| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
ORIGINAL RESEARCH |
From the Departments of Obstetrics and Gynecology and Graduate School of Health Sciences, New York Medical College, Valhalla, New York.
 |
Abstract |
|---|
Top
 Abstract Materials and MethodsResultsDiscussionReferences |
|---|
Methods: We studied the neonatal outcomes for all women who delivered infants weighing 1750 g or less at birth between January 1990 and July 1997 at our institution. The study population was divided primarily into three clinical groups: preterm labor with intact membranes, PROM, and pregnancy-associated hypertension. Secondarily, the total population was divided based on birth weight and gestational age into AGA and growth-restricted neonates. Within each obstetric subgroup, neonates exposed to antenatal steroids were compared with unexposed neonates for respiratory distress syndrome (RDS), intraventricular hemorrhage and periventricular leukomalacia, the incidence of major brain lesions, necrotizing enterocolitis, proved neonatal sepsis, patent ductus arteriosus, and neonatal death. The subgroups were also compared for gestational age at delivery, birth weight, birth weight percentile, Apgar scores, postnatal surfactant exposure, and clinical and histologic chorioamnionitis. Descriptive statistics, Student t test,
2, Fisher exact test, and logistic regression were used for analysis.
Results: A total of 1148 neonates weighing 1750 g or less were delivered during the study period. There were 447 and 410 neonates delivered after preterm labor with intact membranes and PROM, respectively, and 245 neonates born to mothers with pregnancy-associated hypertension. Nine hundred twenty-eight neonates were AGA and the remaining 220 neonates were growth restricted. Antenatal steroids significantly decreased the incidence of RDS, the incidence and severity of intraventricular hemorrhage and periventricular leukomalacia, necrotizing enterocolitis, and neonatal mortality in preterm labor with intact membranes. In the presence of PROM, it significantly decreased the incidence and severity of intraventricular hemorrhage and periventricular leukomalacia and decreased neonatal mortality, with no apparent effect on the incidence of RDS. Antenatal steroids did not show any beneficial effect in pregnancy-associated hypertension and fetal growth restriction (FGR). Additionally, a significant increase was observed in the incidence of proved neonatal sepsis when antenatal steroids were used in pregnancy-associated hypertension.
Conclusion: The effectiveness of antenatal steroids varies with the obstetric population studied. Antenatal steroids significantly decreased the incidence of major neonatal morbidity and mortality in the AGA preterm neonate delivered after preterm labor with intact membranes. Antenatal steroids did not show any benefit in cases of pregnancy associated with maternal hypertension or FGR. Its effect in the presence of PROM is limited to a significant reduction in the incidence and severity of intraventricular hemorrhage and periventricular leukomalacia and in neonatal death.
The 1994 report of the National Institutes of Health (NIH) Consensus Development Conference on the use of corticosteroids for fetal maturation and their effect on perinatal outcomes has had a profound effect on the utilization of antenatal steroids in women at risk of preterm delivery.1 Before this report, only 12–18% of women who delivered preterm neonates weighing 501–1500 g at birth were treated with antenatal corticosteroids; now, approximately 60% of at-risk women are being given antenatal corticosteroids.2 Although the consensus report acknowledged that data were insufficient to assess the effectiveness of antenatal corticosteroids in certain maternal high-risk conditions, such as hypertension in pregnancy and fetal growth restriction (FGR), it stated that it would be reasonable to treat these patients as if they were at risk of preterm delivery. Hence, various obstetric populations are being exposed to antenatal steroids for benefits yet unproved and with potential adverse effects that have not been fully elucidated. On the other hand, the remaining 40% of at-risk women currently not receiving treatment may well be denied treatment because of unresolved concerns about its benefits and potential adverse effects in certain clinical situations. The purpose of this study was primarily to determine the effectiveness of antenatal steroids in the reduction of neonatal morbidity and mortality in obstetric subgroups of preterm labor with intact membranes, preterm premature rupture of membranes (PROM), and pregnancy-associated hypertension. The secondary objective was to determine the effect of antenatal steroids in appropriate for gestational age (AGA) and growth-restricted neonates.
|
Materials and Methods |
|---|
|
Top
AbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Preterm labor with intact membranes was diagnosed in the presence of six to eight contractions per hour or four contractions in 20 minutes associated with cervical changes but with no prelabor rupture of membranes. Preterm PROM included patients delivering after prelabor rupture of membranes, documented by pooling of fluid on sterile speculum examination, ferning, and alkaline pH by phenaphthazine pH indicator paper tested on fluid obtained from the posterior vaginal fornix. Pregnancy-associated hypertension included severe preeclampsia, eclampsia, and chronic hypertension with superimposed severe preeclampsia. Fetal growth restriction was defined as birth weight less than the tenth percentile expected for gestational age using the birth-percentile criteria of Brenner et al.3 Gestational age was estimated by using the last menstrual period when reliable or an ultrasonogram performed in the first 20 weeks of pregnancy.
