Antenatal treatment with corticosteroids for preterm neonates
impact on the incidence of respiratory distress syndrome and intra-hospital mortality
Keywords:
Newborn, Infant, Respiratory, Distress, Syndrome, Antenatal, CorticosteroidsAbstract
CONTEXT: Although the benefits of antenatal corticosteroids have been widely demonstrated in other countries, there are few studies among Brazilian newborn infants. OBJECTIVE: To evaluate the effectiveness of antenatal corticosteroids on the incidence of respiratory distress syndrome and intra-hospital mortality among neonates with a gestational age of less than 34 weeks. TYPE OF STUDY: Cross-sectional. SETTING: A tertiary-care hospital. PARTICIPANTS: Neonates exposed to any dose of antenatal corticosteroids for fetal maturation up to 7 days before delivery, and newborns paired by sex, birth weight, gestational age and time of birth that were not exposed to antenatal corticosteroids. The sample obtained consisted of 205 exposed newborns, 205 non-exposed and 39 newborns exposed to antenatal corticosteroids for whom it was not possible to find an unexposed pair. PROCEDURES: Analysis of maternal and newborn records. MAIN MEASUREMENTS: The primary clinical outcomes for the two groups were compared: the incidence of respiratory distress syndrome and intra-hospital mortality; as well as secondary outcomes related to neonatal morbidity. RESULTS: Antenatal corticosteroids reduced the occurrence of respiratory distress syndrome (OR: 0.33; 95% CI: 0.21-0.51) and the protective effect persisted when adjusted for weight, gestational age and the presence of asphyxia (adjusted OR: 0.27; 95% CI: 0.17-0.43). The protective effect could also be detected through the reduction in the need for and number of doses of exogenous surfactant utilized and the number of days of mechanical ventilation needed for the newborns exposed to antenatal corticosteroids. Their use also reduced the occurrence of intra-hospital deaths (OR: 0.51: 95% CI: 0.38-0.82). However, when adjusted for weight, gestational age, presence of prenatal asphyxia, respiratory distress syndrome, necrotizing enterocolitis and use of mechanical ventilation, the antenatal corticosteroids did not maintain the protective effect in relation to death. With regard to other outcomes, antenatal corticosteroids reduced the incidence of intraventricular hemorrhage grades III and IV (OR: 0.28; 95% CI: 0.10-0.77). CONCLUSIONS: Antenatal corticosteroids were effective in the reduction of morbidity and mortality among premature newborns in the population studied, and therefore their use should be stimulated within our environment.
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Maranhão AGK, Joaquim MMC, Siu C. Mortalidade perinatal e neonatal no Brasil. Tema 1999;17:6-17.
Silva LK, Costa TP, Reis AF, Iamada NO, Azevedo AP, Albuquerque CP. Avaliação da qualidade da assistência hospitalar obstétrica: uso de corticóides no trabalho de parto prematuro. Cad saúde pública 1999;15(4):817-29.
Liggins GC. Premature delivery of foetal lambs infused with glucocorticoids. J Endocrinol 1969;45(4):515-23.
Liggins GC, Howie RN. A controlled trial of antepartum glu- cocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 1972;50(4):515-25.
Caspi E, Schreyer P, Weinraub Z, Reif R, Levi I, Mundel G. Prevention of the respiratory distress syndrome in premature infants by antepartum glucocorticoid therapy. Br J Obstet Gynaecol 1976;83(3):187-93.
Block MF, Kling OR, Crosby WM. Antenatal glucocorticoid therapy for the prevention of respiratory distress syndrome in the premature infant. Obstet Gynecol 1977;50(2):186-90.
Morrison JC, Whybrew WD, Bucovaz ET, Schneider JM. In- jection of corticosteroids into mother to prevent neonatal res- piratory distress syndrome. Am J Obstet Gynecol 1978;131(4):358-66.
Papageorgiou AN, Desgranges MF, Masson M, Colle E, Shatz R, Gelfand MM. The antenatal use of betamethasone in the prevention of respiratory distress syndrome: a controlled dou- ble-blind study. Pediatrics 1979;63(1):73-9.
Taeusch HW, Frigoletto F, Kitzmiller J, et al. Risk of respira- tory distress syndrome after prenatal dexamethasone treatment. Pediatrics 1979;63(1):64-72.
