Subscribe to RSS
![](/products/assets/desktop/img/oa-logo.png)
DOI: 10.1055/a-2202-5363
Administration of Antenatal Corticosteroids: Optimal Timing
Article in several languages: English | deutsch![](https://www.thieme-connect.de/media/gebfra/202401/lookinside/thumbnails/10-1055-a-2202-5363_en-1.jpg)
Abstract
The effectiveness of antenatal corticosteroids (ACS) in significantly reducing respiratory distress syndrome (RDS) depends crucially on the timing. It is successful if delivery takes place between 24 hours and seven days following administration; after this period, the side effects seem to predominate. In addition, an increased rate of mental impairment and behavioral disorders are observed in children born full-term after ACS administration. The optimal timing of ACS administration depends crucially on the given indication; to date, it has been achieved in only 25–40% of cases. ACS administration is always indicated in PPROM, in severe early pre-eclampsia, in fetal IUGR with zero or reverse flow in the umbilical artery, in placenta previa with bleeding, and in patients experiencing premature labor with a cervical length < 15 mm. The risk of women with asymptomatic cervical insufficiency giving birth within seven days is very low. In this case, ACS should not be administered even if the patient’s cervical length is less than 15 mm, provided that the cervix is closed and there are no other risk factors for a premature birth. The development of further diagnostic methods with improved power to predict premature birth is urgently needed in order to optimize the timing of ACS administration in this patient population. Caution when administering ACS is also indicated in women experiencing premature labor who have a cervical length ≥ 15 mm. Further studies using amniocentesis are needed in order to identify the patient population with microbial invasion of the amniotic cavity/intra-amniotic infection (MIAC/IAI), and to define threshold values at which delivery is indicated. ACS administration is not performed as an emergency measure, usually not even before transfer to a perinatal center. Therefore, whenever possible, the indication for ACS administration should be determined by a clinician who is highly experienced in perinatology.
Publication History
Received: 31 July 2023
Accepted after revision: 31 October 2023
Article published online:
03 January 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References/Literatur
- 1 Roberts D, Brown J, Medley N. et al. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2017; (03) CD004454 DOI: 10.1002/14651858.CD004454.pub3. (PMID: 28321847)
- 2 Berger R, Kyvernitakis I, Maul H. Administration of Antenatal Corticosteroids: Current State of Knowledge. Geburtshilfe Frauenheilkd 2022; 82: 287-296 DOI: 10.1055/a-1555-3444. (PMID: 35250378)
- 3 Biedermann R, Schleussner E, Lauten A. et al. Inadequate Timing Limits the Benefit of Antenatal Corticosteroids on Neonatal Outcome: Retrospective Analysis of a High-Risk Cohort of Preterm Infants in a Tertiary Center in Germany. Geburtshilfe Frauenheilkd 2022; 82: 317-325 DOI: 10.1055/a-1608-1138. (PMID: 35250380)
- 4 Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2006; (03) CD004454 DOI: 10.1002/14651858.CD004454.pub2. (PMID: 16856047)
- 5 Fortmann I, Mertens L, Boeckel H. et al. A Timely Administration of Antenatal Steroids Is Highly Protective Against Intraventricular Hemorrhage: An Observational Multicenter Cohort Study of Very Low Birth Weight Infants. Front Pediatr 2022; 10: 721355 DOI: 10.3389/fped.2022.721355. (PMID: 35372176)
- 6 Liebowitz M, Clyman RI. Antenatal Betamethasone: A Prolonged Time Interval from Administration to Delivery Is Associated with an Increased Incidence of Severe Intraventricular Hemorrhage in Infants Born before 28 Weeks Gestation. J Pediatr 2016; 177: 114-120.e1 DOI: 10.1016/j.jpeds.2016.07.002. (PMID: 27514239)
