Microbiota intestinal y cólicos infantiles: ¿hay lugar para los prebióticos, probióticos y posbióticos? / Gut Microbiota and Infant Colic: is there a Place for Prebiotics, Probiotics, and Postbiotics?

El consumo de probióticos, prebióticos y posbióticos, o su combinación, puede contribuir a mantener una microbiota intestinal saludable ya que permite la regulación de su disbiosis en el caso de algunas enfermedades o trastornos, principalmente en los trastornos gastrointestinales funcionales (TGIF). El microbioma intestinal es protagonista esencial en la fisiopatología de los TGIF a través de sus funciones metabólicas y nutricionales, el mantenimiento de la integridad de la mucosa intestinal y la regulación de la respuesta inmunitaria. Las investigaciones realizadas hasta la fecha indican que los probióticos, prebióticos y posbióticos pueden tener efectos inmunomoduladores directos y clínicamente relevantes. Existen pruebas del uso de esta familia de bióticos en individuos sanos para mejorar la salud general y aliviar los síntomas en una serie de enfermedades como los cólicos infantiles. La colonización y establecimiento de la microbiota comienza en el momento del nacimiento; los primeros 2-3 años de vida son fundamentales para el desarrollo de una comunidad microbiana abundante y diversa. Diversos estudios científicos realizados mediante técnicas tradicionales dependientes de cultivo y más recientemente por técnicas moleculares han observado diferencias en las poblaciones bacterianas de bebés sanos y aquellos que sufren TGIF, estos últimos caracterizados por un aumento de especies patógenas y una menor población de bifidobacterias y lactobacilos, en comparación con los primeros. En tal contexto, se considera que la microbiota intestinal como protagonista en el desarrollo de esos trastornos, entre ellos los cólicos infantiles, a través de sus funciones metabólicas, nutricionales, de mantenimiento de la integridad de la mucosa intestinal y regulación de la respuesta inmunitaria. Esto ha abierto la puerta al estudio de la utilización de prebióticos, probióticos y posbióticos en el tratamiento y/o prevención de los TGIF infantiles. El parto vaginal y de término así como la lactancia son fundamentales en la constitución de una microbiota saludable. Como herramientas de apoyo, existen estudios de eficacia que sustentan la administración de esta familia de bióticos, principalmente en los casos en que la lactancia no sea posible o esté limitada. (AU)

The consumption of probiotics, prebiotics, and postbiotics, or a combination of them, can contribute to maintaining a healthy intestinal microbiota as it allows the regulation of its dysbiosis in the case of some diseases or disorders, mainly in functional gastrointestinal disorders (FGIDs). The gut microbiome is an essential player in the pathophysiology of FGIDs through its metabolic and nutritional functions, the maintenance of intestinal mucosal integrity, and the regulation of the immune response. Research results thus far indicate that probiotics, prebiotics, and postbiotics may have direct and clinically relevant immunomodulatory effects. There is evidence regarding the prescription of this family of biotics in healthy individuals to improve overall health and alleviate symptoms in many conditions like infantile colic. The colonization and microbiota establishment begins at birth; the first 2-3 years of life are critical for developing an abundant and diverse microbial community. Several scientific studies performed by traditional culture-dependent techniques and more recently by molecular techniques have observed differences in the bacterial populations of healthy infants and those suffering from FGIDs, the latter characterized by an increase in pathogenic species and a lower population of bifidobacteria and lactobacilli, compared to the former. In this context, the intestinal microbiota plays a leading role in the onset of these disorders, including infantile colic, through its metabolic and nutritional functions, maintenance of the integrity of the intestinal mucosa, and regulation of the immune response. That has opened the door to the study of prebiotics, probiotics, and postbiotics usage in the treatment and or prevention of infantile FGIDs. Vaginal and term delivery and breastfeeding are fundamental in the constitution of a healthy microbiota. As supportive tools, there are efficacy studies that support the administration of this family of biotics, mainly in cases where lactation is not possible or is limited.

