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Antenatal corticosteroid therapy for reduction of neonatal morbidity and mortality from preterm delivery

INTRODUCTION

In a landmark paper, Liggins and Howie demonstrated that a single course of antenatal corticosteroid therapy administered to women at risk for preterm delivery (PTD) reduced the incidence and severity of respiratory distress syndrome (RDS) and mortality in offspring [1]. Over a dozen randomized trials have subsequently confirmed these findings [2]. In addition, antenatal corticosteroid therapy improves circulatory stability in preterm neonates, resulting in less intraventricular hemorrhage (IVH) or necrotizing enterocolitis compared with unexposed preterm neonates.

The National Institutes of Health (NIH) [3,4], the American College of Obstetricians and Gynecologists (ACOG) [5], the Royal College of Medicine (RCP) [6], and other major organizations have recommended antenatal corticosteroid treatment for women at risk for preterm delivery prior to 34 weeks of gestation to reduce the morbidity and mortality associated with preterm birth.

This topic will review the evidence supporting the use of antenatal corticosteroids to improve neonatal outcomes in women at risk for preterm delivery, pharmacological issues associated with this therapy, and other clinical concerns from administration of antenatal corticosteroids.

MECHANISM OF ACTION

Antenatal corticosteroid therapy leads to architectural and biochemical changes that improve both lung mechanics (maximal lung volume, compliance) and gas exchange. These changes are primarily the result of accelerated morphologic development of type 1 and type 2 pneumocytes [7-11]. Type 1 pneumocytes are responsible for gas exchange in the alveoli, while type 2 pneumocytes are responsible for production and secretion of surfactant (figure 1). Antenatal corticosteroids also alter production of surfactant binding proteins and enhance fetal lung antioxidant enzymes. For these changes to occur, however, the lungs need to have reached a stage of development that is biologically responsive to corticosteroids (see 'Gestational age at administration' below).

The biologic rationale for repeating antenatal corticosteroid therapy is based upon the observation that biochemical stimulation of surfactant production appears to be reversible in cell culture models (eg, surfactant protein mRNA levels decline to control levels after cortisol is removed) [8,12]. However, other beneficial effects, such as cytostructural maturation, persist (in rhesus monkeys) after steroid exposure is withdrawn [13].

                                 

