Respiratory benefit in preterm lambs is progressively lost when the concentration of fetal plasma betamethasone is titrated below two nanograms per milliliter

Author:

Fee Erin L.12ORCID,Takahashi Tsukasa13ORCID,Takahashi Yuki13,Carter Sean W. D.1,Clarke Michael W.42,Milad Mark A.5,Usuda Haruo13ORCID,Ikeda Hideyuki13,Kumagai Yusaku3,Saito Yuya3,Ireland Demelza J.12,Newnham John P.1,Saito Masatoshi13,Jobe Alan H.16ORCID,Kemp Matthew W.1378

Affiliation:

1. Division of Obstetrics and Gynaecology, Medical School, The University of Western Australia, Perth, Western Australia, Australia

2. School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia

3. Centre for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan

4. Metabolomics Australia, Centre for Microscopy, Characterization and Analysis, The University of Western Australia, Perth, Western Australia, Australia

5. Milad Pharmaceutical Consulting LLC, Plymouth, Michigan, United States

6. Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio, United States

7. School of Veterinary Medicine, Murdoch University, Perth, Western Australia, Australia

8. Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Abstract

Lung maturation benefits in preterm lambs were progressively lost when fetal plasma betamethasone concentrations fell below 2 ng/mL. The effective floor threshold for a robust, lung-maturing exposure likely lies between 1 and 2 ng betamethasone per milliliter of plasma. Hypothalamic pituitary adrenal axis signaling and immunocyte populations remained materially disrupted at subtherapeutic steroid concentrations. These data demonstrate the potential to improve antenatal steroid therapy using reduced dose regimens informed by glucocorticoid pharmacokinetics and pharmacodynamics.

Funder

Ministry of Education, Government of Singapore

Channel 7 Telethon Trust

Stan Perron Charitable Foundation

Women and Infants Research Foundation

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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