The effect of two types of minimal acupuncture on stooling, sleeping and feeding in infants with colic: secondary analysis of a multicentre RCT in Sweden (ACU-COL).

BACKGROUND: Evidence for the effect of minimal acupuncture in infants with colic is limited. AIM: To compare the effect of standardized minimal acupuncture, individualized acupuncture (where traditional acupuncture points were chosen according to the infant's symptoms) and no acupuncture on objective measures of stooling, feeding and sleeping in infants with colic (based on diaries) and perceived changes in these parameters (based on parental questionnaires). METHODS: This was a secondary analysis of a multicentre randomized controlled three-armed trial conducted in four counties in Sweden between January 2013 and May 2015 (ACU-COL). The effect on crying has already been published and showed a decrease in crying time for the acupuncture groups. Infants, 2-8 weeks old, who cried and fussed for more than 3 h/day for more than 3 days/week, and thereby fulfilled the criteria for infantile colic, received four extra visits to their ordinary child health centre. The infants (n = 147) were randomly allocated via a computer-generated list to standardized minimal acupuncture at LI4 for 5 s (group A, n = 48), semi-standardized individual acupuncture with a maximum of five insertions for up to 30 s (group B, n = 49), or no acupuncture (group C, n = 48). The parents and the ordinary staff were blinded. Data were collected using: (1) diaries at baseline, during the two intervention weeks and 1-week follow-up; and (2) questionnaires with quantitative and qualitative components used at the second and fourth visits and during a follow-up telephone call. Outcomes were the changes in frequency of stooling and in hours of sleep per day. RESULTS: There were no differences between groups for stooling, feeding, or sleeping at any time point according to data from the diaries. At the follow-up phone call, more parents in groups A and B (compared to group C) perceived that feeding and sleep had changed and that the symptoms of colic had improved.

Shedding light on excessive crying in babies.

BACKGROUND: Excessive and inconsolable crying behavior in otherwise healthy infants (a condition called infant colic (IC)) is very distressing to parents, may lead to maternal depression, and in extreme cases, may result in shaken baby syndrome. Despite the high prevalence of this condition (20% of healthy infants), the underlying neural mechanisms of IC are still unknown. METHODS: By employing the latest magnetic resonance imaging (MRI) techniques in newborns, we prospectively investigated whether newborns' early brain responses to a sensory stimulus (smell) is associated with a subsequent crying behavior. RESULTS: In our sample population of 21 healthy breastfed newborns, those who developed IC at 6 weeks exhibited brain activation and functional connectivity in primary and secondary olfactory brain areas that were distinct from those in babies that did not develop IC. Different activation in brain regions known to be involved in sensory integration was also observed in colicky babies. These responses measured shortly after birth were highly correlated with the mean crying time at 6 weeks of age. CONCLUSIONS: Our results offer novel insights into IC pathophysiology by demonstrating that, shortly after birth, the central nervous system of babies developing IC has already greater reactivity to sensory stimuli than that of their noncolicky peers. IMPACT: Shortly after birth, the central nervous system of colicky infants has a greater sensitivity to olfactory stimuli than that of their noncolicky peers. This early sensitivity explains as much as 48% of their subsequent crying behavior at 6 weeks of life. Brain activation patterns to olfactory stimuli in colicky infants include not only primary olfactory areas but also brain regions involved in pain processing, emotional valence attribution, and self-regulation. This study links earlier findings in fields as diverse as gastroenterology and behavioral psychology and has the potential of helping healthcare professionals to define strategies to advise families.

Efficacy of Bifidobacterium breve CECT7263 for infantile colic treatment: an open-label, parallel, randomised, controlled trial.