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Literature review current through: Jul 2014. | This topic last updated: May 20, 2014.
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References
Top
  1. Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 1972; 50:515.
  2. Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2006; :CD004454.
  3. Report on the Consensus Development Conference on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. U.S. Department of Health and Human Services, Public Health Service, NIH Pub No. 95-3784, November 1994.
  4. Antenatal Corticosteroids Revisited: Repeat Courses. National Institutes of Health Consensus Development Conference Statement August 17-18, 2000. http://consensus.nih.gov/2000/2000AntenatalCorticosteroidsRevisted112html.htm (Accessed on August 29, 2013).
  5. ACOG Committee on Obstetric Practice. ACOG Committee Opinion No. 475: antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol 2011; 117:422.
  6. RCOG Guidelines. Number 7. ACS to prevent respiratory distress syndrome. London:RCOG 1996.
  7. Smolders-de Haas H, Neuvel J, Schmand B, et al. Physical development and medical history of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome: a 10- to 12-year follow-up. Pediatrics 1990; 86:65.
  8. Ballard PL, Ballard RA. Scientific basis and therapeutic regimens for use of antenatal glucocorticoids. Am J Obstet Gynecol 1995; 173:254.
  9. Ballard PL. Hormonal regulation of surfactant in fetal life. Mead Johnson Symp Perinat Dev Med 1978; :25.
  10. Walther FJ, David-Cu R, Mehta EI, et al. Higher lung antioxidant enzyme activity persists after single dose of corticosteroids in preterm lambs. Am J Physiol 1996; 271:L187.
  11. Polk DH, Ikegami M, Jobe AH, et al. Preterm lung function after retreatment with antenatal betamethasone in preterm lambs. Am J Obstet Gynecol 1997; 176:308.
  12. Vidaeff AC, Ramin SM, Gilstrap LC 3rd, Alcorn JL. In vitro quantification of dexamethasone-induced surfactant protein B expression in human lung cells. J Matern Fetal Neonatal Med 2004; 15:155.
  13. Bunton TE, Plopper CG. Triamcinolone-induced structural alterations in the development of the lung of the fetal rhesus macaque. Am J Obstet Gynecol 1984; 148:203.
  14. Crowley PA. Antenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972 to 1994. Am J Obstet Gynecol 1995; 173:322.
  15. Gates S, Brocklehurst P. Decline in effectiveness of antenatal corticosteroids with time to birth: real or artefact? BMJ 2007; 335:77.
  16. Smith LM, Altamirano AK, Ervin MG, et al. Prenatal glucocorticoid exposure and postnatal adaptation in premature newborn baboons ventilated for six days. Am J Obstet Gynecol 2004; 191:1688.
  17. Brownfoot FC, Gagliardi DI, Bain E, et al. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2013; 8:CD006764.
  18. Bar-Lev MR, Maayan-Metzger A, Matok I, et al. Short-term outcomes in low birth weight infants following antenatal exposure to betamethasone versus dexamethasone. Obstet Gynecol 2004; 104:484.
  19. Baud O, Foix-L'Helias L, Kaminski M, et al. Antenatal glucocorticoid treatment and cystic periventricular leukomalacia in very premature infants. N Engl J Med 1999; 341:1190.
  20. Walfisch A, Hallak M, Mazor M. Multiple courses of antenatal steroids: risks and benefits. Obstet Gynecol 2001; 98:491.
  21. Goldenberg RL, Wright LL. Repeated courses of antenatal corticosteroids. Obstet Gynecol 2001; 97:316.
  22. Ballard PL, Granberg P, Ballard RA. Glucocorticoid levels in maternal and cord serum after prenatal betamethasone therapy to prevent respiratory distress syndrome. J Clin Invest 1975; 56:1548.
  23. Hashima JN, Lai Y, Wapner RJ, et al. The effect of maternal body mass index on neonatal outcome in women receiving a single course of antenatal corticosteroids. Am J Obstet Gynecol 2010; 202:263.e1.
  24. Gyamfi C, Mele L, Wapner RJ, et al. The effect of plurality and obesity on betamethasone concentrations in women at risk for preterm delivery. Am J Obstet Gynecol 2010; 203:219.e1.
  25. Moore LE, Martin JN Jr. When betamethasone and dexamethasone are unavailable: hydrocortisone. J Perinatol 2001; 21:456.
  26. Morrison JC, Whybrew WD, Bucovaz ET, Schneider JM. Injection of corticosteroids into mother to prevent neonatal respiratory distress syndrome. Am J Obstet Gynecol 1978; 131:358.
  27. Crowther CA, Alfirevic Z, Han S, Haslam RR. Thyrotropin-releasing hormone added to corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease. Cochrane Database Syst Rev 2013; 11:CD000019.
  28. Raju TN, Mercer BM, Burchfield DJ, Joseph GF Jr. Periviable birth: executive summary of a joint workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists. Am J Obstet Gynecol 2014; 210:406.
