Neonatal Number Two May Foretell Allergy

Contents of baby’s first stool were a biomarker for early-life allergy risk in a study of 100 infants.

Infants who developed IgE-mediated atopy by age 1 showed a significantly poorer environment in their meconium — the fecal matter accumulated prior to birth and typically expelled within a few days of delivery — for microbiotal development compared with those without signs of allergic sensitization, reported Charisse Petersen, PhD, of the University of British Columbia in Vancouver, and colleagues in Cell Reports Medicine.

While the metabolomic compositions didn’t differ starkly enough in this study to serve as a clinical prognostic tool — a meconium metabolite panel showed an area under the receiver operating characteristic curve (AUC) of 0.59 — the study’s findings do provide another indication that intestinal bacteria play a role in allergic sensitization and may ultimately find clinical application.

“Understanding prenatal factors determining infant meconium composition and uncoupling the direct versus indirect effects of different meconium metabolites on immune development and bacterial colonization within neonates could lead to timely interventions to prevent the development of allergic sensitization,” the researchers wrote.

As Petersen and colleagues explained, previous studies had shown associations between atopic disorders (i.e., those involving excessive IgE activation) and low levels of intestinal bacteria thought to be beneficial. That raises the question of how infants’ microbiota develop in the first place. Babies already come with some when they’re born — and the meconium “is not only a rich source of metabolites reflecting perinatal influences but also contains the starting material for the initial microbiota,” the group wrote.

Test results on meconia obtained from 950 infants enrolled in the Canadian Healthy Infant Longitudinal Development study underpinned the analysis. Stool samples in this large cohort were collected at median ages of 3 months and 1 year, which allowed the researchers to track microbiota development over time and to identify the bacterial types most closely associated with healthy development.

This initial analysis showed that babies “with an atopic response at 1 year had a significantly less-mature microbiota than healthy non-atopic infants had at early time points but not at the time of the [skin prick test] administration,” by which the researchers determined allergic sensitivity. Petersen and colleagues determined that this was not an age effect but instead was attributable to differences in microbiota composition.

The group then turned to meconium samples from 100 infants, performing a metabolomics survey. Fetuses don’t eat, of course, but they nevertheless accumulate material in their digestive tract, including “skin and gut cells, amniotic fluid, vernix, and lanugo hair,” which serves as a growth medium for their future intestinal microflora. This analysis confirmed that babies who became atopic during their first year, on average, already lacked the foundation for healthy microbial diversity. Petersen and colleagues found “modest correspondence between the meconium metabolome and the microbiota composition at the early visit,” they wrote.

Analysis for prenatal factors associated with the unhealthy type of meconium identified several: parental atopy, maternal smoking, infants’ sex, having at least one older sibling, and race/ethnicity (white vs “other”). Addition of these variables to the predictive model linking meconium factors to subsequent allergic sensitivity raised the AUC from 0.59 to 0.75.

Limitations to the study included the small number of infants with meconium analysis, thus requiring further confirmation of the results in larger and more diverse populations, Petersen and colleagues noted.