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)

Abstract

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.

Keywords: allergy; community child health; paediatric dermatology; paediatric gastroenterology.

Figure 1

The change in Cow’s Milk-related Symptom Score (CoMiSS) from baseline to the end of the elimination diet trial (visit 2) is shown for the 217 infants with confirmed cow’s milk protein allergy (CMPA) and 33 infants without CMPA (median, IQR). The change in median CoMiSS is depicted for the total composite score, as well as for each of its five clinical domains (crying, regurgitation, stool, skin and respiratory scores).

Figure 2

The flow diagram summarises the disposition of subjects according to the Standards for Reporting of Diagnostic Accuracy Studies 2015 guidelines for reporting diagnostic accuracy studies. The index test (baseline Cow’s Milk-related Symptom Score (CoMiSS)) was validated against the oral food challenge as the reference standard for diagnosing cow’s milk protein allergy (CMPA).

Figure 3

The receiver operating characteristic) curve is based on the logistic regression model of the Cow’s Milk-related Symptom Score (CoMiSS) and plots the sensitivity against (1-specificity) of CoMiSS for predicting cow’s milk protein allergy status. The area under the curve (AUC) of 0.67 remained below the predefined primary study endpoint of ≥0.75.