- 7 Räikkönen K, Gissler M, Kajantie E. Associations Between Maternal Antenatal Corticosteroid Treatment and Mental and Behavioral Disorders in Children. JAMA 2020; 323: 1924-1933 DOI: 10.1001/jama.2020.3937. (PMID: 32427304)
- 8 Räikkönen K, Gissler M, Tapiainen T. et al. Associations Between Maternal Antenatal Corticosteroid Treatment and Psychological Developmental and Neurosensory Disorders in Children. JAMA Netw Open 2022; 5: e2228518 DOI: 10.1001/jamanetworkopen.2022.28518. (PMID: 36001315)
- 9 Tao S, Du J, Chi X. et al. Associations between antenatal corticosteroid exposure and neurodevelopment in infants. Am J Obstet Gynecol 2022; 227: 759.e1-759.e15 DOI: 10.1016/j.ajog.2022.05.060. (PMID: 35667419)
- 10 Levin HI, Ananth CV, Benjamin-Boamah C. et al. Clinical indication and timing of antenatal corticosteroid administration at a single centre. BJOG 2016; 123: 409-414 DOI: 10.1111/1471-0528.13730. (PMID: 26485686)
- 11 Razaz N, Skoll A, Fahey J. et al. Trends in optimal, suboptimal, and questionably appropriate receipt of antenatal corticosteroid prophylaxis. Obstet Gynecol 2015; 125: 288-296 DOI: 10.1097/AOG.0000000000000629. (PMID: 25568996)
- 12 Makhija NK, Tronnes AA, Dunlap BS. et al. Antenatal corticosteroid timing: accuracy after the introduction of a rescue course protocol. Am J Obstet Gynecol 2016; 214: 120.e1-120.e6 DOI: 10.1016/j.ajog.2015.08.018. (PMID: 26283458)
- 13 Mercer BM, Miodovnik M, Thurnau GR. et al. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. JAMA 1997; 278: 989-995 (PMID: 9307346)
- 14 Melamed N, Hadar E, Ben-Haroush A. et al. Factors affecting the duration of the latency period in preterm premature rupture of membranes. J Matern Fetal Neonatal Med 2009; 22: 1051-1056 DOI: 10.3109/14767050903019650. (PMID: 19900043)
- 15 Pergialiotis V, Bellos I, Fanaki M. et al. The impact of residual oligohydramnios following preterm premature rupture of membranes on adverse pregnancy outcomes: a meta-analysis. Am J Obstet Gynecol 2020; 222: 628-630 DOI: 10.1016/j.ajog.2020.02.022. (PMID: 32109463)
- 16 Borgida AF, Mills AA, Feldman DM. et al. Outcome of pregnancies complicated by ruptured membranes after genetic amniocentesis. Am J Obstet Gynecol 2000; 183: 937-939 DOI: 10.1067/mob.2000.108872. (PMID: 11035342)
- 17 Berger R, Abele H, Bahlmann F. et al. Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, September 2022) – Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and on the Management of Preterm Premature Rupture of Membranes. Geburtshilfe Frauenheilkd 2023; 83: 569-601 DOI: 10.1055/a-2044-0345. (PMID: 37169014)
- 18 Porreco R, Garite TJ, Combs CA. et al. Booster course of antenatal corticosteroids after preterm prelabor rupture of membranes: a double-blind randomized trial. Am J Obstet Gynecol MFM 2023; 5: 100896 DOI: 10.1016/j.ajogmf.2023.100896. (PMID: 36796641)
- 19 Brookfield KF, El-Sayed YY, Chao L. et al. Antenatal corticosteroids for preterm premature rupture of membranes: single or repeat course?. Am J Perinatol 2015; 32: 537-544 DOI: 10.1055/s-0034-1396690. (PMID: 25545441)
- 20 Gyamfi-Bannerman C, Son M. Preterm premature rupture of membranes and the rate of neonatal sepsis after two courses of antenatal corticosteroids. Obstet Gynecol 2014; 124: 999-1003 DOI: 10.1097/AOG.0000000000000460. (PMID: 25437730)
- 21 Webster JC, Oakley RH, Jewell CM. et al. Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative beta isoform: a mechanism for the generation of glucocorticoid resistance. Proc Natl Acad Sci U S A 2001; 98: 6865-6870 DOI: 10.1073/pnas.121455098. (PMID: 11381138)
- 22 Marketon JI, Sternberg EM. The glucocorticoid receptor: a revisited target for toxins. Toxins (Basel) 2010; 2: 1357-1380 DOI: 10.3390/toxins2061357. (PMID: 22069642)
