Parental-reported allergic disorders and emergency department presentations for allergy in the first five years of life; a longitudinal birth cohort

This study links data on children enrolled in a prospective birth cohort (Environments for Healthy Living [EFHL]: Griffith Birth Cohort study [10], registered Australian and New Zealand Clinical Trials Registry ACTRN12610000931077) to data from i) the Emergency Department Information System (EDIS) of four public hospitals, ii) the nationwide Medicare Benefit Scheme (MBS) and iii) the Pharmaceutical Benefits Scheme (PBS).

From 2006 to 2011 inclusive, pregnant women from 24 weeks gestation who attended one of the only three public hospitals in the area with a birthing service were enrolled in the EFHL cohort [10]. This area services a population of approximately 800,000 people. A fourth new public hospital ED opened in the area in September 2007. ED data were available for EFHL children for the period from November 2006 to December 2013.

The EFHL dataset included maternal, pregnancy/child, and household data and was collected by self-completed questionnaires by the primary caregiver at enrolment and when their child reached 12 months, 3 and 5 years of age. The baseline survey consisted of 48 self-report items including maternal, household and demographic factors during pregnancy [11]. Parents also provided consent at the time of enrolment to access additional gestational and birth information from hospital perinatal records after the delivery, hospital data and emergency department data.

Study subjects were children born to mothers enrolled in the EFHL study. The primary outcomes of interest included the rate of parental-reported allergic disorders as obtained through questionnaires returned at 1, 3 and 5 years (Table 1), and the rate of ED presentations with an ICD-10 code of allergy or allergic disorder (Fig. 1). Asthma was not included as an allergic disorder. We included ‘rash’, as an allergic disorder, although other etiologies could be the cause of this diagnosis. As such (sensitivity) analyses were conducted for ED diagnoses of allergy with and without ‘rash’ included. Mothers or primary caregivers completed the surveys and are hereafter grouped as parents for ease of reporting. The one-year questionnaire data was included as source data for potential risk factors (e.g. breast feeding or introduction of solids) for the parental-report of allergy analysis, comparing risk factors amongst children with and without a parental-reported allergy. For the ED presentation analysis, baseline questionnaire data were used to identify risk factors for children with an ED presentation for allergy, compared to children with other ED presentations. For both parental-report and ED presentation analyses, PBS data were utilized. Table 2 summarises the available subjects for both parental-reported allergy analysis and ED presentation analysis.

Table 1 summarizes enrolment and consent timeframes for relevant data sets in this study. The following administrative databases were linked to the EFHL data:

EFHL data was managed with Stata 12.1. Data analyses were undertaken using R [13]. Chi-square tests were used to compare associations between parental-reported allergy and potential risk factors. The presentation rate to ED of children with allergic disorders was calculated based on the whole EFHL cohort (n = 3404, Table 1). A p-value of < 0.05 was considered statistically significant. Prevalence rates and 95% confidence intervals were computed using the Mid-p exact test for person-time rates. Person-years (PYs) for prevalence rates of parental-report allergy were calculated by adding the number of years each child had contributed to the study. Person-years for the prevalence of presentation to ED with allergy was calculated for each child based on the last date of ED data available (31 December 2013) minus the child’s date of birth, and summed across the cohort. Logistic regression analyses were conducted to identify variables independently associated with parental report of allergy as well as ED diagnosis of allergy (including and excluding ‘rash’). For the parental report model, variables significant at a p < 0.10 level in the univariate analysis and with complete data on at least 90% of children were considered in a forward stepwise conditional regression model with entry and exit criteria of p < 0.10. The same regression technique was used for models determining variables associated with ED presentation for allergy (including and excluding “rash” lead to two separate models). However, because some of the key univariate predictors had > 10% missing data for this model, various models were built on the full sample as well as for subsets with complete data on key variables found to be significant in univariate analysis. Interactions between variables were assessed; significant interactions (p < .05) were accounted for in all models. In determining the best model, the number of records, the strength of the associations, the persistence of covariates across models, and the Negelkerke’s R square value were considered.

The Human Research Ethics Committees of both the participating health service districts, and Griffith University approved this study, including linkage of data. For each participant written informed consent was obtained (from the parent or primary caregiver) for completion of a maternal baseline survey, the release of hospital perinatal data related to the birth of their child and linkage of their child’s inpatient state hospital records.

Of the 3404 children in EFHL, questionnaire data for at least one time point were available for 2452 unique children (72%), including 2201 children with available one-year data (Table 1). The allergy questions were answered for 2182 children at 1 year, and for 1213 and 627 children at 3 and 5 years, respectively (Table 1). Allergy at any time in the child’s life was reported in 7.8% of children at 1 year, in 7.8% of children at 3 years, and in 12.6% of children with 5 years follow-up (Table 3). By 5 years of age, 255 children had an allergy as reported by their parent, representing 10.4% of the starting cohort of children who returned at least one questionnaire.

Table 4 describes univariate analysis of parental report of allergy by duration of follow up and potential risk factors in proportions and person-years, respectively.

