Background/Objectives: Infant functional disorders, including colic, irritability, and sleep disturbances, often overlap with symptoms of cow's milk protein allergy (CMPA). While extensively hydrolyzed formulas are commonly used to address these issues, the short-term efficacy of amino acid formulas (AAF) for managing colic remains understudied. This secondary analysis of a previously published prospective cohort, the largest of its kind in the United States, evaluated the short-term impact of AAF in improving colic and associated symptoms in infants under six months of age with suspected CMPA. Methods: This real-world prospective cohort study analyzed data from 138 infants with suspected CMPA initiated on AAF at Visit 1. After excluding 34 infants due to incomplete data or treatment changes, 104 infants were included in the final analysis. Symptom severity and resolution were assessed through outcomes across two visits, with care provided by general pediatricians (82%) and pediatric gastroenterologists (18%). Results: At baseline, the most common symptoms were colic (n = 83), gassiness (n = 72), fussiness (n = 66), and sleep disturbances (n = 58). By the next follow-up visit (Visit 2), parents reported symptom improvements in colic (94%), gassiness (81%), fussiness (83%), and sleep disturbances (86%). Complete symptom resolution was observed in 73% of infants with colic, 68% with gassiness, 65% with fussiness, and 81% with sleep difficulties. By Visit 2, no infants had severe symptoms, with only mild residual symptoms reported. Conclusions: AAF was associated with significant short-term improvements in colic and related symptoms in infants with suspected CMPA. These preliminary findings highlight AAF as a promising dietary intervention during early infancy. Larger controlled studies are necessary to confirm these results and explore long-term outcomes.

The present study aimed to assess the psychiatric characteristics of children with chronic functional constipation using the Aberrant Behavior Checklist-Japanese version and the Pervasive Developmental Disorders/Autism Society Japan Rating Scale, and to examine the frequency of autism spectrum disorder in children with chronic functional constipation. We also investigated differences in treatment duration between children with and without autism spectrum disorder.

Treatment outcomes were examined retrospectively for 55 participants (chronic functional constipation group: n = 30, mean age 3.4 years; control group: n = 25, mean age, 4.5 years). The association between chronic functional constipation and autism spectrum disorder was evaluated using multivariable logistic regression analysis.

The mean Aberrant Behavior Checklist score and frequency of individuals with autism spectrum disorder were significantly higher in the chronic functional constipation group. After adjusting for age and sex, chronic functional constipation was significantly associated with autism spectrum disorder. In the chronic functional constipation group, the frequency of onset was significantly higher in children with autism spectrum disorder under 1 year of age. When treated, the mean duration of constipation was significantly longer in children with autism spectrum disorder.

Pediatricians, pediatric surgeons, and child psychiatrists should work closely to ensure appropriate treatment of chronic functional constipation in children with autism spectrum disorder.

Colic in infants is defined as excessive crying in an otherwise healthy and thriving baby. Colic is a common but poorly understood and often frustrating problem for caregivers.

To study whether osteopathic treatments of infants with infantile colic / excessive crying (IC/EC) have an impact on the subjectively perceived psychological stress of caregivers compared to usual care.

The study was designed as a prospective, multicenter, randomized controlled trial. Infants aged 1 week to 3 months and who met Rome IV criteria for IC/EC were included. By means of external randomization, infants were allocated to an intervention group or a control group. Infants in the intervention group received three osteopathic treatments at intervals of one weeks. The treatments were custom-tailored and based on osteopathic principles. Controls received their osteopathic treatment after a 3 week untreated period. The primary outcome parameter was the assessment of parental psychological stress (three questions), measured using a numeric rating scale (NRS; 0-10). Furthermore, the average daily crying time (measured using the Likert scale), the crying intensity (measured using the NRS) and the parents' self-confidence (measured using the Karitane Parenting Confidence Scale) were assessed.

A total of 103 infants (average age 39.4 ±19.2 days) were included, 52 in the intervention group and 51 in the control group. An inter-group comparison of changes revealed clinically relevant improvements in favor of the intervention group for the main outcome - parameter psychological stress - for all 3 questions (e.g., for question 2 respectively 3, NRS: between group difference of means 3.5; 95% CI: 2.6 to 4.4; p < 0.001). For the secondary outcome parameters of crying intensity and crying time/day, the changes were of similar magnitude.

Three osteopathic treatments given over a period of two weeks led to statistically significant and clinically relevant positive changes of parental psychological stress.

German Clinical Trials Register: DRKS00025867, registration date 10.08.21.

Functional constipation is common in children and accurate diagnostic methods are essential for early diagnosis and effective management. The diagnostic accuracy of transabdominal ultrasound to diagnose functional constipation is unclear.

To evaluate the diagnostic accuracy of transverse rectal diameter measurement via transabdominal ultrasound in diagnosing children with functional constipation and in identifying fecal impaction.

Electronic databases were searched from inception to March 2023. Original studies investigating the diagnostic accuracy of measuring transverse rectal diameter via transabdominal ultrasound, including children with and without functional constipation, or with and without fecal impaction were included. Data extraction and quality assessment were performed independently by two reviewers.

Sixteen studies were included (n = 1,801 children, 0-17 years). Thirteen studies investigated the diagnostic accuracy for functional constipation, and five for fecal impaction. High risk of bias was found across the majority of studies mainly due to un-blinded case-control designs. Cut-off transverse rectal diameter values to diagnose functional constipation ranged from 2.4 cm to 3.8 cm. Meta-analysis (seven studies, n = 509 children) estimated mean sensitivity and specificity to diagnose functional constipation were 0.68 (95% confidence interval (CI) 0.55-0.78) and 0.81 (95% CI 0.71-0.88), respectively. Meta-analysis of diagnostic accuracy of identifying fecal impaction was not feasible. Studies reported a sensitivity and specificity ranging between 68-100% and 83-100%, respectively.

Transabdominal ultrasound may be a valuable non-invasive diagnostic tool to diagnose functional constipation by measuring transverse rectal diameter and identifying fecal impaction in children. Heterogeneous study methods and lack of age-dependent normal values impair current clinical recommendations. Future research should focus on separating age groups and developing a standardized protocol.

Objective Digital evacuation (DE) is an intervention used to address severe constipation. Literature exists on easily administered laxatives; however, reports on mildly invasive DE usage are limited. This study aimed to elucidate the fundamental data regarding constipation management using a comprehensive national database of DE incidence. Methods This observational epidemiological study analyzed the age- and sex-stratified DE incidence per 1,000 person-years during 2014-2021 using the medical receipt database in Japan. The annual trends were evaluated using Poisson regression models. We examined the month-stratified incidence during 2019-2021 to assess potential seasonal variations using a one-way analysis of variance and unpaired t-tests with the Bonferroni correction for comparisons across the four seasons. Correlation coefficients were calculated to determine the relationship between the meteorological variables and DE incidence. Results Over the 8-year period, the DE incidence amounted to 32,361,846 procedures, with a median of 10.3 procedures per 1,000 person-years. A demographic analysis revealed a minor peak, nadir, and progressive increase peaking in the 0-4-year (22.1 procedures), 5-9-year (1.5 procedures), and ≥90-year (370.7 procedures) age groups, respectively. The age-adjusted DE incidence across all age groups per 1,000 person-years showed a declining annual trend [incidence rate ratio: 0.971 (P<0.0001)]. A seasonal analysis revealed a significant increase in DE procedures during winter compared with summer (P<0.0125). A correlation was observed between the DE incidence and certain meteorological variables, particularly the temperature. Conclusion This study highlights the notable demographic patterns and the impact of seasonal and meteorological factors on the DE incidence.

