Self-reported diagnoses of dietary allergens and fecundability in a North American cohort.

study questionTo what extent are self-reported diagnoses of food allergies associated with fecundability, the per-cycle probability of conception? SUMMARY ANSWER: Fecundability was not appreciably associated with self-reported food allergy diagnoses, number of food allergies, age at first diagnosis, or time since last allergic reaction. WHAT IS KNOWN ALREADY: Food allergies are atopic diseases that are characterized by an inappropriate immune response to a normally harmless dietary substance. While some studies have observed associations between atopic disorders and infertility, no study has examined the association between food allergies and fecundability, the per-cycle probability of conception. STUDY DESIGN, SIZE, DURATION: A prospective cohort study including 7711 females trying to conceive without fertility treatment at enrollment (2018-2022) and followed for up to 12 months. PARTICIPANTS/MATERIALS, SETTING,

methodsWe analyzed data from an internet-based prospective cohort of pregnancy planners in North America. At baseline, female participants completed an online questionnaire on demographic, medical, and lifestyle factors that included questions on food allergy diagnoses, age at diagnosis, and time since last reaction. Participants completed bimonthly follow-up questionnaires for up to 12 months to ascertain pregnancy status. The analysis included 7711 PRESTO participants with ≤6 menstrual cycles of pregnancy attempt time at enrollment (2018-2022). We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs, adjusted for demographic, lifestyle, and behavioral characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1028 (13%) participants reported a history of diagnosed food allergy, with the most commonly reported allergy being dairy or shellfish. A history of diagnosed food allergy (vs none) was not appreciably associated with fecundability (FR = 0.93, 95% CI: 0.86-1.02), though specific allergens were associated with fecundability in opposing directions (e.g. inverse association with egg and positive association with soy). We observed non-monotonic associations between fecundability and number of food allergies, age at first allergy diagnosis, and time since last allergic reaction. Inverse associations between self-reported diagnosed food allergens (all types combined) and reduced fecundability were slightly stronger among those with BMI ≥25 (FR = 0.90, 95% CI: 0.80-1.01) than those with BMI <25 (FR = 0.97, 95% CI: 0.86-1.10) and among those born ≥1990 (FR = 0.91, 95% CI: 0.80-1.03) compared with those born <1990 (FR = 0.96, 95% CI: 0.86-1.08). LIMITATIONS, REASONS FOR CAUTION: Non-differential misclassification of food allergies was likely given that we relied on self-reported diagnoses. Confounding by unmeasured dietary factors may have influenced associations between specific food allergens and fecundability, if participants were deficient in specific nutrients because they excluded or substituted selected foods due to the allergy. Generalizability may be reduced given our study population was restricted to North American pregnancy planners. WIDER IMPLICATIONS OF THE

findingsDiagnoses of food allergies have substantially increased over the past several decades. Our findings indicate that self-reported diagnoses of food allergies were not meaningfully associated with subfertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by NIH/NICHD grant R01-HD086742. S.L.M. was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. In the last 3 years, PRESTO has received in-kind donations from Swiss Precision Diagnostics and Kindara.com for primary data collection. L.A.W. is a paid consultant for AbbVie, Inc. and the Gates Foundation. The other authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.