  29. 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.
  30. Moore KL, Persaud TVN. The respiratory system. In: The Developing Human, 5th ed, WB Saunders, Philadelphia 1993. p.226.
  31. Stutchfield P, Whitaker R, Russell I, Antenatal Steroids for Term Elective Caesarean Section (ASTECS) Research Team. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ 2005; 331:662.
  32. Shanks A, Gross G, Shim T, et al. Administration of steroids after 34 weeks of gestation enhances fetal lung maturity profiles. Am J Obstet Gynecol 2010; 203:47.e1.
  33. Porto AM, Coutinho IC, Correia JB, Amorim MM. Effectiveness of antenatal corticosteroids in reducing respiratory disorders in late preterm infants: randomised clinical trial. BMJ 2011; 342:d1696.
  34. Stutchfield PR, Whitaker R, Gliddon AE, et al. Behavioural, educational and respiratory outcomes of antenatal betamethasone for term caesarean section (ASTECS trial). Arch Dis Child Fetal Neonatal Ed 2013; 98:F195.
  35. American College of Obstetricians and Gynecologists, Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin no. 127: Management of preterm labor. Obstet Gynecol 2012; 119:1308.
  36. 2010 Antenatal corticosteroids to reduce neonatal morbidity and mortality. Greentop Guideline no 7. London: Royal College of Obstetricians and Gynaecologists. Available at www.rcog.org.uk (Accessed on October 18, 2012).
  37. Gross I, Ballard PL, Ballard RA, et al. Corticosteroid stimulation of phosphatidylcholine synthesis in cultured fetal rabbit lung: evidence for de novo protein synthesis mediated by glucocorticoid receptors. Endocrinology 1983; 112:829.
  38. Ikegami M, Polk D, Jobe A. Minimum interval from fetal betamethasone treatment to postnatal lung responses in preterm lambs. Am J Obstet Gynecol 1996; 174:1408.
  39. Elimian A, Figueroa R, Spitzer AR, et al. Antenatal corticosteroids: are incomplete courses beneficial? Obstet Gynecol 2003; 102:352.
  40. Verdurmen KM, Renckens J, van Laar JO, Oei SG. The Influence of Corticosteroids on Fetal Heart Rate Variability: A Systematic Review of the Literature. Obstet Gynecol Surv 2013; 68:811.
  41. Subtil D, Tiberghien P, Devos P, et al. Immediate and delayed effects of antenatal corticosteroids on fetal heart rate: a randomized trial that compares betamethasone acetate and phosphate, betamethasone phosphate, and dexamethasone. Am J Obstet Gynecol 2003; 188:524.
  42. Mulder EJ, Derks JB, Visser GH. Antenatal corticosteroid therapy and fetal behaviour: a randomised study of the effects of betamethasone and dexamethasone. Br J Obstet Gynaecol 1997; 104:1239.
  43. Senat MV, Minoui S, Multon O, et al. Effect of dexamethasone and betamethasone on fetal heart rate variability in preterm labour: a randomised study. Br J Obstet Gynaecol 1998; 105:749.
  44. Rotmensch S, Liberati M, Vishne TH, et al. The effect of betamethasone and dexamethasone on fetal heart rate patterns and biophysical activities. A prospective randomized trial. Acta Obstet Gynecol Scand 1999; 78:493.
  45. Rotmensch S, Lev S, Kovo M, et al. Effect of betamethasone administration on fetal heart rate tracing: a blinded longitudinal study. Fetal Diagn Ther 2005; 20:371.
  46. Kelly MK, Schneider EP, Petrikovsky BM, Lesser ML. Effect of antenatal steroid administration on the fetal biophysical profile. J Clin Ultrasound 2000; 28:224.
  47. Rotmensch S, Liberati M, Celentano C, et al. The effect of betamethasone on fetal biophysical activities and Doppler velocimetry of umbilical and middle cerebral arteries. Acta Obstet Gynecol Scand 1999; 78:768.
  48. Katz M, Meizner I, Holcberg G, et al. Reduction or cessation of fetal movements after administration of steroids for enhancement of lung maturation. I. Clinical evaluation. Isr J Med Sci 1988; 24:5.
  49. Lee BH, Stoll BJ, McDonald SA, et al. Adverse neonatal outcomes associated with antenatal dexamethasone versus antenatal betamethasone. Pediatrics 2006; 117:1503.
  50. Schwab M, Coksaygan T, Nathanielsz PW. Betamethasone effects on ovine uterine and umbilical placental perfusion at the dose used to enhance fetal lung maturation. Am J Obstet Gynecol 2006; 194:572.
  51. Derks JB, Giussani DA, Jenkins SL, et al. A comparative study of cardiovascular, endocrine and behavioural effects of betamethasone and dexamethasone administration to fetal sheep. J Physiol 1997; 499 ( Pt 1):217.
  52. Koenen SV, Mecenas CA, Smith GS, et al. Effects of maternal betamethasone administration on fetal and maternal blood pressure and heart rate in the baboon at 0.7 of gestation. Am J Obstet Gynecol 2002; 186:812.
  53. Smith RP, Miller SL, Igosheva N, et al. Cardiovascular and endocrine responses to cutaneous electrical stimulation after fentanyl in the ovine fetus. Am J Obstet Gynecol 2004; 190:836.