Cow's milk protein allergy (CMPA) affects 2% to 3% of infants and is managed with hypoallergenic formulas. The 2022 recalls of infant formulas due to factors including contamination led to specialty formula shortages, highlighting CMPA management challenges. Understanding health care providers' (HCPs) decision-making in transitioning to alternative formulas during shortages is crucial. Limited attention has been given to how pediatric physicians make these choices. This study utilized US HCPs' de-identified survey data to assess driving factors when switching extensively hydrolyzed formulas during shortages. A total of 104 eligible HCPs participated, including general pediatrics, pediatric allergy/immunology, and pediatric gastroenterology specialists. Safety, tolerability, and efficacy were identified as top factors for switching formulas. Formula 1 was considered well-tolerated, patient-accepted, and safe by all HCPs. Most expressed strong belief in Formula 1's safety and effectiveness. Findings inform CMPA management during shortages, offering guidance to HCPs for suitable formula selection and enhanced infant care.

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.

Investigate the association between gastrointestinal (GI) issues and psychometric scores among children with developmental delays and typical development. We examined the association between GI issues and the Mullen Scale of Early Learning (MSEL), Vineland Adaptive Behavior Subscales (VABS), and Aberrant Behavior Checklist (ABC) scores from participants with autism spectrum disorder (ASD), Down syndrome (DS), other developmental delays (DD) and typical development (TD) from the CHildhood Autism Risk from Genetics and Environment (CHARGE) Study (n = 1603). Approximately 32% of children with ASD, 31% of children with DD, and 20% of children with DS reported at least one GI issue, compared to 7% of TD controls. Constipation was the most frequently reported symptom for the entire population, including controls. In general, GI issues correlated with poorer behavioral scores (decreased communication, daily living, socialization, and motor skills on the VABS, and increased irritability/agitation, lethargy/social withdrawal, stereotypic behavior, and hyperactivity/noncompliance on the ABC) among ASD cases. Analysis by sex indicated that GI issues also correlated with poorer cognitive scores (fine motor, receptive language, expressive language, and MSEL composite scores), and adaptive behavior (communication skills, daily living skills, motor, and VABS composite scores) among boys with DD, but not girls with DD-suggesting sex differences among DD cases. Even TD controls showed increased stereotypic behavior and social withdrawal in association with GI issues. However, GI issues were not correlated with impairments in psychometric scores among DS cases. Given that GI issues correlate with deficits in behavioral and cognitive scores, future studies should investigate the treatment of GI symptoms in children with ASD and DD.

Infantile colic has a multifactorial etiology. Recent studies have suggested that probiotics may be effective in its management.

This study was carried out to evaluate the effect of the Actiregularis strain (5×106 cfu\ml) included in maternal nutrition on gastrointestinal problems, growth development, and breastfeeding outcomes in infantile colic.

The study was a randomized controlled trial conducted in the neonatal outpatient clinic of a training and research hospital in Turkey.

A probiotic drink containing the Actiregularis (5×106 cfu\ml) strain was added to the diet of mothers in the probiotics group once daily for 15 consecutive days. Data were collected for each infant's 0th (birth), 1st, 4th, and 6th months.

Infants whose mothers were administered Actiregularis for 15 days had decreased crying intensity (P = 0.000). When the difference in breastfeeding rates between the groups was significant at the 4th and 6th months (P = 0.044; P = 0.035). There was no difference in anthropometric values except the babies' weights at the 6th month. (P < 0.001).

Infants treated with Actiregularis, which was added to their mothers' diet for 15 days, showed a decrease in the frequency of crying, and the difference in breastfeeding rates between the groups was significant at the 4th and 6th months. There was no difference in anthropometric values except the babies' weights at the 6th month.

NCT04374955 (https://clinicaltrials.gov/ct2/show/).

The aim of this study was to develop a nomogram for predicting the probability of postoperative soiling in patients aged greater than 1 year operated for Hirschsprung disease (HSCR).

The authors retrospectively analyzed HSCR patients with surgical therapy over 1 year of age from January 2000 and December 2019 at our department. Eligible patients were randomly categorized into the training and validation set at a ratio of 7:3. By integrating the least absolute shrinkage and selection operator [LASSO] and multivariable logistic regression analysis, crucial variables were determined for establishment of the nomogram. And, the performance of nomogram was evaluated by C-index, area under the receiver operating characteristic curve, calibration curves, and decision curve analysis. Meanwhile, a validation set was used to further assess the model.

This study enrolled 601 cases, and 97 patients suffered from soiling. Three risk factors, including surgical history, length of removed bowel, and surgical procedures were identified as predictive factors for soiling occurrence. The C-index was 0.871 (95% CI: 0.821-0.921) in the training set and 0.878 (95% CI: 0.811-0.945) in the validation set, respectively. And, the AUC was found to be 0.896 (95% CI: 0.855-0.929) in the training set and 0.866 (95% CI: 0.767-0.920) in the validation set. Additionally, the calibration curves displayed a favorable agreement between the nomogram model and actual observations. The decision curve analysis revealed that employing the nomogram to predict the risk of soiling occurrence would be advantageous if the threshold was between 1 and 73% in the training set and 3-69% in the validation set.

This study represents the first efforts to develop and validate a model capable of predicting the postoperative risk of soiling in patients aged greater than 1 year operated for HSCR. This model may assist clinicians in determining the individual risk of soiling subsequent to HSCR surgery, aiding in personalized patient care and management.

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.

The combination of Bifidobacterium longum and Pediococcus pentosaceus is a clinically effective probiotic formulation for alleviating infantile colic; however, their utilization characteristics and mechanism of action surrounding their combined use of sugar sources remains unclear. Using in vitro simulation technology, this study set up individual and mixed cultures of the two probiotics at unique concentrations, and different types of prebiotics, carbohydrates and polyols were added. Gas and short-chain fatty acid production, substrate utilization, as well as growth of the individual and mixed probiotics were detected at the beginning of fermentation, 24 h, and 48 h. Further, the mechanism of the syntrophic effect of the two probiotics was explored based on their growth characteristics. It was found that neither strain produced gas after 24 h and 48 h of cultivation, but could synergistically utilize fructo oligosaccharides (FOS) when mixed. There was an increasing trend of acetic acid production for B. longum in yeast extract, casitone and fatty acid (YCFA) and FOS medium with increasing of bacterial concentrations at 24 h and 48 h; whereas the trend for P. pentosaceus was less obvious. When bacterial concentrations were >5 billion CFU·g-1, the mixed culture showed significantly lower acetic acid production than B. longum alone. By adding lactic and acetic acids to the YCFA medium and observing P. pentosaceus growth, the results suggested that Pediococcus pentosaceus could use the acetic acid and lactic acid produced by Bifidobacterium longum for growth. When the bacterial concentration was 5 billion CFU·g-1, the acetic acid production of B. longum was significantly higher in the mixed cultures in lactulose, lactose, FOS, galactooligosaccharide, and inulin medium; whereas the reverse was true for culturing in xylitol, carboxymethyl cellulose sodium, and sorbitol medium. Further, the mixed cultures produced significantly more acetic acid than B. longum alone. In summary, through in vitro simulation experiments, the optimal ratio and potential interaction mechanisms between B. longum and P. pentosaceus were revealed here, offers a basis for understanding how the probiotic combinations may improve infant colic symptoms by influencing the gut pH and regulating the gut microbiota mechanisms.

Studies have reported the relationship between functional constipation and obesity in pediatric population. However, the results are contradictory. The purpose of this study is to evaluate the possible association between these two disorders in pediatric population.

Four databases including PubMed, Embase, CENTRAL, and Web of Science were searched until 30 September 2022. The review was done in accordance with PRISMA guidelines and registered in PROSPERO (CRD42022328992) RESULTS: Nine studies met the eligibility criteria, including 7444 participants. Studies showed the risk of obesity was significantly increased in boys with functional constipation (CI: 1.12, 3.07; P = 0.016). Such an association was also observed in girls (CI: 1.42-4.47; P = 0.00). A statistically significant association was observed between overweight/obesity and increased risk of functional constipation in children and adolescents (CI: 1.14-3.97; P = 0.02). Especially in developed countries (CI: 1.49-3.46; P = 0.00); however, no significant association was observed in developing countries (CI: 0.81-5.3; P = 0.13).