Infantile colic is a prevalent condition characterised by excessive crying with no effective treatment available. We aimed to evaluate the efficacy of Bifidobacterium breve CECT7263 and a combination of this and Lactobacillus fermentum CECT5716 versus simethicone in reducing the daily time spent crying in colicky infants. A multicentre randomised, open-label, parallel, controlled trial of 28 days was performed in 150 infants who were diagnosed with colic according to the Rome III criteria and who randomly received simethicone (80 mg/day; Simethicone group), B. breve CECT7263 (2×108 cfu/day, Bb group), or a combination of L. fermentum CECT5716 and B. breve CECT7263 (1×108 cfu/day per strain, Bb+Lf group). The main outcomes were minutes of crying per day and the percentage of reduction in daily crying from baseline. Data were analysed per intention to treat. All treatments significantly decreased the daily crying time at the end of the intervention (P-time <0.001). However, the infants in the Bb group had significantly decreased crying time from the first week of the study (P<0.05), whereas the Bb+Lf group and the simethicone group had significantly decreased crying time from the second week (P<0.05). The percentage of reduction in the minutes of crying from baseline in the Bb group was significantly higher than that in the Simethicone group every week of the intervention (-40.3 vs -27.6% at 1-week; -59.2 vs -43.2% at 2-weeks; -64.5 vs -53.5% at 3-week and -68.5 vs -59.5% at 4-weeks, P<0.05). Additionally, in the Bb group, infants had better night sleep, and parents reported a more positive mood at the end of the intervention. All the products used in the study were safe and well tolerated. In conclusion, the breastmilk-isolated probiotic strain B. breve CECT7263 is a safe and effective treatment for infantile colic, presenting an earlier and more robust effect than the reference prescribed drug, simethicone.

Clinical, hematologic, hemostatic, and serum biochemical findings related to survival in Arabian horses with colic.

BACKGROUND: The efficacy of clinical examinations, and hematologic, hemostatic, and serum biochemical assessments to determine appropriate early medical or surgical therapy in Arabian horses with colic have not been well-described. OBJECTIVES: We aimed to evaluate clinical and hematologic findings, coagulation-fibrinolytic parameters, and organ dysfunction markers in association with survival in horses with colic. METHODS: Seventeen Arabian horses with colic and ten healthy horses were enrolled. After clinical examinations, including heart rates (HRs), capillary refill times (CRTs), abdominal sounds, rectal palpations, and nasogastric (NG) reflux assessments in both healthy and diseased horses, blood samples were collected and hematologic parameters, coagulation indices such as the prothrombin time (PT), activated partial thromboplastin time (APTT), plasma d-dimer (PDD), platelet count, fibrinogen, and hepatorenal biomarkers were measured. Based on the outcomes, horses with colic were divided into survival (10) and nonsurvival (7) groups, and all mentioned parameters were compared with the control group horses. RESULTS: Unlike HRs, CRTs, and abdominal sounds, rectal palpations (57.1%) and NG reflux (28.6%) findings were least sensitive in being able to determine survival. At least three of the five coagulation indices were significantly abnormal (prolonged PT, increased PDD, and decreased plasma fibrinogen) in 71.4% of the horses in the nonsurvival group compared with the control and survival groups. Significantly increased urea, creatinine, and bilirubin levels, and AST activities were also observed in the survival group compared with the control and nonsurvival groups. CONCLUSIONS: The combination of prolonged PT, increased PDD, and hypofibrinogenemia could be a reliable predictor of survival in horses with colic. The significant renal and hepatic dysfunctions in nonsurviving horses with colic appeared to be consistent with disseminated intravascular coagulation (DIC) and a grave prognosis.

Risk factors for acute abdominal pain (colic) in the adult horse: A scoping review of risk factors, and a systematic review of the effect of management-related changes.

