To assess the extent to which risks of atopic and respiratory conditions throughout childhood and adolescence differ by history of (1) infant colic, characterized by apparent abdominal discomfort and unsoothable crying, (2) excessive crying without colic, or (3) neither condition.

Among 1249 children participating in the prospective, unselected Project Viva cohort, we examined associations of history of infant colic or excessive crying without colic with risks of eczema, allergic rhinitis, asthma, and respiratory infections, measured in toddlerhood, early childhood, mid-childhood, early adolescence, and mid-adolescence using multinomial logistic regression models.

The study sample was 50% female and 71% non-Hispanic White; 26% had colic and 9% excessive crying. Children with colic (vs no colic or excessive crying) had higher risk of eczema (relative risk ratio [RRR], 2.1; 95% CI, 1.2-3.8), allergic rhinitis (RRR, 1.6; 95% CI, 1.1-2.4), and asthma (RRR, 1.6; 95% CI,1.1-2.4) in mid-childhood, and a higher risk of respiratory infections in toddlerhood (RRR, 1.6; 95% CI, 1.2-2.2) and mid-adolescence (RRR, 2.1; 95% CI, 1.2, 3.7). The risk of 2-3 concurrent atopic conditions (eczema, allergic rhinitis, and/or asthma) was nearly twice that among the colic group (vs unaffected) at all life stages. The group with excessive crying without colic did not have increased risk of atopic and respiratory outcomes.

Colic characterized by unsoothable crying and parent perceptions of abdominal distress may be an early marker of atopic susceptibility.

Our aims are 1) to assess whether sleeping problems persist from early childhood until adolescence, and 2) to investigate whether infant colic is associated with more sleeping problems throughout childhood and adolescence. Furthermore, we explore a moderation by parent-infant room sharing of potential associations between infant colic and sleeping problems. Data originate from a prospective longitudinal study in a healthy community sample (N = 185). Infant colic data were collected using cry diaries, filled in by the mothers for four days at age six weeks. The number of weeks of parent-infant room sharing from zero to six months of age were recorded using daily maternal diaries. Sleeping problems were assessed through maternal report at ages 2.5, 6 and 10 years, and child report at ages 12.5, 14 and 16.5 years. We used a score of Total Sleeping Problems, as well as subscales on Night Waking and Sleep Duration. Correlations were found between sleeping problems measured from 2.5 through 16.5 years for the Total Sleeping Problems, as well as for Night Waking and Sleep Duration. Compared to participants without infant colic, those with colic showed higher scores of Total Sleeping Problems between ages 12.5 and 16.5 years. We found no differences in sleeping problems between 2.5 and 10 years, nor evidence of a moderation by room sharing. Current findings suggest that sleeping problems developing in early and middle childhood persist throughout adolescence, and that children with infant colic may be prone to developing sleeping problems during adolescence.

We aimed to compare the efficacy of Bifidobacterium longum KABP042 + Pediococcus pentosaceus KABP041 (BL + PP) vs. Limosilactobacillus reuteri DSM17938 (LR) in alleviating the symptoms of infant colic, as commercially available formulations. A randomized, multicenter, parallel, single-blind (investigator) trial was conducted in 112 colicky infants diagnosed as per Rome IV criteria and randomly allocated to receive BL + PP orally (109 colony-forming units [CFU]/day, n = 55) or LR (108 CFU/day, n = 57) for 21 days. Primary study outcomes were percentage of responders (≥ 50% reduction in crying and fussing time from baseline, as reported by parents in a structured diary) and daily crying and fussing time (minutes/day) on days 7, 14, and 21 after randomization. Study groups were comparable at baseline. Responder rate was significantly higher in BP + PP group vs. LR group at days 7 (61.1% vs. 37.5%, p = 0.013) and 14 (84.6% vs. 59.3%, p = 0.004). Crying and fussing time (median [IQR]) became significantly lower in BL + PP group vs. LR group on day 7 (119 [60-210] vs. 180 [110-270]; p = 0.028), day 14 (60.0 [30-105] vs. 120 [60-180]; p = 0.017), and day 21 (29 [0-85] vs. 67 [30-165]; p = 0.011). No significant differences were found in the number of adverse events between the groups.

The specific formulation of B. longum KABP042 and P. pentosaceus KABP041 achieved a higher response rate and a larger reduction in crying and fussing time in colicky infants. Both probiotic interventions were well tolerated.

The study was retrospectively registered as NCT05271747 on February 28th, 2022.