There is a risk of obesity in either boys or girls with functional constipation. An association exists between the risk of functional constipation and children/adolescents with obesity, especially in developed countries, but not in developing countries.

Our study encourages further research in this field because early detection and intervention are crucial for both functional constipation and overweight/obesity in children, to better identify its complex biology and possibly optimize the treatment approaches.

This investigation assessed the impact of dog and/or cat ownership during infancy on the presence of functional constipation (FC) at 3 years of age.

The fixed data of 73,936 singleton births from a large national birth cohort study commencing in 2011 were used to identify FC as estimated by Rome III at 3 years of age. Multiple logistic regression analysis was employed to search for correlations between FC development and dog and/or cat ownership in early childhood.

A total of 8,459 toddlers (11.6%) met the Rome III criteria for FC at 3 years of age. Overall, 57,264 (77.5%) participants had never owned a dog or cat. We identified 7,715 (10.4%) infant-period owners, 1,295 (1.8%) current owners, and 7,762 (10.5%) long-term owners. Multivariate analysis showed that infant-period ownership remained significantly associated with the risk of developing FC at 3 years of age after adjusting for covariates (adjusted OR [95% CI] 1.09 [1.01-1.19] based on non-ownership).

This Japanese large nationwide survey uncovered a possible adverse effect of infant-period dog and/or cat ownership prior to 6 months of age on FC status at 3 years of age.

There is a lack of large, nationwide, birth cohort studies in Japan that examine the relationships of initial feeding habits and breastfeeding period duration with offspring functional constipation at 3 years of age. This study assessed the impact of breastfeeding during infancy on early childhood functional constipation.

The fixed data of 70,078 singleton births from the ongoing Japan Environment and Children's Study cohort study that commenced in 2011 were used to identify functional constipation as estimated by Rome III at 3 years of age. The exposure variables were breastfeeding period duration until 12 months of age (never, up to 6 months, or ≥ 7 months) as well as breastfeeding status at 1 month and 6 months of age (breastfeeding exclusively, partial breastfeeding, or infant formula feeding only). Multiple logistic regression analysis was employed to search for correlations for functional constipation development with breastfeeding period duration until 12 months of age and breastfeeding status during infancy.

We identified 8,118 toddlers (11.6%) who met the Rome III criteria at 3 years of age. After controlling for potential covariates, a breastfeeding period duration of 7 months or more was inversely related to functional constipation development (≥ 7 months: adjusted odds ratio [OR] [95% confidence interval (CI)] 0.76 [0.65, 0.88] versus never breastfed, P for trend < 0.001). Other initial feeding methods were significantly related to an increased risk of functional constipation as compared with breastfeeding exclusively at 1 month of age (partial breastfeeding: adjusted OR [95% CI] 1.17 [1.11, 1.23], formula feeding only: 1.23 [1.07, 1.40]) and 6 months of age (partial breastfeeding: adjusted OR [95% CI] 1.18 [1.12, 1.24], formula feeding only: adjusted OR [95% CI] 1.42 [1.20, 1.68]).

This large nationwide survey revealed a possible protective effect of a prolonged breastfeeding period duration and early exclusive breastfeeding in infancy on functional constipation at 3 years.

Transabdominal rectal ultrasound (TRU) is used to measure transverse rectal diameter (TRD) in order to diagnose functional constipation (FC) and megarectum, and to evaluate treatment. The proposed cut-off value is 3.0 cm. Currently, no standardised values exist for children below the age of 4. We used repeated TRUs to establish reference TRD values in healthy infants and to describe rectal diameter in infants with FC.

This prospective observational cohort study enrolled healthy term babies from a maternity department. TRD measurements were taken at 2 and 12 months of age, and questionnaires completed in interviews helped diagnose FC according to Rome III criteria.

Two hundred TRUs were performed on 110 infants (62 males). In infants without FC anytime, the mean TRD at 2 months was 1.56 (SD 0.32) cm and at 12 months 1.78 (0.47) cm, while the 95th percentiles were 2.26 and 2.64 cm, respectively. In 77 infants with two TRUs, the mean increase was 0.21 cm (95% confidence interval: 0.099-0.318). Thirteen infants were diagnosed with FC during the study period. At 2 and 12 months of age, there was no difference in TRD between infants with and without FC.

TRD increased from 2 to 12 months. We suggest 2.3 cm as an upper limit for normal TRD at 2 months and 2.6 cm at 12 months. Infants diagnosed with FC did not have a greater TRD than infants without, either before or after treatment. Further studies are needed to evaluate the usefulness of TRU in infants with FC or megarectum.

Functional gastrointestinal disorders (FGIDs) are common in children and adolescents. In recent years, interest in the role of diet in the treatment of FGIDs has increased. Currently, interest focuses on the low-FODMAP diet (LFD), the fructose- or lactose-restricted diet (FRD or LRD), the gluten-free diet (GFD), and the Mediterranean diet (MD). In this review, we focus on the role of these dietary patterns in the FGIDs most commonly diagnosed in clinical practice, namely irritable bowel syndrome (IBS), functional abdominal pain (FAP), functional dyspepsia (FD), and functional constipation (FC). Fifteen clinical trials were systematically reviewed (both RCTs and single-arm clinical trials). We demonstrated the lack of high-quality intervention trials. Based on current evidence, low-FODMAP diet, LRD, FRD, and GFD have no place in daily clinical practice for the management of children and adolescents with FGIDs. Nevertheless, some patients with IBS or RAP may experience some benefit from the use of a low-FODMAP diet or FRD/LRD. Limited data suggest that MD may be promising in the management of FGIDs, especially in IBS patients, but more data are required to investigate the mechanisms of its protective effects.

Infant colic is a common condition with unclear biologic underpinnings and limited treatment options. We hypothesized that complex molecular networks within human milk (i.e., microbes, micro-ribonucleic acids (miRNAs), cytokines) would contribute to colic risk, while controlling for medical, social, and nutritional variables. This hypothesis was tested in a cohort of 182 breastfed infants, assessed with a modified Infant Colic Scale at 1 month. RNA sequencing was used to interrogate microbial and miRNA features. Luminex assays were used to measure growth factors and cytokines. Milk from mothers of infants with colic (n = 28) displayed higher levels of Staphylococcus (adj. p = 0.038, d = 0.30), miR-224-3p (adj. p = 0.023, d = 0.33), miR-125b-5p (adj. p = 0.028, d = 0.29), let-7a-5p (adj. p = 0.028, d = 0.27), and miR-205-5p (adj. p = 0.029, d = 0.26) compared to milk from non-colic mother-infant dyads (n = 154). Colic symptom severity was directly associated with milk hepatocyte growth factor levels (R = 0.21, p = 0.025). A regression model involving let-7a-5p, miR-29a-3p, and Lactobacillus accurately modeled colic risk (X² = 16.7, p = 0.001). Molecular factors within human milk may impact colic risk, and provide support for a dysbiotic/inflammatory model of colic pathophysiology.

No study has examined the association between constipation and atopic dermatitis (AD) in infants and toddlers. We aimed to explore that association in toddlers using the data from a nationwide birth cohort study.

From the Japan Environment and Children's Study, a nationwide prospective birth cohort study that began in 2011, children born in a singleton live birth were analyzed. Participants completed questionnaires containing questions related to bowel movements and AD, during 1.5 to 3 years after birth. Constipation at 1 year of age was defined as having ≤2 bowel movements per week. AD was defined based on participant's responses to the modified ISAAC questionnaire and/or self-reported physician's diagnosis. Outcome was defined as the cumulative number of AD cases that occurred until 3 years of age. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for development of AD were calculated by a multivariable logistic regression.