In the total population and within each obstetric subgroup, neonates exposed to antenatal steroids were compared with unexposed neonates for respiratory distress syndrome (RDS), intraventricular hemorrhage and periventricular leukomalacia, the incidence of major brain lesions, necrotizing enterocolitis, proved neonatal sepsis, patent ductus arteriosus, and neonatal death. Subgroups were also compared for confounding variables including gestational age at delivery, birth weight, birth weight percentile, Apgar scores, postnatal surfactant exposure, and clinical and histologic chorioamnionitis. Antenatal steroids were administered in the form of two 12-mg intramuscular doses of betamethasone 24 hours apart, with a repeat course 7 days from the first dose if undelivered.
Respiratory distress syndrome was diagnosed clinically and by the need for mechanical ventilation and oxygen for at least 48 hours and the presence of radiologic chest findings. Each neonate had transfontanelle head ultrasound scans on days 3 and 7 of life. Neurosonograms were evaluated by an experienced sonographer unaware of the antenatal steroid exposure status of the parturient. Intraventricular hemorrhage was graded as described by Papile et al.4 Periventricular leukomalacia was diagnosed by the presence of echolucent areas or persistent echogenicity in the periventricular areas on coronal and sagittal views. Major brain lesions included intraventricular hemorrhage grades 3 and 4, intraventricular hemorrhage with periventricular leukomalacia, and periventricular leukomalacia. Necrotizing enterocolitis was diagnosed clinically and radiologically and confirmed at surgery or autopsy. Proved neonatal sepsis included positive blood or cerebrospinal fluid cultures.
The distributional characteristics of the variables were examined. Continuous data were normally distributed. As such, differences between groups defined by exposure to antenatal steroids were examined using Student t test for continuous variables and 2 tests for categoric variables. Fisher exact test was used when expected cell frequencies were equal to or less than five. Logistic regression was used to examine the influence of antenatal steroids on selected outcomes, adjusting for potential confounding factors. A comparison of the unadjusted and adjusted odds ratios (OR) indicates the degree to which the factors in the logistic regression model influence the association between steroid use and the outcome of interest. For sample-size computations, we assumed that approximately 30% of patients were exposed to antenatal steroids. For conditions with an incidence of 50% (eg, RDS) a sample of 200 neonates (60 exposed compared with 140 unexposed) would provide more than 80% power to detect a 50% reduction in incidence (ie, 50% compared with 25%) for a two-sided test of significance at a critical level of .05. For conditions with incidences of 25%, a sample of 280 neonates (80 exposed compared with 200 unexposed) would provide 80% power to detect a 70% reduction in incidence of the condition (ie, 25% compared with 7.5%). For some comparisons, the larger sample size provided reasonable power to detect small differences.
|
Results |
|---|
|
Top
AbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Three hundred twenty-six (28.3%) of the 1148 neonates were exposed to antenatal steroids; the remaining 822 (71.7%) were not. Although there were no differences between the steroid-exposed and the steroid-unexposed groups with respect to demographic characteristics, there was a significant reduction in the incidence of Apgar scores less than 7, RDS, intraventricular hemorrhage and periventricular leukomalacia, major brain lesions, and neonatal death in the steroid-exposed group (Table 1
). In addition, there was significant reduction in the incidence of clinical chorioamnionitis, with no difference in the rate of neonatal sepsis.
|
). The reduction in clinical chorioamnionitis approached statistical significance (P = .06).
|
). However, no beneficial effect was noted with regard to the rates of RDS or necrotizing enterocolitis.