Doran TA, Swyer P, MacMurray B, Mahon W, Enhorning G, Bernstein A, Falk M, Wood MM. Results of a double-blind controlled study on the use of betamethasone in the prevention of respiratory distress syndrome. Am J Obstet Gynecol 1980;136(3):313-20.
Teramo K, Hallman M, Raivio KO. Maternal glucocorticoid in unplanned premature labor. Controlled study on the effects of betamethasone phosphate on the phospholipids of the gas- tric aspirate and on the adrenal cortical function of the new- born infant. Pediatr Res 1980;14(4 Pt 1):326-9.
Effect of antenatal dexamethasone administration on the pre- vention of respiratory distress syndrome. Am J Obstet Gynecol 1981;141(3):276-87.
Schmidt PL, Sims ME, Strassner HT, Paul RH, Mueller E, McCart D. Effect of antepartum glucocorticoid administration upon neonatal respiratory distress syndrome and perinatal in- fection. Am J Obstet Gynecol 1984;148(2):178-86.
Iams JD, Talbert ML, Barrows H, Sachs L. Management of preterm prematurely ruptured membranes: a prospective randomized comparison of observation versus use of steroids and timed delivery. Am J Obstet Gynecol 1985;151(1):32-8.
Morales WJ, Diebel ND, Lazar AJ, Zadrozny D. The effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome in preterm gestations with pre- mature rupture of membranes. Am J Obstet Gynecol 1986;154(3):591-5.
Gamsu HR, Mulliner BM, Donnai P, Dash CH. Antenatal ad- ministration of betamethasone to prevent respiratory distress syndrome in preterm infants: report of a UK multicentre trial. Br J Obstet Gynaecol 1989;96:401-10.
Crowley P, Chalmers I, Keirse MJ. The effects of corticosteroid administration before preterm delivery: an overview of the evi- dence from controlled trials. Br J Obstet Gynaecol 1990;97(1):11-25.
National Institutes of Health Effect of corticosteroids for fetal maturation on perinatal outcome. NIH Consensus Statement. Washington: NIH 1994;12:1-24.
Schimmer BP, Parket KL. Hormônio adreno corticotrófico; esteróides adrenocorticais e seus análogos sintéticos; inibidores da síntese e das ações dos hormônios adrenocorticais. In: Gilman AG, Rall TW, Nies AS, eds. Godman & Gilman’s - As bases farmacológicas da terapêutica. Rio de Janeiro: McGraw-Hill; 1996.p.1082-102.
Ballard PL, Ballard RA. Scientific basis and therapeutic regi- mens for use of antenatal glucocorticoids. Am J Obstet Gynecol 1995;173(1):254-62.
Bunton TE, Plopper CG. Triamcinolone-induced structural al- terations in the development of the lung of the fetal rhesus macaque. Am J Obstet Gynecol 1984;148(2):203-15.
Frank L, Lewis PL, Sosenko IR. Dexamethasone stimulation of fetal rat lung antioxidant enzyme activity in parallel with sur- factant stimulation. Pediatrics 1985;75(3):569-74.
Celsi G, Wang ZM, Akusjärvi G, Aperia A. Sensitive peri- ods for glucocorticoids regulation of Na+, K(+)-ATPase mRNA in the developing lung and kidney. Pediatr Res 1993;33(1):5-9.
Sasidharan P. Role of corticosteroids in neonatal blood pressure homeostasis. Clin Perinatol 1998;25(3):723-40.
Omar SA, DeCristofaro JD, Agarwal BI, LaGamma EF. Effect of prenatal steroids on potassium balance in extremely low birth weight neonates. Pediatrics 2000;106(3):561-7.
Leviton A, Kuban KC, Pagano M, Allred EN, Van Marter L. Antenatal corticosteroids appear to reduce the risk of postnatal germinal matrix hemorrhage in intubated low birth weight newborns. Pediatrics 1993;91(6):1083-8.
Shulman RJ, Schanler RJ, Lau C, Heitkemper M, Ou CN, Smith EO. Early feeding, antenatal glucocorticoids, and hu- man milk decrease intestinal permeability in preterm infants. Pediatr Res 1998;44(4):519-23.