From a total of 62,777 participants who met the study inclusion criteria, 14,188 children (22.6%) were affected by AD between the ages of 1.5 and 3 years. The adjusted OR of developing AD for the presence versus absence of constipation at 1 year of age was 1.18 (95% CI, 1.01-1.38).

Constipation at 1 year of age was associated with a slightly higher risk of AD until 3 years of age.

Rosa × damascena Herrm., known as damask rose, is a bushy shrub that is found abundantly in Fars province, Iran. This species has been used in Iranian traditional practices for the treatment of abdominal pain and constipation, as gastrointestinal diseases. Brown sugar (Saccharum officinarum L.) has also shown laxative effects in pediatric patients with functional constipation.

This study aimed to compare the effects of Polyethylene Glycol (PEG) and a syrup made of R. damascena and brown sugar on the treatment of functional constipation in children aged above 12 months.

This double-blind randomized clinical trial was performed on 100 patients. One group received PEG and the other received an herbal syrup containing the decocted extract of 0.1 g R. damascena petals mixed with 0.85 g brown sugar per 1 mL. The patients were followed up for two and four weeks and their progresses were recorded.

The cure rate was 100% in the R. damascena group and 91.7% in the control group. R. damascena and brown sugar syrup had an odds ratio of 1.09 in the treatment of functional constipation compared to PEG, but the difference was not statistically significant. The only adverse effect detected in the R. damascena group after four weeks was the bad taste of the medication that was too sweet. Nonetheless, this could be solved during the pharmaceutical processes.

The R. damascena extract and brown sugar syrup can be used as an effective, safe, and inexpensive agent in the treatment of functional constipation.

The prevalence of feeding disorders (FDs) and picky eating in children is high in our region, based on the parents' perceptions. Although organic disease or a nutritional impact is rarely observed in these children, the problem frequently has an effect on family dynamics. We aimed to estimate the impact of these disorders on the stress level, quality of life and psychological health of families.

Study of cases (FDs) and controls (healthy controls and controls with digestive disorders or other illness). We assessed parental stress and the risk of psychological distress in these families using validated scales (Parent Stress Index Short Form [PSI-SF] and Goldberg's General Health Questionnaire [GHQ-28]) and a parental opinion survey.

We collected a total of 238 surveys, 102 corresponding to healthy controls, 88 to controls with digestive disorders and 48 to children with FDs. We found that 45.8% of parents in the FD group felt neglected by their paediatricians and 47.9% did not agree with the paediatrician's recommendations. In addition, 54.2% reported limitations to their social life, 25% problems in their relationship, 47.9% feeling judged by others (12.5% by their own partner) for how they managed mealtimes, and 37.5% having sought or considered seeking psychological support. All these problems were significantly more frequent compared to controls. Based on the GHQ-28, the risk of anxiety and depression was more frequent in parents in the FD group: 54.2% compared to the reference (adjusted odds ratio [aOR] compared to controls, 4.18; 95% confidence interval [CI], 1.96-8.87; OR compared to sick controls, 6.25; 95% CI, 2.79-13.98) and 33.3% compared to the healthy control group. They also had higher stress scores (PSI-SF) compared to the healthy control group (adjusted mean difference [AMD], 21; 95% CI, 12.19-29.81) and the sick control group (AMD, 20; 95% CI, 9.81-30.19).

Parents of children with FDs have a high level of stress and risk of anxiety and depression, with repercussions at the social, family, couple and work levels. The relationship with the paediatrician may also be affected.

Infant dyschezia is a functional gastrointestinal disorder that occurs in children less than nine months of age. This disorder causes much anxiety among parents who consult different physicians when suspecting major intestinal problems. The aim of this study is to verify whether infant dyschezia involves an anatomic abnormality (redundancy) of the colon. In this retrospective study (48 months) we analyzed all the children younger than 9 months who came to our attention through the suspicion of gastrointestinal abnormality (Hirschsprung’s disease, anorectal malformations, colonic disorders or constipation). They all had a complete medical history, clinical examination and diagnostic tests, such as blood samples, suction rectal biopsy, a study of stool characteristics and, finally, a contrast enema. In cases with infant dyschezia, different colonic sizes and rectosigmoid length were measured, which created a ratio with the diameter of the second lumbar vertebra. These values were compared with those reported in the literature as normal for the age of one year. Of the 24 patients evaluated (mean age 4 months), 9 were excluded for different diagnoses (aganglionic megacolon, hypothyroidism, constipation). The comparison of the ratios obtained in the remaining 15 cases showed a significantly higher rectosigmoid length (redundancy) in children with dyschezia, 18.47 vs. 9.75 (p < 0.001). The rectosigmoid redundancy, a congenital anomaly already reported as a cause of refractory constipation, may be present in children with infant dyschezia.

Antibiotics may contribute to the development of functional gastrointestinal disorders (FGIDs). This study aimed to determine whether antibiotics during the first week of life, infantile colic in the first year of life, gut-associated immune markers at 1 year of age, and allergies at 4-6 years of age in term-born children were associated with a higher prevalence of FGIDs at 4-6 years of age.

A prospective observational cohort of 436 term-born infants was followed up at the age of 4-6 years; 151 received broad-spectrum antibiotics (AB+), and 285 healthy controls (AB-). Validated Questionnaire On Pediatric Gastrointestinal Symptoms-Rome III and International Study of Asthma and Allergy in Childhood questionnaires were sent to parents of 418 available children. The independent t-test, chi-squared test or non-parametric test and logistic multivariate regression analyses were used.

In total, 340 of 418 (81%) questionnaires were completed. Only the presence of functional abdominal pain was significantly higher in AB+ than AB- (4% vs 0.4%, respectively, P  = 0.045). Children with food allergy fulfilled significantly more often the criteria for irritable bowel syndrome (IBS) and abdominal migraine (26% vs 9%, P  = 0.002 and 7% vs 1%, P  = 0.043, respectively) compared to non-allergic children. No differences in FGIDs existed at the age of 4-6 years between children with and without a history of infantile colic. There were significant differences in gut-associated immune markers between children with and without FGIDs.

Antibiotics during the first week of life resulted in a higher risk for functional abdominal pain at 4-6 years. Furthermore, food allergy was associated with IBS and abdominal migraine at 4-6years.

Functional gastrointestinal disorders (FGIDs) are common early in life. The prevalence of FGIDs varies among countries but is unknown in Vietnam. The aim of this study is to assess the prevalence of FGIDs in healthy Vietnamese infants and young children.

This was a cross-sectional, observational study involving healthy infants and young children between 0 - 48 months old in Hanoi, Vietnam. A representative total of 1511 subjects completed the validated questionnaire on paediatric FGIDs. Rome IV criteria were used to define FGIDs.

For Vietnamese infants (0-6 months) and young children (7-48 months), the prevalence of having at least one FGID was 10.0% and only 0.6% was having more than one FGID. Infantile regurgitation (9.3%) was the most prevalent FGID among infants 0-6 months of age while all other FGIDs had a low prevalence between 0-2.5%. For young children between 7 - 48 months old, functional constipation was the most common disorder at the rate of 5.6%. Association analysis revealed that the risk of infant regurgitation was significantly lower among infants with exclusively breastfeeding at 2 - 3 months and 3 - 4 months, formula initiation at 0 - 1 months, and higher paternal education level. The prevalence of functional constipation was significantly higher in male subjects, children in families with annual household income between 273,000,000 - 546,999,999 VND (or estimate around 11,800 - 23,800 USD), families with one child only, and formula feeding initiation at 1 - 2 months.

The prevalence of FGIDs in Vietnamese infants and young children is relatively low compared to the published literature using Rome IV diagnostic criteria. Infantile regurgitation was the most common FGID in Vietnamese infants while functional constipation was most prevalent among Vietnamese young children.

Netherlands Trial Registry Identifier: NL7286/NTR7495 .

Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder characterized by recurrent stereotypic episodes of vomiting. The pathophysiology of CVS remains obscure. Previous studies have supported the hypotheses of mitochondrial dysfunction. However, data on association studies between mitochondrial DNA (mtDNA) polymorphisms and pediatric-onset CVS are limited and inconsistent. The aims of this study were to describe clinical characteristics, evaluate association of mtDNA polymorphisms 16519T and 3010A with pediatric-onset CVS and identify new mtDNA candidate variants.

This study involved Thai patients diagnosed with CVS according to the Rome III or IV criteria before the age of 15 years. Patients' demographic data, clinical characteristics, previous investigations and treatment outcomes were obtained. Blood samples were collected for next-generation (whole exome) sequencing, followed by analysis of chromosome M (mitochondrial. Variants were filtered according to clinical significance using ClinVar and MITOMAP. mtDNA polymorphisms in 148 normal Thai individuals were used as controls.

Forty-eight children were enrolled in the clinical study, and 30 participated in the genetic analysis. The median age at onset and median age at diagnosis was 3.0 (1.5-5.6) and 6.3 (3.0-8.6) years, respectively. Maternal history of migraine was positive in 16.7%. About 45.7% (21 of 46) of the patients achieved complete clinical remission, with the mean symptom duration of 5.9 ± 3.3 years. The prevalence of mtDNA variants 16519T and 3010A among the patient group and Thai general population (control) were as follows: 40.0% (12/30) vs. 27.7% (P = 0.18) and 6.7% (2/30) vs. 0.7% (P = 0.07), respectively. Five known pathogenic variants were identified in 6 patients, including mtDNA 8528C in one patient who also had infantile hypertrophic cardiomyopathy. Six likely pathogenic variants were found but without statistical significance. We identified 11 variants with significant prevalence in the patient group. Though, these variants were classified as variants of unknown significance (VUS), several of them were located in mt functional regions and therefore they deserve further investigations as new candidates for association with pediatric CVS.

There were no associations of mtDNA polymorphisms 16519T and 3010A with CVS in our pediatric cohort. Five pathogenic variants and 11 VUS were found associated with pediatric-onset CVS.

Infantile colic, a common functional gastrointestinal condition, causes distress and frustration in families. Its prevalence and incidence vary from community to community. The purpose of our study was to demonstrate the incidence of and factors associated with infantile colic in Thai infants.

We conducted a prospective analytic study to explore the incidence and factors associated with infantile colic in 386 Thai infants aged between one month and six months. Caregivers were interviewed using a questionnaire about infants' symptoms of colic based on the definition from the Rome IV criteria. Family background and potential precipitating factors of colic were also evaluated.

The incidence of colic in infants younger than 6 months was 6.5%. All infants' colic started within 12 weeks of life and lasted approximately 6 weeks. Sex, gestational age, birth weight, delivery route, birth order, family factors, and parental factors were not correlated with the occurrence of colic. Infants who were exclusively breastfed for the first 2 months of life had a lower incidence of infantile colic than those who were mixed- or formula-fed (odds ratio=3.0; 95% confidence intervals=1.3 to 7.2).

The incidence of infantile colic in Thai infants in our study was 6.5%, which is similar to that in other reports. Being exclusively breastfed for the first two months was the only risk factor in our cohort.

Functional constipation is defined as chronic constipation with no identifiable underlying cause. It is a significant cause of morbidity in children, accounting for up to 25% of visits to paediatric gastroenterologists. Probiotic preparations may sufficiently alter the gut microbiome and promote normal gut physiology in a way that helps relieve functional constipation. Several studies have sought to address this hypothesis, as well as the role of probiotics in other functional gut disorders. Therefore, it is important to have a focused review to assess the evidence to date.

To evaluate the efficacy and safety of probiotics for the management of chronic constipation without a physical explanation in children.

On 28 June 2021, we searched CENTRAL, MEDLINE, Embase, CINAHL, AMED, WHO ICTR, and ClinicalTrials.gov, with no language, date, publication status, or document type limitations.

We included randomised controlled trials (RCTs) that assessed probiotic preparations (including synbiotics) compared to placebo, no treatment or any other interventional preparation in people aged between 0 and 18 years old with a diagnosis of functional constipation according to consensus criteria (such as Rome IV).

We used standard methodological procedures expected by Cochrane.

We included 14 studies (1127 randomised participants): 12 studies assessed probiotics in the treatment of functional constipation, whilst two studies investigated synbiotic preparations. Three studies compared probiotics to placebo in relation to the frequency of defecation at study end, but we did not pool them as there was very significant unexplained heterogeneity. Four studies compared probiotics to placebo in relation to treatment success. There may be no difference in global improvement/treatment success (RR 1.29, 95% CI 0.73 to 2.26; 313 participants; low-certainty evidence). Five studies compared probiotics to placebo in relation to withdrawals due to adverse events, with the pooled effect suggesting there may be no difference (RR 0.64, 95% CI 0.21 to 1.95; 357 participants; low-certainty evidence). The pooled estimate from three studies that compared probiotics plus an osmotic laxative to osmotic laxative alone found there may be no difference in frequency of defecation (MD -0.01, 95% CI -0.57 to 0.56; 268 participants; low-certainty evidence). Two studies compared probiotics plus an osmotic laxative to osmotic laxative alone in relation to global improvement/treatment success, and found there may be no difference between the treatments (RR 0.95, 95% CI 0.79 to 1.15; 139 participants; low-certainty evidence). Three studies compared probiotics plus osmotic laxative to osmotic laxative alone in relation to withdrawals due to adverse events, but it is unclear if there is a difference between them (RR 2.86, 95% CI 0.12 to 68.35; 268 participants; very low-certainty evidence). Two studies compared probiotics versus magnesium oxide. It is unclear if there is a difference in frequency of defecation (MD 0.28, 95% CI -0.58 to 1.14; 36 participants), treatment success (RR 1.08, 95% CI 0.74 to 1.57; 36 participants) or withdrawals due to adverse events (RR 0.50, 95% CI 0.05 to 5.04; 77 participants). The certainty of the evidence is very low for these outcomes. One study assessed the role of a synbiotic preparation in comparison to placebo. There may be higher treatment success in favour of synbiotics compared to placebo (RR 2.32, 95% CI 1.54 to 3.47; 155 participants; low-certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group. One study assessed a synbiotic plus paraffin compared to paraffin alone. It is uncertain if there is a difference in frequency of defecation (MD 0.74, 95% CI -0.96, 2.44; 66 participants; very low-certainty evidence), or treatment success (RR 0.91, 95% CI 0.71 to 1.17; 66 participants; very low-certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group. One study compared a synbiotic preparation to paraffin. It is uncertain if there is a difference in frequency of defecation (MD -1.53, 95% CI -3.00, -0.06; 60 participants; very low-certainty evidence) or in treatment success (RR 0.86, 95% CI 0.65, 1.13; 60 participants; very low-certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group. All secondary outcomes were either not reported or reported in a way that did not allow for analysis.

There is insufficient evidence to conclude whether probiotics are efficacious in successfully treating chronic constipation without a physical explanation in children or changing the frequency of defecation, or whether there is a difference in withdrawals due to adverse events when compared with placebo. There is limited evidence from one study to suggest a synbiotic preparation may be more likely than placebo to lead to treatment success, with no difference in withdrawals due to adverse events. There is insufficient evidence to draw efficacy or safety conclusions about the use of probiotics in combination with or in comparison to any of the other interventions reported. The majority of the studies that presented data on serious adverse events reported that no events occurred. Two studies did not report this outcome. Future studies are needed to confirm efficacy, but the research community requires guidance on the best context for probiotics in such studies, considering where they should be best considered in a potential treatment hierarchy and should align with core outcome sets to support future interpretation of findings.

Functional gastrointestinal disorders (FGD) are common during early childhood. In severe defecation disorders, anorectal manometry (AM) is done to exclude aganglionosis. High-resolution anorectal manometry (HRAM) can probably improve diagnostics but normative data in infants are scarce. This study aims to provide HRAM data in healthy infants overall and in subgroups of infants with FGD, defined as functional constipation (FC), infant colic (IC), and infant dyschezia (ID) (ROME 3 criteria).

