Antenatal corticosteroids: The good, the bad and the unknown

Current Opinion in Obstetrics and Gynecology

Volumn 14, Issue 6, 2002, Pages 607-612

  Newnham, John P ^a   Moss, Timothy J M ^a   Nitsos, Ilias ^a   Sloboda, Deborah M ^a  

^a UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

Author keywords

Antenatal corticosteroids; Fetus; Preterm birth; Respiratory distress syndrome

Indexed keywords

CORTICOSTEROID; HYDROCORTISONE;

BRAIN DEVELOPMENT; FETUS; HUMAN; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; INSULIN RESISTANCE; INTRAUTERINE GROWTH RETARDATION; LUNG FUNCTION; NEWBORN DEATH; PREMATURE LABOR; PRENATAL CARE; PRIORITY JOURNAL; RESPIRATORY DISTRESS SYNDROME; REVIEW;

CEREBRAL HEMORRHAGE; EMBRYONIC AND FETAL DEVELOPMENT; FEMALE; FETAL DISEASES; GLUCOCORTICOIDS; HUMANS; INFANT, NEWBORN; OBSTETRIC LABOR, PREMATURE; PREGNANCY; RESPIRATORY DISTRESS SYNDROME, NEWBORN;

EID: 0036917308     PISSN: 1040872X     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001703-200212000-00006     Document Type: Review

References (53)

