The Cow's Milk-Related Symptom Score (CoMiSSTM) in Presumed Healthy Egyptian Infants.

BACKGROUND: The Cow's Milk-Related Symptom Score (CoMiSS) was created as an awareness tool for cow's milk-related symptoms. After different trials, a score of ≥10 was selected to raise awareness. The CoMiSS in healthy infants needs to be determined because the score does not return to 0 during a diagnostic elimination diet. This study aims to establish normal values in healthy Egyptian infants. METHODS: In this prospective cross-sectional study, pediatricians determined the CoMiSS in healthy infants ≤ 12 months. Infants seeking medical help due to cow's milk allergy (CMA) symptoms and infants with any known or suspected diseases, preterm delivery, medication, or food supplements were excluded. RESULTS: A total of 808 infants were included with a median (Q1; Q3) age of 7 (3;10) months (50.7% boys). The median (Q1; Q3) CoMiSS was 5 (5;6). The 95th percentile was 7. There was no significant difference in the median CoMiSS according to gender (p = 0.621) or due to breastfeeding exclusively (p = 0.603). A significant difference was seen in the CoMiSS according to age, although all the age categories had a median CoMiSS of 5. CONCLUSIONS: This study revealed the median CoMiSS is 5 in presumed healthy Egyptian infants aged 0-12 months. The CoMiSS was not dependent on feeding. The determination of the CoMiSS in healthy infants allows for the determination of a cut-off under which CMA is unlikely, and a cut-off to raise awareness of CMA, thereby preventing under- and overdiagnosis. Since the median CoMiSS was not different in European infants, the outcome suggests that the CoMiSS may be a reliable awareness tool for CMA independent of ethnicity. However, additional studies are needed to confirm the previous hypothesis.

The evolution of Cow's Milk-related Symptom Score (CoMiSS™) in presumed healthy infants.

The Cow's Milk-related Symptom Score (CoMiSS™) is a scoring system that reflects the appearance and intensity of symptoms possibly related to consumption of cow's milk. The original tool was recently updated by changing the cut-off, and the stool scale and by adding angioedema. There is no data available regarding the natural evolution of CoMiSS in infants with no cow's milk allergy (no-CMA) or a comparison between original and updated CoMiSS values. We determined the original and the updated CoMiSS in infants not diagnosed with cow's milk allergy. The evolution of CoMiSS during the first year of life was assessed repetitively during predefined check-ups at 1.5, 3, 4, 6, 8, 10, and 12 months. The original and updated scores were compared with the Wilcoxon Signed-Rank Test. We also tested the impact of feeding type, age, gender, and order in the family on the CoMiSS. One hundred and twenty-two infants were included. CoMiSS values during the first year of life showed an inverse relation to age. The difference in CoMiSS between the original and updated versions was significant at 6,8,10, and 12 months (p < 0.001), related to the switch from the Bristol Stool Form Scale to the Brussels Infants and Toddlers Stool Scale (BITSS). The difference between both versions of CoMiSS was not significantly different in infants < 6 months (p = 0.999 at 1.5 and 4 months, and p = 0.586 at 3 months, respectively).Conclusion: CoMiSS decreases with age during the first year of life. While there is no difference between the two CoMiSS versions in healthy infants under 6 months of age, the CoMiSS value in the updated version is lower than the original 1 in infants aged 6 to 12 months. What is known? • The Cow's Milk-related Symptom Score (CoMiSS) is a validated awareness tool for cow's milk allergy (CMA). • A CoMiSS of ≥ 10 indicates a risk for cow's milk allergy. What is new? • The natural evolution of CoMiSS in infants not diagnosed with CMA (no-CMA) shows an inverse relation to age. • There is no difference between the original and the updated CoMiSS versions in no-CMA-infants under six months of age, but the updated CoMiSS is lower in infants 6-12 months than the original one.

A nomogram for predicting food allergy in infants with feeding problems and malnutrition.