• L. reuteri DSM17938 (LR) is the most researched probiotic strain for infant colic against placebo in randomized, controlled clinical trials, and is recommended in various guidelines. A novel probiotic combining strains B. longum KABP042 and P. pentosaceus KABP041 (BL + PP) has also demonstrated efficacy in infant colic against placebo.

• This randomized study provides the first direct comparison of two probiotics for infant colic. BL + PP seems to be superior to LR in reducing crying time.

Infant colic is defined as a recurrent and prolonged period of fussing, crying and/or irritability that cannot be prevented or resolved by caregivers. The aim of this study is to evaluate the efficacy of a synbiotic (Bactecal D Liquid) in infants consulting a primary health care professional for inconsolable crying. A randomized trial was conducted in 68 infants diagnosed by the consulted primary health care professional as "probably suffering from infant colic". Patients were randomized into two groups and given the synbiotic once (group 1) or twice (group 2) a day for 28 days. Quality of life (QoL) of the caregivers, evaluated with a Likert scale, was the primary outcome. Secondary outcomes included the total number of crying episodes, total crying time, gassiness and "balling of the fists". The median (Q1;Q3) QoL scores were significantly (p < 0.001) higher on day 28 than at baseline: 6 (5;7) vs 2 (1;3). At baseline, there was no significant difference (p = 0.527) in QoL between both groups. The improvement in QoL was already significant after one week of intervention for both groups. The median number of crying episodes, overall crying time, gassiness and "balling of fists" were significantly lower on day 28 compared to baseline (p < 0.001).

The synbiotic tested was shown to be efficacious in the management of infant colic. A significant improvement was observed after 7 days of intervention, which is much earlier than the expected decrease related to the natural evolution of infant colic.

• Some probiotic strains are reported to be effective in the management of infants presenting with colic, if breastfed.

• The synbiotic studied improved quality of life of caregivers of infants presenting infant colic. • Two doses of the synbiotic were not more effective than one dose. • The improved occurred within one week. • The improvement was independent of feeding (breastfeeding, formula feeding or mixed feeding).

Infantile Colic (IC) poses a significant challenge for parents as it manifests through repeated and extended episodes of fussiness, crying, or irritability occurring before the age of 5 months. The precise cause of IC is currently unknown. The association between IC, a family history of atopy, and the development of individual atopy in the future remains uncertain, given conflicting findings from prior studies.

This study aimed to investigate the impact of parental atopy on IC severity and the effectiveness of the mother's hypoallergenic Dairy-Free Diet in alleviating pain in infants with colic.

This non-randomized trial conducted at Amirkabir Hospital in Arak, Iran, from January 2023 to October 2023, involving 206 eligible IC patients non-randomly assigned to two groups based on parental atopy history. Breastfed infants were prescribed a dairy-free diet, involving the removal of dairy products from the mother's diet. Pain severity was assessed using the FLACC scale at baseline and after one-month of intervention.

The research initially involved 206 subjects with an average age of 28.77 ± 9.99 days, evenly distributed based on parental atopy history. However, there was a 28.6% loss to follow-up, resulting in a final analyzed population of 147 individuals. The intervention, a maternal dairy-free diet, demonstrated a significant reduction in pain symptoms within both groups and overall (P = 0.001), with no significant difference in efficacy between infants with and without parental atopy history (P = 0.219). Parental history of atopy did not exhibit a significant association with colic pain severity (P = 0.404). The study revealed that the impact of the diet on colic severity varied, with more pronounced effects observed in cases of severe and moderate colic compared to mild cases.

Adopting a Dairy-Free Diet significantly reduced colic symptoms, irrespective of parental atopy history. The severity of colic appears unrelated to parental atopy, and the observed improvement with a Dairy-Free diet is potentially attributed to milk intolerance rather than milk allergy.