Acute abdominal pain (colic) is the most common reason for emergency veterinary treatment in the horse. Consolidation of data through a systematic review is important to inform evidence-based medicine and clinical guidelines, but there are currently no published systematic reviews on colic in the horse. The aim of this study was to identify, categorize and appraise the evidence on factors associated with increased risk of developing abdominal pain (colic) due to gastrointestinal disease in the adult horse. A scoping review was performed to identify and categorize evidence on all risk factors for colic. A systematic review of management-related risk factors was then performed following PRISMA guidelines. Both searches were conducted in Medline, CAB Abstracts and Web of Science databases, and publications were assessed against inclusion and exclusion criteria. For the scoping review, study and participant characteristics of included publications and key results were extracted and tabulated. For the systematic review, cohort, case-control or cross-sectional studies investigating acute abdominal pain in horses within two weeks of management changes were assessed. Study characteristics, participant characteristics and study results of included publications for the systematic review were extracted and tabulated. Included publications were appraised using the Joanna Briggs Institute Critical Appraisal Tools for cohort, case-control and cross-sectional studies. The scoping review search identified 3,756 publications. Fifty eight studies met final inclusion criteria, and 22 categories of risk factors were identified. These were grouped into three broad areas: horse-related factors, management-related factors and environment-related factors. The largest body of evidence related to management change. The systematic review of management change identified 410 publications: 14 met inclusion criteria for analysis. These consisted of one cohort, eight case-control and five cross-sectional studies. The studies were conducted between 1990-2008, and the majority of studies were located in the USA (8/14) or UK (3/14). The risk factors related to management change that were assessed were feed, carer, exercise, pasture, water and housing. The largest bodies of evidence for increased risk of colic associated with management change were changes in feed (5/14 publications) and recent change in housing (3/14). Most studies (8/14) did not meet the JBI criterion on confounding factors. There was marked heterogeneity of study methodologies and measures. This is the first study to use a combined scoping and systematic review to analyse evidence for modifiable risk factors for a common condition in the horse. It provides a comprehensive review that will be a key resource for researchers, veterinary practitioners and horse owners. It identified modifiable risk factors associated with an increased risk of colic which should be a key target for preventative health programmes. The findings from the critical appraisal were used to develop recommendations for future research to improve the quality of evidence-based veterinary medicine.

Comparison of three acute colic pain scales: Reliability, validity and usability.

A valid, reliable and usable scale is needed for assessing severity of acute abdominal pain in horses. The study aim was to compare three different scales: (1) the equine acute abdominal pain scale (EAAPS); (2) a scale described by Mair and Smith (2005; M and S); and (3) a numerical rating scale (NRS). Forty brief films of horses (35 of colic cases and five of control horses) were randomly presented to 46 equine veterinarians from different countries. Participants, randomly divided into three groups, each used one scale. Five randomly selected films were shown twice for determining intra-observer reliability. Speed, ease of use and face validity of the scales were evaluated based on expert opinion. Response rate was excellent: 89% for the EAAPS (16/18), and 100% for the M and S (18/18) and NRS groups (10/10). The intraclass correlation (ICC) of 0.86 [95% confidence interval (CI); 0.80-0.92] for EAAPS indicated significantly better inter-observer reliability compared to 0.68 for the M and S and 0.71 for the NRS. Moreover, intra-observer reliability of EAAPS (weighted κ 0.95 [95%CI; 0.92-0.98]) was superior to the other scales (weighted κ 0.78, 0.77, for the M and S and NRS, respectively). Other validity measures (convergent, extreme group, predictive validities), usability (time taken to score the films-speed) and the ease of use of the scales were not significantly different. Face validity (endorsement by experts) was better for the M and S scale than for the EAAPS. The EAAPS showed superior reliability, the M and S scale better face validity, with comparable usability and other tests of validity.

Behavioral Outcomes of Infant Colic in Toddlerhood: A Longitudinal Study.