  54. Miller SL, Supramaniam VG, Jenkin G, et al. Cardiovascular responses to maternal betamethasone administration in the intrauterine growth-restricted ovine fetus. Am J Obstet Gynecol 2009; 201:613.e1.
  55. Edwards A, Baker LS, Wallace EM. Changes in umbilical artery flow velocity waveforms following maternal administration of betamethasone. Placenta 2003; 24:12.
  56. Robertson MC, Murila F, Tong S, et al. Predicting perinatal outcome through changes in umbilical artery Doppler studies after antenatal corticosteroids in the growth-restricted fetus. Obstet Gynecol 2009; 113:636.
  57. Wallace EM, Baker LS. Effect of antenatal betamethasone administration on placental vascular resistance. Lancet 1999; 353:1404.
  58. Wijnberger LD, Bilardo CM, Hecher K, et al. Effect of antenatal glucocorticoid therapy on arterial and venous blood flow velocity waveforms in severely growth-restricted fetuses. Ultrasound Obstet Gynecol 2004; 23:584.
  59. Simchen MJ, Alkazaleh F, Adamson SL, et al. The fetal cardiovascular response to antenatal steroids in severe early-onset intrauterine growth restriction. Am J Obstet Gynecol 2004; 190:296.
  60. Banks BA, Cnaan A, Morgan MA, et al. Multiple courses of antenatal corticosteroids and outcome of premature neonates. North American Thyrotropin-Releasing Hormone Study Group. Am J Obstet Gynecol 1999; 181:709.
  61. Ashwood PJ, Crowther CA, Willson KJ, et al. Neonatal adrenal function after repeat dose prenatal corticosteroids: a randomized controlled trial. Am J Obstet Gynecol 2006; 194:861.
  62. Davis EP, Townsend EL, Gunnar MR, et al. Effects of prenatal betamethasone exposure on regulation of stress physiology in healthy premature infants. Psychoneuroendocrinology 2004; 29:1028.
  63. Schäffer L, Luzi F, Burkhardt T, et al. Antenatal betamethasone administration alters stress physiology in healthy neonates. Obstet Gynecol 2009; 113:1082.
  64. Waffarn F, Davis EP. Effects of antenatal corticosteroids on the hypothalamic-pituitary-adrenocortical axis of the fetus and newborn: experimental findings and clinical considerations. Am J Obstet Gynecol 2012; 207:446.
  65. Effects of antenatal dexamethasone administration in the infant: long-term follow-up. J Pediatr 1984; 104:259.
  66. Doyle LW, Kitchen WH, Ford GW, et al. Antenatal steroid therapy and 5-year outcome of extremely low birth weight infants. Obstet Gynecol 1989; 73:743.
  67. MacArthur BA, Howie RN, Dezoete JA, Elkins J. School progress and cognitive development of 6-year-old children whose mothers were treated antenatally with betamethasone. Pediatrics 1982; 70:99.
  68. Dessens AB, Haas HS, Koppe JG. Twenty-year follow-up of antenatal corticosteroid treatment. Pediatrics 2000; 105:E77.
  69. Dalziel SR, Walker NK, Parag V, et al. Cardiovascular risk factors after antenatal exposure to betamethasone: 30-year follow-up of a randomised controlled trial. Lancet 2005; 365:1856.
  70. Dalziel SR, Lim VK, Lambert A, et al. Antenatal exposure to betamethasone: psychological functioning and health related quality of life 31 years after inclusion in randomised controlled trial. BMJ 2005; 331:665.
  71. Alexander N, Rosenlöcher F, Stalder T, et al. Impact of antenatal synthetic glucocorticoid exposure on endocrine stress reactivity in term-born children. J Clin Endocrinol Metab 2012; 97:3538.
  72. Kelly BA, Lewandowski AJ, Worton SA, et al. Antenatal glucocorticoid exposure and long-term alterations in aortic function and glucose metabolism. Pediatrics 2012; 129:e1282.
  73. Stubblefield PG. Pulmonary edema occurring after therapy with dexamethasone and terbutaline for premature labor: a case report. Am J Obstet Gynecol 1978; 132:341.
  74. Ogburn PL Jr, Julian TM, Williams PP, Thompson TR. The use of magnesium sulfate for tocolysis in preterm labor complicated by twin gestation and betamimetic-induced pulmonary edema. Acta Obstet Gynecol Scand 1986; 65:793.
  75. Ogunyemi D. Risk factors for acute pulmonary edema in preterm delivery. Eur J Obstet Gynecol Reprod Biol 2007; 133:143.
  76. Amorim MM, Santos LC, Faúndes A. Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia. Am J Obstet Gynecol 1999; 180:1283.
  77. Mastrobattista JM, Patel N, Monga M. Betamethasone alteration of the one-hour glucose challenge test in pregnancy. J Reprod Med 2001; 46:83.
  78. Gurbuz A, Karateke A, Ozturk G, Kabaca C. Is 1-hour glucose screening test reliable after a short-term administration of antenatal betamethasone? Am J Perinatol 2004; 21:415.
  79. Vaisbuch E, Levy R, Hagay Z. The effect of betamethasone administration to pregnant women on maternal serum indicators of infection. J Perinat Med 2002; 30:287.