- 23 Garite TJ, Kurtzman J, Maurel K. et al. Impact of a ‘rescue course’ of antenatal corticosteroids: a multicenter randomized placebo-controlled trial. Am J Obstet Gynecol 2009; 200: 248.e1-248.e9 DOI: 10.1016/j.ajog.2009.01.021. (PMID: 19254583)
- 24 Baghlaf H, Snelgrove JW, Li Q. et al. One vs 2 courses of antenatal corticosteroids in pregnancies at risk of preterm birth: a secondary analysis of the MACS trial. Am J Obstet Gynecol MFM 2023; 5: 101002 DOI: 10.1016/j.ajogmf.2023.101002. (PMID: 37149145)
- 25 Peltoniemi OM, Kari MA, Tammela O. et al. Randomized trial of a single repeat dose of prenatal betamethasone treatment in imminent preterm birth. Pediatrics 2007; 119: 290-298 DOI: 10.1542/peds.2006-1549. (PMID: 17272618)
- 26 Verlohren S, Brennecke SP, Galindo A. et al. Clinical interpretation and implementation of the sFlt-1/PlGF ratio in the prediction, diagnosis and management of preeclampsia. Pregnancy Hypertens 2022; 27: 42-50 DOI: 10.1016/j.preghy.2021.12.003. (PMID: 34915395)
- 27 Sovio U, Gaccioli F, Cook E. et al. Prediction of Preeclampsia Using the Soluble fms-Like Tyrosine Kinase 1 to Placental Growth Factor Ratio: A Prospective Cohort Study of Unselected Nulliparous Women. Hypertension 2017; 69: 731-738 DOI: 10.1161/HYPERTENSIONAHA.116.08620. (PMID: 28167687)
- 28 Dragan I, Wright D, Fiolna M. et al. Development of pre-eclampsia within 4 weeks of sFlt-1/PlGF ratio > 38: comparison of performance at 31–34 vs 35–37 weeks’ gestation. Ultrasound Obstet Gynecol 2017; 49: 209-212 DOI: 10.1002/uog.17310. (PMID: 27671743)
- 29 Cerdeira AS, O’Sullivan J, Ohuma EO. et al. Performance of soluble fms-like tyrosine kinase-1-to-placental growth factor ratio of ≥ 85 for ruling in preeclampsia within 4 weeks. Am J Obstet Gynecol 2021; 224: 322-323 DOI: 10.1016/j.ajog.2020.11.007. (PMID: 33207235)
- 30 Rana S, Salahuddin S, Mueller A. et al. Angiogenic biomarkers in triage and risk for preeclampsia with severe features. Pregnancy Hypertens 2018; 13: 100-106 DOI: 10.1016/j.preghy.2018.05.008. (PMID: 30177034)
- 31 Villalaín C, Herraiz I, Valle L. et al. Maternal and Perinatal Outcomes Associated With Extremely High Values for the sFlt-1 (Soluble fms-Like Tyrosine Kinase 1)/PlGF (Placental Growth Factor) Ratio. J Am Heart Assoc 2020; 9: e015548 DOI: 10.1161/JAHA.119.015548. (PMID: 32248765)
- 32 Zeisler H, Llurba E, Chantraine FJ. et al. Soluble fms-like tyrosine kinase-1 to placental growth factor ratio: ruling out pre-eclampsia for up to 4 weeks and value of retesting. Ultrasound Obstet Gynecol 2019; 53: 367-375 DOI: 10.1002/uog.19178. (PMID: 30014562)
- 33 Cluver CA, Hannan NJ, van Papendorp E. et al. Esomeprazole to treat women with preterm preeclampsia: a randomized placebo controlled trial. Am J Obstet Gynecol 2018; 219: 388.e1-388.e17 DOI: 10.1016/j.ajog.2018.07.019. (PMID: 30055127)
- 34 Haddad B, Deis S, Goffinet F. et al. Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks’ gestation. Am J Obstet Gynecol 2004; 190: 1590-1595 DOI: 10.1016/j.ajog.2004.03.050. (PMID: 15284743)
- 35 Chammas MF, Nguyen TM, Li MA. et al. Expectant management of severe preterm preeclampsia: is intrauterine growth restriction an indication for immediate delivery?. Am J Obstet Gynecol 2000; 183: 853-858 DOI: 10.1067/mob.2000.109049. (PMID: 11035325)
- 36 Sibai BM, Mercer BM, Schiff E. et al. Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks’ gestation: a randomized controlled trial. Am J Obstet Gynecol 1994; 171: 818-822 DOI: 10.1016/0002-9378(94)90104-x. (PMID: 8092235)
- 37 Odendaal HJ, Pattinson RC, Bam R. et al. Aggressive or expectant management for patients with severe preeclampsia between 28–34 weeks’ gestation: a randomized controlled trial. Obstet Gynecol 1990; 76: 1070-1075 (PMID: 2234715)
- 38 von Dadelszen P, Payne B, Li J. et al. Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model. Lancet 2011; 377: 219-227 DOI: 10.1016/S0140-6736(10)61351-721185591.
