Cow's Milk-related Symptom Score (CoMiSS) values in presumed healthy European infants aged 6-12 months: a cross-sectional study.

The Cow's Milk-related Symptom Score (CoMiSS) is an awareness tool for evaluating cow's milk-related symptoms. Previous studies have focused on providing CoMiSS values for healthy and symptomatic infants aged 0-6 months. However, there is a notable gap in the literature concerning CoMiSS values for infants older than 6 months. This cross-sectional study aimed to determine CoMiSS values in presumed healthy infants who have completed 6 months and are up to 12 months old, hereafter referred to as 6 to 12 months old. Physicians from six European countries prospectively determined CoMiSS values in infants attending well-child clinics. Exclusion criteria included preterm delivery, acute or chronic disease, and the consumption of a therapeutic formula, dietary supplements (except vitamins), or medication. The following information was collected: gestational age, gender, age, type of feed (breast milk or infant formula), and complementary feeding. Descriptive statistics were summarized with mean and standard deviation for normally distributed continuous variables, median and IQR for non-normally distributed variables, and differences in CoMiSS values were analyzed with appropriate tests. Data from 609 infants were obtained. The overall median (Q1-Q3) CoMiSS values were 3 (1-5). Significant differences were found across age groups (p < 0.001), but not across groups based on gender (p = 0.551) or feeding type (p = 0.880).   Conclusions: This study provided CoMiSS values in presumed healthy infants aged 6-12 months. Additional studies should be conducted to establish the use of CoMiSS to assess cow's milk-related symptoms in infants 6 months and older. What is Known: • The Cow's Milk-related Symptom Score (CoMiSS) is an awareness tool for evaluating symptoms related to cow's milk. • CoMiSS values for presumed healthy infants aged 0-6 months infants are already available. What is New: • CoMiSS values in European infants aged 6-12 months are provided. • These CoMiSS values differed across various age groups but not across groups based on gender or feeding type.

Cow's Milk-Related Symptom Score (CoMiSS): From Bristol to Brussels Stool Scale.

OBJECTIVES: The Cow's Milk-related Symptom Score (CoMISS) is an awareness tool for evaluating cow's milk-related symptoms in otherwise healthy infants <1 year of age. This study assessed whether replacing the Bristol Stool Form Scale (BSFS) with the Brussels Infants and Toddlers Stool Scale (BITSS) in non-toilet-trained infants would modify the overall CoMiSS and change the clinical approach regarding potential cow's milk allergy. METHODS: Non-toilet-trained infants aged <13 months were assessed by CoMiSS using the 7 images from the BSFS (CoMiSS-BSFS) compared to the 4 images of stools from BITSS (CoMiSS-BITSS). The Wilcoxon signed-rank test and Pearson correlation coefficient were calculated. A post hoc analysis using identical tests was performed in subsets of CoMiSS-BSFS scores ≥10, ≥12, ≤5, and ≥6. RESULTS: Eight hundred forty-four pairwise scores were collected. Applying the Wilcoxon test over the complete dataset, the difference between CoMiSS-BSFS and CoMiSS-BITSS was statistically significant ( P < 0.001). However, there was no significant difference in the subsets with CoMiSS-BSFS ≥10, ≥12, and ≥6 ( P = 0.84, P = 0.48, and P = 0.81, respectively). The significant difference remained restricted to the group with CoMiSS-BSFS ≤5, considered at low risk for CM-related symptoms ( P < 0.001). CONCLUSION: Replacing BSFS with BITSS does not change the cutoff for awareness of possible CM-related symptoms and will not impact the use of CoMiSS in clinical practice. Changes in CoMiSS remained limited to the subgroup with a low risk for CM-related symptoms.

The Cow's Milk Related Symptom Score: The 2022 Update.

CoMiSS® was developed 7 years ago to increase the awareness of health care professionals towards the possibility that symptoms presented by infants could be related to cow's milk. While CoMiSS was conceived mostly on theoretical concepts, data is now available from 25 clinical trials. Based on this extensive research using the tool since 2015, we aim to propose an updated CoMiSS. The evidence was reviewed, debated and discussed by 10 experts, of whom seven were part of the original group. The panel concluded that the cut-off previously proposed to indicate the likelihood that symptoms may be cow's milk related should be lowered from ≥12 to ≥10. Data in healthy infants > 6 months are missing. Since the Brussels Infant and Toddlers Stool Scale (BITSS) was recently developed for non-toilet trained children, the Bristol Stool Scale was changed to the BITSS without changing the impact of stool characteristics on CoMiSS. Overall, CoMiSS raises awareness that symptoms might be cow's milk related. New studies are needed to determine if the change in cut-off and other small adaptions improve its sensitivity and specificity. Data for CoMiSS is still needed in presumed healthy infants between 6 and 12 months old. There may also be regional differences in CoMiSS, in healthy infants as well as in those with cow's milk allergy. Finally, we emphasize that CoMiSS is an awareness tool and not a diagnostic test.

