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ORIGINAL RESEARCH |
From the *Department of Neonatology, The Edmond and Lily Safra Children’s Hospital; Department of Pharmacy Services, Radiology Department, and Department of Obstetrics and Gynecology, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Israel.
Address reprint requests to: Jacob Kuint, MD, Department of Neonatology, Sheba Medical Center 52621, Ramat Gan, Israel; e-mail: kuint-j{at}sheba.health.gov.il.
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ABSTRACT |
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1,750 g) exposed prenatally to either dexamethasone or betamethasone. METHODS: We retrospectively analyzed a cohort comprising 550 infants who were born alive at our center during the period January 1999 through December 2001, who weighed 1,750 g or less at birth, and who were exposed to prenatal steroid treatment. We compared brain ultrasound findings, such as intraventricular hemorrhage and cystic periventricular leukomalacia (PVL), as well as other clinical findings, including respiratory distress syndrome (RDS), necrotizing enterocolitis, retinopathy of prematurity, and bronchopulmonary dysplasia, for all premature infants whose mothers received either dexamethasone (from January 1, 1999 to June 30, 2000, n = 263) or betamethasone (July 1, 2000 to December 31, 2001, n = 287).
RESULTS: Patient characteristics (mothers and infants) were the same in both groups, with the exception of the number of steroid courses administered, the number of women with premature rupture of membranes (defined as > 24 hours), and the number of women who had received tocolysis. No significant difference was found between the 2 groups with respect to intraventricular hemorrhage and cystic PVL frequencies. No significant differences were found in the incidence of short-term outcomes examined, despite the fact that the dexamethasone group was exposed to a statistically significantly greater number of courses than the betamethasone group.
CONCLUSION: There seem to be no advantages to maternal antenatal treatment with betamethasone compared with dexamethasone in reducing the risk of PVL in low birth weight ( 1,750 g) infants. Both drugs have the same effect on all short-term outcome parameters checked.
LEVEL OF EVIDENCE: II-2
The recommended steroid regimens are either betamethasone or dexamethasone. Both are long-acting synthetic adrenocorticosteroids with identical biological activity (primarily glucocorticoid activity). Both are weak immunosuppressors with a long half-life (up to 72 hours), and they cross the placenta in their active form. Their chemical composition is identical; they differ, however, in the configuration of the methyl group in position 16.10 Another difference between the 2 steroids is found in the drug regimens used. The dexamethasone regimen has sulfites that may be neurotoxic, especially in combination with peroxy nitrite.2,10–11 In a number of randomized studies, betamethasone (although not dexamethasone) was found to temporarily reduce fetal movement and heart-rate variability.1,11–15 In the last few years, some animal models have shown better neurological outcomes using betamethasone rather than dexamethasone.16
In 1999, Baud et al13 published a large retrospective analysis demonstrating a connection between antenatal exposure to betamethasone and a decrease in the risk of periventricular leukomalacia (PVL), a primary risk factor for cerebral palsy in premature infants. This decrease in risk was not observed in the premature infants exposed to dexamethasone in the study. One possible explanation was the preservative used in dexamethasone but not in betamethasone.
Our study compared the short-term outcomes of infants exposed in the antenatal period to betamethasone and with those exposed to dexamethasone to find possible differences between the groups.
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MATERIALS AND METHODS |
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At the time of the study, the recommended antenatal steroid regimen consisted of either 2, 12-mg doses of betamethasone administered intramuscularly 24 hours apart or dexamethasone. In some women, additional courses were given at 7-day intervals if the mothers had not delivered and were still at risk for preterm delivery.
Until June 2000, our center routinely treated the mothers with dexamethasone. As a result of the Baud et al13 study, in June 2000, our obstetricians switched to treatment with betamethasone.
Apart from the change in the steroid treatment, there were no major changes in the organizational structure, key personnel, or medical approaches in either the obstetrics or the neonatal departments during the entire study period.
The trade name of the dexamethasone used by our obstetrician is Dexacort (Teva, Petah-Tikva, Israel); it contains dexamethasone phosphate as its active ingredients, as well as inactive ingredients such as sodium citrate, creatinine, methylparaben (preservative), sodium metabisulfite (preservative), propyl paraben, sodium hydroxide normal 1 N (excipient), and water for injection. The trade name of the dexamethasone described by Baud et al13 is Soludecadron (Merck, Paris, France) and contained the same active and inactive ingredients.
The trade name of the betamethasone used by our obstetricians is Celestone Chronodose (Schering-Plough, Kenilworth, NJ), the same agent described by Baud et al; it contains betamethasone acetate, betamethasone (as disodium phosphate), and benzalkonium chloride (preservative).