- 39 Thornton JG, Hornbuckle J, Vail A. et al. Infant wellbeing at 2 years of age in the Growth Restriction Intervention Trial (GRIT): multicentred randomised controlled trial. Lancet 2004; 364: 513-520 DOI: 10.1016/S0140-6736(04)16809-8. (PMID: 15302194)
- 40 Lees CC, Marlow N, van Wassenaer-Leemhuis A. et al. 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial. Lancet 2015; 385: 2162-2172 DOI: 10.1016/S0140-6736(14)62049-3. (PMID: 25747582)
- 41 Melamed N, Baschat A, Yinon Y. et al. FIGO (international Federation of Gynecology and obstetrics) initiative on fetal growth: best practice advice for screening, diagnosis, and management of fetal growth restriction. Int J Gynaecol Obstet 2021; 152 (Suppl. 01) 3-57 DOI: 10.1002/ijgo.13522. (PMID: 33740264)
- 42 Cahill LS, Whitehead CL, Hobson SR. et al. Effect of maternal betamethasone administration on feto-placental vascular resistance in the mouse†. Biol Reprod 2019; 101: 823-831 DOI: 10.1093/biolre/ioz128. (PMID: 31318405)
- 43 Schaap AH, Wolf H, Bruinse HW. et al. Effects of antenatal corticosteroid administration on mortality and long-term morbidity in early preterm, growth-restricted infants. Obstet Gynecol 2001; 97: 954-960 DOI: 10.1016/s0029-7844(01)01343-6. (PMID: 11384702)
- 44 Magann EF, Haram K, Ounpraseuth S. et al. Use of antenatal corticosteroids in special circumstances: a comprehensive review. Acta Obstet Gynecol Scand 2017; 96: 395-409 DOI: 10.1111/aogs.13104. (PMID: 28130929)
- 45 Familiari A, Napolitano R, Visser GHA. et al. Antenatal corticosteroids and perinatal outcome in late fetal growth restriction: analysis of prospective cohort. Ultrasound Obstet Gynecol 2023; 61: 191-197 DOI: 10.1002/uog.26127. (PMID: 36412975)
- 46 Esplin MS, Elovitz MA, Iams JD. et al. Predictive Accuracy of Serial Transvaginal Cervical Lengths and Quantitative Vaginal Fetal Fibronectin Levels for Spontaneous Preterm Birth Among Nulliparous Women. JAMA 2017; 317: 1047-1056 DOI: 10.1001/jama.2017.1373. (PMID: 28291893)
- 47 Tsakiridis I, Dagklis T, Sotiriadis A. et al. Third-trimester cervical length assessment for the prediction of spontaneous late preterm birth. J Matern Fetal Neonatal Med 2023; 36: 2201368 DOI: 10.1080/14767058.2023.2201368. (PMID: 37037654)
- 48 Gulersen M, Divon MY, Krantz D. et al. The risk of spontaneous preterm birth in asymptomatic women with a short cervix (≤ 25 mm) at 23–28 weeks’ gestation. Am J Obstet Gynecol MFM 2020; 2: 100059 DOI: 10.1016/j.ajogmf.2019.100059. (PMID: 33345952)
- 49 Richards DS, Wong LF, Esplin MS. et al. Anticipatory Corticosteroid Administration to Asymptomatic Women with a Short Cervix. Am J Perinatol 2018; 35: 397-404 DOI: 10.1055/s-0037-1607444. (PMID: 29100259)
- 50 Zork N, Gulersen M, Mardy A. et al. The utility of fetal fibronectin in asymptomatic singleton and twin pregnancies with a cervical length ≤ 10 mm. J Matern Fetal Neonatal Med 2020; 33: 2865-2871 DOI: 10.1080/14767058.2018.1562541. (PMID: 30572777)
- 51 Magro-Malosso E, Seravalli V, Cozzolino M. et al. Prediction of preterm delivery by fetal fibronectin in symptomatic and asymptomatic women with cervical length ≤ 20 mm. J Matern Fetal Neonatal Med 2017; 30: 294-297 DOI: 10.3109/14767058.2016.1171309. (PMID: 27052846)
- 52 Kyvernitakis I, Lauer P, Malan M. et al. A novel aspiration technique to assess cervical remodelling in patients with or without cervical shortening: Sequence of first changes, definition of cut-off values and impact of cervical pessary, stratified for cervical length. PLoS One 2023; 18: e0283944 DOI: 10.1371/journal.pone.0283944. (PMID: 37023066)