|
). The relation between antenatal steroids and neonatal sepsis was investigated further through logistic regression by controlling for gestational age, birth weight, RDS, intraventricular hemorrhage and periventricular leukomalacia, histologic chorioamnionitis, and neonatal death. Adjusting for the six variables had little influence on the significant association between antenatal steroids and neonatal sepsis. The unadjusted OR was 3.3 (95% confidence interval [CI] 1.2, 9.4; P < .01), whereas the adjusted OR from the logistic regression model was 3.5 (95% CI 1.4, 8.7; P < .01).
|
compares these groups with regard to demographic characteristics, major neonatal morbidities, and neonatal mortality. There was a significant reduction in the incidence of Apgar scores less than 7, RDS, intraventricular hemorrhage and periventricular leukomalacia, major brain lesions, and neonatal mortality in the steroid-exposed AGA group compared with the unexposed AGA group. In addition, there was a significant reduction in the incidence of clinical chorioamnionitis, with no difference in the rate of neonatal sepsis.
|
).
|
|
Discussion |
|---|
|
Top
AbstractMaterials and MethodsResultsDiscussionReferences |
|---|
It is now widely accepted that antenatal steroids result in substantial decreases in neonatal morbidity and mortality as well as in health care costs. However, as the NIH consensus report1 on antenatal steroids acknowledges, the benefits and potential adverse effects of antenatal steroids have not been fully elucidated in certain high-risk situations, such as FGR and hypertension in pregnancy. Thus, there is a need for better understanding of the effects of antenatal steroids in obstetric subpopulations. Our study supports the general concept that antenatal steroids significantly reduce the incidence and severity of the major neonatal morbidities and mortality. However, we noted that the effectiveness of antenatal steroids depended on the obstetric population being studied.
Our experience indicates that antenatal steroids significantly decreased the incidence of RDS, the incidence and severity of intraventricular hemorrhage and periventricular leukomalacia, and neonatal mortality in preterm labor with intact membranes. This reinforces the experience of other investigators,5–9 justifying steroid use in this obstetric subpopulation.
Twenty to fifty percent of preterm births follow preterm PROM. The benefits of antenatal steroids in this group are controversial. Our study shows that in the presence of preterm PROM, antenatal steroids significantly decreased the incidence and severity of intraventricular hemorrhage and periventricular leukomalacia and the rate of neonatal death, with no apparent effect on RDS. The apparent lack of effect on RDS is in agreement with some previously published studies,6,10–13 although other investigators have reported a decrease in the incidence of RDS.14–16 However, because intraventricular hemorrhage and periventricular leukomalacia are important contributors to mortality and long-term neurologic disability, the use of steroids is beneficial in this subgroup.
Although the original work of Liggins and Howie5 suggested an increased risk of fetal death in women with severe preeclampsia who were managed expectantly, several subsequent studies, including ours, found no such increase in risk. This discrepancy probably reflects modern management methods in severe preeclampsia. However, we found no apparent benefit to the use of antenatal steroids in pregnancy-associated hypertension with respect to all major morbidities and mortality. A significant increase in the rate of neonatal sepsis was noted. In 1984, Ruvinsky et al17 found no apparent reduction in the RDS rate but reported no adverse effects after the administration of corticosteroids in pregnancy-associated hypertension. Other studies6,18 also did not reveal any beneficial role of antenatal steroids in this subgroup of patients. Lamont et al19 similarly found no decrease in the RDS rate but reported a nonsignificant decrease in the rate of intraventricular hemorrhage in the subgroup of 26–29 weeks’ gestation. There were two cases of intraventricular hemorrhage among six steroid-exposed neonates, as opposed to six cases among seven steroid-unexposed neonates. In this study, however, the sample size was small, only 85% of the neonates had neurosonograms, patients with incomplete courses of steroids were included in the untreated group, and no attempt was made to distinguish major from minor brain lesions. Elliott et al20 reported the additional association of pulmonary edema with steroids in women with severe preeclampsia.
In our study, there were 19 cases of neonatal sepsis in all, of which 17 infants had positive blood cultures, one had positive blood and cerebrospinal fluid cultures, and one had positive cerebrospinal fluid culture alone. Four of the 19 cases of sepsis manifested in the first week, while the remaining 15 became evident after the first week. Of interest, the actual incidence of neonatal sepsis in the steroid-exposed neonates with pregnancy-associated hypertension was similar to that in the other subgroups. However, the incidence in the control group (pregnancy-associated hypertension, steroid-unexposed) was low, making the difference significant. Additionally, because 79% of the cases occurred after the first week of life, this observation may be peculiar to our population and deserves further study.
