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Editorial

Indian Pediatr 2009;46: 291-292

	Simplifying the WHO Guidelines for Managing Severe Malnutrition
Megan Hodder, Meri K Tulic and Susan L Prescott From the School of Pediatrics and Child Health Research, University of Western Australia, Perth, Western Australia, PO Box D184, Princess Margaret Hospital, Perth WA 6001, Australia. Email: [email protected]
As more effective interventions towards the prevention of allergic disease are developed, accurate ways of identifying children who will develop disease will become more crucial. At present, a positive "family history" (i.e any first degree relatives with allergic disease) remains the only commonly used predictor of allergic disease. This is crude at best with a variable specificity (48-67%) and sensitivity (22-72%) and a positive predictive value generally less than 40%(1-3). There have been a number of attempts to find early biological markers of disease predisposition, but none of these has any established predictive value for future allergic disease(4). The level of IgE in cord blood was one of the first measures to be investigated in this context in the 1980’s, however this has been disappointing. Although the specificity of the IgE tests ranges between 60-70% in several studies, the sensitivity (26-47%) and positive predictive value (22-42%) are generally very poor in predicting allergic disease(1-3,5,6). Ongoing research into the early immune function of newborns with allergic predisposition have revealed a number of functional differences compared with low risk infants, particularly in cytokine responses such as interferon gamma (IFNg). Despite the consistent relationships between lower neonatal IFNg responses and allergy risk(7-12), methods to assess this are not standardized and high variability in this and other functional responses have limited their value as predictive markers. The paper presented by Shah and Bapat(13) in this edition of Indian Pediatrics shows a novel "algorithmic" approach using multiple measures to more accurately predict allergic disease with the use of cord serum. This study assessed the development of allergic symptoms at the age of 1 year in relation to a combination of potential neonatal markers measured in cord blood, including IgE and IFNg together with levels of ubiquitous perennial house dust mite (HDM) allergens (Der p1 and Blo t5), also measured in cord blood. The infants who were diagnosed with allergic diseases by 1 year of age had higher IgE, Der p1, Blo t5, and lower IFNg levels in cord serum than those infants who had not been diagnosed with allergy by 1 year of age. The authors have shown that individually these parameters cannot accurately predict whether a child is at risk for allergy. However, when two out of three of the tests were used in combination, the specificity and sensitivity increased to over 90%. Of these measures the levels of HDM allergens was of the least value, but it is curious that the sensitivity and specificity of this marker was better than any previously reported predictor including family history(1-4). It is important to note that at this stage the role and significance of in utero exposure to allergens in the development of allergic disease (or tolerance) remains controversial(14). In summary, the results of this study illustrate that there is a potential role for exploring predictive algorithms that use multiple measure, rather than relying on inaccurate individual predictors of allergic disease. The significance of this particular model is as yet unclear as this is based on a small population of only 100 infants and allergic outcomes have only been determined at 1 year of age when the allergic phenotype may still be unclear. Thus, it would be ideal to assess the effectiveness of this algorithmic model in a larger and more diverse cohort with a longer follow up period to ascertain whether this method is useful in predicting allergic disease beyond the first year of life. Funding: None. Competing interests: None stated. References 1. Hide DW, Arshad SH, Twiselton R, Stevens M. Cord serum IgE: an insensitive method for prediction of atopy. Clin Exp Allergy 1991; 21:739-743. 2. Bergmann, RL, Edenharter G, Bergmann KE, Guggenmoos-Holzmann I, Forster J, Bauer CP, et al. Predictability of early atopy by cord blood-IgE and parental history. Clin Exp Allergy 1997; 27: 752-760. 3. Hansen LG, Halken S, Host A, Møller K, Østerballe O. Prediction of allergy from family history and cord blood IgE levels. Pediatr Allergy Immunol 1993; 4: 34-40. 4. Allam JP, Zivanovic O, Berg C, Gembruch U, Bieber T, Novak N. In search for predictive factors for atopy in human cord blood. Allergy 2005; 60: 743-750. 5. Croner S, Kjellman NI. Predictors of atopic disease: cord blood IgE and month of birth. Allergy 1986; 41: 68-70. 6. Edenharter G, Bergmann RL, Bergmann KE, Wahn V, Forster J, Zepp F, et al. Cord blood-IgE as risk factor and predictor for atopic diseases. Clin Exp Allergy 1998; 28: 671-678. 7. Tang MLK, Kemp AS, Thorburn J, Hill D. Reduced interferon gamma secretion in neonates and subsequent atopy. Lancet 1994; 344: 983-985. 8. Warner JA, Miles EA, Jones AC, Quint DJ, Colwell BM, Warner JO. Is deficiency of interferon gamma production by allergen triggered cord blood cells a predictor of atopic eczema? Clin Exp Allergy 1994; 24: 423-430. 9. Martinez F, Stern D, Wright A, Holberg C, Taussig L, Halonen M. Association of interleukin-2 and interferon-g production by blood mononuclear cells in infancy with parental allergy skin tests and with subsequent development of atopy. J Allergy Clin Immunol 1995; 96: 652-660. 10. Kondo N, Kobayashi Y, Shinoda S, Takenaka R, Teramoto T, Kaneko H, et al. Reduced interferon gamma production by antigen-stimulated cord blood mononuclear cells is a risk factor of allergic disorders -6 year follow- up study. Clin Exp Allergy 1998; 28: 1340-1344. 11. Prescott S, Macaubas C, Smallacombe T, Holt B, Sly P, Loh R, et al. Development of allergen-specific T-cell memory in atopic and normal children. Lancet 1999; 353: 196-200. 12. Prescott SL, Macaubas C, Smallacombe T, Holt BJ, Sly PD, Loh R, et al. Reciprocal age-related patterns of allergen-specific T-cell immunity in normal vs. atopic infants. Clin Exp Allergy 1998; 28 Suppl 5: 39-44. 13. Shah S, Bapat M. Cord serum screening test and the newborns allergic status. Indian Pediatr 2009; 46: 295-299. 14. Prescott SL. Maternal allergen exposure as a risk factor for childhood asthma. Current Asthma Allergy Reports 2006; 6: 75-80.