- 53 Gudicha DW, Romero R, Gomez-Lopez N. et al. The amniotic fluid proteome predicts imminent preterm delivery in asymptomatic women with a short cervix. Sci Rep 2022; 12: 11781 DOI: 10.1038/s41598-022-15392-3. (PMID: 35821507)
- 54 American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics. Practice Bulletin No. 171: Management of Preterm Labor. Obstet Gynecol 2016; 128: e155-e164 DOI: 10.1097/AOG.0000000000001711. (PMID: 27661654)
- 55 Nijman TA, van Vliet EO, Koullali B. et al. Antepartum and intrapartum interventions to prevent preterm birth and its sequelae. Semin Fetal Neonatal Med 2016; 21: 121-128 DOI: 10.1016/j.siny.2016.01.004. (PMID: 26875954)
- 56 van Baaren GJ, Vis JY, Wilms FF. et al. Predictive value of cervical length measurement and fibronectin testing in threatened preterm labor. Obstet Gynecol 2014; 123: 1185-1192 DOI: 10.1097/AOG.0000000000000229. (PMID: 24807328)
- 57 Palacio M, Cobo T, Bosch J. et al. Cervical length and gestational age at admission as predictors of intra-amniotic inflammation in preterm labor with intact membranes. Ultrasound Obstet Gynecol 2009; 34: 441-447 DOI: 10.1002/uog.6437. (PMID: 19731395)
- 58 Combs CA, Gravett M, Garite TJ. et al. Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol 2014; 210: 125.e1-125.e15 DOI: 10.1016/j.ajog.2013.11.032. (PMID: 24274987)
- 59 Romero R, Miranda J, Chaiworapongsa T. et al. Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Reprod Immunol 2014; 72: 458-474 DOI: 10.1111/aji.12296. (PMID: 25078709)
- 60 Cobo T, Aldecoa V, Figueras F. et al. Development and validation of a multivariable prediction model of spontaneous preterm delivery and microbial invasion of the amniotic cavity in women with preterm labor. Am J Obstet Gynecol 2020; 223: 421.e1-421.e14 DOI: 10.1016/j.ajog.2020.02.049. (PMID: 32147290)
- 61 Cobo T, Aldecoa V, Bartha JL. et al. Assessment of an intervention to optimise antenatal management of women admitted with preterm labour and intact membranes using amniocentesis-based predictive risk models: study protocol for a randomised controlled trial (OPTIM-PTL Study). BMJ Open 2021; 11: e054711 DOI: 10.1136/bmjopen-2021-054711. (PMID: 34588268)
- 62 Yoon BH, Romero R, Park JY. et al. Antibiotic administration can eradicate intra-amniotic infection or intra-amniotic inflammation in a subset of patients with preterm labor and intact membranes. Am J Obstet Gynecol 2019; 221: 142.e1-142.e22 DOI: 10.1016/j.ajog.2019.03.018. (PMID: 30928566)
- 63 IQTIG. Bundesauswertung zum Erfassungsjahr 2021 Geburtshilfe. Accessed December 01, 2023 at: https://iqtig.org/downloads/auswertung/2021/pmgebh/DeQS_PM-GEBH_2021_BUAW_V01_2022-06-30.pdf
- 64 Hamm RF, Combs CA, Aghajanian P. et al. Society for Maternal-Fetal Medicine Special Statement: Quality metrics for optimal timing of antenatal corticosteroid administration. Am J Obstet Gynecol 2022; 226: B2-B10 DOI: 10.1016/j.ajog.2022.02.021. (PMID: 35189094)
- 65 Carlo WA, McDonald SA, Fanaroff AA. et al. Association of antenatal corticosteroids with mortality and neurodevelopmental outcomes among infants born at 22 to 25 weeks’ gestation. JAMA 2011; 306: 2348-2358 DOI: 10.1001/jama.2011.1752. (PMID: 22147379)
- 66 Travers CP, Clark RH, Spitzer AR. et al. Exposure to any antenatal corticosteroids and outcomes in preterm infants by gestational age: prospective cohort study. BMJ 2017; 356: j1039 DOI: 10.1136/bmj.j1039. (PMID: 28351838)
- 67 Norman M, Piedvache A, Borch K. et al. Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals With Survival and Morbidity Among Very Preterm Infants: Results From the EPICE Cohort. JAMA Pediatr 2017; 171: 678-686 DOI: 10.1001/jamapediatrics.2017.0602. (PMID: 28505223)