The other major situation in which clinicians must decide on the wisdom of antenatal steroids is in the presence of FGR. There is a paucity of data on the benefit of steroids in this group. Clinicians must decide whether leaving the fetus in utero for the 24–48 hours needed for steroid effect is worth the risk of further deterioration. Although our study supports a beneficial role of steroids in AGA neonates, no such benefit was found for growth-restricted neonates. One mechanism to explain this finding is that the latter fetuses are maximally stressed and may already have elevated endogenous steroid levels.21 This is reflected in the fact that the steroid-unexposed growth-restricted neonates had a decreased rate of neonatal morbidity compared with the steroid-unexposed AGA neonates in this study, as well as those previously reported by Procianoy et al.22
|
Footnotes |
|---|
Received March 30, 1998. Received in revised form July 21, 1998. Accepted July 30, 1998.
|
References |
|---|
|
Top
AbstractMaterials and MethodsResultsDiscussionReferences |
|---|
2. Gardner MO, Papile LA, Wright LL. Antenatal corticosteroids in pregnancies complicated by preterm premature rupture of membranes. Obstet Gynecol 1997;90:851–3.[Abstract]
3. Brenner WE, Edelman DA, Hendricks CH. A standard of fetal growth for the United States of America. Am J Obstet Gynecol 1976;126:555–64.[Medline]
4. Papile LA, Burstein J, Koffier H. Incidence and evolution of subependymal and intraventricular hemorrhage: A study of infants with birthweights less than 1500 gm. J Pediatr 1978;92:529–34.[Medline]
5. Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 1972;50:515–25.
6. Collaborative Group on Antenatal Steroid Therapy. Effect of antenatal dexamethasone administration on prevention of respiratory distress syndrome. Am J Obstet Gynecol 1981;141:276–87.[Medline]
7. Taeusch HW, Frigoletto F, Kitzmiller J, Avery ME, Hehre A, Fromm B, et al. Risk of respiratory distress syndrome after prenatal dexamethasone treatment. Pediatrics 1979;63:64–72.
8. Doran TA, Swyer P, MacMurray B, Mahon W, Enhorhing G, Bernstein A, et al. Results of a double-blind controlled study on the use of betamethasone in the prevention of respiratory distress syndrome. Am J Obstet Gynecol 1980;136:313–20.[Medline]
9. Gamsu HR, Mullinger BM, Donnai P, Dash CH. Antenatal administration of betamethasone to prevent respiratory distress syndrome in preterm infants: Report of a UK multicentre trial. Br J Obstet Gynaecol 1989;96:401–10.[Medline]
10. Block MF, Kling OR, Crosby WM. Antenatal glucocorticoid therapy for the prevention of respiratory distress syndrome in the premature infant. Obstet Gynecol 1977;50:186–90.
11. Garite TJ, Freeman RK, Linzey EM, Braly PS, Dorchester WL. Prospective randomized study of corticosteroids in the management of premature rupture of the membranes and the premature gestation. Am J Obstet Gynecol 1981;141:508–15.[Medline]
12. 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;151:32–8.[Medline]
13. Nelson LH, Meis PJ, Hatjis CG, Ernest JM, Dillard R, Schey HM. Premature rupture of membranes: A prospective, randomized evaluation of steroids, latent phase, and expectant management. Obstet Gynecol 1985;66:55–8.
14. 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 double-blind study. Pediatrics 1979;63:73–9.
15. Crowley P. Corticosteroids after preterm premature rupture of membranes. Obstet Gynecol Clin North Am 1992;19:317–26.[Medline]
16. Morales WJ, Diebel D, Lazar AJ, Zadrozny D. The effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome in preterm gestations with premature rupture of membranes. Am J Obstet Gynecol 1986;154:591–5.[Medline]
17. Ruvinsky ED, Douvas SG, Roberts WE, Martin JN Jr, Palmer SM, Rhodes PG, et al. Maternal administration of dexamethasone in severe pregnancy-induced hypertension. Am J Obstet Gynecol 1984;149:722–6.[Medline]
18. Ricke PS, Elliot JP, Freeman RK. Use of corticosteroids in pregnancy induced hypertension. Obstet Gynecol 1980;55:206–10.
