International Cross-Sectional Survey among Healthcare Professionals on the Management of Cow's Milk Protein Allergy and Lactose Intolerance in Infants and Children.

Purpose: The present international survey among healthcare providers aimed to collect data on theoretical knowledge and clinical practices in the diagnosis and management of cow's milk protein allergy (CMPA) and lactose intolerance (LI) in infants. Methods: A global survey was conducted in several countries with diverse health care settings. The survey consisted of multiple-choice questions in 3 main domains: (1) understanding and clinical practices around CMPA and LI; (2) case scenarios; and (3) disease-specific knowledge and potential educational needs. Results: Responses were available from 1,663 participants. About 62% of respondents were general practitioners or general pediatricians, and the remainder were pediatric allergists/gastroenterologists (18%) or other health practitioners (20%). The survey identified knowledge gaps regarding the types of CMPA (IgE-mediated vs. non-IgE-mediated) and the clinical overlap with LI. The survey suggested diverse clinical practices regarding the use of hypoallergenic formulas, as well as misconceptions about the prebiotic benefits of lactose in extensively hydrolyzed formulas in non-breastfed infants with CMPA. Responses to the two case scenarios highlighted varying levels of awareness of the relevant clinical practice guidelines. While respondents generally felt confident in managing infants with CMPA and LI, about 80% expressed an interest for further training in this area. Conclusion: The current survey identified some knowledge gaps and regional differences in the management of infants with CMPA or LI. Local educational activities among general and pediatric healthcare providers may increase the awareness of clinical practice guidelines for the diagnosis and treatment of both conditions and help improve clinical outcomes.

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.

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.

Growth in Infants with Cow's Milk Protein Allergy Fed an Amino Acid-Based Formula.

PURPOSE: The present study assessed the role of an amino acid-based formula (AAF) in the growth of infants with cow's milk protein allergy (CMPA). METHODS: Non-breastfed, term infants aged 0-6 months with symptoms suggestive of CMPA were recruited from 10 pediatric centers in China. After enrollment, infants were started on AAF for two weeks, followed by an open food challenge (OFC) with cow's milk-based formula (CMF). Infants with confirmed CMPA remained on AAF until 9 months of age, in conjunction with a cow's milk protein-free complementary diet. Body weight, length, and head circumference were measured at enrollment and 9 months of age. Measurements were converted to weight-for-age, length-for-age, and head circumference-for-age Z scores (WAZ, LAZ, HCAZ), based on the World Health Organization growth reference. RESULTS: Of 254 infants (median age 16.1 weeks, 50.9% male), 218 (85.8%) were diagnosed with non-IgE-mediated CMPA, 33 (13.0%) tolerated CMF, and 3 (1.2%) did not complete the OFC. The mean WAZ decreased from 0.119 to -0.029 between birth and enrollment (p=0.067), with significant catch-up growth to 0.178 at 9 months of age (p=0.012) while being fed the AAF. There were no significant changes in LAZ (0.400 vs. 0.552; p=0.214) or HCAZ (-0.356 vs. -0.284; p=0.705) from the time of enrollment to age 9 months, suggesting normal linear and head growth velocity. CONCLUSION: The amino acid-based study formula, in conjunction with a cow's milk protein-free complementary diet, supported normal growth till 9 months of age in a cohort of Chinese infants with challenge-confirmed non-IgE-mediated CMPA.

Pooled Analysis of the Cow's Milk-related-Symptom-Score (CoMiSS™) as a Predictor for Cow's Milk Related Symptoms.

PURPOSE: The diagnosis of cow's milk (CM) allergy is a challenge. The Cow's Milk-related-Symptom-Score (CoMiSS™) was developed to offer primary health care providers a reliable diagnostic tool for CM related symptoms. The predictive prospective value of the CoMiSS™ was evaluated in three clinical trials. METHODS: Pooled analyses of the three studies were conducted based on regressing the results of the month-1 challenge test on the month-1 CoMiSS™, adjusting for baseline CoMiSS™ using a logistic regression model. In addition a logistic regression model was also fitted to the month-1 challenge test result with the change in CoMiSS™ from baseline as a predictor. RESULTS: Results suggest that infants having a low CoMiSS™ (median, 5) after 1 month dietary treatment free from intact CM protein have a significant risk of having a positive challenge test (odds ratio, 0.83; 95% confidence interval, 0.75-0.93; p=0.002). Pooled data suggest that the change in CoMiSS™ from baseline to month-1 can predict CM related symptoms as a confirmed diagnosis according to the challenge test at month-1. However, in order to validate such a tool, infants without CM related symptoms would also need to be enrolled in a validation trial. A concern is that it may not be ethical to expose healthy infants to a therapeutic formula and a challenge test. CONCLUSION: Pooled data analysis emphasizes that the CoMiSS™ has the potential to be of interest in infants suspected to have CM-related-symptoms. A prospective validation trial is needed.

Fatty fish in the diet of patients with type 2 diabetes: comparison of the metabolic effects of foods rich in n-3 and n-6 fatty acids.

BACKGROUND: Dietary advice, including modification of dietary fat quality, is the basis of treatment of diabetes, but there is some uncertainty about the optimal amount of polyunsaturated fatty acids of the n-6 (omega-6) and n-3 (omega-3) series. OBJECTIVE: The objective was to compare the effects of diets rich in n-3 or n-6 fatty acids on glucose and lipoprotein metabolism in type 2 diabetes. DESIGN: In a crossover study during 2 consecutive 3.5-wk periods, the participants were provided diets with identical nutrient compositions containing either a high proportion of n-3 (n-3 diet) or n-6 (n-6 diet) fatty acids through the inclusion of fatty fish or lean fish and fat containing linoleic acid, respectively. RESULTS: Blood glucose concentrations at fasting and during the day were lower with the n-6 than with the n-3 diet (P = 0.009 and P = 0.029, respectively), and the area under the insulin curve during the day was significantly higher (P = 0.03) with the n-6 diet. Both diets showed similar effects on insulin sensitivity and plasminogen activator inhibitor 1 concentrations. The reductions in VLDLs and serum apolipoprotein B concentrations were more pronounced after the n-3 diet. CONCLUSIONS: The risk related to the moderately higher blood glucose concentrations with the n-3-enriched diet may be counteracted by positive effects with regard to lipoprotein concentrations. An increase in long-chain n-3 fatty acids from fatty fish, and of n-6 fatty acids from linoleic acid, may be recommended for patients with type 2 diabetes.