Human Milk Oligosaccharides and Food Sensitization at 12 months in the CHILD Cohort
Bibliographic record
Abstract
Rationale Human milk oligosaccharides (HMOs) provide selective substrates for infant gut microbiota and influence immune system maturation. HMOs appear to modify allergic disease development in rodent models, but this has not been confirmed in humans. Methods We studied a representative subset of 421 mother‐infant dyads from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Milk samples were collected at 4 months postpartum (median 16 weeks, interquartile range 14 – 19) and analyzed by rapid high‐throughput HPLC to quantify the 20 most abundant HMOs. Skin prick testing was performed at 12 months to determine sensitization (≥2mm wheal) to egg, milk, soy and peanut. Associations were examined for total and individual HMO levels (univariate analysis: Wilcoxon rank‐sum test) and overall HMO profiles (multivariable classifier: partial least squares discriminant analysis tested for significance by leave‐one‐out‐cross‐validation). Discriminant scores were examined in regression models with adjustment for potential confounders and known allergy risk factors. Results Overall, 59/421 infants (14.0%) were sensitized to one or more food allergen by 12 months. Total HMO levels were similar in milk consumed by sensitized vs. non‐sensitized infants (14,010 ± 3,510 vs. 13,937 ± 4,085 nmol/mL; p=0.96) and individual HMO levels were not significantly associated with food sensitization (all p>0.09). However, overall HMO profiles differed significantly (mean discriminant score: 0.129 vs. 0.209, p<0.001; area‐under‐the‐curve: 0.73, 95%CI 0.66–0.79). This association was robust to cross‐validation and remained significant in adjusted models, where each 0.1‐unit increase in HMO discriminant score was associated with a 2.5‐fold increased odds of food sensitization (adjusted OR 2.46, 95%CI 1.78–3.41, p<0.001), independent of maternal food allergy, ethnicity, household pets, and lactation time postpartum. HMO profiles associated with higher odds of food sensitization were characterized by lower concentrations of fucosyl‐disialyllacto‐N‐hexaose (FDSLNH), lacto‐N‐fucopentaose‐I (LNFPI), LNFPII, and higher concentrations of lacto‐N‐hexaose (LNH) and lacto‐N‐tetraose (LNT). Conclusion HMO composition is associated with food sensitization in the first year of life. Ongoing research in the CHILD study will seek to confirm these findings in a larger sample of mother‐infant dyads, and evaluate associations with confirmed food allergy at 3 and 5 years of age. Support or Funding Information This study was funded by Research Manitoba and supported by the Canadian Institutes of Health Research and the Allergy, Genes and Environment Network of Centres of Excellence.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".