BACKGROUND AND OBJECTIVE: As oral food challenge (OFC) cannot be performed routinely in the general outpatient, this study aimed to construct a nomogram to predict the odds of food allergy in infants with idiopathic feeding problems and malnutrition. METHODS: From August 2018 to December 2021, 289 infants (median age, 6 months; P25-P75, 4-8) with idiopathic feeding problems and malnutrition were enrolled from seven hospitals in Shanghai, China. Food allergy was defined as a positive response to a skin prick test or OFC, with gastrointestinal, dermatologic, or respiratory symptom improvement after 4 weeks of avoidance of the suspected food. Demographic characteristics, Cow's Milk-related Symptom Scores (CoMiSS), and blood eosinophil amounts were evaluated for their associations with food allergy. Multivariable logistic regression analysis was used to identify variables to develop a nomogram model with the bootstrapped-concordance index as an assessment metric. RESULTS: Totally 249 of 289 infants had food allergy (86.2%). After logistic regression analysis, the feeding pattern (odds ratio [OR] = 5.28, 95% confidence interval [CI]: 2.13-13.09), a family history of allergy (OR = 1.79, 95% CI: 0.71-4.51), CoMiSS (OR = 1.45, 95% CI: 1.19-1.77), and eosinophil percentage (OR = 1.33, 95% CI: 1.11-1.60) were used to develop the model, which had a good performance with an area under the curve of 0.868 (95% CI: 0.792-0.944) and a bootstrapped-concordance index of 0.868. CONCLUSION: Food allergy is common in infants with idiopathic feeding problems and malnutrition. The developed nomogram may help identify infants with food allergy for further diagnosis.

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.

Cultural adaptation and validation of the Spanish version of the Cow's Milk-related Symptom Score (CoMiSS) for cow's milk protein allergy.

INTRODUCTION AND AIMS: The prevalence of cow's milk protein allergy in the first year of life varies from 1.8 to 7.5%. The Cow's Milk-related Symptom Score (CoMiSS) was published in 2014 and facilitates the diagnosis of cow's milk protein allergy. It is not meant to replace the clinical diagnosis, but rather to guide the treating team in the diagnostic process and reduce unnecessary diets. The aim was to translate the CoMiSS from English to Spanish and culturally adapt and validate the resulting Spanish version. MATERIALS AND METHODS: An adaptation and validation study on the CoMiSS questionnaire was carried out in two phases: First, the CoMiSS was translated from English to Spanish, after which interrater reliability of the translated score was assessed. Second, interrater reliability tests were carried out on 32 pediatric patients under 7 years of age that were treated for the first time at the Food Allergy Clinic of the Hospital Italiano de Buenos Aires, were suspected of having cow's milk protein allergy, and had not received any treatment, within the time frame of May 2018 and May 2019. RESULTS: Thirty-two patients were evaluated, 14 of whom were females (45%), and the median patient age was 3 months (IQR 2-4). The median result of the first measurement of the scale was 7.0 (IQR 4.5-9.0) and the median of the second measurement was 5.0 (IQR 4.0-8.0). The final intraclass correlation coefficient was 0.80 (95% CI 0.63-0.9). CONCLUSION: The Spanish translation of the CoMiSS was comparable to the original English version, with excellent interrater reliability. This simple and little-known tool has the benefit of being a noninvasive, rapid, reliable, and easy-to-use strategy.

Non-invasive diagnostic test for cow's milk allergy: A cross-sectional, descriptive study.

BACKGROUND: Cow's milk allergy is a common type of allergy in infants that is caused by the immune response to proteins in cow's milk. Digestive manifestations, atopic dermatitis, and respiratory discomfort are some of the clinical manifestations that appear; however, none of them are objective criteria to confirm the diagnosis, which may result in misdiagnosis, treatment hindrance, and parental concerns. Therefore, new methodologies for an accurate and immediate diagnosis is essential. METHODS: In this descriptive study, infants referred to the pediatric health center in Sulaymaniah were selected during a period of 1 year. The data were collected using a demographic questionnaire and the Cow's Milk Related Symptom Score (CoMiSS). Chi-squared and independent t tests were used to analyze the data. RESULTS: The findings of the present study indicated that among 250 infants (117 boys, 133 girls), with a mean ±  SD age of 2.9 ± 1.6 years, 21% were breastfed, 39% were fed both cow's milk and breast milk, and 60% were fed only cow's milk. The contingency of cow's milk allergy was positive in 35% of infants. According to this questionnaire, 18% of the participants got a score of 0-5, 47% scored 6-11, and 35% scored ≥ 12. A significant relationship was found between cow's milk allergy and the participants' diet (p < 0.001). A significant association was also found between age-dependent growth index (weight p = 0.04, height p = 0.01, and head circumstance p = 0.02) and cow's milk allergy. CONCLUSION: Although common problems in infancy such as colic and reflux may interfere with an accurate diagnosis of cow's milk allergy, give false-positive results, and decrease the reliability of CoMiSS; there is a need for non-invasive and easy methods for early diagnosis and improving awareness to encourage parents to take preventive measures.