The Cow's Milk-Related Symptom Score (CoMiSS™): A Useful Awareness Tool.

The Cow's Milk-related Symptom Score (CoMiSS™) was developed as a clinical tool aimed at increasing the awareness of health care professionals for the presence and intensity of clinical manifestations possibly related to cow's milk (CM) intake. This review summarizes current evidence on CoMiSS. We found twenty-five original studies, one pooled analysis of three studies, and two reviews on CoMiSS. Infants exhibiting symptoms possibly related to CM, present with a higher median CoMiSS (6 to 13; 16 studies) than apparently healthy infants (median from 3 to 4; and mean 3.6−4.7; 5 studies). In children with cow's milk allergy (CMA), 11 studies found that a CoMiSS of ≥12 predicted a favorable response to a CM-free diet; however, sensitivity (20% to 77%) and specificity (54% to 92%) varied. The decrease of CoMiSS during a CM elimination diet was also predictive of a reaction to an oral food challenge to diagnose CMA. A low CoMiSS (<6) was predictive for the absence of CMA. It was shown that no special training is required to use the tool in a reliable way. Intra-rater reliability was high with very low variability (intra-class correlation 0.93; 95% confidence interval 0.90−0.96; p < 0.001) in repeated assessments. This review found that CoMiSS cannot be considered as a stand-alone CMA diagnostic tool, but that it is a useful awareness tool for CMA as well as for monitoring symptom improvement.

Assessment of the Cow's Milk-related Symptom Score (CoMiSS) as a diagnostic tool for cow's milk protein allergy: a prospective, multicentre study in China (MOSAIC study).

OBJECTIVES: The MOSAIC study aimed to evaluate if the Cow's Milk-related Symptom Score (CoMiSS) can be used as a stand-alone diagnostic tool for cow's milk protein allergy (CMPA). DESIGN: Single-blinded, prospective, multicentre diagnostic accuracy study. SETTING: 10 paediatric centres in China. PARTICIPANTS: 300 non-breastfed infants (median age 16.1 weeks) with suspected CMPA. INTERVENTIONS: After performing the baseline CoMiSS, infants commenced a cow's milk protein elimination diet with amino acid-based formula for 14 days. CoMiSS was repeated at the end of the elimination trial. Infants then underwent an open oral food challenge (OFC) with cow's milk-based formula (CMF) in hospital. Infants who did not react during the OFC also completed a 14-day home challenge with CMF. A diagnosis of CMPA was made if acute or delayed reactions were reported. PRIMARY OUTCOME MEASURES: A logistic regression model for CoMiSS to predict CMPA was fitted and a receiver-operator characteristic (ROC) curve generated. An area under the curve (AUC) of ≥0.75 was deemed adequate to validate CoMiSS as a diagnostic tool (target sensitivity 80%-90% and specificity 60%-70%). RESULTS: Of 254 infants who commenced the OFC, 250 completed both challenges, and a diagnosis of CMPA made in 217 (85.4%). The median baseline CoMiSS in this group fell from 8 (IQR 5-10) to 5 (IQR 3-7) at visit 2 (p<0.000000001), with a median change of -3 (IQR -6 to -1). A baseline CoMiSS of ≥12 had a low sensitivity (20.3%), but high specificity (87.9%) and high positive predictive value (91.7%) for CMPA. The ROC analysis with an AUC of 0.67 fell short of the predefined primary endpoint. CONCLUSIONS: The present study did not support the use of CoMiSS as a stand-alone diagnostic tool for CMPA. Nevertheless, CoMiSS remains a clinically useful awareness tool to help identify infants with cow's milk-related symptoms. TRIAL REGISTRATION NUMBER: NCT03004729; Pre-results.

Regional Incidence of Inflammatory Bowel Disease in a Czech Pediatric Population: 16 Years of Experience (2002-2017).

