Race is a Modifier between Parental Allergy and Food Allergy in Offspring

Amy A. Eapen, MD, MS*¹, Erica Ridley MD*¹, Alexandra R. Sitarik MS², Christine Joseph PhD², Christian Nageotte, MD¹, Rana Misiak, MD¹, Dennis Ownby MD³, Christine Johnson PhD², Edward Zoratti MD¹, Haejin Kim MD¹.

¹Division of Allergy and Clinical Immunology, Henry Ford Health System, Detroit, Michigan

²Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan

³Department of Pediatrics, Augusta University, Augusta, Georgia.

*Dr. Eapen and Dr. Ridley are listed as co-first authors

Corresponding author: Amy A. Eapen, MD, One Ford Place, 4B Detroit, MI 48202; Telephone (313) 971-6182; Fax (313) 876-2094; E-mail: aeapen1@hfhs.org

Funding: Grants from the National Institute of Allergy and Infectious Diseases (R01 A1051598 and P01 A1089473) and the Fund for Henry Ford Hospital.

Financial disclosure : There are no financial disclosures of conflicts of interest.

Word count: 1191

Keywords : Food allergy, race, parental allergy, total IgE

Studies indicate associations between maternal allergy and development of food allergy in their offspring¹, with higher food allergy risk among those with more than one first degree relative with allergic disease². However, unnecessary food avoidance among children of allergic parents has important implications since diverse diets in children may decrease risk for food allergy, and early food introduction with foods such as peanut, can be protective for food allergy³. We sought to assess the association between parental allergic markers and offspring food sensitization and clinical allergy to milk, egg, or peanut.

We analyzed data from the racially and socioeconomically diverse population birth cohort, Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS) that enrolled pregnant women between 21 to 45 years of age and their offspring following recruitment between September 2003 to December 2007. Details regarding the cohort have been previously published^4,5. Institutional Review Board (IRB) approval was obtained for all aspects of the study.

Parental factors assessed included questionnaire responses regarding history of allergy or asthma; maternal total IgE and maternal serum allergen specific IgE (sIgE) levels during pregnancy or one month postpartum were also evaluated. Atopy was defined as at least one sIgE ≥ 0.35 IU/mL to eight allergens (dust mite, dog, cat, grass, ragweed,Alternaria , egg, cockroach). Maternal asthma, atopic dermatitis, and food allergy were determined by questionnaire. Due to a paucity of paternal data, only paternal asthma was assessed.

Offspring sensitization to milk, egg, or peanut was determined at 2 years of age by sIgE≥ 0.35 IU/mL and also skin prick testing (SPT; wheal size ≥3 mm larger than the saline control defined a positive test). As sensitization to foods does not translate to clinical allergy in all cases, we formed an algorithm to determine those most likely to have true IgE-mediated food allergy⁶. A consensus panel of allergists determined food allergy status in offspring based on review of the aforementioned data and abstracted chart informations as previously described⁷. Briefly, infant data were forwarded to the panel only if more than one of the following criteria were met for milk, egg, or peanut allergens: (1) 1 sIgE ≥0.35 IU/mL; (2) a positive SPT; or (3) parental report of infant symptoms potentially related to food allergy plus at least one specific IgE greater than 0.10 IU/mL. To enhance standardization in classifying infants to the presence of IgE- mediated food allergy (IgE-FA), physicians were asked to combine professional experience with investigator-developed protocols based on the Guidelines for the Diagnosis and Management of Food Allergy in the United States⁸. A third allergist independently reviewed and ruled on discordant decisions.

Logistic regression models of parental variables with each outcome were fit. Interaction terms were added to logistic regression models to assess differences in associations based on race, (p<0.10 was considered a significant interaction). Predicted probabilities were used to construct receiver operating characteristic (ROC) curves and calculate area-under-the-curve (AUC) values.

Of 1258 maternal-child pairs, 761 had sufficient data for analysis (Supplemental Figure el). Participant characteristics indicated that families not lost to follow up had higher household incomes, as well as higher maternal education, and a higher proportion of mothers who were married, kept pets, and breastfed the child. rates (Table e1).