OBJECTIVE: To assess whether infants with colic that resolved before 6 months of age have poorer medium-term outcomes than infants without colic. STUDY DESIGN: Comparative study of 2 prospective, community-based cohorts of children aged 2-3 years in Melbourne, Australia: children from the Baby Biotics study, with previously diagnosed Wessel criteria of colic without problem crying at 6 months (True Colic Cohort), vs children from the Baby Business trial, without problem crying at 1, 4, and 6 months (No Colic Cohort). Caregiver report of child internalizing and externalizing behaviors (primary outcome), temperament, regulatory (crying/sleeping/feeding) problems, and family functioning at child age 2-3 years was collected. We conducted regression analyses of mean differences/ORs adjusted for child sex, age, social disadvantage, parental education, and maternal mental health. RESULTS: In total, 74% of the original Baby Biotics (n = 124) sample and 75% of the Baby Business (n = 503) sample completed questionnaires. In adjusted analyses, there were no significant differences between the True Colic Cohort (n = 99) and No Colic Cohort (n = 182) in internalizing behavior problems (adjusted mean difference 0.73; 95% CI -3.96 to 5.43, P = .76) or externalizing behavior problems (adjusted mean difference -1.53; 95% CI -6.02 to 2.97, P = .51). There were no statistically significant differences between groups in temperament, parental perception of regulatory problems, or family functioning. CONCLUSIONS: Infants with colic whose crying self-resolves do not experience adverse effects regarding child behavior, regulatory abilities, temperament, or family functioning in the medium term. Parents and clinicians can be reassured that infant crying as the result of colic, and related stress, is short-lived and will likely resolve.

The effect of chiropractic treatment on infantile colic: study protocol for a single-blind randomized controlled trial.

Background: Infantile colic is a common condition during early childhood affecting around one of six newborns. The condition is characterized by inconsolable crying and fussing in otherwise healthy and thriving infants. The most used definition is excessive crying for at least three hours a day for at least three days for at least three weeks. The cause of colic is still unknown although many hypotheses and thereby many different treatment modalities have been investigated. Chiropractic care is used increasingly in treatment of infants, including for infantile colic, although the evidence worldwide is sparse. A randomized, controlled trial was designed to evaluate the effect of chiropractic treatment on infantile colic. This paper describes the protocol as well as results from a pilot study examining the acceptability and feasibility of the intervention. Method: The study is designed as a single-blind randomized, controlled trial. The invited families are residents on the Island of Funen and information about the project is distributed from the maternity wards and health visitors. Children at the age of 2-14 weeks with unexplained excessive crying are screened for eligibility and recruited by the primary investigator through home visits. Eligible children are then randomized to chiropractic treatment or control. All children attend in the chiropractor clinic two times a week for two weeks. The parents are unaware of their child's allocation during the project period. The primary outcome measure is change in daily hours of crying based on the parental diaries.The study intends to include 200 children, and the intervention has, during a pilot study, been found acceptable and feasible among families with newborns. Discussion: In a single-blind randomized controlled design we will evaluate the effectiveness of chiropractic treatment on infantile colic. The study will contribute to determine the effect of chiropractic treatment on infantile colic in an area where limited evidence exists. Furthermore, the study aims to explore if subgroups of children with suspected musculoskeletal problems will benefit more from the intervention than others. If they obtain better results, this could imply the need for stratified care. Trial registration: Clinicaltrials.gov and Identifier: NCT02595515 (registered 2 November 2015).

Effect of Reflexology on Infantile Colic.

OBJECTIVE: The aim of this study was to explore the effect of reflexology on infantile colic. DESIGN: A total of 64 babies with colic were included in this study (n = 31: study group; n = 33: control group). Following a pediatrician's diagnosis, two groups (study and control) were created. Sociodemographic data (including mother's age, educational status, and smoking habits of parents) and medical history of the baby (including gender, birth weight, mode of delivery, time of the onset breastfeeding after birth, and nutrition style) were collected. The Infant Colic Scale (ICS) was used to measure the colic severity in the infants. Reflexology was applied to the study group by the researcher and their mother 2 days a week for 3 weeks. The babies in the control group did not receive reflexology. Assessments were performed before and after the intervention in both groups. RESULTS: The groups were similar regarding sociodemographic background and medical history. While there was no difference between the groups in ICS scores before application of reflexology (p > 0.05), the mean ICS score of the study group was significantly lower than that of control group at the end of the intervention (p < 0.001). CONCLUSION: Reflexology application for babies suffering from infantile colic may be a promising method to alleviate colic severity.

