European guidelines on perinatal care: corticosteroids for women at risk of preterm birth

Abstract

Summary of recommendations

1. Corticosteroids should be administered to women at a gestational age between 24⁺⁰ and 33⁺⁶weeks, when preterm birth is anticipated in the next seven days, as these have been consistently shown to reduce neonatal mortality and morbidity. (Strong-quality evidence; strong recommendation). In selected cases, extension of this period up to 34⁺⁶weeks may be considered (Expert opinion). Optimal benefits are found in infants delivered within 7 days of corticosteroid administration. Even a single-dose administration should be given to women with imminent preterm birth, as this is likely to improve neurodevelopmental outcome (Moderate-quality evidence; conditional recommendation).

2. Either betamethasone (12 mg administered intramuscularly twice, 24-hours apart) or dexamethasone (6 mg administered intramuscularly in four doses, 12-hours apart, or 12 mg administered intramuscularly twice, 24-hours apart), may be used (Moderate-quality evidence; Strong recommendation). Administration of two “all” doses is named a “course of corticosteroids”.

3. Administration between 22⁺⁰ and 23⁺⁶weeks should be considered when preterm birth is anticipated in the next seven days and active newborn life-support is indicated, taking into account parental wishes. Clear survival benefit has been observed in these cases, but the impact on short-term neurological and respiratory function, as well as long-term neurodevelopmental outcome is still unclear (Low/moderate-quality evidence; Weak recommendation).

4. Administration between 34 + 0 and 34 + 6 weeks should only be offered to a few selected cases (Expert opinion). Administration between 35⁺⁰ and 36⁺⁶weeks should be restricted to prospective randomized trials. Current evidence suggests that although corticosteroids reduce the incidence of transient tachypnea of the newborn, they do not affect the incidence of respiratory distress syndrome, and they increase neonatal hypoglycemia. Long-term safety data are lacking (Moderate quality evidence; Conditional recommendation).

5. Administration in pregnancies beyond 37⁺⁰weeks is not indicated, even for scheduled cesarean delivery, as current evidence does not suggest benefit and the long-term effects remain unknown (Low-quality evidence; Conditional recommendation).

6. Administration should be given in twin pregnancies, with the same indication and doses as for singletons. However, existing evidence suggests that it should be reserved for pregnancies at high-risk of delivering within a 7-day interval (Low-quality evidence; Conditional recommendation). Maternal diabetes mellitus is not a contraindication to the use of antenatal corticosteroids (Moderate quality evidence; Strong recommendation).

7. A single repeat course of corticosteroids can be considered in pregnancies at less than 34⁺⁰weeks gestation, if the previous course was completed more than seven days earlier, and there is a renewed risk of imminent delivery (Low-quality evidence; Conditional recommendation).

Keywords:

