Maternal vitamin D–related metabolome and offspring risk of asthma outcomes
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Maternal vitamin D–related metabolome and offspring risk of asthma outcomes. / Kim, Min; Brustad, Nicklas; Ali, Mina; Gürdeniz, Gözde; Arendt, Morten; Litonjua, Augusto A.; Wheelock, Craig E.; Kelly, Rachel S.; Chen, Yulu; Prince, Nicole; Guo, Feng; Zhou, Xiaobo; Stokholm, Jakob; Bønnelykke, Klaus; Weiss, Scott T.; Bisgaard, Hans; Lasky-Su, Jessica; Chawes, Bo.
In: Journal of Allergy and Clinical Immunology, Vol. 152, No. 6, 2023, p. 1646-1657.e11.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Maternal vitamin D–related metabolome and offspring risk of asthma outcomes
AU - Kim, Min
AU - Brustad, Nicklas
AU - Ali, Mina
AU - Gürdeniz, Gözde
AU - Arendt, Morten
AU - Litonjua, Augusto A.
AU - Wheelock, Craig E.
AU - Kelly, Rachel S.
AU - Chen, Yulu
AU - Prince, Nicole
AU - Guo, Feng
AU - Zhou, Xiaobo
AU - Stokholm, Jakob
AU - Bønnelykke, Klaus
AU - Weiss, Scott T.
AU - Bisgaard, Hans
AU - Lasky-Su, Jessica
AU - Chawes, Bo
N1 - Publisher Copyright: © 2023 The Authors
PY - 2023
Y1 - 2023
N2 - Background: Gestational vitamin D deficiency is implicated in development of respiratory diseases in offspring, but the mechanism underlying this relationship is unknown. Objective: We sought to study the link between gestational vitamin D exposure and childhood asthma phenotypes using maternal blood metabolomics profiling. Methods: Untargeted blood metabolic profiles were acquired using liquid chromatography-mass spectrometry at 1 week postpartum from 672 women in the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) mother-child cohort and at pregnancy weeks 32 to 38 from 779 women in the Vitamin D Antenatal Asthma Reduction Trial (VDAART) mother-child cohort. In COPSAC2010, we employed multivariate models and pathway enrichment analysis to identify metabolites and pathways associated with gestational vitamin D blood levels and investigated their relationship with development of asthma phenotypes in early childhood. The findings were validated in VDAART and in cellular models. Results: In COPSAC2010, higher vitamin D blood levels at 1 week postpartum were associated with distinct maternal metabolome perturbations with significant enrichment of the sphingomyelin pathway (P < .01). This vitamin D–related maternal metabolic profile at 1 week postpartum containing 46 metabolites was associated with decreased risk of recurrent wheeze (hazard ratio [HR] = 0.92 [95% CI 0.86-0.98], P = .01) and wheeze exacerbations (HR = 0.90 [95% CI 0.84-0.97], P = .01) at ages 0 to 3 years. The same metabolic profile was similarly associated with decreased risk of asthma/wheeze at ages 0 to 3 in VDAART (odds ratio = 0.92 [95% CI 0.85-0.99], P = .04). Human bronchial epithelial cells treated with high-dose vitamin D3 showed an increased cytoplasmic sphingolipid level (P < .01). Conclusions: This exploratory metabolomics study in 2 independent birth cohorts demonstrates that the beneficial effect of higher gestational vitamin D exposure on offspring respiratory health is characterized by specific maternal metabolic alterations during pregnancy, which involves the sphingomyelin pathway.
AB - Background: Gestational vitamin D deficiency is implicated in development of respiratory diseases in offspring, but the mechanism underlying this relationship is unknown. Objective: We sought to study the link between gestational vitamin D exposure and childhood asthma phenotypes using maternal blood metabolomics profiling. Methods: Untargeted blood metabolic profiles were acquired using liquid chromatography-mass spectrometry at 1 week postpartum from 672 women in the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) mother-child cohort and at pregnancy weeks 32 to 38 from 779 women in the Vitamin D Antenatal Asthma Reduction Trial (VDAART) mother-child cohort. In COPSAC2010, we employed multivariate models and pathway enrichment analysis to identify metabolites and pathways associated with gestational vitamin D blood levels and investigated their relationship with development of asthma phenotypes in early childhood. The findings were validated in VDAART and in cellular models. Results: In COPSAC2010, higher vitamin D blood levels at 1 week postpartum were associated with distinct maternal metabolome perturbations with significant enrichment of the sphingomyelin pathway (P < .01). This vitamin D–related maternal metabolic profile at 1 week postpartum containing 46 metabolites was associated with decreased risk of recurrent wheeze (hazard ratio [HR] = 0.92 [95% CI 0.86-0.98], P = .01) and wheeze exacerbations (HR = 0.90 [95% CI 0.84-0.97], P = .01) at ages 0 to 3 years. The same metabolic profile was similarly associated with decreased risk of asthma/wheeze at ages 0 to 3 in VDAART (odds ratio = 0.92 [95% CI 0.85-0.99], P = .04). Human bronchial epithelial cells treated with high-dose vitamin D3 showed an increased cytoplasmic sphingolipid level (P < .01). Conclusions: This exploratory metabolomics study in 2 independent birth cohorts demonstrates that the beneficial effect of higher gestational vitamin D exposure on offspring respiratory health is characterized by specific maternal metabolic alterations during pregnancy, which involves the sphingomyelin pathway.
KW - childhood asthma
KW - metabolomics
KW - pregnancy
KW - sphingomyelin
KW - Vitamin D
U2 - 10.1016/j.jaci.2023.06.030
DO - 10.1016/j.jaci.2023.06.030
M3 - Journal article
C2 - 37558060
AN - SCOPUS:85169896398
VL - 152
SP - 1646-1657.e11
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 6
ER -
ID: 369354333