  80. Kadanali S, Ingeç M, Küçüközkan T, et al. Changes in leukocyte, granulocyte and lymphocyte counts following antenatal betamethasone administration to pregnant women. Int J Gynaecol Obstet 1997; 58:269.
  81. Crowther CA, McKinlay CJ, Middleton P, Harding JE. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes. Cochrane Database Syst Rev 2011; :CD003935.
  82. Wapner RJ, Sorokin Y, Thom EA, et al. Single versus weekly courses of antenatal corticosteroids: evaluation of safety and efficacy. Am J Obstet Gynecol 2006; 195:633.
  83. Sawady J, Mercer BM, Wapner RJ, et al. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network Beneficial Effects of Antenatal Repeated Steroids study: impact of repeated doses of antenatal corticosteroids on placental growth and histologic findings. Am J Obstet Gynecol 2007; 197:281.e1.
  84. Murphy KE, Willan AR, Hannah ME, et al. Effect of antenatal corticosteroids on fetal growth and gestational age at birth. Obstet Gynecol 2012; 119:917.
  85. Murphy KE, Hannah ME, Willan AR, et al. Maternal side-effects after multiple courses of antenatal corticosteroids (MACS): the three-month follow-up of women in the randomized controlled trial of MACS for preterm birth study. J Obstet Gynaecol Can 2011; 33:909.
  86. Asztalos EV, Murphy KE, Willan AR, et al. Multiple courses of antenatal corticosteroids for preterm birth study: outcomes in children at 5 years of age (MACS-5). JAMA Pediatr 2013; 167:1102.
  87. Stålnacke J, Diaz Heijtz R, Norberg H, et al. Cognitive outcome in adolescents and young adults after repeat courses of antenatal corticosteroids. J Pediatr 2013; 163:441.
  88. Battin M, Bevan C, Harding J. Growth in the neonatal period after repeat courses of antenatal corticosteroids: data from the ACTORDS randomised trial. Arch Dis Child Fetal Neonatal Ed 2012; 97:F99.
  89. Zephyrin LC, Hong KN, Wapner RJ, et al. Gestational age--specific risks vs benefits of multicourse antenatal corticosteroids for preterm labor. Am J Obstet Gynecol 2013; 209:330.e1.
  90. 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.
  91. 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.
  92. McEvoy C, Schilling D, Peters D, et al. Respiratory compliance in preterm infants after a single rescue course of antenatal steroids: a randomized controlled trial. Am J Obstet Gynecol 2010; 202:544.e1.
  93. Crowther CA, Haslam RR, Hiller JE, et al. Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial. Lancet 2006; 367:1913.
  94. Ballard PL. Hormones and lung maturation. In: Monographs on Endocrinology, Springer-Verlag, Berlin 1986. Vol 28, p.1.
  95. Ballard PL, Ballard RA. Glucocorticoid receptors and the role of glucocorticoids in fetal lung development. Proc Natl Acad Sci U S A 1972; 69:2668.
  96. Oakley RH, Cidlowski JA. Homologous down regulation of the glucocorticoid receptor: the molecular machinery. Crit Rev Eukaryot Gene Expr 1993; 3:63.
  97. Howie RN, Liggins GC. The New Zealand study of antepartum glucocorticoid treatment. In: Lung development: biological and clinical perspectives, Farrell PM (Ed), Academic Press, New York 1983. Vol 2, p.255.
  98. Khandelwal M, Chang E, Hansen C, et al. Betamethasone dosing interval: 12 or 24 hours apart? A randomized, noninferiority open trial. Am J Obstet Gynecol 2012; 206:201.e1.
  99. Haas DM, McCullough W, McNamara MF, Olsen C. The first 48 hours: Comparing 12-hour and 24-hour betamethasone dosing when preterm deliveries occur rapidly. J Matern Fetal Neonatal Med 2006; 19:365.
  100. Egerman RS, Mercer BM, Doss JL, Sibai BM. A randomized, controlled trial of oral and intramuscular dexamethasone in the prevention of neonatal respiratory distress syndrome. Am J Obstet Gynecol 1998; 179:1120.
  101. Spellacy WN, Buhi WC, Riggall FC, Holsinger KL. Human amniotic fluid lecithin-sphingomyelin ratio changes with estrogen or glucocorticoid treatment. Am J Obstet Gynecol 1973; 115:216.
  102. Piazze JJ, Maranghi L, Nigro G, et al. The effect of glucocorticoid therapy on fetal lung maturity indices in hypertensive pregnancies. Obstet Gynecol 1998; 92:220.
  103. Effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome. Am J Obstet Gynecol 1981; 141:276.
  104. Farrell PM, Engle MJ, Zachman RD, et al. Amniotic fluid phospholipids after maternal administration of dexamethasone. Am J Obstet Gynecol 1983; 145:484.
  105. Della Torre M, Hibbard JU, Jeong H, Fischer JH. Betamethasone in pregnancy: influence of maternal body weight and multiple gestation on pharmacokinetics. Am J Obstet Gynecol 2010; 203:254.e1.
  106. Andrews EB, Marcucci G, White A, Long W. Associations between use of antenatal corticosteroids and neonatal outcomes within the Exosurf Neonatal Treatment Investigational New Drug Program. Am J Obstet Gynecol 1995; 173:290.