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CC BY V4.0, Open Access
Journal article
A reduction in antenatal steroid dose was associated with reduced cardiac dysfunction in a Sheep model of pregnancy
Reproductive sciences (Thousand Oaks, Calif.), Vol.30(11), pp.3222-3234
2023
PMID: 37264260
Abstract
Despite widespread use, dosing regimens for antenatal corticosteroid (ACS) therapy are poorly unoptimized. ACS therapy exerts a programming effect on fetal development, which may be associated with an increased risk of cardiovascular disease. Having demonstrated that low-dose steroid therapy is an efficacious means of maturing the preterm lung, we hypothesized that a low-dose steroid exposure would exert fewer adverse functional and transcriptional changes on the fetal heart. We tested this hypothesis using low-dose steroid therapy (10 mg delivered to the ewe over 36 h via constant infusion) and compared cardiac effects with those of a higher dose treatment (30 mg delivered to the ewe over 24 h by intramuscular injection; simulating currently employed clinical ACS regimens). Fetal cardiac function was assessed by ultrasound on the day of ACS treatment initiation. Transcriptomic analyses were performed on fetal myocardial tissue. Relative to saline control, fetuses in the higher-dose clinical treatment group had significantly lower ratios between early diastolic ventricular filling and ventricular filling during atrial systole, and showed the differential expression of myocardial hypertrophy-associated transcripts including βMHC, GADD45γ, and PPARγ. The long-term implications of these changes remain unstudied. Irrespective, optimizing ACS dosing regimens to maximize respiratory benefit while minimizing adverse effects on key organ systems, such as the heart, offers a means of improving the acute and long-term outcomes associated with this important obstetric therapy.
Details
- Title
- A reduction in antenatal steroid dose was associated with reduced cardiac dysfunction in a Sheep model of pregnancy
- Authors/Creators
- Yusaku Kumagai - Tohoku University HospitalMatthew W Kemp - National University of SingaporeHaruo Usuda - Tohoku UniversityTsukasa Takahashi - Tohoku University HospitalYuki Takahashi - Tohoku University HospitalHirotaka Hamada - Tohoku University HospitalAugusto F Schmidt - University of MiamiTakushi Hanita - Tohoku University HospitalShimpei Watanabe - Tohoku University HospitalShinichi Sato - Tohoku University HospitalHideyuki Ikeda - Tohoku University HospitalErin L Fee - The University of Western AustraliaLucy Furfaro - Division of Obstetrics and Gynecology, The University of Western Australia, Perth, WA, AustraliaJohn P Newnham - King Edward Memorial HospitalAlan H Jobe - Cincinnati Children's Hospital Medical CenterNobuo Yaegashi - Tohoku University HospitalMasatoshi Saito - The University of Western Australia
- Publication Details
- Reproductive sciences (Thousand Oaks, Calif.), Vol.30(11), pp.3222-3234
- Publisher
- Springer Nature
- Number of pages
- 13
- Identifiers
- 991005583965507891
- Copyright
- © 2023 Springer Nature
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.72 Obstetrics & Gynecology
- 1.72.924 Preterm Birth Causes
- Web Of Science research areas
- Obstetrics & Gynecology
- Reproductive Biology
- ESI research areas
- Clinical Medicine