Crowley PA. Antenatal corticosteroid therapy: a meta-analysis of the randomized trial, 1972 to 1994. Am J Obstet Gynecol 1995;173(1):322-35.
Crowley P. Corticosteroids prior to preterm delivery. In: Neilson JP, Crowther CA, Hodnett ED, Hofmeyr GJ, eds. Pregnancy and Childbirth Module of the Cochrane Database of System- atic Reviews. The Cochrane Collaboration; Issue 4. Oxford: Update Software; 1997.
Crowley P. Prophylactic corticosteroids for preterm birth (Cochrane Review). The Cochrane Collaboration; Issue 4. Oxford: Update Software; 2001.
Doyle LW, Kitchen WH, Ford GW, Rickards AL, Lissenden JV, Ryan MM. Effects of antenatal steroid therapy on mortality and morbidity of very low birth weight infants. J Pediatr 1986;108(2):287-92.
Kari MA, Hallman M, Eronen M, et al. Prenatal dexametha- sone treatment in conjunction with rescue therapy of human surfactant: a randomized placebo-controlled multicenter study. Pediatrics 1994;93(5):730-6.
Maher JE, Cliver SP, Goldenberg RL, Davis RO, Copper RL. The effect of corticosteroid therapy in the very premature in- fant. March Of Dimes Multicenter Study Group. Am J Obstet Gynecol 1994;170(3):869-73.
Andrews EB, Marcucci G, White A, Long W. Associations be- tween use of antenatal corticosteroids and neonatal outcome within the Exosurf Neonatal Treatment Investigational New Drug Program. Am J Obstet Gynecol 1995;173(1):290-5.
Shankaran S, Bauer CR, Bain R, Wright LL, Zachary J. Rela- tionship between antenatal steroid administration and grades III and IV intracranial hemorrhage in low birth weight infants. The NICHD Neonatal Research Network. Am J Obstet Gynecol 1995;173(1):305-12.
Volpe JJ. Intracranial hemorrhage: germinal matrix-intraventricu- lar hemorrhage of the premature infant. In: Volpe JJ, ed. Neurology of the newborn. Philadelphia: Saunders; 2000.p.428-93.
Padbury JF, Ervin MG, Polk DH. Extrapulmonary effects of antenatally administered steroids. J Pediatr 1996;128(2):167-72.
Gardner MO, Papile LA, Wright LL. Antenatal corticosteroids in pregnancies complicated by preterm premature rupture of membranes. Obstet Gynecol 1997;90(5):851-3.
Lemons JA, Bauer CR, Oh W, et al. Very low birth weight out- comes of the National Institute of Child health and human development neonatal research network, January 1995 through December 1996. NICHD Neonatal Research Network. Pediatrics 2001;107(1):E1.
Ramírez VS, Reyes GLA, suárez MM, et al. Uso de surfactante pulmonar exógeno en el neonato pretérmino con síndrome de dificultad respiratoria, estrategia de rescate: experiencia del Instituto Nacional de Perinatología 1997-1998. Perinatol reprod hum 1999;13(4):286-96.
Gallardo R, Tartaret A, Serantes M, et al. El uso de inductores de la maduración pulmonar en pacientes con trabajo de parto prematuro. Rev med Oriente 1994;5(2):4-8.
Suárez M, Larguía AM. Epidemiología del recién nacido de muy bajo peso: incidencia de enfermedad de membrana hialina. Rev Hosp Matern Infant Ramon Sardá 1986;7(2):45-8.
Leone CR, Sadeck LSR, Vaz FC, et al. Brazilian Neonatal Re- search Network: very low birth weight infant morbidity and mortality. Pediatr Res 2001;49:405A.
Chung CS, Myrianthopoulos NC. Congenital anomalies: mor- tality and morbidity, burden and classification. Am J Med Genet 1987;27(3):505-23.
Guinsburg R, Almeida MFB. Infecções bacterianas. In: Almeida MFB, Kopelman BI, eds. Rotinas Médicas: Disciplina de Pediatria Neonatal da Escola Paulista de Medicina. São Paulo: Atheneu; 1995.p.129-38.
