Hui Xing Lau1, Sarah El-Heis2, Qai Ven Yap3, Yiong Huak Chan3, Cheryl Pei Ting Tan4, Neerja Karnani1, Karen Mei Ling Tan1, Elizabeth Huiwen Tham1,4,5, Anne Eng Neo Goh6, Oon Hoe Teoh7, Kok Hian Tan8, Johan Gunnar Eriksson1,9,10,11, Yap Seng Chong1,9, Mary Foong-Fong Chong1,12, Hugo Van Bever4,5, Bee Wah Lee4, Lynette P Shek4, Keith M Godfrey13, Evelyn Xiu Ling Loo1,4. 1. Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore City, Singapore. 2. Medical Research Council Lifecourse Epidemiology Unit, Southampton, UK. 3. Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore. 4. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore. 5. Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore City, Singapore. 6. Allergy Service, Department of Paediatrics, KK Women's and Children's Hospital (KKWCH), Singapore City, Singapore. 7. Respiratory Service, Department of Paediatrics, KK Women's and Children's Hospital (KKWCH), Singapore City, Singapore. 8. Department of Maternal Fetal Medicine, KK Women's and Children's Hospital (KKWCH), Singapore City, Singapore. 9. Department of Obstetrics & Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore City, Singapore. 10. Folkhälsan Research Center, Helsinki, Finland. 11. Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland. 12. Saw Swee Hock School of Public Health, National University of Singapore, Singapore City, Singapore. 13. NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Abstract
BACKGROUND: Nicotinamide (vitamin B3) is a metabolite of tryptophan and dietary precursor of enzymes involved in many regulatory processes, which may influence fetal immune development. OBJECTIVE: We examined whether maternal plasma concentrations of nicotinamide, tryptophan or nine related tryptophan metabolites during pregnancy were associated with the risk of development of infant eczema, wheeze, rhinitis or allergic sensitization. METHODS: In the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, we analysed the associations between maternal plasma levels of nicotinamide, tryptophan and tryptophan metabolites at 26-28 weeks of gestation and allergic outcomes collected through interviewer-administered questionnaires at multiple time-points and skin prick testing to egg, milk, peanut and mites at age 18 months. Multivariate analysis was undertaken adjusting for all metabolites measured and separately adjusting for relevant demographic and environmental exposures. Analyses were also adjusted for multiple comparisons using the false discovery method. RESULTS: Tryptophan metabolites were evaluated in 976/1247 (78%) women enrolled in GUSTO. In multivariate analysis including all metabolites, maternal plasma 3-hydrokynurenine was associated with increased allergic sensitization at 18 months (AdjRR 2.6, 95% CI 1.3-5.2 for highest quartile) but the association with nicotinamide was not significant (AdjRR 1.8, 95% CI 0.9-3.6). In analysis adjusting for other exposures, both 3-hydrokynurenine and nicotinamide were associated with increased allergic sensitization (AdjRR 2.0, 95% CI 1.1-3.6 for both metabolites). High maternal plasma nicotinamide was associated with increased infant eczema diagnosis by 6 and 12 months, which was not significant when adjusting for all metabolites measured, but was significant when adjusting for relevant environmental and demographic exposures. Other metabolites measured were not associated with allergic sensitization or eczema, and maternal tryptophan metabolites were not associated with offspring rhinitis and wheeze. CONCLUSIONS AND CLINICAL RELEVANCE: Maternal tryptophan metabolism during pregnancy may influence the development of allergic sensitization and eczema in infants.
BACKGROUND: Nicotinamide (vitamin B3) is a metabolite of tryptophan and dietary precursor of enzymes involved in many regulatory processes, which may influence fetal immune development. OBJECTIVE: We examined whether maternal plasma concentrations of nicotinamide, tryptophan or nine related tryptophan metabolites during pregnancy were associated with the risk of development of infant eczema, wheeze, rhinitis or allergic sensitization. METHODS: In the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, we analysed the associations between maternal plasma levels of nicotinamide, tryptophan and tryptophan metabolites at 26-28 weeks of gestation and allergic outcomes collected through interviewer-administered questionnaires at multiple time-points and skin prick testing to egg, milk, peanut and mites at age 18 months. Multivariate analysis was undertaken adjusting for all metabolites measured and separately adjusting for relevant demographic and environmental exposures. Analyses were also adjusted for multiple comparisons using the false discovery method. RESULTS: Tryptophan metabolites were evaluated in 976/1247 (78%) women enrolled in GUSTO. In multivariate analysis including all metabolites, maternal plasma 3-hydrokynurenine was associated with increased allergic sensitization at 18 months (AdjRR 2.6, 95% CI 1.3-5.2 for highest quartile) but the association with nicotinamide was not significant (AdjRR 1.8, 95% CI 0.9-3.6). In analysis adjusting for other exposures, both 3-hydrokynurenine and nicotinamide were associated with increased allergic sensitization (AdjRR 2.0, 95% CI 1.1-3.6 for both metabolites). High maternal plasma nicotinamide was associated with increased infant eczema diagnosis by 6 and 12 months, which was not significant when adjusting for all metabolites measured, but was significant when adjusting for relevant environmental and demographic exposures. Other metabolites measured were not associated with allergic sensitization or eczema, and maternal tryptophan metabolites were not associated with offspring rhinitis and wheeze. CONCLUSIONS AND CLINICAL RELEVANCE: Maternal tryptophan metabolism during pregnancy may influence the development of allergic sensitization and eczema in infants.
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