European Journal of Pediatrics

, Volume 172, Issue 3, pp 385–391 | Cite as

Towards better triage of infants suspected of cow's milk allergy: development of a preliminary multivariable diagnostic index

  • Anders van ThuijlEmail author
  • Anne-Fleur Schoemaker
  • Stef Menting
  • Jennifer van Dulmen
  • Janne Boeting
  • Wim van Aalderen
  • Gerben ter Riet
  • Aline Sprikkelman
Original Article


The double-blind placebo-controlled food challenge (DBPCFC) is currently the gold standard to diagnose cow's milk allergy (CMA). However, DBPCFCs are burdensome, expensive and require specialised facilities. For primary care physicians, selective and consistent referral to DBPCFC of infants suspected of CMA may be difficult. The objective of this study was to assess the predictive value of clinical parameters for a positive DBPCFC in infants suspected of CMA. Clinical data from 124 infants suspected of CMA that had undergone a DBPCFC were collected. Out of a total of 23 parameters, nine candidate predictors were selected on clinical grounds. We used bootstrapped logistic regression analysis to find a more parsimonious and practical model. The prevalence of a positive DBPCFC was 34.7 % (95 % CI from 27 to 43). A well-calibrated diagnostic model containing as predictors abdominal cramps, inconsolable crying and the objective SCORAD index discriminated moderately well between infants with and without a positive DBPCFC. The area under the ROC curve was 0.68 (95 % CI from 0.58 to 0.78). The fifth and 95th percentiles of the positive DBPCFC predictive probability distribution were 17 and 73 % (17 and 59 % after correction for over-optimism). We conclude that a diagnostic model with three clinical parameters may be used for better referral of children suspected of CMA and the decision to either initially perform an open food challenge or directly perform a DBPCFC. Large prospective studies are needed to validate these findings and provide additional precision.


Cow's milk allergy Infants Diagnosis Logistic regression Retrospective cohort study 



Bootstrap inclusion fraction


Cow's milk allergy


Cow's milk protein


Double-blind placebo-controlled food challenge


SCORing atopic dermatitis


Interquartile range


Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Anders van Thuijl
    • 1
    Email author
  • Anne-Fleur Schoemaker
    • 1
  • Stef Menting
    • 1
  • Jennifer van Dulmen
    • 1
  • Janne Boeting
    • 1
  • Wim van Aalderen
    • 1
  • Gerben ter Riet
    • 2
  • Aline Sprikkelman
    • 1
  1. 1.Department of Paediatric Respiratory Medicine and AllergyEmma Children’s HospitalAmsterdamThe Netherlands
  2. 2.Department of General Practice, Division of Clinical Methods and Public Health, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands

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