The role of melatonin and cortisol circadian rhythms in the pathogenesis of infantile colic.

BACKGROUND: Despite the high prevalence of infantile colic, the pathogenesis remains incompletely understood. Cortisol and melatonin hormones affect gastrointestinal system development in several ways, and interestingly, both cortisol and melatonin's circadian rhythms begin around the 3rd month in which infantile colic symptoms start to decrease. We hypothesized that infantile colic might associate with desynchronization of normal circadian rhythms of these hormones. In this study, we aimed to investigate the role of melatonin and cortisol in the pathogenesis of infantile colic. METHODS: Patients who were diagnosed as infantile colic according to Wessel's "rule of three" were enrolled in the colic group. We measured the saliva melatonin and cortisol levels of colic group and control group infants. In both groups, the saliva samples were taken in mornings and at evenings, at the time of diagnosis and 6th month. RESULTS: Fifty-five infants finished the study. Melatonin circadian rhythm developed earlier in the control group than the infantile colic group in our study. We found no significant difference between the daily mean cortisol levels. However, infants with colic had flatter daily cortisol slope than controls which pointed out the probability that they had a less clearly defined cortisol rhythm than infants without colic. CONCLUSIONS: We found an association between melatonin levels and infantile colic. However, more research is needed to fully understand the role of hypothalamic-pituitary-adrenal axis and hormone's role on infantile colic physiopathology.

Preterm Stress Behaviors, Autonomic Indices, and Maternal Perceptions of Infant Colic.

BACKGROUND: While biological and behavioral stress response systems are intact in early gestation, preterm infants' behaviors are often more subtle and difficult to interpret compared with full-term infants. They are also more vulnerable for regulatory issues (ie, colic) that are known to impact caregiver-infant interactions. Biobehavioral measures such as behavioral responsivity and heart rate variability (HRV), particularly cardiac vagal tone, may help elucidate preterm infants' stress/regulatory systems. PURPOSE: To test the hypotheses that preterm infants' consoling behaviors and high-frequency (HF) HRV in the first week of life are significantly associated and they are inverse correlates of future colic risk. METHODS/SEARCH STRATEGY: Thirty preterm (mean ± SE = 32.7 ± 0.3 weeks postmenstrual age [PMA]) infants underwent direct NIDCAP (Newborn Individualized Development and Assessment Program) observation during routine care and had HRV measurements during their first week postbirth. Sixty-three percent of mothers completed the Infant Colic Scale at 6 to 8 weeks adjusted postnatal age. Nonparametric tests were used to determine associations among behaviors, HRV, and maternal perceptions of infant colic. FINDINGS/RESULTS: Self-consoling behaviors were positively associated with HF-HRV (vagal tone). In addition, stress behaviors were positively associated with low-frequency/high-frequency HRV (sympathetic dominance). Infants who displayed more stress behaviors also demonstrated more self-consoling behaviors. No significant associations were found with colic. IMPLICATIONS FOR PRACTICE: HF-HRV provides information on the infant's capacity to modulate stress and is a useful, noninvasive measure when behaviors are more difficult to discern. IMPLICATIONS FOR RESEARCH: Further study in a larger sample is needed to determine whether behavioral stress measures and HF-HRV may be useful to determine colic risk.

Impact of Lactobacillus reuteri colonization on gut microbiota, inflammation, and crying time in infant colic.