1. Liggins G. Premature parturition after infusion of corticotrophin or cortisol into foetal lambs. J Endocrinol 1968; 42:323-329.
2. Liggins G, Howie R. A controlled trial of antepartum glucocorticoid treatment for prevention of respiratory distress syndrome in premature infants. Pediatrics 1972; 50:515-525.
3. Crowley P. Prophylactic corticosteroids for pre-term birth. Cochrane Database Syst Rev 2000; (2):CD000065.
4. Harding JE, Pang J, Knight DB, Liggins GC. Do antenatal corticosteroids help in the setting of pre-term rupture of membranes? Am J Obstet Gynecol 2001; 184:131-139. This paper is a review of the original data in Liggins' randomized controlled trial.
5. Leviton A, Dammann O, Allred EN, et al. Antenatal corticosteroids and cranial ultrasonographic abnormalities. Am J Obstet Gynecol 1999; 181:1007-1017.
6. Canterino JC, Verma U, Visintainer PF, et al. Antenatal steroids and neonatal periventricular leukomalacia. Obstet Gynecol 2001; 97:135-139. This study of a cohort of preterm infants describes mathematically the protective action of antenatal corticosteroids on the brain.
7. Agarwal R, Chiswick ML, Rimmer S, et al. Antenatal steroids are associated with a reduction in the incidence of cerebral white matter lesions in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2002; 86:F96-F101. A cohort study describing the effects of antenatal corticosteroids in protecting the brain, delineating the role of gestational age and completeness of the course of treatment.
8. Demarini S, Dollberg S, Hoath SB, et al. Effects of antenatal corticosteroids on blood pressure in very low birth weight infants during the first 24 hours of life. J Perinatol 1999; 19:419-425.
9. Gray PH, Jones P, O'Callaghan MJ. Maternal antecedents for cerebral palsy in extremely pre-term babies: A case control study. Dev Med Child Neurol 2001; 43:580-585. In this case-control study, the authors have provided evidence that antenatal corticosteroids may prevent cerebral palsy.
10. Doyle LW, Ford GW, Riokards AL, et al. Antenatal corticosteroids and outcome at 14 years of age in children with birth weight less than 1501 grams. Pediatrics 2000; 106:E2.
11. Schaap AH, Wolf H, Bruinse HW, et al. Effects of antenatal corticosteroid administration on mortality and long-term morbidity in early pre-term, growth-restricted infants. Obstet Gynecol 2001; 97:954-960. A case-control study that is important because it includes behavioural and physical development up to school age.
12. Arad I, Durkin MS, Hinton VJ, et al. Long-term cognitive benefits of antenatal corticosteroids for prematurely born children with cranial ultrasound abnormalities. Am J Obstet Gynecol 2002; 186:818-825. An important prospective cohort study including verbal and nonverbal testing up to 8 years of age.
13. Willet KE, McMenamin P, Pinkerton KE, et al. Lung morphology and collagen and elastin content: Changes during normal development and after prenatal hormone exposure in sheep. Pediatr Res 1999; 45:615-625.
14. Jobe AH, Polk DH, Ikegami M, et al. Lung responses to ultrasound guided fetal treatments with corticosteroids in pre-term lambs. J Appl Physiol 1993; 75:2099-2105.
15. Ikegami M, Jobe AH, Newnham J, et al. Repetitive prenatal glucocorticoids improve lung function and decrease growth in pre-term lambs. Am J Respir Crit Care Med 1997; 156:178-184.
16. Grover TR, Ackerman KG, Le Cras TD, et al. Repetitive prenatal glucocorticoids increase lung endothelial nitric oxide synthase expression in ovine fetuses delivered at term. Pediatr Res 2000; 48:75-83.
17. Moss TJ, Harding R, Newnham JP. Lung function, arterial pressure and growth in sheep during early postnatal life following single and repeated prenatal corticosteroid treatments. Early Hum Dev 2002; 66:11-24. A thorough study of measures of lung function in lambs exposed before birth to corticosteroid treatments.
18. Newnham JP, Moss TJ. Antenatal glucocorticoids and growth: Single versus multiple doses in animal and human studies. Semin Neonatol 2001; 6:285-292. This review article brings together the published evidence regarding the potential effects of glucocorticoid treatments on prenatal growth.
19. Aghajafari F, Murphy K, Mathews S, et al. Repeated doses of antenatal corticosteroids in animals: A systematic review. Am J Obstet Gynecol 2002; 186:843-849. This paper is interesting in that it has attempted to bring to animal-based research studies the systematic review process that is now standard for the clinical literature.
20. Newnham JP, Evans SF, Godfrey M, et al. Maternal, but not fetal, administration of corticosteroids restricts fetal growth. J Matern Fetal Med 1999; 8:81-87.