Associations between parental variables and physician panel determination of food allergy are shown in Table 1. After adjusting for child race, seven out of eight parental characterics of the were significant or of borderline signficance. However, the maximum AUC for ROC curves for any individual variable was 0.54 (maternal total IgE), indicating poor prognostic value (Supplemental Table e2). Maternal atopy, multi-sensitization, and total IgE significantly interacted with race (p=0.012, 0.092, 0.068, respectively) indicating strong associations among African American (AA) children only (Table 1). For example, maternal atopy in non-AA children was not associated with food allergy, but was highly associated among AA children (OR [95% CI]=3.56 [1.55, 9.66], p=0.006).

Maternal current asthma was also associated with childhood food allergy (OR [95% CI]=2.27 [1.02, 4.71], p=0.034), and patterns varied by race with history of maternal asthma associated with food allergy only in non-AA children (OR [95% CI]= 4.92 [1.22, 17.14], p=0.015), and current asthma among AA children (OR [95% CI]=2.64 [1.10, 5.92], p=0.022; Table 1).

Combined, parental variables only modestly impacted food allergy ROC analyses resulting in an AUC of 0.66. However, the ROC curves differed by race (non-AA AUC 0.36 vs AA AUC 0.71, p=0.002) as shown in Figure 1.

Apart from food allergy, parental variables were analysed for associations with offspring sensitization (positive sIgE or SPT) to peanut, milk, or egg at age 2 years. Maternal atopy, multi-sensitization, and total IgE were associated with offspring positive food sIgE sensitization to at least one food. Analysis stratified by race indicated these associations were significant only among AA children. (Supplemental Table e3). Furthermore, maternal current asthma was associated with food sIgE sensitization only among non-AA children (OR [95% CI]=4.90 [1.69, 16.20], p=0.005). ROC curves were significantly different between AA and non-AA children (p=0.036) but predictive ability remained poor in both (AUC 0.55 and 0.44 respectively as in supplemental Figure e2).

Maternal multisensitization, total IgE and current asthma, and paternal asthma were statistically significantly associated with any positive food SPTs only among AA children. (Supplemental Table e4). Additionally, race modified the relationship between maternal atopy and SPTs (p=0.039); AA children of atopic mothers had elevated odds of food SPT positivity (OR [95% CI]=1.96 [1.15, 3.45], p=0.016). Despite ROC differences by race (p=0.015; Figure e3), parental variables again had minimal predictive ability.

The importance of genetic factors in food allergy is supported by twin studies showing higher concordance of peanut allergy among monozygotic compared with dizygotic twins (64.3% and 6.8%, respectively)⁹. In addition, heritability among parents and offspring for overall food sensitization have been reported¹. However, our report indicates parental variables related to allergy have poor predictive ability for offspring food sensitization. The results from the physician panel demonstrate a moderate degree of risk and capability of predicting food allergy in offspring from parents having clinical characteristics of allergy.

We previously reported similar food allergy prevalence for milk, egg, and peanut in AA and non-AA children⁷. We report here that the inherited risk as measures by parental allergic variables and predictive ability of parental allergic variables on food allergy development in offspring varies by race and is more strongly associated with clinical food allergy versus sensitization, among AA children. The potential mechanisms behind this racial discrepancy are require further studies.

Potential study limitations include the physician panel to determine clinical food allergy status as opposed to performing oral food challenges. These challenges are time consuming and impractical to implement in large epidemiological studies¹⁰. Another limitation is that non-AA children included multiple ethnicites, which was done to preserve sample size. These groups may have different incidences of disease, and risk may vary. Finally, included and excluded WHEALS participants differed by demographic variables, so findings may not be generalizable to the target population.

Parental allergy and atopy, although associated with offspring food allergy, is only a weak predictor and depends upon race. Further studies of familial factors contributing to food allergy and these disparities are needed to precisely identify children at risk for food allergy.

Amy A. Eapen, MD, MS*¹, Erica Ridley MD*¹, Alexandra R. Sitarik MS², Christine Joseph PhD², Christian Nageotte, MD¹, Rana Misiak, MD¹, Dennis Ownby MD³, Christine Johnson PhD², Edward Zoratti MD¹, Haejin Kim MD¹.

¹Division of Allergy and Clinical Immunology

²Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan

³Department of Pediatrics, Augusta University, Augusta, Georgia.

*Dr. Eapen and Dr. Ridley are listed as co-first authors