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.

Validation of a modified cow's milk-related symptom score (CoMISS) for screening of lactose intolerance in adults.

INTRODUCTION: Lactose intolerance (LI) is the failure to digest foods and beverages containing the lactose present in milk. LI can present by many digestive symptoms. OBJECTIVE: To validate the modified CoMiSS score for prediction of LI, that was confirmed by a stool acidity test. PATIENTS AND METHODS: A cross-sectional study, was conducted at Ain Shams University Hospitals/Gastrointestinal Clinics, and included one hundred adult participants during the period from December 2018 to December 2019. Enrolled patients had one or more gastrointestinal symptoms and were subjected to a stool acidity test (fecal PH test) as a reference test and modified CoMiSS as an index test. RESULTS: The mean age of participants was 35.30 ± 10.714 years old; 55% were females, and their mean body mass index (BMI) was 23.08 ± 2.080 kg/m2, with no significant relation between LI and patients` gender or BMI. Out of the studied participants 24% had positive stool PH, LI diagnosed according to modified CoMISS was present among 19% of them. The mean value of modified CoMISS Score was significantly higher in positive cases (12.37) compared to negative LI participants (2.33) as p < .001. Area under ROC Curve was 0.998, at the selected cut-off value 8, the sensitivity was 89.5% and specificity was 100% thus, levels of questionnaire scoring of 8 or higher would indicate presence of lactose intolerance. CONCLUSION: Modified CoMiSS is a simple, fast, and easy-to-use tool that can predict LI, with a cut-off value of >8, the Area under the ROC Curve was 0.998, sensitivity 89.5%, and specificity was 100%.

Managing Cow's Milk Protein Allergy with an Extensively Hydrolyzed Formula: Results from a Prospective, Non-Interventional Study in France (EVA Study).

Symptoms related cow's milk proteins allergy (CMPA) usually improve between two to four weeks following an elimination diet, firstly with extensively hydrolyzed formulas (eHF). The aim of the EVA study was to observe the evolution of CMPA-related symptoms in real life after initiation of a whey-based extensively hydrolyzed formula (w-eHF, Althéra®, Nestlé Health Science, Switzerland). This cross-sectional prospective non-interventional study was carried out alongside paediatricians in private practice in France between June 2019 and June 2020. Infants aged 0−3 years presenting with confirmed diagnosis or clinical symptoms suggesting CMPA were enrolled. Data were collected at enrolment (baseline visit) and three to five weeks later (follow-up visit). Symptoms were assessed using the Cow's Milk-related Symptom Score (CoMiSS®). The per protocol population included 135 infants. The average number of symptoms per infant significantly decreased under the study formula (from 2.81 to 1.36, p < 0.001) and the proportions of infants with any CMPA related symptoms decreased. Daily crying and regurgitation showed the largest decline, respectively −44.4% and −31.85% (p < 0.001). These results describe the early management of symptoms suspected to be related to CMPA in routine practice that was rarely described in the literature. The number and severity of symptoms decreased most of the cases after commencing the study formula.

An Observational Real-Life Study with a New Infant Formula in Infants with Functional Gastro-Intestinal Disorders.

Functional gastro-intestinal disorders (FGIDs) impair the quality of life of many infants and their families. A formula with partial whey hydrolysate, starch, high magnesium content, prebiotic fructo-oligosaccharide and galacto-oligosaccharide and the probiotic Lactobacillus reuteri DSM 17938 was given during two weeks to 196 infants with at least two FGIDs. The efficacy was evaluated with the Cow Milk-associated Symptom Score (CoMiSS®) and quality of life with the QUALIN score. The formula was shown to decrease FGIDs within three days (decrease of CoMiSS -1.29 (3.15) (mean (SD), p < 0.0001) followed by an improvement of quality of life after seven days (increase QUALIN +1.4 (7.8); p: 0.008). Constipation decreased from 18.8% to 6.5% within three days. In combination with reassurance and guidance, the nutritional intervention was shown to be effective in infants with FGIDS in real-life circumstances.