21. Huang WL, Beazley LD, Quinlivan JA, et al. Effect of corticosteroids on brain growth in fetal sheep. Obstet Gynecol 1999; 94:213-218.
22. Dunlop SA, Archer MA, Quinlivan JA, et al. Repeated prenatal corticosteroids delay myelination in the ovine central nervous system. J Matern Fetal Med 1997; 6:309-313.
23. Huang WL, Harper CG, Evans SF, et al. Repeated prenatal corticosteroid administration delays myelination of the corpus callosum in fetal sheep. Int J Dev Neurosci 2001; 19:415-425. This is a detailed study of the development of the corpus callosum in sheep, demonstrating the effects of corticosteroids on myelination.
24. Huang WL, Harper CG, Evans SF, et al. Repeated prenatal corticosteroid administration delays astrocyte and capillary tight junction maturation in fetal sheep. Int J Dev Neurosci 2001; 19:487-493. Detailed study of the blood-brain barrier in the developing sheep, giving insights into possible issues that need to be addressed with clinical use of corticosteroids.
25. Quinlivan JA, Beazley LD, Archer M, et al. Repeated prenatal corticosteroids reduce glial fibrillary acidic protein in the ovine central nervous system. J Perinat Med 2002; 30:209-219. A further study showing profound effects of antenatal corticosteroids on various aspects of brain development in sheep.
26. Quinlivan JA, Beazley LD, Evans SF, et al. Retinal maturation is delayed by repeated, but not single, maternal injections of betamethasone in sheep. Eye 2000; 14:93-98.
27. Sloboda DM, Newnham JP, Challis JR. Effects of repeated maternal betamethasone administration on growth and hypothalamic-pituitary-adrenal function of the ovine fetus at term. J Endocrinol 2000; 165:79-91.
28. Sloboda DM, Newnham JP, Challis JRG. Repeated maternal glucocorticoid administration and the developing liver in fetal sheep. J Endocrinol (in press). This paper describes in the sheep model the effects of glucocorticoids on enzyme function in the fetal liver, providing fundamental information on the mechanisms by which these agents alter fetal metabolism.
29. Fletcher AJ, Goodfellow MR, Forhead AJ, et al. Low doses of dexamethasone suppress pituitary-adrenal function but augment the glycemic response to acute hypoxemia in fetal sheep in late gestation. Pediatr Res 2000; 47:684-691.
30. Karlsson R, Kallio J, Toppari J, et al. Antenatal and early postnatal dexamethasone treatment decreases cortisol secretion in pre-term infants. Horm Res 2000; 53:170-176.
31. 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; 186:812-817. A study in nonhuman primates designed to mimic clinical treatments using maternal intramuscular injections.
32. Johnson JW, Mitzner W, London WT, et al. Betamethasone and the rhesus fetus: Multisystemic effects. Am J Obstet Gynecol 1979; 133:677-684.
33. Novy MJ, Walsh SW. Dexamethasone and estradiol treatment in pregnant rhesus macaques: Effects on gestational length, maternal plasma hormones, and fetal growth. Am J Obstet Gynecol 1983; 145:920-931.
34. French NP, Hagan R, Evans SF, et al. Repeated antenatal corticosteroids: Size at birth and subsequent development. Am J Obstet Gynecol 1999; 180:114-121.
35. Thorp JA, Jones PG, Knox E, Clark RH. Does antenatal corticosteroid therapy affect birth weight and head circumference? Obstet Gynecol 2002; 99:101-108. A large study involving data from 100 neonatal intensive care units suggesting a preferential adverse effect of antenatal corticosteroids on head growth.
36. Moss TJ, Sloboda DM, Gurrin LG, et al. Programming effects in sheep of prenatal growth restriction and glucocorticoid exposure. Am J Physiol Regul Integr Comp Physiol 2001; 281:R960-R970. The first published study linking clinically relevant antenatal glucocorticoid treatments with outcomes to 1 year of age. Glucose metabolism was altered by antenatal glucocorticoids, regardless of their route of administration.
37. Challis JRG, Sloboda D, Mathews SG, et al. The fetal placental hypothalamic-pituitary-adrenal (HPA) axis, parturition and post natal health. Mol Cell Endocrinol 2001; 185:135-144. A thorough review of the hypothalamic-pituitary-adrenal axis and the role of cortisol in labor and programming the fetus.
38. Newnham JP. Is prenatal glucocorticoid administration another origin of adult disease? Clin Expert Pharmacol Physiol 2001; 28:957-961. This review outlines evidence from the perspective of the 'fetal origins of adult disease' that cortisol is a key intra-uterine trigger in prenatal programming.
39. Brocklehurst P, Gates S, McKenzie-McHarg K, et al. Are we prescribing multiple courses of antenatal corticosteroids? A survey of practice in the UK. Br J Obstet Gynaecol 1999; 106:977-979.