Bloom RS, Cropley C. Textbook of Neonatal Resuscitation. Illinois: American Heart Association; 1994.
Apgar V. A proposal for a new method for evaluation of the newborn infant. Curr Res Anes Anal 1952;32:260-7.
Capurro H, Konichezky S, Fonseca D, Caldeyro-Barcia R. A simplified method for diagnosis of gestational age in the new- born infant. J Pediatr 1978;93(1):120-2.
Dubowitz LMS, Dubowitz V, Goldberg C. Clinical assessment of gestational age in the newborn infant. J Pediatr 1970;77(1):1-10.
Ballard JL, Khoury JC, Wedig K, Wang L, Eilers-Walsman BL, Lipp R. New Ballard Score, expanded to include extremely pre- mature infants. J Pediatr 1991;119(3):417-23.
Battaglia FC, Lubchenco LO. A practical classification of newborn infants by weight and gestational age. J Pediatr 1967;71(2):159-63.
Kopelman BI. Síndrome do desconforto respiratório. In: Kopelman BI, ed. Distúrbios Respiratórios do recém-nascido. São Paulo: Atheneu; 1984.p.179-89.
Lederman H. Radiologia do aparelho respiratório do recém- nascido. In: Kopelman BI, ed. Distúrbios Respiratórios do recém-nascido. São Paulo: Atheneu; 1984.p.141-63.
Bancalari E, Abdenour GE, Feller R, Gannon J. Bronchopul- monary dysplasia: clinical presentation. J Pediatr 1979;95(5 Pt 2):819-23.
Papile LA, Burstein J, Burstein R, Kofflet H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978;92(4):529-34.
Walsh MC, Kliegman RM. Necrotizing enterocolitis: treatment based on staging criteria. Pediatr Clin North Am, 1986;33:179-201.
Agresti A. Categorical data analysis. New York: John Wiley and Sons; 1990.
Spiegel MR. Estatística. São Paulo: McGraw Hill; 1985.
Siegel S. Estadistica no Parametrica. Mexico: Trillas; 1975.
Kleinbaum DG. Logistic Regression: a self-learning text. New York: Springer; 1996.
Merrill JD, Ballard RA. Clinical use of antenatal corticosteroids: benefits and risks. Pediatr Rev 2000;1(5):E91-8.
Baud O, Foix-L’Helias L, Kaminski M, et al. Antenatal gluco- corticoid treatment and cystic periventricular leukomalacia in very premature infants. N Engl J Med 1999;341(16):1190-6.
Gluck L, Kulovich MV. Lecithin-sphingomyelin ratios in am- niotic fluid in normal and abnormal pregnancy. Am J Obstet Gynecol 1973;115(4):539-46.
Pena IC, Teberg AJ, Finello KM. The premature small-for-gesta- tional-age infant during the first year of life: comparison by birth weight and gestational age. J Pediatr 1988;113(6):1066-73.
Thompson PJ, Greenough A, Gamsu HR, Nicolaides KH. Ventilatory requirements for respiratory distress syndrome in small for gestational age infants. Eur J Pediatr 1992;151(7):528-31.
Stein HM, Oyama K, Martinez A, et al. Effects of corticosteroids in preterm sheep on adaptation and sympathoadrenal mecha- nisms at birth. Am J Physiol 1993;264(5 Pt 1):E763-9.
Gunkel JH, Mitchell BR. Observational evidence for the effi- cacy of antenatal steroids from randomized studies of surfactant replacement. Am J Obstet Gynecol 1995;173(1):281-5.
White A, Marcucci G, Andrews E, et al. Antenatal steroids and neonatal outcomes in controlled clinical trials of surfactant re- placement. The American Exosurf Neonatal Study Group I and The Canadian Exosurf Neonatal Study Group. Am J Obstet Gynecol 1995;173(1):286-90.
Horbar JD. Antenatal corticosteroid treatment and neonatal outcomes for infants 501 to 1500gm in the Vermont-Oxford Trial Network. Am J Obstet Gynecol 1995;173(1):275-81.
Wright LL, Horbar JD, Gunkel H, et al. Evidence from multicenter networks on the current use and effectiveness of antenatal corticosteroids in low birth weight infants. Am J Obstet Gynecol 1995;173(1):263-9.