This prospective observational cohort study enrolled healthy term infants, having HRAM at 2 and 6 months, using a water-perfused pediatric anorectal silicone catheter. Data were provided for presence of anorectal waves and recto anal inhibitory reflex (RAIR), volume needed to elicit RAIR and anal resting pressure (ARP). Questionnaires at 2 and 6 months identified subjects with FC, IC, and ID.

A total of 187 HRAM investigations were done in 107 infants, without any complications. Normal RAIR was found in all, at least on one occasion. Mean ARP increased between 2- and 6-month investigations in infants without FGD. No other differences in HRAM data could be seen between infants with or without an FGD. At 2 months FC, IC, and ID were seen (2%, 4%, and 17%), whereas at 6 months only FC and ID were seen (7% and 1%).

We can provide data on HRAM in infants at 2 and 6 months of age. When performing repeated HRAM in healthy infants, RAIR was found in all subjects. HRAM is safe, easy tolerable, and can be recommended in infants with or without FGD.

Infant regurgitation is common during infancy and can cause substantial parental distress. Regurgitation can lead to parental perception that their infant is in pain. Parents often present in general practitioner surgeries, community baby clinics and accident and emergency departments which can lead to financial burden on parents and the health care system. Probiotics are increasingly reported to have therapeutic effects for preventing and treating infant regurgitation. The objective of this systematic review and meta-analysis was to evaluate the efficacy of probiotic supplementation for the prevention and treatment of infant regurgitation. Literature searches were conducted using MEDLINE, CINAHL, and the Cochrane Central Register of Controlled trials. Only randomised controlled trials (RCTs) were included. A meta-analysis was performed using the Cochrane Collaboration methodology where possible. Six RCTs examined the prevention or treatment with probiotics on infant regurgitation. A meta-analysis of three studies showed a statistically significant reduction in regurgitation episodes for the probiotic group compared to the placebo group (mean difference [MD]: -1.79 episodes/day: 95% confidence interval [CI]: -3.30 to -0.27, N = 560), but there was high heterogeneity (96%). Meta-analysis of two studies found a statistically significant increased number of stools per day in the probiotic group compared to the placebo group at 1 month of age (MD: 1.36, 95% CI: 0.99 to 1.73, N = 488), with moderate heterogeneity (69%). Meta-analysis of two studies showed no statistical difference in body weight between the two groups (MD: -91.88 g, 95% CI: 258.40-74.63: I2  = 23%, N = 112) with minimal heterogeneity 23%. Probiotic therapy appears promising for infant regurgitation with some evidence of benefit, but most studies are small and there was relatively high heterogeneity. The use of probiotics could potentially be a noninvasive, safe, cost effective, and preventative positive health strategy for both women and their babies. Further robust, well controlled RCTs examining the effect of probiotics for infant regurgitation are warranted.

To evaluate the effectiveness and safety of nonpharmacologic interventions for the treatment of childhood functional constipation.

Randomized controlled trials (RCTs) evaluating nonpharmacologic treatments in children with functional constipation which reported at least 1 outcome of the core outcome set for children with functional constipation.

We included 52 RCTs with 4668 children, aged between 2 weeks and 18 years, of whom 47% were females. Studied interventions included gut microbiome-directed interventions, other dietary interventions, oral supplements, pelvic floor-directed interventions, electrical stimulation, dry cupping, and massage therapy. An overall high risk of bias was found across the majority of studies. Meta-analyses for treatment success and/or defecation frequency, including 20 RCTs, showed abdominal electrical stimulation (n = 3), Cassia Fistula emulsion (n = 2), and a cow's milk exclusion diet (n = 2 in a subpopulation with constipation as a possible manifestation of cow's milk allergy) may be effective. Evidence from RCTs not included in the meta-analyses, indicated that some prebiotic and fiber mixtures, Chinese herbal medicine (Xiao'er Biantong granules), and abdominal massage are promising therapies. In contrast, studies showed no benefit for the use of probiotics, synbiotics, an increase in water intake, dry cupping, or additional biofeedback or behavioral therapy. We found no RCTs on physical movement or acupuncture.

More well-designed high quality RCTs concerning nonpharmacologic treatments for children with functional constipation are needed before changes in current guidelines are indicated.

There are few studies that compare polyethylene glycol (PEG) 3350 and magnesium hydroxide (MH), as long-term treatment of functional constipation (FC) in children, and they do not include infants as young as 6 months of age. Our aim was to determine the efficacy, safety, and acceptability of PEG vs MH in FC, in the long term, in pediatric patients.

An open-label, parallel, controlled clinical trial was conducted on patients from 6 months to 18 years of age, diagnosed with FC, that were randomly assigned to receive PEG 3350 or MH for 12 months. Success was defined as: ≥ 3 bowel movements/week, with no fecal incontinence, fecal impaction, abdominal pain, or the need for another laxative. We compared adverse events and acceptability, measured as rejected doses of the laxative during the study, in each group and subgroup.

Eighty-three patients with FC were included. There were no differences in success between groups (40/41 PEG vs 40/42 MH, p = 0.616). There were no differences in acceptability between groups, but a statistically significant higher number of patients rejected MH in the subgroups > 4 to 12 years and > 12 to 18 years of age (P = .037 and P = .020, respectively). There were no differences regarding adverse events between the two groups and no severe clinical or biochemical adverse events were registered.

The two laxatives were equally effective and safe for treating FC in children from 0.5 to 18 years of age. Acceptance was better for PEG 3350 than for MH in patients above 4 years of age. MH can be considered first-line treatment for FC in children under 4 years of age.

It has been proven that gut microbiota alterations are involved in the development of Henoch-Schönlein Purpura (HSP). However, the pathogenesis of HSP hasn't been eluciated. This study was to investigate the impact of gut microbiota from HSP on ASIC3 expression and interactions between microbiota and ASIC3 expression in the development of HSP.

Feces collected from HSP and healthy children at the First Affiliated Hospital of Anhui Medical University were made into fecal microbial solutions. Germ-free rats were randomly assigned to either the control or HSP groups. The HSP group of rats were administered the fecal microbiota solution of HSP children, while the control group rats were administered the fecal microbiota solution of healthy children. Abdominal withdrawal reflex (AWR) and intestinal propulsion rate of the rats were used to determine visceral sensitivity. Composition of the gut microbiota of HSP children was determined using 16S rRNA gene sequencing. ASIC3 expression in the colon was ascertained through qRT-PCR as well as western blotting analysis.

The results showed a reduction in the number of species and abundance in the intestinal microbiota of children with HSP. Visceral sensitivity and intestinal propulsion rate of HSP group rats increased significantly, compared with the control group. Colon ASIC3 mRNA and protein levels in the HSP group were found to be upregulated. The microbiota dysbiosis of HSP patients could stimulate ASIC3 expression in the colon of Germ-free rats, which in turn affected intestinal motility.

These results suggested that HSP children had intestinal microbiota disorder, which might affect gut motility by down-regulating colon ASIC3 expression in rats.

