The use of antenatal corticosteroids for fetal maturation in COVID-19: clinical practice statement by WAPM-World Association of Perinatal Medicine  and the PMF-Perinatal Medicine Foundation

Themistoklis Dagklis; Cihat Şen; Ioannis Tsakiridis; Cecilia Villalaín; Karel Allegaert; Sven Wellmann; Satoshi Kusuda; Bernat Serra; Manuel Sanchez Luna; Erasmo  Huertas; Nicola Volpe; Rodrigo Ayala; Nelly Jekova; Amos Grunebaum; Milan Stanojevic

The use of antenatal corticosteroids for fetal maturation in COVID-19: clinical practice statement by WAPM-World Association of Perinatal Medicine and the PMF-Perinatal Medicine Foundation

Themistoklis Dagklis, Cihat Şen, Ioannis Tsakiridis, Cecilia Villalaín, Karel Allegaert, Sven Wellmann, Satoshi Kusuda, Bernat Serra, Manuel Sanchez Luna, Erasmo Huertas, Nicola Volpe, Rodrigo Ayala, Nelly Jekova, Amos Grunebaum, Milan Stanojevic

Article info

The use of antenatal corticosteroids for fetal maturation in COVID-19: clinical practice statement by WAPM-World Association of Perinatal Medicine and the PMF-Perinatal Medicine Foundation. Perinatal Journal 2022;30(1):12-13 DOI: 10.2399/prn.22.0301005

Author(s) Information

Themistoklis Dagklis¹,

Cihat Şen²,

Ioannis Tsakiridis¹,

Cecilia Villalaín³,

Karel Allegaert⁴,

Sven Wellmann⁵,

Satoshi Kusuda⁶,

Bernat Serra⁷,

Manuel Sanchez Luna⁸,

Erasmo Huertas⁹,

Nicola Volpe¹⁰,

Rodrigo Ayala¹¹,

Nelly Jekova¹²,

Amos Grunebaum¹³,

Milan Stanojevic¹⁴

Third Department of Obstetrics & Gynaecology, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
Perinatal Medicine Foundation and Department of Obstetrics & Gynecology, Memorial Bahçelievler Hospital, Istanbul, Turkey
Fetal Medicine Unit, Department of Obstetrics & Gynecology, University Hospital 12 de Octubre, Complutense University of Madrid, Madrid, Spain
Department of Development and Regeneration, and Department of Pharmaceutical & Pharmacological Sciences, KU Leuven, Leuven, Belgium; and Hospital Pharmacy, Erasmus MC, Rotterdam, the Netherlands
Department of Neonatology, University Children’s Hospital Regensburg (KUNO), Hospital St. Hedwig of the Order of St. John, University of Regensburg, Regensburg, Germany
Department of Pediatrics, Kyorin University, Tokyo, Japan
Department of Obstetrics, Gynecology & Reproduction, Hospital Universitari Dexeus, Barcelona, Spain
Neonatology Division and NICU, Hospital General Universitario “Gregorio Marañón” Complutense University of Madrid, Madrid, Spain
Department of Obstetrics & Gynecology, San Marcos National University, Lima, Peru
Fetal Medicine Unit, Department of Obstetrics & Gynecology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
Department of Obstetrics & Gynecology, Centro Medico ABC Santa Fe, Mexico City, Mexico
Department of Neonatology, University Hospital of Obstetrics & Gynecology “Maichin dom”, Medical University Sofia, Bulgaria
Department of Obstetrics & Gynecology, Barbara and Donald Zucker School of Medicine at Hofstra/Northwell and Lenox Hill Hospital, New York, USA
Neonatal Unit, Department of Obstetrics & Gynecology, Clinical Hospital “Sveti Duh”, Zagreb, Medical School, University of Zagreb, Croatia

Correspondence

Cihat Şen, Perinatal Medicine Foundation and Department of Obstetrics & Gynecology, Memorial Bahçelievler Hospital, Istanbul, Turkey, [email protected]

Publication History

Manuscript Received: February 05, 2022

Last Revision Date: February 05, 2022

Manuscript Accepted: February 05, 2022

Earlyview Date: February 06, 2022

Publication date: April 05, 2022

Conflicts of Interest

Research funding: None declared.

Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

Conflicts of interest: Authors state no conflict of interest.

Informed consent: Not applicable.

Ethical approval: Not applicable.

This statement follows the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation, bringing together groups and individuals throughout the world with the goal of improving the use of antenatal corticosteroids (ACS) for fetal maturation in Coronavirus Disease 2019 (COVID-19). Pregnant women with COVID-19 are at increased risk of hospitalization, admission to intensive care unit and mechanical ventilation compared to non-pregnant patients. Thus, obstetricians may face the dilemma of initiating maternal corticosteroid therapy for maternal indication while weighing its potential adverse effects on the fetus. As there is no evidence on the effect of betamethasone in pregnant women with COVID-19, dexamethasone should be preferably used for fetal maturation, if available. As a recommendation, for pregnant women with COVID-19 who are oxygen dependent or under mechanical ventilation and meet the criteria for ACS, the usual doses of dexamethasone should be administered, followed by oral prednisolone 40 mg OD or intravenous hydrocortisone 80 mg BD for up to 10 days.

Keywords

Corticosteroids, fetal maturation, COVID-19.

Pregnant women with Coronavirus Disease 2019 (COVID-19) are at increased risk of hospitalization, admission to intensive care unit and mechanical ventilation compared to non-pregnant patients. Thus, obstetricians may face the dilemma of initiating maternal corticosteroid therapy for maternal indication while weighing its potential adverse effects on the fetus.[1] On the other hand, the neonatal benefits of antenatal corticosteroids (ACS) in women at high risk of preterm birth within the next 7 days have been well established.[2]
The use of glucocorticoids as a means of immune-modulatory therapy in oxygen dependent COVID-19 patients is supported by the results of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial;[3] the use of dexamethasone for up to 10 days significantly reduced 28-day mortality in COVID-19 patients receiving invasive mechanical ventilation or oxygen without invasive mechanical ventilation (29.3% vs. 41.4%; RR: 0.64; 95% CI: 0.51–0.81) and in those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; RR: 0.82; 95% CI: 0.72–0.94). Conversely, there was a trend towards increased mortality in those patients receiving no respiratory support at randomization (17.8% vs 14.0%; RR: 1.19; 95% CI: 0.91–1.55).[3] It is worthy of note that only six pregnant women were included in the RECOVERY trial and, as per protocol for pregnant women, they received either oral prednisolone or intravenous hydrocortisone instead of dexamethasone, as these, contrary to dexamethasone, do not cross the placenta in significant quantity.[4] Based on this safety signal of possibly increased mortality among patients with mild COVID-19 receiving dexamethasone, the indications for ACS should be limited to obstetrical indications with expected preterm delivery within the next 7 days.[5] As there is no evidence on the effect of betamethasone in pregnant women with COVID-19, dexamethasone should be preferably used for fetal maturation, if available.

Recommendation

For pregnant women with COVID-19 who are oxygen dependent or under mechanical ventilation and meet the criteria for ACS, the usual doses of dexamethasone (4 doses of 6 mg IM at 12 h intervals) should be administered, followed by oral prednisolone 40 mg OD or intravenous hydrocortisone 80 mg BD for up to 10 days.

References

Allotey J, Stallings E, Bonet M, Yap M, Chatterjee S, Kew T, et al.; PregCOV-19 Living Systematic Review Consortium. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ 2020;370:m3320. [PubMed] [CrossRef]

Dagklis T, Tsakiridis I, Papazisis G, Athanasiadis A. Efficacy and safety of corticosteroids’ administration for pulmonary immaturity in anticipated preterm delivery. Curr Pharm Des 2021;27:3754–61. [PubMed] [CrossRef]

Group RC, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al.; RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021;384:693–704. [PubMed] [CrossRef]

Kemp MW, Newnham JP, Challis JG, Jobe AH, Stock SJ. The clinical use of corticosteroids in pregnancy. Hum Reprod Update 2016;22:240–59. [PubMed] [CrossRef]

Vidaeff AC, Aagaard KM, Belfort MA. Antenatal corticosteroids in COVID-19 perspective. World J Exp Med 2021;11:37–43. [PubMed] [CrossRef]

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