Protocol for the validation of sensitivity and specificity of the Cow's Milk-related Symptom Score (CoMiSS) against open food challenge in a single-blinded, prospective, multicentre trial in infants

Abstract

Introduction: The symptoms of cow's milk protein allergy (CMPA) in infancy can be non-specific which may delay a correct diagnosis and cause adverse clinical outcomes. The diagnosis of non-IgE-mediated CMPA is particularly complex as it involves a 2 to 4 week elimination diet followed by oral food challenge (OFC). The Cow's Milk-related Symptom Score (CoMiSS) is a clinical resource for primary healthcare providers which aims to increase awareness of CMPA symptoms to facilitate an earlier diagnosis. The aim of the present study is to assess if the CoMiSS can be used as a potential diagnostic tool in infants with suspected CMPA.

Methods and analysis: Exclusively formula-fed infants aged 0-6 months presenting with symptoms suggestive of CMPA will be included in this prospective, multicentre trial which will be conducted in 10 centres in China. All infants will commence a 2-week trial of an amino acid-based formula (AAF) while eliminating all cow milk protein from their diets. After the AAF treatment period, infants will undergo an open OFC in hospital with standard cow's milk formula, followed by an open home challenge for another 2 weeks. Clinical symptoms will be documented on standardised symptom scorecards. The CoMiSS will be determined at study entry (CoMiSS 1, before the start of the AAF), after 2 weeks (CoMiSS 2, before the OFC) and after a further period of 2 weeks or when symptoms suggestive of CMPA reappear (CoMiSS 3). Weight and length will be measured at each visit. The difference between CoMiSS 1 and 2 as a predictor of the OFC outcome will also be assessed. The diagnostic accuracy of the baseline CoMiSS will be calculated.

Ethics and dissemination: The study was approved by the Hunan Children's Hospital Medical Ethics Committee, Hunan, China. The findings of this trial will be submitted for publication in a peer-reviewed journal in paediatric nutrition or gastroenterology. Abstracts will be submitted to the relevant national and international conferences.

Trial registration number: NCT03004729; Pre-results.

Keywords: cow’s milk protein allergy; diagnosis; infant; study design; symptom score; validation.

Conflict of interest statement

Competing interests: PE has received lecture honoraria from Danone and Sodilac and research grants from Nestlé. AH has received honoraria for lectures for Danone and Nestlé. CR-K has participated as consultant and/or speaker for Mead Johnson International, Hero Institute, Alter-Nutriben, Danone and Nestlé. NS is a member of the medical advisory board for Mead Johnson in the UK. HS has participated as a clinical investigator and/or speaker for Arla, Biogaia, Biocodex, Danone, Dicofarm, HiPP, Nestlé, Nestlé Nutrition Institute, Nutricia, Mead Johnson, Merck and Sequoia. YV has participated as a clinical investigator, and/or advisory board member, and/or consultant and/or speaker for Abbott Nutrition, Biocodex, Danone, Mead Johnson, Merck, Menarini, Nestlé Health Science, Nestlé Nutrition Institute, Nutricia, Phacobel, Sari Husada, Sucampo, United Pharmaceuticals and Yakult. RGH is an employee of Nestlé Health Science.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

CoMiSS. All parameters included in the CoMiSS (evaluation of regurgitation: see ref ; evaluation of stool composition: see ref 12). CoMISS, Cow’s Milk-related Symptom Score.

Figure 2

Study design. CMPA, cow’s milk protein allergy; CoMISS, Cow’s Milk-related Symptom Score.