How Are Infants Suspected to Have Cow's Milk Allergy Managed? A Real World Study Report.

The purpose of this study was to evaluate the diagnosis and management of infants presenting with symptoms attributable to cow's milk allergy (CMA) in a real life setting and to test how the Cow's Milk-related Symptom Score (CoMiSS®) can be used to support the awareness to diagnose cow's milk protein allergy in primary care practice. The CoMiSS is an awareness tool based on various symptoms such as crying, gastrointestinal symptoms, dermatological and respiratory symptoms. The study was conducted on 268 infants from four countries (Belgium, Czech Republic, Germany, UK) aged 0 to 18 months consulting for CMA related symptoms. The analysis was based on two visits of these subjects. The results show an average CoMiSS of 11 at the first visit. After a therapeutic dietary intervention, the score at the second visit, which happened 3 weeks ± 5 days after the first one, dropped to an average value of 4. A satisfaction questionnaire completed by the primary care practitioners suggested an overall high level of satisfaction with the application of the CoMiSS tool in routine practice. These data highlight a huge discrepancy in the diagnosis and management of infants suspected of CMA in the different countries. The findings suggest that the CoMISS questionnaire is an effective tool in aiding awareness of CMPA in primary health care.

Assessment of cows milk-related symptom scoring awareness tool in young Turkish children.

BACKGROUND: The diagnosis of cows milk protein allergy (CMPA) is not always easy. Cow's Milk-related Symptom Score (CoMiSS) has been developed to raise the awareness of CMPA among the primary health-care providers. In this study, we aimed to evaluate the validity of CoMiSS as a diagnostic approach of CMPA in infants in our country. METHODS: Infants with a CoMiSS of more than 12 points were included. An elimination diet was implemented in these infants for 4 weeks, and CoMiSS was reapplied. Infants with a reduction of ≥3 points in CoMiSS were considered responsive to the elimination diet, and an open oral challenge test was performed. Infants with symptom recurrence were diagnosed with CMPA. RESULTS: The study included 168 infants. When they were included in the study, the first CoMiSS score was 13.6 ± 1.9. After the elimination diet, the number of responsive infants was 154 (91.7%). Of the infants, 91 (54.2%) were diagnosed with CMPA with positive challenge. The majority of the patients diagnosed with CMPA presented with gastrointestinal and/or dermatological symptoms (80.3%). Positive family history of allergy was more prevalent in CMPA(+) infants (P < 0.001). The mean atopic dermatitis score was higher in CMPA(+) infants (P = 0.001). Eosinophilia and cows milk-specific IgE (CM-sIgE) positivity were more prevalent in infants with CMPA (P = 0.01 and P < 0.001, respectively). CONCLUSIONS: CoMiSS is a valuable tool to evaluate CMPA in primary care. The presence of multiple symptoms, especially skin involvement, helps to recognise infants with CMPA. Family history and eosinophilia also support the diagnosis of CMPA.

The Cow's Milk-Related Symptom Score (CoMiSSTM): Health Care Professional and Parent and Day-to-Day Variability.

The Cow's Milk-related Symptom Score (CoMiSSTM) was created as an awareness tool for cow's milk allergy. The aim of the present study was to analyze the inter-rater variability between a pediatrician, parents, and day to day variability. A Health Care Professional (HCP) and parent filled in the CoMiSS independently and blinded for each other to evaluate inter-rater variability. In order to validate day-to-day variability, a parent filled in the CoMiSS during 3 consecutive days and was compared to the CoMiSS scored by the HCP. The absolute agreement between parent and HCP was 75%, and 92.6% and 100% with a tolerance of 0, 1, and 2 points, respectively, resulting in excellent agreement with an intraclass correlation coefficient (ICC) 0.981 (95% Confidence Interval 0.974-0.986, p < 0.001). Day-to-day variability during 3 consecutive days resulted in an absolute agreement of 30%, increasing to 80% and 88.6% when 2 and 3 points, respectively, were accepted. The ICC was excellent for the parental prospective scores (0.93, 95% CI 0.90-0.96; p < 0.001). Day-to-day variability indicates that CoMiSS has a moderate inter-rater reliability. A very low variability was observed when scored prospectively over three days. Data suggest that the CoMiSS can reliably be scored by parents without additional training.