To evaluate the administration of Bifidobacterium animalis subsp. lactis, BB-12^® (BB-12) on infant colic in breastfed infants, a double-blind, placebo-controlled randomised study was conducted in Chengdu, China from April 2016 to October 2017 with 192 full-term infants less than 3 months of age and meeting the ROME III criteria for infant colic. After a 1-week run-in the infants were randomly assigned to receive daily BB-12 (1×10⁹ cfu/day) or placebo for 3 weeks. Crying/fussing time were recorded using a 24 h structured diary. The primary endpoint was the proportion of infants achieving a reduction in crying and fussing time of ≥50% from baseline. Parent's/caregiver's health related quality of life was measured using a modified PedsQL^™ 2.0 Family Impact Module and immunological biomarkers were evaluated from faecal samples at baseline and after the 21-day intervention. The percentage of infants achieving a reduction in the daily crying/fussing time ≥50% after the 21-day intervention was significantly higher in the infants supplemented with BB-12 (P<0.001). The mean number of crying episodes was significantly reduced in the BB-12 group compared to the placebo group (10.0±3.0 to 5.0±1.87 vs 10.5±2.6 to 7.5±2.8, respectively) (P<0.001) and the mean daily sleep duration was markedly increased from baseline to end of intervention in the BB-12 group compared to the infants in the placebo group (60.7±104.0 vs 31.9±102.7 min/day, respectively) (P<0.001). The faecal levels of human beta defensin 2, cathelicidin, slgA, calprotectin and butyrate were statistically higher in the BB-12 group compared to the placebo group after the 21-day intervention. At the end of the intervention the parent's/caregiver's physical, emotional and social functioning scores were significantly higher for the BB-12 group compared to the placebo group (all P<0.05). Supplementation of BB-12 is effective in reducing crying and fussing in infants diagnosed with infant colic.

Background: Polyethylene glycol (PEG) is recommended as first-line treatment of pediatric functional constipation. However, the oral route of administration is often poorly feasible in children mostly due to poor palatability. Promelaxin microenemas exert a topical evacuative action and may offer a valuable option in pediatric FC. Aim: To assess whether Promelaxin microenemas would be non-inferior to PEG 4000 in young children with FC. Methods: This is a randomized, open-label, multi-centric, non-inferiority trial enrolling infants and young children aged 6-48 months, with FC according to Rome III criteria. After 1 week of run in, children were randomized to 2 weeks of Promelaxin or PEG, followed by a 6-week on-demand treatment period. Primary endpoint was response rate to randomized treatment, with "response" defined as at least 3 evacuations per week and an average increase of at least one evacuation per week as compared to baseline. Safety, stool consistency and the analysis of fecal microbiota were secondary endpoints. Results: Out of the 158 patients who entered the trial, 153 patients were treated (77 and 76, PEG and Promelaxin arm, respectively). In the primary analysis, the 95% confidence interval (CI) for the treatment's effect lay entirely above the non-inferiority margin in both Full Set (FAS) and Per Protocol (PP) analyses, providing evidence of the non-inferiority of Promelaxin vs. PEG 4000 [response rate difference: 16.5% (CI 1.55-31.49%) and 11.03% (CI -5.58 to 27.64%), FAS and PP analyses, respectively]. Mean compliance to the randomized treatment was >80% in both arms. Secondary endpoints did not significantly differ between the two arms, except for the average number of total days of on-demand treatment that was significantly lower in the Promelaxin arm [14.6 (12.7) vs. 9.8 (9.1), mean (SD); primary endpoint responders in PEG and Promelaxin arm, respectively; p = 0.027]. Microbiota evenness significantly increased in the PEG 4000 arm at V4 as compared to the Promelaxin arm (p < 0.05). In addition, at V5, patients treated with PEG showed a significantly decreased microbiota density as compared to patients treated with Promelaxin (p = 0.036). Conclusions: Promelaxin microenemas are non-inferior to oral PEG in children with FC. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02751411.

Nowadays there is still no ideal treatment for paediatric overactive bladder. Initial management measures (urotherapy and constipation control), resolve 40% of cases. The second line of treatment in overactive bladder is anticholinergic drugs, above all oxybutynin. Although most patients improve with these therapies, the complete resolution rate is around 30-40%. Sacral transcutaneous electrical nerve stimulation has recently emerged as a new alternative in the management of patients with refractory paediatric overactive bladder. However, only a few studies have been done to compare the effectiveness of this therapy versus conventional drugs.

The objective of the present study is to compare, in children with overactive bladder, the efficacy of the sacral transcutaneous electrical nerve stimulation versus oxybutynin therapy.

We performed a prospective and randomized study of patients with diagnosis of overactive bladder treated with sacral transcutaneous electrical nerve stimulation versus oxybutynin, during the period July 2018-July 2020. Patients refractory to standard urotherapy and constipation management randomly received one of the therapeutic alternatives. Treatment was maintained for 6 months.

86 patients were included in the study: 40 patients received electrotherapy (group 1) and 46 patients received oxybutynin (group 2). Before starting the treatment assigned both groups were comparable related to the voiding symptomatology as well as the severity of the overactive bladder. Sacral transcutaneous electrical nerve stimulation was significantly more effective than oxybutynin, with a higher percentage of complete resolution of symptoms in the management of paediatric overactive bladder.

All the parameters obtained with the voiding calendar significantly improved in both groups at the end of the treatment. The increase in MaVV was significantly higher in group-1.

We observed a progressive decrease in the mean score obtained in the DVISS questionnaire over time in both groups. This decrease was significantly higher in group-1 compared to group-2 (p < 0.005). The mean value obtained in the DVISS questionnaire in group-1 was 6 (interquartile range: 3-9) at the end of the treatment (lower than the diagnostic cut-off point for daytime condition in the DVISS, 8.5). In group-2, the mean value obtained in the DVISS questionnaire was 10 (interquartile range: 8.75-13.25), higher than the cut-off point.

A greater number of adverse effects was obtained in group-2 (26.1% versus 15%, p < 0.05). Constipation (n: 6, 10.9%), and abdominal pain (n: 2,4.3%) were the most frequent adverse effects in this group. The adverse events reported in group-1 were contact dermatitis (n: 1.2%) and fecal losses [2] or urgency [5].

Oxybutynin and sacral transcutaneous electrical nerve stimulation are both effective therapies in the management of paediatric overactive bladder. However, electrotherapy has been shown to be a more effective therapy with a complete clinical resolution rate in a larger number of patients. Furthermore, the rate of adverse effects secondary to electrotherapy is significantly lower than those treated with oxybutynin.

Functional constipation is an important clinical problem among chidren all over the world. Its main cause is not completely understood. Motilin is a gastrointestinal hormone that increases intestinal motility. In this study, we aimed to investigate the serum motilin levels and its relationship with stool consistency and motilin gene polymorphisms in constipated children.

In this study we investigated 91 constipated patients (mean age 6.84±3.55 years) and 100 healthy controls (mean age 7.78±4.25 years). Serum motilin levels were assessed by sandwich enzyme-linked immunosorbent assay. rs2281820 (c.44 C>T) and rs2281818 (c.66 C>T) mutations were evaluated for motilin gene polymorphisms.

Serum motilin levels were significantly lower in constipated children than healthy controls (6.20±7.86 vs. 11.54±17.89 pg/mL, respectively, P=0.008). Serum motilin levels were significantly correlated with Bristol stool scale rate (r=0.193, P=0.011) in whole study group, but in the constipation group there was no significant correlation (r=-0.072, P=0.528). There were no differences in terms of presence or distribution of the polymorphisms of rs2281820 (c.44 C>T) and rs2281818 (c.66 C>T) in both groups. There was not a significant difference between different polymorphism groups regarding serum motilin concentrations in whole study group and also in both of the study groups.

This study indicated for the first time that serum motilin levels decreased in constipated children. Further studies are needed to clarify whether motilin or motilin gene polymorphisms has a role in pathogenesis of functional constipation.

The association between delivery mode and subsequent development of diseases is a growing area of research. Cesarean delivery affects the diversity of the microbiota in the infant gut, which may be associated with gastrointestinal disorders, including functional constipation, in infants. In this study, we investigated the association between delivery mode and prevalence of functional constipation in 3-year-old Japanese toddlers.

This study used data from the Japan Environment and Children's Study, an ongoing nationwide birth cohort study. We analyzed 71,878 toddler-mother pairs. The presence of functional constipation was determined according to the Rome III diagnostic criteria. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis.