OBJECTIVES: Inflammatory bowel disease (IBD) is today a global disease, the incidence of which is growing in the pediatric population. This prospective study aims to decipher IBD incidence and its trend in a pediatric population through 16 years in the South Moravian Region of the Czech Republic. METHODS: We evaluated data concerning 358 pediatric patients with newly diagnosed IBD at University Hospital Brno, which is a gastroenterology center for the entire pediatric population (0-18 years) and cares for all pediatric IBD patients in the South Moravian Region (1,187,667 inhabitants). RESULTS: The study encompassed 3,488,907 children during 16 years. We diagnosed 192 children (53.6%) with Crohn disease (CD), 123 (34.4%) with ulcerative colitis (UC), and 43 (12.0%) with IBD-unclassified (IBD-U). The incidence of IBD increased from 3.8 (CD 2.9, UC 0.9, and IBD-U 0.0) per 100 000/year in 2002 to 14.7 (CD 9.8, UC 4.0, and IBD-U 0.9) per 100,000/year in 2017 (P < 0.001). The overall IBD incidence per 100,000/year was 9.8 (95% confidence interval [CI]: 8.8--10.9). Constituent incidences per 100,000/year were CD 5.2 (95% CI: 4.5--6.0), UC 3.4 (95% CI: 2.8--4.0), and IBD-U 1.2 (95% CI: 0.9--1.6). IBD incidence was projected to reach 18.9 per 100,000/year in 2022. CONCLUSIONS: The overall incidence of pediatric IBD in the Czech Republic is increasing, and especially that of CD, whereas trends in UC and IBD-U appear to be constant. These data highlight the need to identify risk factors involved in the rising incidence of IBD.

Paediatric Home Parenteral Nutrition in the Czech Republic and Its Development: Multicentre Retrospective Study 1995-2011.

BACKGROUND: Treatment quality and outcomes of paediatric home parenteral nutrition (HPN) program during its development in the Czech Republic. METHODS: A retrospective study of patients receiving HPN from May 1995 till June 2011. RESULTS: Sixty-six patients were treated in 8 centres. In 48 patients, long-term PN began in the first year of life and in 35 of them in the first month. Sixty children had gastrointestinal and 6 had non-gastrointestinal disease. In a majority of the patients, the Broviac catheter was used. Thirty-two (48.5%) patients were weaned from PN after 1-117 months, 21 (32.8%) continued on HPN after 7-183 months, and 13 (19.7%) patients died, all on PN. The mortality in patients with primary gastrointestinal disease was significantly lower than in patients with non-gastrointestinal disease. Thirty-one paediatric patients were receiving HPN for 14,480 catheter days in 2009-2010. Fourteen patients had 23 Catheter Related Blood Stream Infections (CRBSI) episodes. The incidence of CRBSI in 2009-2010 was 1.58/1,000 catheter days. CONCLUSION: Submitted data showed that even in the absence of expert centres, patient care may achieve results comparable to countries with well-developed HPN program. A majority of Czech HPN patients are at present treated in specialized centres, following the most desirable pattern of care.

Association of IL23R p.381Gln and ATG16L1 p.197Ala with Crohn disease in the Czech population.

OBJECTIVES: An association of variants in the genes encoding the interleukin 23 receptor (IL23R, p.Arg381Gln, rs11209026), and the autophagy-related gene 16-like 1 (ATG16L1, p.Ala197Thr, rs2241880) with Crohn disease (CD) was identified by whole genome association studies, and subsequently confirmed by other works. The aim of this study was to assess this association in the Czech population. SUBJECTS AND METHODS: In a case-control study 333 patients with CD (137 paediatric and 196 adult-onset) and 499 unrelated healthy controls were genotyped using TaqMan SNP assays. RESULTS: The IL23R p.381Gln allele was protective against CD in the Czech population (allelic frequency 3.2% in patients vs 5.5% in control subjects; OR 0.56, 95% CI 0.33-0.93, P=0.02). ATG16L1 p.197Ala allele conferred increased risk of CD (allelic frequency 60% in patients vs 51% in controls; OR 1.25, 95% CI 1.02-1.52, P=0.03). There was no appreciable difference in the effect of the associated alleles across the strata of CARD15-conferred risk. The IL23R and ATG16L1 variants did not influence the age at diagnosis, and in the genotype-phenotype analysis, the only detected association was a weak one between IL23R p.381Gln and involvement of the upper gastrointestinal tract (uncorrected P=0.031). CONCLUSIONS: We confirmed the role of IL23R and ATG16L1 in the CD susceptibility in the Czech population, and found a weak protective effect of IL23R p.381Gln against upper gastrointestinal tract involvement.