Aim: We aimed to explore whether there is an association between maternal perceived infant discomfort due to suggestive gastrointestinal alterations and oral-health-related quality of life (OHRQoL) through a survey. Materials and Methods: The present study included two main phases involving Portuguese-speaking parents with full-term infants aged 2-12 weeks old who were not previously hospitalized in a neonatal nursery. First, the original French Infant Colic Questionnaire (ColiQ) was translated, cross-culturally adapted and validated to Portuguese (ColiQ-PT). Then, a survey was distributed, and included sociodemographics, the ColiQ-PT, an oral health value scale, OHRQoL, self-perceived periodontal status, and smoking and oral health habits. Data were analyzed through inferential, correlation and multivariate logistic models in this cross-sectional study. Results: The ColiQ-PT revealed reliability and validity. From a total of 421 responses, higher infant discomfort was correlated with less maternal professional dental care prioritization (ρ = -0.096, p < 0.05). Self-perceived periodontitis correlated with all items of OHRQoL (p < 0.001), all seven OHIP-14 domains, and with the physical (p < 0.001), psychological (p = 0.006), and social (p = 0.011) super-domains. While the infant-related score was associated with baby age (p = 0.023) and physical pain (p = 0.040) related to OHRQoL, the parent score was associated with education (p = 0.005), unemployment (p = 0.035), and physical pain (p = 0.017). The total ColiQ-PT score was significantly associated with more deteriorated social disability related to maternal OHRQoL (ρ = -0.130, p < 0.05). Conclusions: Perceived infant discomfort seems to be linked to maternal deteriorated OHRQoL. This finding highlights the importance of prioritizing oral health in postpartum care. Further research is needed to explore the mechanisms underlying this association and to develop targeted interventions.

Infantile colic may represent gastrointestinal distress, yet most definitions emphasize excessive crying. Each may have distinct etiologies.

In a pre-birth cohort, we used maternal reports of infant crying and apparent abdominal discomfort at 6mos to categorize infants as (1) unaffected (no excessive crying or colic), (2) excessive crying only, and (3) colic (abdominal discomfort +/- excessive crying). We examined associations of potential risk factors in separate models with excessive crying and colic (each vs. unaffected) using unadjusted multinomial logistic regression, and associations between count of risk factors and colic using logistic regression.

Of 1403 infants, 140 (10%) had excessive crying, and 346 (25%) colic. Infants that were non-Hispanic white, low birthweight, firstborn, or had a maternal history of atopy, high postpartum depressive symptoms, or persistent prenatal nausea, had a 40-80% higher relative risk of colic. Preterm birth was associated with double the risk. Being firstborn, low birthweight, and preterm birth predicted excessive crying. Infants with ≥four (vs. 0-1) of the seven identified risk factors had 3.9 times (95% CI: 2.6, 6.1) higher odds of colic.

Colic characterized by apparent abdominal discomfort can be phenotypically distinguished from excessive crying only. Multiple risk factors may further increase colic risk.

Infant colic characterized by apparent gastrointestinal distress may be phenotypically distinct from excessive crying only. Literature that defines colic only based on crying behaviors may miss important predictors. Mother-reported colic and excessive crying appear to have overlapping risk factors, with additional risk factors identified for colic. The presence of multiple risk factors increases the risk of colic, supporting a multifactorial etiology.

Disorders of gut-brain interaction (DGBIs) may originate in childhood. There are currently limited data on persistence of DGBI into adulthood and risk factors for persistence. Furthermore, there are no data on this question from general practice, where the majority of DGBIs are diagnosed and managed. This study documents the proportion of childhood-diagnosed DGBIs that persisted into adulthood and what factors were associated with persistence.

General practice records were obtained for more than 60,000 patients whose medical record spanned both childhood and adulthood years. Patients with diagnosed organic gastrointestinal disorder were excluded. Medical records were also interrogated for potential risk factors.

Eleven percent of patients with irritable bowel syndrome (IBS) and 20% of patients with functional dyspepsia (FD) diagnosed in childhood had repeat diagnoses of the same condition in adulthood. Female sex (odds ratio [OR] 2.02) was associated with persistence for IBS, while a childhood diagnosis of gastritis (OR 0.46) was risk-protective. Childhood non-steroidal anti-inflammatory drug use (OR 1.31, 95% confidence interval [CI] 1.09-1.56) was a risk factor for persistence in IBS. For FD, a childhood diagnosis of asthma (OR 1.30, 95% CI 1.00-1.70) was a risk factor, as was anxiety for both IBS (OR 1.24, 95% CI 1.00-1.54) and FD (OR 1.48 95% CI 1.11-1.97) with a similar finding for depression for IBS (OR 1.34, 95% CI 1.11-1.62) and FD (OR 1.88 95% CI 1.47-2.42).

Childhood DGBIs persist into adulthood in 10%-20% of patients, suggesting that management monitoring should continue into adulthood. Those diagnosed with anxiety or mood disorders in childhood should receive particular attention, and prescription of non-steroidal anti-inflammatory drugs in children should be made judiciously.