Continuous variables were compared using analysis of variance. Categorical variables were compared using the Pearson 
2 test. P .05 was considered significant.
The study was approved by the institutional review board of the Chaim Sheba Medical Center.
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RESULTS |
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No statistically significant differences were found between the 2 groups with regard to the following variables: gestational age, birth weight, percentage of small for gestational age (SGA, defined as birth weight below the third percentile for gestational age using Usher charts), gender, multiplicity, and mode of delivery (Table 1).
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A statistically significant difference in the number of steroid courses given to the mothers was found between the groups. In the dexamethasone group, a higher number of courses (2.6 ± 1.6) were given than in the betamethasone group (1.85 ± 1), P < .001.
No statistically significant differences were found between the 2 groups with regard to the number of mothers suffering from hypertension or amnionitis, as well as in the number of mothers who were treated with magnesium sulfate. There were, however, a statistically significantly greater number of mothers with premature rupture of membranes (PROM), and more mothers received tocolytic therapy in the betamethasone group.
There were no statistically significant differences between the 2 groups in the incidence of respiratory and other neonatal complication of prematurity, nor were there differences in the incidence of sepsis and antibiotic treatment (Table 2)
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No statistically significant differences were found in the incidence or the severity of intraventricular hemorrhage. There was, however, a difference, although not statistically significant, in the frequency of cystic PVL, which was higher in the betamethasone group (Table 3).
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A logistic regression analysis including gestational age, birth weight, gender, multiple pregnancies, delivery mode, amnionitis, maternal hypertension, tocolisis, PROM, number of steroid courses, and type of steroids showed that gestational age was the only significant predictor of PVL, with an odds ratio of 0.8 (95% confidence interval 0.7–0.9).
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DISCUSSION |
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This retrospective analysis did not find a significant difference between maternal characteristics in either group, with the exception of more courses in the dexamethasone group, reflecting a change in policy over the years. This finding can only reinforce our conclusion that dexamethasone does not pose a major risk for the development of cystic PVL in comparison with betamethasone. More women in the betamethasone group had their membranes ruptured 24 hours and more before birth, and a higher number of women were treated with tocolysis, as was found by Baud’s study as well13. We do not know whether these 2 parameters are related, but the results might reflect greater efforts over the years devoted to delaying labor to improve the maternal steroid effect.
Although the current study is observational, it has the advantage of being a large study conducted at a single medical center, thus representing a uniform diagnostic and therapeutic approach with no changes in therapy other than the type and number of courses of the steroid used as antenatal therapy administered to the mothers. Baud’s study13 was conducted in 3 different perinatal centers, which might reflect different obstetric practice patterns as well as different neonatal intensive care unit protocols. The rate of SGA in our study was similar in both study groups, in contrast to Baud’s study. Although the increased use of tocolysis in the betamethasone group may have led to higher rates of amnionitis and neonatal sepsis, no such differences were found. The rate of intraventricular hemorrhage was similar in the 2 groups, despite a possible protective influence resulting from repeated doses of dexamethasone. The main aim of this study was to discover whether there is a trend toward differences in short-term outcomes, such as PVL, intraventricular hemorrhage, and necrotizing enterocolitis, in antenatal treatment with dexamethasone versus that with betamethasone. The sample size should be larger to achieve more statistical validity.
To summarize, the results of this study seem to indicate that there is no advantage to betamethasone over dexamethasone as an antenatal steroid therapy in low birth weight infants with respect to reducing brain damage (cystic PVL). Furthermore, there is no difference between the 2 steroids in their capacity to decrease respiratory and other complications related to low birth weight. Additional larger human-based prospective studies and longer follow-up periods are needed to confidently recommend one steroid over the other.
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Footnotes |
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10.1097/01.AOG.0000137351.71015.ac
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REFERENCES |
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2. Goldenberg RL, Wright LL. Repeated courses of antenatal corticosteroids. Obstet Gynecol 2001;97:316–7.
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This article has been cited by other articles:
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  W. A. Campbell Antenatal Betamethasone Compared With Dexamethasone (Betacode Trial): A Randomized Controlled Trial Obstet. Gynecol., October 1, 2007; 110(4): 930 - 930. [Full Text] [PDF]
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A. Elimian, D. Garry, R. Figueroa, A. Spitzer, V. Wiencek, and J. G. Quirk Antenatal Betamethasone Compared With Dexamethasone (Betacode Trial): A Randomized Controlled Trial Obstet. Gynecol., July 1, 2007; 110(1): 26 - 30. [Abstract] [Full Text] [PDF]
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