30 (P = .028). Furthermore, the probiotic increased the percentage of Lactobacillus (P = .049) and decreased fecal calprotectin (P = .0001).

Infants with colic treated with L reuteri for 30 days had a significantly decreased crying time and an increased FOXP3 concentration, resulting in a decreased RORγ/FOXP3 ratio. The treatment reduced fecal calprotectin.

ClinicalTrials.gov: NCT00893711.

Recommendations for probiotics are available in several regions. This paper proposes recommendations for probiotics in pediatric gastrointestinal diseases in the Asia-Pacific region. Epidemiology and clinical patterns of intestinal diseases in Asia-Pacific countries were discussed. Evidence-based recommendations and randomized controlled trials in the region were revised. Cultural aspects, health management issues and economic factors were also considered. Final recommendations were approved by applying the Likert scale and rated using the GRADE system. Saccharomyces boulardii CNCM I-745 (Sb) and Lactobacillus rhamnosus GG (LGG) were strongly recommended as adjunct treatment to oral rehydration therapy for gastroenteritis. Lactobacillus reuteri could also be considered. Probiotics may be considered for prevention of (with the indicated strains): antibiotic-associated diarrhea (LGG or Sb); Clostridium difficile-induced diarrhea (Sb); nosocomial diarrhea (LGG); infantile colic (L reuteri) and as adjunct treatment of Helicobacter pylori (Sb and others). Specific probiotics with a history of safe use in preterm and term infants may be considered in infants for prevention of necrotizing enterocolitis. There is insufficient evidence for recommendations in other conditions. Despite a diversity of epidemiological, socioeconomical and health system conditions, similar recommendations apply well to Asia pacific countries. These need to be validated with local randomized-controlled trials.

To assess the safety of probiotic Lactobacillus reuteri strain Deutsche Sammlung von Mikroorganismen (DSM) 17938 with daily administration to healthy infants with colic and to determine the effect of L reuteri strain DSM 17938 on crying, fussing, inflammatory, immune, and microbiome variables.

We performed a controlled, double-blinded, phase 1 safety and tolerability trial in healthy breast-fed infants with colic, aged 3 weeks to 3 months, randomly assigned to L reuteri strain DSM 17938 (5 × 10⁸ colony-forming units daily) or placebo for 42 days and followed for 134 days.

Of 117 screened infants, 20 were randomized to L reuteri strain DSM 17938 or placebo (sunflower oil) (in a 2:1 ratio) with 80% retention. Eleven of the 20 (55%) presented with low absolute neutrophil counts (<1500/mm³), which resolved in all subjects by day 176. L reuteri strain DSM 17938 produced no severe adverse events and did not significantly change crying time, plasma bicarbonate, or inflammatory biomarkers. Fecal calprotectin decreased rapidly in both groups. In the infants with dominant fecal gram negatives (Klebsiella, Proteus, and Veillonella), resolution of colic was associated with marked decreases in these organisms.

Daily administration of L reuteri strain DSM 17938 appears to be safe in newborn infants with colic, including those with neutropenia, which frequently coexists. A placebo response of 66% suggests that many infants with colic will have resolution within 3 weeks.

ClinicalTrials.gov: NCT01849991.

Infant colic (IC) is a prevalent physiological event of infants, which can disrupt the child's home environment. We aimed to investigate the effectiveness of a mixture of Matricariae chamomilla L., Melissa officinalis L. and tyndallized Lactobacillus acidophilus (HA122) compared with Lactobacillus reuteri DSM 17938 and with simethicone for the treatment of IC.

A multicenter randomized comparative study was conducted in infants with colic, according to Rome III criteria, who were randomly assigned to receive M. chamomilla L., M. officinalis L. and tyndallized L. acidophilus (HA122) (Colimil^® Plus^® ; Milte Italia Spa, Milan, Italy) (Group A), L. reuteri DSM 17938 (Group B) and simethicone (Group C). Treatment was given to subjects for 28 days.

One-hundred and seventy-six patients completed the study. Mean daily crying time at day 28 was significantly lower in group A (-44, 95% CI: -58 to -30, P<.001) and group B (-35, 95% CI: -49 to -20, P<.001) when compared to group C. No significant difference was observed between Group A and Group B (mean difference: -9 minutes, 95% CI -23 to +5, P=.205). At day 28, 39 of 57 (68.4%) of infants in Group C responded to the treatment compared with 57 out of 60 patients (95%) of Group A and 51 out of 59 (86.4%) of Group B (P<.001).

This study suggests that administration of M. chamomilla L., M. officinalis L. and tyndallized L. acidophilus (HA122) and L. reuteri DSM 17938 are significantly more effective than simethicone in IC.

ClinicalTrials.gov: NCT02708238.

Excessive crying is a common complaint in young infants, especially in those less than 3 mo of age. Altered circadian rhythm, immaturity of central nervous system and alteration of intestinal microbiota are some of the proposed mechanisms for this problem. Although it is commonly benign, crying can be the only clinical manifestation of many serious underlying illnesses, thus warranting careful clinical examination for ruling out organic causes. Urgent care clinics are best suited for evaluation and treatment of benign etiologies and promptly referring children with red flags to an emergency department. Routine investigations are not indicated in an afebrile infant with no signs of illness on history and physical examination. Excessive crying due to colic often results in parental stress and exhaustion. Treatment in such cases revolves more on reassuring the parents and avoiding drugs with uncertain action and potential side-effects.