• Corticosteroids
• guideline
• preterm birth
• antenatal

Disclosure statement

George Daskalakis, Vasilios Pergialiotis, Ariadne Malamitsi-Puchner, Elko Gliozheni, Artur Beke, Katarzyna Kosińska-Kaczyńska, Ana Luisa Areia, and Simona Vladareanu have no conflicts of interest. No lectures, presentations, travel or personal reimbursement has been financed by any company. Magnus Domellöf received Consultation honoraria or speaker fees from Baxter AB, Baxter Deutschland GmbH, Danone Nutricia, Elgan Pharma, BioQuest Solutions Pvt. Ltd., Medscape Education/WebMD, Nestec Ltd. (Nestlé) and Nestlé Nutrition Institute. Grants/research supports from Arla Foods Ingredients. CEO of Nutrium AB. Harald Ehrhardt received Research grants from the German Research Foundation (DFG), Federal Ministry of Education and Research (BMBF), von Behring-Röntgen-Foundation and Chiesi Foundation. Member European Neonatal Research Consortium of the European Society for Paediatric Research (ESPR) and member EAPM special interest group of preterm delivery. Ehrhardt is the Member of the expert commission perinatal medicine (QS PM) of the federal quality assurance office of Hesse (LAGQH). No lectures, presentations, travel or personal reimbursement has been financed by any company. Gian Carlo Di Renzo received Research grants from Kedrion, Italy, Diabetomics Inc USA and from Italian Ministry of Health. Renzo is the Director of the PREIS School in Florence which receives unrestricted educational grants from several companies. No conflicts of interest. No lectures, presentations, travel or personal reimbursement has been financed by any company. Esin Koç received Clinical trial grants from Turkish Neonatal Society and Gazi University and also an ongoing clinical trial, products provided by Chiesi company. Koç is the President of Turkish Neonatal Society, board member of UENPS and WAPM. Marian Kacerovsky received Research grants from the Czech Research Foundation, Czehc Health Research Foundation, Ministry of Health of the Czech Republic Ministry of Education, Youth and Sports of the Czech Republic, and Ministry of Regional Development of the Czech Republic. Chairman of the Czech Society of Perinatal and Maternal-Fetal Medicine. No lectures, presentations, travel or personal reimbursement has been financed by any company. Neena Modi NM reports grants outside the submitted work from the National Institute for Health Research, Medical Research Council, British Heart Foundation, Health Data Research UK, HCA International, Nestle, Takeda Pharmaceuticals, Prolacta Life Sciences, Chiesi Pharmaceuticals and March of Dimes. NM reports a lecture fee from Nestle International and Chiesi Pharmaceuticals, and reimbursement of travel and accommodation expenses from Nestle International, Chiesi Pharmaceuticals and Prolacta Life Sciences. NM is a member of the Nestle Scientific Advisory Board, president of the UK Medical Women's Federation, vice-chair of the Strategy and Advocacy Committee of the Medical Women's International Association, past-president of the UK Royal College of Paediatrics and Child Health, president-elect of the British Medical Association, president-elect of the European Association of Perinatal Medicine, patron of the charities Keep Our NHS Public and HealthProm, trustee of the charities TheirWorld, Action Cerebral Palsy and David Harvey Trust, and trustee and council member of the UK Academy of Medical Sciences. Andrew Shennan AS has a number of research grants in the last three years related to the prediction of preterm birth, from Guys and St Thomas's Charity and government UK funding agencies. He has given online talks organised by Hologic, expences paid to instiitue. Other funding is unrelated to the subject atter of this review. Diego Ayres-de-Campos received Consultation honoraria and speaker fees for Philips Medical, Boeblingen, Germany. No conflicts of interest to declare related to the topic of this guideline. Kristiina Rull has no conflicts of interest to declare. Rull is the Member of board of Estonian Perinatology Society (2019–2022) and Member of board of Estonian Gynecologists’ Society (since 2022) Research project financed by the Clinical Medicine Institute, University of Tartu, Estonia “Fetal malformations and genetic defects: prevalence, prenatal detection rate, prognosis and treatment in Estonia 2019–2023. Thorsten Braun received Research grants from the German Research Foundation (DFG), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Developmental Origins of Health and Disease (DOHaD), Stiftung für das behinderte Kind, Haackert Stiftung. No lectures, presentations, travel or personal reimbursement has been financed by any company. Tanja Premru-Sršen received Research grants from Slovenian Research Agency and University Medical Centre Ljubljana, Slovenia. No lectures, presentations, travel, or personal reimbursement has been financed by any company. Dr. Thomas Schmitz reports receiving consulting fees from Dilafor. Bo Jacobsson received Research grants from Swedish Research Council, Norwegian Research Council, March of Dimes, Burroughs Wellcome Fund and the US National Institute of Health. During the last years performed clinical diagnostic trials on NIPT with Ariosa (completed), Natera (ongoing), Vanadis (completed) and Hologic (ongoing) with expenditures reimbursed per patient. Jacobsson also performed clinical probiotic studies with the probiotic product provided by FukoPharma (ongoing, no funding) and BioGaia (ongoing; also provided a research grant for the specific study) Previously (2018–2020) he was a collaborator in IMPACT study where Roche, Perkin Elmer and Thermo Fisher provided reagenses to PLGF analyses. No lectures, presentations, travel or personal reimbursement has been financed by any company. He is the Division Director of Maternal and Neonatal Health of the International Federation of Gynecology and Obstetrics (FIGO), Board member of the European Association of Perinatal Medicine and chair the EAPM special interest group of preterm delivery. He is the Steering group member of Genomic Medicine Sweden and is in charge of the Genomic Medicine Sweden complexe diseases group. Jacobsson is the Swedish representative in Nordic Society of Precision Medicine.