Infant colic is a distressing condition of unknown etiology. An aberrant gastrointestinal microbiota has been associated, and Lactobacillus reuteri supplementation has been shown to reduce crying and/or fussing time ('crying time') in some infants with colic. The relationship between L. reuteri gut colonization and crying time has not been examined. We investigated the relationship between L. reuteri colonization and fecal microbiota (microbial diversity and Escherichia coli), intestinal inflammation, and crying time in infants with colic, using a subset of 65 infants from the Baby Biotics trial, which randomized healthy term infants aged <13 weeks with infant colic to receive probiotic L. reuteri DSM 17938 (1 × 108 colony forming units) or placebo daily for 28 days. We observed an overall reduction in median crying time, regardless of L. reuteri colonization status (n = 14 colonized). There were no differences in E. coli colonization rates or densities, microbial diversity or intestinal inflammation by L. reuteri colonization status. We found that L. reuteri density positively correlated with crying time, and E. coli density negatively correlated with microbial diversity. As density of L. reuteri was associated with increased crying time, L. reuteri supplementation may not be an appropriate treatment for all infants with colic.

[Functional gastrointestinal disorders in neonate and toddler. The Rome IV criteria]. / Zaburzenia czynnosciowe przewodu pokarmowego u niemowlat i malych dzieci. IV Kryteria Rzymskie.

Functional disorders of the gastrointestinal tract in infants and children are very frequent. To the most common belong: infant colic, regurgitation and functional constipation. In the year 2016 modified IV Rome criteria of functional gastrointestinal disorders were published. In the current work the authors discuss diagnostic criteria and therapy in regurgitation, rumination syndrome in infants, cyclic vomiting syndrome, infant colic, infant dyschezia and functional constipation in children younger than four years.

Developing a core outcome set for infant colic for primary, secondary and tertiary care settings: a prospective study.

OBJECTIVE: Infant colic (IC) is defined as recurrent and prolonged crying without an obvious cause or evidence of failure to thrive or illness. It is a common problem with a prevalence of 5%-25%. The unknown aetiology results in a wide variety in interventions and use of heterogeneous outcome measures across therapeutic trials. Our aim was to develop a core outcome set (COS) for IC to facilitate and improve evidence synthesis. DESIGN AND SETTING: Prospective study design; primary, secondary and tertiary care. METHODS: The COS was developed using a modified Delphi technique. First, healthcare professionals (HCPs) and parents of infants with IC were asked to list up to five outcomes they considered relevant in the treatment of IC. Outcomes mentioned by >10% of participants were forwarded to a shortlist. In the second round, outcomes on this shortlist were rated and prioritised. The final COS was defined in a face-to-face expert meeting of paediatricians. RESULTS: F of invited stakeholders (133 HCPs and 55 parents of infants with IC) completed both Delphi rounds. Duration of crying, family stress, sleeping time of infant, quality of life (of family), discomfort of infant and hospital admission/duration were rated as most important outcomes in IC, framing the final COS. CONCLUSIONS: The use of this COS should serve as a minimum of outcomes to be measured and reported. This will benefit evidence synthesis, by enhancing homogeneity of outcomes, and enable evaluation of success in therapeutic trials on IC. Researchers are strongly encouraged to use this COS when setting up a clinical trial in primary, secondary and/or tertiary care or performing a systematic review on IC.

Is sensory processing an issue for infants with colic?

OBJECTIVES: To determine the association between sensory functioning, sleep, cry/fuss, and feeding behaviors of infants with colic younger than 4 months of age. METHODS: Dunn's Infant/Toddler Sensory Profile™ and a modified Barr Baby Day Diary© were used to assess 44 breastfed infants with colic under four months of age. Colic was defined according to Wessel's criteria. RESULTS: Thirty-four of the 44 infants with colic (77%) scored as atypical for sensory processing. Of these, 56% scored atypical for sensory processing on quadrant one (Q1) (Low Registration), with 24%, 65%, and 18% scoring as atypical for sensory processing on Q2 (Sensory seeking), Q3 (Sensory sensitivity), and Q4 (Sensation avoiding), respectively. All infants demonstrating sensation avoiding also scored as Low Threshold. A moderate statistically significant correlation was found between sensation seeking and time spent sleeping (r=0.31; p=0.04). No other statistically significant associations between infant behaviors and their sensory functioning were demonstrated. Overall, infants demonstrating atypical sensory responses (in any quadrant) slept significantly more than infants demonstrating typical sensory responses (mean difference=-67.8min/day; 95% CI=-133.6 to -2.1; p=0.04). CONCLUSION: Very limited associations between infant behaviors and sensory functioning were demonstrated, suggesting that sensory functioning may not be a significant factor in the multifactorial nature of infant colic. Further well-designed studies using validated tools for infants with colic are required to determine whether associations between infant behaviors and sensory functioning exist.

