Our study demonstrates that the trajectory of IgE in early life is affected by the presence of pets in the home during pregnancy, and the magnitude of this effect varies by the mode of delivery and self-reported race. Studies in multiple settings have evaluated the effects of both early life pet exposure11–15
and mode of delivery16;17
on the risks of allergic disease. While previous studies are not uniform, many suggest that early life pet exposures are associated with decreased risk of allergic disease18
and that delivery via caesarean-section is associated with increased risk.19
Further, it is well established that African American children and adolescents have higher IgE levels than other race groups.20
The biological mechanism explaining the effects of pets on allergy development is unknown. We hypothesize that indoor pet ownership is associated with exposure to a distinct, more broadly diverse bacterial populations in the home environment, and that this broadly diverse exposure influences early infant development of immune function in a manner that decreases the risk of development of allergy and atopic asthma. Our previous study supports this hypothesis, demonstrating that house dust from homes with dogs possessed significantly greater bacterial diversity than house dust from no-pet homes.7
Delivery by caesarean-section, which has been associated with as much as a 20% increase in the risk for allergic disease development,21
has been associated with distinct gastrointestinal microbiota deficient in Lactobaccillus
and dominated by Clostridia
It is possible that an enhanced household bacterial diversity provided by pets would have a greater impact on such babies. Indeed, in a Finnish study, the beneficial effects of bacterial probiotics on the risk of allergic sensitization was only apparent among children delivered by cesarean-section.24
We speculate that individuals with a predominant African ancestry and therefore an evolutionary history founded in an equatorial climate with a relatively voluminous and presumably highly diverse microbial burden may have a preponderance of genetic variants that render a differential susceptibility to the effects on IgE of microbial exposures afforded by household dogs and cats.
Few longitudinal studies of IgE have taken maximum statistical advantage of the repeated measures within children. A recent exception is a publication from the Multi-centre Allergy Study (MAS); however, their primary focus was to compare trends of total IgE to trends of allergen-specific IgE.25
While only participants with complete data over time (6% of the total sample) were analyzed in this report, and very different statistical methods were used, our results were consistent with theirs in showing a rapid increase in IgE during early childhood. Using a random effects model, the Tucson Children's Respiratory Study showed trends of general increase through childhood that were affected by breastfeeding and maternal total IgE levels, but there was only one post-natal data collection point in infancy.26
Most relevant are the results from Rothers et al. from another Tucson-based birth cohort.27
Using samples collected at 3 months and 1, 2 and 3 years of age in a cohort of 362 children and again deploying a random effects model, they reported that day care attendance by age 3 months was associated with decreased total IgE levels, but only among children whose mothers were atopic, asthmatic or both, another example of effect modification. The MLM method used in this paper differs from the random effects model in that it accounts for measures at different time points and is focused on the evaluation of within-individual change, as well as allowing the inclusion of subjects with missing data.
Examination of factors affecting early within-person total IgE trends over time is important as it may provide insight into immune mechanisms that increase the risk of developing clinical allergic disorders. In addition to the association between high total IgE and atopic dermatitis and allergic rhinitis, numerous studies have reported higher IgE among children with asthma and/or wheezing.9;10;28;29
As we follow the children in our cohort over time, we will be able to examine whether certain longitudinal patterns of total IgE are associated with increased risk of subsequent allergic disorders and asthma.
The large size of our sample and its inclusion of a high proportion of African Americans were assets of our study. A potential limitation of our study is that we used the six month time point as the `change' point. The model may have changed if a 3 or 9 month blood collection were completed. A test for a change point at the 1 year time point was not significant. In any case, this did not affect the ability of our methods of analysis to detect a dramatic increase in total IgE in the first six months of life and to analyze the effects of early life exposures on this increase. Our analysis nonetheless does not permit the conclusion that six months is necessarily the optimal time point for early life blood collection in future studies.
Additionally, no testing was done to rule out maternal contamination of the cord blood. However, it has been argued this is unnecessary since maternal IgE does not cross the placenta during gestation and the fetus is capable of producing IgE by the 11th
week of gestation.30
Further, we repeated the analyses excluding the cord measurement and obtained extremely consistent results, both overall and when stratified by delivery mode and maternal race. The overall model excluding the cord measurement gave an estimated 27% decrease with indoor pet exposure as compared to the 28% decrease in the model containing cord measurements.
In summary, our data are evidence in support of the hypotheses that prenatal pet exposure affects a child's very early life immune status resulting in a lower peripheral blood total IgE trajectory. The use of MLMs and all of their advantages facilitated this within person analysis.