Assessment of Cow's milk-related symptom scores in early identification of cow's milk protein allergy in Chinese infants.

BACKGROUND: The diagnosis of cow's milk protein allergy(CMPA) may be easily misdiagnosed due to its lack of specific symptoms. Thus, experts have proposed the use of Cow's milk-related symptom scores (CoMiSS) to predict CMPA. There has been no relevant report on the clinical application value of CoMiSS in Chinese children. This study aimed to evaluate the effect of CoMiSS in early identification of CMPA in Chinese infants. METHODS: We calculated CoMiSS for 38 infants with suspected CMPA diagnosed in the pediatric gastroenterologic clinic in our hospital. After 4 weeks of dietary elimination and symptomatic improvement, these infants returned to our hospital to undergo oral food challenge (OFC). The ROC curve was used to determine the sensitivity and specificity of CoMiSS and evaluate the effect of CoMiSS in early identification of CMPA in Chinese infants. We didn't determine the CoMiSS of presumed healthy infants as control group. RESULTS: Of 38 infants who underwent OFC testing, the average CoMiSS of infants with positive OFC testing was 7.4 ± 2.3, while the average CoMiSS of infants with negative OFC testing was 4.1 ± 1.6, and there was a significant difference between two groups(F = 2.13, P<0.05). The area under the ROC curve (AUC) of CoMiSS was 0.89, and the best diagnostic cut-off point was 5.5. The sensitivity of CoMiSS was 87.5%, while the specificity of CoMiSS was 78.6%. CONCLUSION: CoMiSS is a simple and operable method to screen for CMPA, though there may be a risk of under-diagnosis when CoMiSS≥12 is used as the criterion for early identification of CMPA in Chinese infants. More multi-center studies are needed to evaluate whether the factors such as bloody stool should be included in CoMiSS or CoMiSS≥6 can be used as the criterion for early identification of CMPA in Chinese infants.

Tolerance and growth in children with cow's milk allergy fed a thickened extensively hydrolyzed casein-based formula.

BACKGROUND: In case of cow's milk allergy (CMA), pediatric guidelines recommend for children the use of extensively hydrolyzed formulas (eHFs) as elimination diet. According to the American Academy of Pediatrics, the hypoallergenicity of each specific eHF should be tested in subjects with CMA. METHODS: A prospective, multicenter trial was performed to assess the tolerance/hypoallergenicity of a thickened casein-based eHF (eHCF, Allernova AR®, United Pharmaceuticals, France) in infants aged <12 months with CMA proven by a double-blind placebo-controlled food challenge. Its efficacy, measured through allergy symptoms monitoring and Cow's Milk-related Symptom Score (CoMiSS) calculation, and safety were evaluated during a 4-month feeding period. Growth z-scores were computed based on WHO anthropometric data. RESULTS: Thirty infants (mean age: 4.8 ± 3.0 months) with CMA proven by a DBPCFC tolerated the eHCF during the 4-month study. The CoMiSS, crying and regurgitation scores significantly decreased by 4.2 ± 4.0, 0.9 ±1.2 and 0.7 ± 1.1 respectively, after 14 days of feeding (p < 0.001). The Scoring Atopic Dermatitis index, of 33.2 ± 14.8 at inclusion in 9 patients, significantly decreased by 15.5 ± 6.7 and 21.1 ± 11.2, after 14 and 45 days of feeding, respectively (p < 0.001). The percentage of infants having normal stool consistency (soft or formed stools) significantly improved from 66.7 % (20/30) at inclusion to 90.0 % (27/30) after 14 days of feeding (p = 0.020). The growth z-scores, negative at study inclusion, significantly improved over the 4-month study. No adverse event was related to the eHCF. CONCLUSION: The thickened eHCF was tolerated by more than 90 % of included allergic infants with 95 % confidence interval and can therefore be considered as hypoallergenic in accordance with current guidelines. The improvement of growth indices and absence of related adverse events confirmed its safety. Results of this trial back the use of the tested thickened eHCF as an efficient and safe alternative in children with CMA. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02351531 , registered on 27 January 2015.