To assess the prevalence of functional gastrointestinal disorders (FGIDs), health-related quality of life (HRQOL), and behavioural problems in a cohort of adolescents with a history of infant colic (IC), as defined by Wessel's criteria.

388 adolescents, aged 15-18 years, who participated in a randomised controlled trial for infants with colic, were invited for our observational follow-up study. Prevalence of FGIDs was assessed with the Rome IV Questionnaire on Paediatric Gastrointestinal Disorders (RIV-QPGD), HRQOL through self-report of the Paediatric Quality of Life Inventory (PedsQL), and behavioural problems through parent-report of the child behaviour checklist (CBCL). Multivariable models were used to compare prevalence rates of FGIDs and HRQOL scores.

190 (49%) adolescents with a history of IC (cases) and 381 controls were included (median age 17.0 [IQR 16.0-17.0] and 16.0 [15.0-17.0] years, respectively). Cases had a significantly higher risk for postprandial distress syndrome compared to controls (aOR 2.49 (95%CI 1.18-5.25), p = 0.002). After multivariable regression, total, physical and school HRQOL scores were significantly lower in cases compared to controls (p = 0.003, 0.001, and 0.009).

Adolescents with a history of IC demonstrate higher prevalence rates of postprandial distress syndrome compared to controls. However, conclusions should be made with caution due to attrition and information bias.

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.

Infant colic is a common functional gastrointestinal disorder that affects infants during their first months of life. The etiology of this condition remains unclear. However, some studies suggest lactase deficiency may be a contributing factor. Currently, the evidence on dietary treatment and lactase supplementation for management of infant colic is limited. We aim to systematically review evidence on the efficacy and safety of using a lactase supplementation for managing infant colic. The Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), MEDLINE, and EMBASE will be searched to identify randomized controlled trials comparing oral lactase supplementation with placebo or no intervention in infants aged less than 6-month-old with infant colic using any recognized definition. The risk of bias will be assessed using the second version of the Cochrane Collaboration's risk-of-bias tool. The main outcome will be the number of responders in each group after treatment, defined as infants who experienced a decrease in daily crying as reported by the study authors. Additional outcomes will include the duration and frequency of crying episodes, infant sleep duration, parental satisfaction, discomfort of infants, number of hospital admissions, family quality of life, and adverse events during the intervention. The study findings will be published in a peer-reviewed journal and will be submitted to relevant conferences.

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.

The most frequent functional gastrointestinal disorders (FGID) in children include infantile colic, constipation, functional abdominal pain (FAP), and irritable bowel syndrome (IBS). Unfortunately, treatment options for FGID in children are limited, therefore many dietary interventions have been evaluated, including probiotics. This chapter summarizes currently available evidence and recommendations for probiotic use in the treatment of frequent FGIDs in children. The strongest evidence exists for the use of Limosilactobacillus (L.) reuteri DSM 17938 and Bifidobacterium animalis subsp. lactis BB-12 for the treatment of infantile colic in breastfed infants. Limited but yet encouraging evidence exists for Lacticaseibacillus rhamnosus GG (LGG) for the treatment of IBS and L. reuteri DSM 17938 for FAP.

Digestive system diseases have evolved into a growing global burden without sufficient therapeutic measures. Lactobacillus reuteri (L. reuteri) is considered as a new potential economical therapy for its probiotic effects in the gastrointestinal system. We have provided an overview of the researches supporting various L. reuteri strains' application in treating common digestive system diseases, including infantile colic, diarrhea, constipation, functional abdominal pain, Helicobacter pylori infection, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases.

The summarized literature in this review was derived from databases including PubMed, Web of Science, and Google Scholar.

The therapeutic effects of L. reuteri in digestive system diseases may depend on various direct and indirect mechanisms, including metabolite production as well as modulation of the intestinal microbiome, preservation of the gut barrier function, and regulation of the host immune system. These actions are largely strain-specific and depend on the activation or inhibition of various certain signal pathways. It is well evidenced that L. reuteri can be effective both as a prophylactic measure and as a preferred therapy for infantile colic, and it can also be recommended as an adjuvant strategy to diarrhea, constipation, Helicobacter pylori infection in therapeutic settings. While preclinical studies have shown the probiotic potential of L. reuteri in the management of functional abdominal pain, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases, its application in these disease settings still needs further study.

This review focuses on the probiotic effects of L. reuteri on gut homeostasis via certain signaling pathways, and emphasizes the importance of these probiotics as a prospective treatment against several digestive system diseases.