40. Chien LY, Ohlsson A, Seshia MM, et al. Variations in antenatal corticosteroid therapy: A persistent problem despite 30 years of evidence. Obstet Gynecol 2002; 99:401-408. A study of antenatal corticosteroid administration conducted in 17 Canadian Neonatal Network intensive care units.
41. Dirnberger DR, Yoder BA, Gordon MC. Single versus repeated-course antenatal corticosteroids: Outcomes in singleton and multiple-gestation pregnancies. Am J Perinatol 2001; 18:267-278. A 5-year review of preterm newborns in a single perinatal centre, finding no evidence of benefit from repeated courses of antenatal corticosteroids.
42. Wijnberger LDE, Mostert JM, van Dam KI, et al. Comparison of single and repeated antenatal corticosteroid therapy to prevent neonatal death and morbidity in the pre-term infant. Early Hum Devel 2002; 67:29-36. A cohort study with matched controls showing that repeated courses of antenatal corticosteroids had no additional benefits over a single course in reducing rates of respiratory distress syndrome, intraventricular haemorrhage or necrotizing enterocolitis.
43. Elimian A, Verma U, Visintainer P, Tejani N. Effectiveness of multidose antenatal steroids. Obstet Gynecol 2000; 95:34-36.
44. Vermillion ST, Bland ML, Soper DE. Effectiveness of a rescue dose of antenatal betamethasone after an initial single course. Am J Obstet Gynecol 2001; 185:1086-1089. A cohort study suggesting reduced frequency of respiratory distress syndrome after a single 'rescue' dose of betamethasone.
45. Banks BA, Cnaan A, Morgan MA, et al. Multiple courses of antenatal corticosteroids and outcome of premature neonates. Am J Obstet Gynecol 1999; 181:709-717.
46. Banks BA, Macones G, Cnaan A. Multiple courses of antenatal corticosteroids are associated with early severe lung disease in pre-term neonates. J Perinatol 2002; 22:101-107. A post-hoc analysis of newborns in the North American Thyrotropin-Releasing Hormone trial, investigating further their previous finding that repeated courses of antenatal corticosteroids were associated with increased neonatal mortality.
47. Caughey AB, Parer JT. Recommendations for repeat courses of antenatal corticosteroids: A decision analysis. Am J Obstet Gynecol 2002; 186:1221-1229. A decision analysis based on existing data providing new insights into the strength of evidence.
48. Guinn DA, Atkinson MW, Sullivan L, et al. Single vs weekly courses of antenatal corticosteroids for women at risk of pre-term delivery: A randomised controlled trial. JAMA 2001; 286:1581-1587. Publication of the first randomized study of repeated courses of antenatal corticosteroids. The study was stopped early due to safety concerns and no benefits were observed from repeated courses.
49. McEvoy C, Bowling S, Williamson K, et al. The effect of a single remote course versus weekly courses of antenatal corticosteroids on functional residual capacity in pre-term infants: A randomised trial. Pediatrics 2002; 110:280-284. A study of functional residual capacity and lung compliance in infants previously randomized to single or repeated courses of antenatal corticosteroids.
50. Antenatal corticosteroids revisited: Repeat courses - National Institutes of Health Consensus Development Conference Statement, August 17-18, 2000. Obstet Gynecol 2001; 98: 144-150. This paper outlines the recommendations of the National Institutes of Health Consensus Development Panel in which it was concluded that single-course corticosteroid treatment should continue, but that repeat courses should be reserved for patients in controlled trials.
51. Newnham JP, Moss TJ, Padbury JF, et al. The interactive effects of endotoxin with prenatal glucocorticoids on short-term lung function in sheep. Am J Obstet Gynecol 2001; 185:190-197. This study demonstrated that the beneficial effects of glucocorticoids on lung function of the preterm newborn are increased by concurrent administration with intra-amniotic endotoxin, providing novel insights into the mechanism of action and possible ways to augment this treatment.
52. Shimoya K, Taniguchi T, Matsuzaki N, et al. Chorioamnionitis decreased incidence of respiratory distress syndrome by elevating fetal interleukin-6 serum concentration. Hum Reprod 2000; 15:2234-2240.
53. Willet KE, Kramer BW, Kallapur SG, et al. Intra-amniotic injection of IL-1 induces inflammation and maturation in fetal sheep lung. Am J Physiol Lung Cell Mol Physiol 2002; 282:L411-L420. This study in sheep describes improved lung function after prenatal interleukin-1 treatment, thus confirming that inflammatory factors can independently 'mature' the fetal lungs. Further research in this field may lead to ways in which the consistency of antenatal corticosteroids may be improved, or by which alternative strategies can be developed.