The prevalence of functional constipation in 3-year-old Japanese toddlers was estimated to be 12.3%. Logistic regression analysis revealed that the prevalence of functional constipation was higher in toddlers born by cesarean delivery (13.1%) compared with those born by vaginal delivery (12.1%), independent of 22 confounders (adjusted odds ratios = 1.064, 95% confidence interval = 1.004-1.128).

We determined the prevalence of functional constipation in 3-year-old Japanese toddlers and found that delivery mode was associated with the prevalence of functional constipation in Japanese toddlers.

This study aimed to compare the transverse diameter and thickness of the anterior wall of the rectum in children with normal bowel movement and children with functional constipation in different age groups. Another objective was to find correlations of rectum sizes with faecal incontinence and constipation duration.

In the study, we included children with normal bowel movement and functional constipation diagnosed based on the Rome III and Rome IV criteria. We collected clinical data from the parents. We measured the rectum transverse diameter and the thickness of the anterior wall by abdominal ultrasound.

The study included 65 children, 31 with normal bowel movement and 34 with functional constipation. The rectum transverse diameter and the thickness of the anterior wall had statistically significant higher values in patients with constipation (P < 0.05). There was a moderate and significant correlation between the duration of the disease (mean ± standard deviation = 31.7 ± 33.1 months) and rectum transverse diameter (r = 0.54; P = 0.0009). The rectum transverse diameter correlated moderately with the presence of faecal incontinence (r = 0.62; P = 0.003), but the thickness of the anterior wall did not correlate with this symptom (r = 0.02; P = 0.39).

We found statistically significant differences between the transverse rectal diameter and thickness of the rectum anterior wall, measured by abdominal ultrasound, in children with functional constipation compared with normal defaecation patterns. Faecal incontinence and long-term constipation were correlated with the increased rectum diameter.

Functional gastrointestinal disorders (FGIDs) are a heterogeneous group of conditions of unclear etiology. The biopsychosocial model approach to FGIDs posits that early-life stressors may trigger a cascade of complex interactions between genetic predisposition and risk factors eventually leading to the occurrence of FGIDs. The relationship between the psychological disposition of the mother and FGIDs occurrence is poorly understood. We conducted a study to investigate if parental psychological factors may contribute to the onset of FGIDs in offspring.

We performed a prospective cohort study of parent-infant pairs who completed a battery of self-reported psychological questionnaires and a validated Rome III questionnaire for the diagnosis of infant and toddler FGIDs. The Edinburgh Postpartum Depression Scale (EPDS) was used to examine postpartum depression (PPD) symptoms; the Maternity Blues Questionnaire (MBQ) was applied to measure maternity blues severity; the Symptoms Checklist-Revised (SCL90-R) was used to assess the presence of relevant psychiatric symptoms; adult attachment style in mothers was assessed in a continuous way through the five dimensions of the Attachment Style Questionnaire (ASQ).

Out of the 360 eligible mothers, 200 were enrolled, 113 completed the 3-month follow-up and were included in the final analysis. PPD symptoms prevalence was 20.4%, 20%, 13.2%, and 13.1% respectively at 3 days, 1 week, 1 month, and 3 months after delivery. 40.4% of mothers suffered from severe blues according to the MBQ. Relevant psychiatric symptoms (SCL90-R) were present in 7.8% and 10.9% of mothers, respectively at 1 week and 3 months after delivery. 48.7% of mothers showed a secure attachment pattern measured through the RQ. At 1-month follow-up, infant regurgitation was diagnosed in 26 (23%) of infants, infantile colic in 31 (27.4%), dyschezia in 17 (15%), and functional constipation in 9 (8%). At 3-month follow-up, FGIDs prevalence was respectively 16 (19.3%), 11 (13.3%), 4 (4.8%), and 11 (13.3%). A significant positive association between PPD symptoms starting 3 days after delivery and the presence of infantile colic on setting 1 month after birth was found (P = 0.028), as well as between PPD symptoms occurrence 7 days after delivery and infantile regurgitation beginning 1 month after birth (P = 0.042). A higher prevalence of infantile colic was found in the offspring of mothers suffering from PPD symptoms from 3 days after delivery (54.5 vs 19.8; P = 0.001). No significant association was found between FGIDs and psychiatric symptoms and maternity blues at any timepoint. On the other hand, mothers of infants with regurgitation with an onset 1 month after birth have higher insecurity score in avoidant and fearful ASQ-related attachment dimensions (respectively, P = 0.03, P = 0.042, P = 0.03).

Maternal psychological factors might contribute to the onset of infant FGIDs in offspring. Early screening of postpartum depression symptoms and early implementation of psychological interventions within the postpartum period might promote the health of the mother-infant dyad.

To evaluate the agreement between the Rome III and Rome IV criteria in diagnosing pediatric functional gastrointestinal disorders (FGIDs), we conducted a prospective cohort study in a public school in Cali, Colombia. Children and adolescents between 11 and 18 years of age were given the Spanish version of the Questionnaire on Pediatric Functional Gastrointestinal Disorders Rome III version on day 0 and Rome IV version on day 2 (48 h later). The study protocol was completed by 135 children. Thirty-nine (28.9%) children were excluded because of not following the instructions of the questionnaire. The final analysis included data of 96 children (mean 15.2 years old, SD ± 1.7, 54% girls). Less children fulfilled the criteria for an FGID according to Rome IV compared to Rome III (40.6% vs 29.2%, p=0.063) resulting in a minimal agreement between the two criteria in diagnosing an FGID (kappa 0.34, agreement of 70%). The prevalence of functional constipation according to Rome IV was significantly lower compared to Rome III (13.5% vs 31.3%, p<0.001), whereas functional dyspepsia had a higher prevalence according to Rome IV than Rome III (11.5% vs 0%).Conclusion: We found an overall minimal agreement in diagnosing FGIDs according to Rome III and Rome IV criteria. This may be partly explained by the differences in diagnostic criteria. However, limitations with the use of questionnaires to measure prevalence have to be taken into account. What is Known: • The Rome IV criteria replaced the previous Rome III criteria providing updated criteria to diagnose functional gastrointestinal disorders (FGIDs). • Differences found between Rome IV and historic Rome III FGID prevalence may have been affected by changes in prevalence over time or differences in sample characteristics. What is New: • We found a minimal agreement between Rome III and Rome IV FGID diagnosis, especially in the diagnoses of functional constipation, irritable bowel syndrome, and functional dyspepsia. • The minimal agreement may be partly explained by changes in diagnostic criteria, but limitations with the use of questionnaires to measure prevalence have to be taken into account.

The purpose of this study was to develop and validate a questionnaire that comprehensively assesses symptoms and severity of crying, symptoms suggesting infant functional gastrointestinal discomfort, and its impact on parents' quality of life: the Infant Colic Questionnaire (ColiQ©). For the first time, parents had access to a web application to follow their infants' evolving symptoms with a daily questionnaire.

The ColiQ was developed with a board of clinical experts (physicians and psychologists) based on extensive parent input. A longitudinal, observational study was conducted in France for 3 months. ColiQ assessments were collected online at six different time points. Psychometric testing demonstrated that ColiQ has acceptable psychometric properties (reliability, internal consistency, construct validity, and responsiveness).

The ColiQ is a 16-question instrument developed in French including ten questions describing symptoms (Infant score) and six questions describing impacts (Parent score). The ColiQ demonstrated good test-retest reliability (ICC >0.70), internal consistency for both the Symptom and Impact subscale scores (Cronbach's α >0.70), and construct validity. Responsiveness was good; the ColiQ was able to detect significant improvement in the target population as early as 1 month (p<0.05). The global ColiQ score discriminated between severity levels (mild, medium, severe).

The ColiQ was developed with input from parents and healthcare professionals and has shown validity, reliably, and responsiveness to change. Parents can use the web application to follow how their infants' symptoms evolve. The ColiQ can help parents quantify and verbalize their concerns during consultations, and provides an opportunity to facilitate conversations between the physician and parents.