Luminal contents from the gut of colicky infants induce visceral hypersensitivity in mice.

BACKGROUND: The pathophysiology of infantile colic is poorly understood, though various studies report gut microbiota dysbiosis in colicky infants. We aimed to test the hypothesis that colic-related dysbiosis is associated with visceral hypersensitivity triggered by an altered luminal milieu. METHODS: Fecal samples from seven colicky and seven non-colicky infants were studied. Fecal supernatants (FS) were infused into the colons of C57/Bl6 mice (n=10/specimen). Visceral sensitivity was subsequently assessed in the animals by recording their abdominal muscle response to colorectal distension (CRD) by electromyography (EMG). Serine and cysteine protease activities were assessed in FS with specific substrates. Infant fecal microbiota composition was analyzed by DNA extraction and 16S rRNA gene pyrosequencing. KEY RESULTS: FS from colicky infants triggered higher EMG activity than FS from non-colicky infants in response to both the largest CRD volumes and overall, as assessed by the area under the curve of the EMG across all CRD volumes. Infant crying time strongly correlated with mouse EMG activity. Microbiota richness and phylogenetic diversity were increased in the colicky group, without showing prominent microbial composition alterations. Only Bacteroides vulgatus and Bilophila wadsworthia were increased in the colicky group. Bacteroides vulgatus abundance positively correlated with visceral sensitivity. No differences were found in protease activities. CONCLUSIONS & INFERENCES: Luminal contents from colicky infants trigger visceral hypersensitivity, which may explain the excessive crying behavior of these infants. Additional studies are required to determine the nature of the compounds involved, their mechanism of action, and the potential implications of intestinal microbiota in their generation.

Exploring hypotheses and rationale for causes of infantile colic.

BACKGROUND: 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. PURPOSE: 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.

Continuous wavelet analysis of postprandial EGGs suggests sustained gastric slow waves may be slow to develop in infants with colic.

BACKGROUND: Electrogastrography in conjunction with Fast Fourier transform has limited success in detecting low grade abnormalities in gastric electrophysiological activity owing to the non-stationarity of the signal. Analysis by continuous wavelet transform is suitable for non-stationary signals and was used to analyse EGG activity in babies with and without colic. METHODS: Thirty minute postprandial EGG recordings were obtained from 23 sleeping breast-fed infants with clinically validated recurrent colic and 26 breast-fed non-colicky infants. Continuous wavelet transform analysis (CWT) identified three principal frequency components. The mean, standard deviation, and the number of frequency maxima that fell below one standard deviation from the mean were determined for each infant and each frequency. KEY RESULTS: Three component frequencies in the ranges 1.4-2.5 cpm, 2.5-4.0 cpm, and 4.0-15 cpm were found in all EGGs. Pairwise comparisons of the characteristics of each of the frequency ranges by univariate analyses showed significant differences between colicky and non-colicky subjects only in the number of maxima in the mid range of frequencies that lay below one standard deviation from the mean. However, CWT based on all frequencies allowed discrimination of the EGGS of colicky from non-colicky babies on a basis of number of frequency maxima below one standard deviation from the mean in the midrange of frequencies and in the mean and standard deviation in the low range of frequencies that was likely a harmonic of the midrange. CONCLUSIONS & INFERENCES: CWT allowed distinction of EGG signals from colicky and healthy babies. The results indicate that colic may result from tardiness in the establishment of coherent propagation of the gastric slow wave in colicky babies.