19. Lamont RF, Dunlop PDM, Levene MI, Elder MG. Use of glucocorticoids in pregnancies complicated by severe hypertension and proteinuria. Br J Obstet Gynaecol 1983;90:199–202.[Medline]
20. Elliott JP, O’Keefe DF, Greenberg P, Freeman RK. Pulmonary edema associated with magnesium sulfate and betamethasone administration. Am J Obstet Gynecol 1979;134:717–9.[Medline]
21. Economides DL, Nicolaides KH, Linton EA, Perry LA, Chard T. Plasma cortisol and adrenocorticotropin in appropriate and small for gestational age fetuses. Fetal Ther 1988;3:158–64.[Medline]
22. Procianoy RS, Garcia-Prats JA, Adams JM, Silvers A, Rudolph AJ. Hyaline membrane disease and intraventricular hemorrhage in small for gestational age infants. Arch Dis Child 1980;55:502–5.[Abstract]
This article has been cited by other articles:
|
|
 |
|
  M. Lohle, T. Muller, C. Wicher, M. Roedel, H. Schubert, O. W Witte, P. W Nathanielsz, and M. Schwab Betamethasone effects on fetal sheep cerebral blood flow are not dependent on maturation of cerebrovascular system and pituitary-adrenal axis J. Physiol., April 15, 2005; 564(2): 575 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Burguet, M Kaminski, P Truffert, A Menget, L Marpeau, M Voyer, J C Roze, B Escande, G Cambonie, J M Hascoet, et al. Does smoking in pregnancy modify the impact of antenatal steroids on neonatal respiratory distress syndrome? Results of the Epipage study Arch. Dis. Child. Fetal Neonatal Ed., January 1, 2005; 90(1): F41 - F45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L Foix-L'Helias, O Baud, R Lenclen, M Kaminski, and T Lacaze-Masmonteil Benefit of antenatal glucocorticoids according to the cause of very premature birth Arch. Dis. Child. Fetal Neonatal Ed., January 1, 2005; 90(1): F46 - F48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Brodsky and H. Christou Current Concepts in Intrauterine Growth Restriction J Intensive Care Med, November 1, 2004; 19(6): 307 - 319. [Abstract] [PDF]
|
|
|
|
 |
|
 E. Kajantie, T. Raivio, O. a. Janne, P. Hovi, L. Dunkel, and S. Andersson Circulating Glucocorticoid Bioactivity in the Preterm Newborn after Antenatal Betamethasone Treatment J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3999 - 4003. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Gilstrapp III and S. M. Ramin Corticosteroids in Pregnancy: Is Further Research Needed? Reproductive Sciences, December 1, 2003; 10(8): 447 - 449. [PDF]
|
|
|
|
 |
|
 R. Resnik Intrauterine Growth Restriction Obstet. Gynecol., March 1, 2002; 99(3): 490 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Jenkins, R. J. Wapner, E. A. Thom, A. F. Das, C. Y. Spong, K. E. Murphy, M. Hannah, P. Brocklehurst, J. L. Ambrus, C. M. Ambrus, et al. Are Weekly Courses of Antenatal Steroids Beneficial or Dangerous? JAMA, January 9, 2002; 287(2): 187 - 190. [Full Text] [PDF]
|
|
|
|
|
|
A. H. SCHAAP, H. WOLF, H. W. BRUINSE, H. S.-D. HAAS, I. VAN ERTBRUGGEN, and P. E. TREFFERS Effects of Antenatal Corticosteroid Administration on Mortality and Long-term Morbidity in Early Preterm, Growth-Restricted Infants Obstet. Gynecol., June 1, 2001; 97(6): 954 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. CANTERINO, U. VERMA, P. F. VISINTAINER, A. ELIMIAN, S. A. KLEIN, and N. TEJANI Antenatal Steroids and Neonatal Periventricular Leukomalacia Obstet. Gynecol., January 1, 2001; 97(1): 135 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. Bada Prevention of Intracranial Hemorrhage NeoReviews, March 1, 2000; 1(3): e48 - 52. [Full Text]
|
|
|
|
 |
|
 Corticosteroids for Preterm Labor Without Growth Retardation or Membrane Rupture Journal Watch Women's Health, April 1, 1999; 1999(401): 13 - 13. [Full Text]
|
|
|
|
 |
|
 Effectiveness of Antenatal Steroids Documented Journal Watch (General), February 23, 1999; 1999(223): 3 - 3. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