Parents of male children were more likely to report allergy in their children at 3 and 5 years (Table 4). The cumulative prevalence of allergy for boys over the period was 1.4 times higher than that for girls (Risk Ratio [RR] 1.4 [95% CI 1.2,1.8], Table 4).

Children with three or more other children in the household had a higher risk of allergy compared to children with 0–2 other children in the household (RR = 1.3 [1.0, 1.7], Table 4).

There appeared to be a trend towards lower parental-report of allergy in children who had solids introduced in the first 3 months of life compared to other children, most notable at the 3-year and 5 year time points (Table 4).

At 5 years, parents who were non-smokers during pregnancy reported more allergic disorders in their children than parents who smoked (14.1% vs. 5.6%; p = 0.03, Table 4). This finding did not persist when the cumulative rate was considered across all time points (Table 4).

The following (potential risk) factors were not significantly associated with parental-reported allergy in univariate analysis: season of birth, birthweight, maternal education level, household annual income, childcare attendance, breast feeding (ever, and duration), and passive smoking exposure (Table 4).

The following variables were univariately statistically significantly associated with parental-reported allergy: birthweight (continuous), age at first food, child has asthma, child has eczema, child care (ever). When combined with other potentially predictive variables, Table 5 shows the best model identified included the following significant variables: parental-report of asthma (adjusted Odds Ratio: aOR 2.2, 95% CI 1.4–3.4), parental-report of eczema (aOR 4.3, 95% CI 3.1–6.1) whether the child had attended childcare (aOR 1.4, 95% CI 1.1–1.9), and age of first solid intake > 6 months (aOR 1.3, 95% CI 1.0–1.7).

There were a total of 5118 ED presentations in this cohort of children aged 0–5 years. Allergic disorders (not including asthma), accounted for 3.6% (182) of these presentations from 160 of the 3404 children in the cohort. The median ED length of stay was 1.9 h. Fifteen children (8.2%) were admitted to hospital; most were assigned an Australian Triage Scale (ATS) category 3 (59%) or 4 (23%), with 14% receiving a more urgent classification (ATS 2; 13% and ATS 1; 1.1%).

Over one-third of presentations (66 of 182) with allergic disorders occurred during the first year of life (Table 6). There were two presentations due to anaphylaxis yielding a prevalence of 0.59 per 1000 PYs for anaphylaxis in the first 5 years of life.

By 12 months of age, 1.8%, of the cohort had presented to ED with an allergic disorder. There was a decreasing cumulative prevalence of allergy presentation to ED, from 19.4 per 1000 person-years to 13.0 per 1000 person years as the children grew older (Table 6). ED presentation with allergy by 1 year of age occurred at a quarter of the rate of parental report of allergy (19.4 per 1000 PY compared to 78.4 per 1000 PY, Tables 3 and 6).

Univariate analysis showed that children who presented to the ED with an allergy during the first 5 years of life were more likely to be born in spring and have a mother with asthma. (Table 7). These findings persisted in the multivariate analysis as shown in Table 8, with an adjusted odds ratio for ED presentation with allergy (including diagnosis of rash) of 1.7 [95% CI 1.1–2.7] and 2.3 [95% CI 1.1–4.9], respectively. The same variables were found to be independent predictors of similar magnitude if diagnoses of ‘rash’ were excluded (Table 9).

There were no statistically significant differences in gender, mother’s socioeconomic status, the number of children living in the household, breastfeeding duration, or the age at introduction of solids for children presenting with an allergy compared to other ED presentations (Table 7).

Not all parents consented to linkage with the PBS database and loss to follow-up occurred. As a result, the study may have been underpowered to find significant associations for known risk factors, although most point estimates findings were consistent with the existing literature. Also, due to the loss to follow-up, selection bias may have been introduced. Nevertheless, we have no reason to believe children with allergic disorders would have a different rate of loss to follow-up than others. We excluded asthma from our analysis, since our focus was on children between 0 and 5 years where diagnosis of asthma is challenging, due to their inability to provide reliable spirometry and the host of competing diagnoses such as bronchiolitis and reactive airway disease [24]. We acknowledge including asthma may have lead to different findings. ED diagnosis of allergy included patients with a diagnosis of ‘rash’, which accounted for half of the ED presentations in the first year of life for allergy and 40% of all presentations. We did not have approval to access patients’ individual medical record and are unable to comment on the exact etiology. A separate audit suggested more than half of these children have an allergic etiology. We conducted a sensitivity analysis by conducting logistic regression with and without patients with ‘rash’ and found a consistent result. As such we have decided to keep patients with rash in our descriptive analyses. We used ICD-10 coding for ED diagnosis which may have led to misclassification. For example, we noted very few cases of anaphylaxis, although our estimated incidence falls within previously reported ranges [25]. Furthermore, we cannot comment on the accuracy of parental report of allergy. Parental-report is considered a valid measurement for allergy, especially as a follow up measurement for a large cohort where patients are not routinely reviewed by a clinician [26].

Parental-report of allergy was unable to be further subdivided to examine specific drug or food associations. We had access to a detailed baseline database, but not all relevant possible predictors may have been included. Lastly, despite having access to multiple datasets, data entry and linkage may have been incomplete.