Colonization of the neonatal gut by beneficial bacteria is important for the establishment and maintenance of the mucosal barrier, thus protecting the neonate from enteric pathogens and local and systemic inflammation. The neonatal microbiome is influenced by infant diet, environment, and the maternal microbiome. Dysbiosis in pregnancy increases the risk of pre-eclampsia, diabetes, infection, preterm labor, and later childhood atopy. Dysbiosis of the neonatal gut plays an important role in colic in the term infant, in the disease processes which plague preterm infants, including necrotizing enterocolitis and sepsis, and in the long-term outcomes of neonates. Administration of enteral prebiotics, probiotics, and synbiotics during pregnancy, lactation, and postnatal life appears to be a safe and feasible method to alter the maternal and neonatal microbiome, thus improving pregnancy and neonatal outcomes.

By performing an in-depth analysis of one high profile example, this article aims to help breastfeeding support professionals understand the methodological flaws that characterize recent studies claiming to show the efficacy of frenotomy for the diagnoses of posterior tongue-tie and upper lip-tie. The example study does not address definitional confusion or control for the effects of the passage of time. It does not consider the effects of caring attention, validation, and lactation consultant support. It also does not consider the extensive research over the past three decades that has established that reflux in the first 6 months of life is benign, even though increased reflux frequency may correlate with unsettled infant behavior. The study authors relied on the hypothesis that reflux is caused by excessive air swallowing in infants with poor latch due to posterior tongue-tie and upper lip-tie, which lacks credible physiological mechanisms or supporting evidence. The authors' claim that conducting a randomized controlled trial to investigate the efficacy of frenotomy would be unethical contradicts the basic principles of good science. This article argues that our breastfeeding women and their babies deserve the most rigorous scientific methods available, and acknowledgment of the biases inherent in less rigorous research, if we are to make appropriate decisions concerning intervention with frenotomy and to prevent unnecessary oral surgery.

The purpose of this paper is to evaluate the efficacy of a lactose- reduced synbiotic partial whey hydrolysate in formula fed infants presenting with colic and the impact of this dietary intervention in mean crying time and quality of life.

Forty infants with infantile colic were treated during one month with parental reassurance and the intervention formula (partial whey hydrolysate, reduced lactose, Bifidobacterium lactis BB12 and galacto-oligosaccharides) and were compared to a control group of 20 infants with infantile colic treated with parental reassurance and a standard infant formula. Parents completed a quality of life (QoL) questionnaire assessing the burden of infantile colic. Wilcoxon test, t-test and Mann-Whitney test were used to compare QoL scores before and after intervention as well as between the intervention and control group.

At inclusion, duration of crying did not differ between both groups. Crying duration decreased with 2.7 hours (from 3.2 to 0.5 hours) in the intervention group while duration of crying decreased only with 1.2 hours in the control group (p<0.001). Stool composition became looser in the intervention group, but defecation frequency did not change. The median scores of the QoL questionnaire improved significantly in the intervention group for all parameters. In the control group, parameters improved significantly also but not for the parent-child and social interaction. The score changes were significantly greater in the intervention than in the control group.

The intervention formula (partial whey hydrolysate, synbiotic, reduced lactose) significantly reduced the duration of crying and improved QoL of the parents and infants.

The practice of pediatrics from an integrative framework is based on physician-patient relationship, informed by evidence, and approaches the health of children and their families from a broad perspective. This article reviews the basic principles of integrative pediatrics and summarizes data and integrative approaches to common pediatric conditions seen in the primary care setting.

Infantile colic is a frequent problem in neonates and infants. This review addresses current management including the results for nutrient modifications; soy-based formulas; and prebiotics, probiotics, and synbiotics.

Given the evidence that there is still an unmet clinical need, as current treatments are incompletely efficacious, we have examined the evidence around three hypothetical mechanisms that could potentially be involved in etiopathogenesis of infantile colic: immaturity of bile acid mechanisms that alter intraluminal and absorptive mechanisms, immaturity in motility and alterations in the microbiome. Understanding these potential mechanisms may lead to the introduction of diagnostic procedures that should enhance the selection or individualization of therapy for infantile colic.

Comparing efficacy and safety of APT198K (xyloglucan plus heat-killed Lactobacillus reuteri SGL01 and Bifidobacterium brevis SGB01) versus a lactase dietary supplement as first-line treatment of infantile colic.

Randomized, multicenter, open-label, parallel group, active-controlled study, in 46 infants aged 3-16 weeks with infantile colic, receiving APT198K or a lactase dietary supplement for 10 days.

Number and duration of crying episodes decreased significantly versus baseline in both groups. On day 8, the mean duration of crying per episode was significantly shorter in the APT198K group compared with the lactase group (9.14 ± 5.34 vs 13.22 ± 5.29 min; p = 0.014) and remained so up to day 11.

APT198K decreased the mean duration per crying episode significantly more than a lactase dietary supplement in infants with colic. Further evaluation in larger studies is warranted. Clinical trial registry: EudraCT number 2014-002860-334; https://eudract.ema.europa.eu .