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)

Yvan Vandenplas, Zheng Yan Zhao, Rajat Mukherjee, Christophe Dupont, Philippe Eigenmann, Mikael Kuitunen, Carmen Ribes Koninckx, Hania Szajewska, Andrea Von Berg, KateÅ™ Ina Bajerová, Rosan Meyer, Silvia Salvatore, Raanan Shamir, Anette Järvi, Ralf G. Heine

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article numbere056641
JournalBMJ Open
Issue number2
StatePublished - 17 Feb 2022


  • allergy
  • community child health
  • paediatric dermatology
  • paediatric gastroenterology


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