Elevated third trimester corticosteroid levels are associated with fewer offspring infections

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  • Nicole Prince
  • Rachel S. Kelly
  • Su H. Chu
  • Priyadarshini Kachroo
  • Yulu Chen
  • Kevin M. Mendez
  • Sofina Begum
  • Hans Bisgaard
  • Bønnelykke, Klaus
  • Min Kim
  • Ofer Levy
  • Augusto A. Litonjua
  • Craig E. Wheelock
  • Scott T. Weiss
  • Chawes, Bo Lund Krogsgaard
  • Jessica A. Lasky-Su

Respiratory infections are a leading cause of morbidity and mortality in early life, and recurrent infections increase the risk of developing chronic diseases. The maternal environment during pregnancy can impact offspring health, but the factors leading to increased infection proneness have not been well characterized during this period. Steroids have been implicated in respiratory health outcomes and may similarly influence infection susceptibility. Our objective was to describe relationships between maternal steroid levels and offspring infection proneness. Using adjusted Poisson regression models, we evaluated associations between sixteen androgenic and corticosteroid metabolites during pregnancy and offspring respiratory infection incidence across two pre-birth cohorts (N = 774 in VDAART and N = 729 in COPSAC). Steroid metabolites were measured in plasma samples from pregnant mothers across all trimesters of pregnancy by ultrahigh-performance-liquid-chromatography/mass-spectrometry. We conducted further inquiry into associations of steroids with related respiratory outcomes: asthma and lung function spirometry. Higher plasma corticosteroid levels in the third trimester of pregnancy were associated with lower incidence of offspring respiratory infections (P = 4.45 × 10–7 to 0.002) and improved lung function metrics (P = 0.020–0.036). Elevated maternal androgens were generally associated with increased offspring respiratory infections and worse lung function, with some associations demonstrating nominal significance at P < 0.05, but these trends were inconsistent across individual androgens. Increased maternal plasma corticosteroid levels in the late second and third trimesters were associated with lower infections and better lung function in offspring, which may represent a potential avenue for intervention through corticosteroid supplementation in late pregnancy to reduce offspring respiratory infection susceptibility in early life. Clinical Trial Registry information: VDAART and COPSAC were originally conducted as clinical trials; VDAART: ClinicalTrials.gov identifier NCT00920621; COPSAC: ClinicalTrials.gov identifier NCT00798226.

OriginalsprogEngelsk
Artikelnummer10461
TidsskriftScientific Reports
Vol/bind13
Antal sider8
ISSN2045-2322
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The Vitamin D Antenatal Asthma Reduction Trial (VDAART) was funded by U01HL091528 from the National Heart, Lung, and Blood Institute (NIH/NHLBI) awarded to STW and AAL. Effort by JALS and metabolomics measurement for both cohorts was supported by R01HL123915 and R01HL141826 from NIH/NHLBI. OL and JALS are also supported in part by NIH/NIAID grant 1U19AI168643-01 under the Immune Development in Early Life (IDEAL). Effort for PK was supported by K99HL159234 from NIH/NHLBI. NP is supported by NIHT32HL007427 from NIH/NHLBI. CEW was supported by the Swedish Heart Lung Foundation (HLF 20210519, 20200693). BLC was supported by European Research Council (ERC) European Union’s Horizon 2020 research and innovation programme: Grant Agreement No. 946228. The external funders played no role in the design or conduct of the study, collection, management, analysis, or interpretation of the data, preparation, review, approval of, or decision to submit the manuscript.

Publisher Copyright:
© 2023, The Author(s).

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