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Betamethasone and cortisol in prevention of respiratory distress syndrome
Correspondence
2. I)ray. niotic
F., and Frvdman, fluid in pregnancy
()BS,‘t.I‘.
GYNECOL.
R.: Primary prostaglandins and spontaneous labor,
126:
13,
in amAM. J.
1976.
3 K&se.
M. J. N. C., Flint, A. P. F.. and Turnbull, A. C.: F prostaglandins in amniotic Huid during pregnancy and labour. ,J. Obstet. Gvnaecol. Br. 81: 131, 1974.
Reply to Dr. Keirse 7‘0 thr Editors: Using a sensitive and specific radioimmunoassay, my colleagues and I’, ’ have been able to measure primary prostaglandins at levels ~0.2 ng. per milliliter. In our study, we” found a level of PGE, in amniotic fluid 11hich increased significantly from 140 pg. per milliliter at 33 to 3.5 weeks to 318 pg. per milliliter at 36 weeks and showed a further slight (and not significant) increase at term (370 pg. per milliliter). Keirse and Turnbull’l reported that “neither PGE, nor PGF,Z rvas detected in 10 of 12 amniotic fluid samples” and gave the range found as
F. Dray, M.D.
REFERENCES
I. Dray. F.. munoassay
Charbonnel. B.. and Maclouf, J.: Radioimof prostaglandins Fez. E,. EP, Eur. J. Clin. Invest. 5: 311. 1975. 2. Maclouf, J., Andrieu, J. M., and Dray, F.: Validity of PG El tradioimmunoassay by using PC El antisera with differenti,d binding. parameters, FEBS Lett. 56: 273. 1975. 3. Dray, F.. and Frydman, R.: Primary prostaglandins in amniotic fuid in pregnant and spontaneous labour, AM. J. ORSTET. GYNECOL. 126: 13. 1976. 4. Keirsc, M. 1. N. C., and Turnbull. A. C.: E prostaglandins in amniotic’ fluid during late pregnancy and labour, Br. J. Ohster
Gvnaecol.
80:
970.
1973.
Betamethasone and cortisol in prevention of respiratory distress syndrome 7-U the Edi/o,lc: In their March 1, 1976, article, “A comparison of two glucocor~icoid regimens for acceleration of fetal lung maturation in premature labor.” Whitt and associates reported that 1 Gm. of intravenous cortisol adminisrcred
to pregnant
women
suppresses
maternal
estriol
475
levels more extensively and more rapidly than an intramuscular dose of 12 mg. of betamethasone. They concluded that cortisol at this dose reaches the fetal circulation more rapidly and achieves higher plasma levels and also suggested that the cortisol regimen may be better suited for lung maturation and prevention of respiratory distress syndrome (RDS). I would point out that this latter conclusion is not justified by the data presented and indeed may increase the risk of adverse effects from prenatal glucocorticoid therapy. Betamethasone reaches peak levels in both the maternal and fetal circulations by one hour after intramuscular injection.’ Thus, there is no significant regimen parison required
delay in therapy with the betamethasone of Liggins and Howie,’ particularly in COIIE with the minimum time of 24 hours which is to observe a beneficial effect on the incidence
of RDS. The indirect measurements by the authors do suggest that the large dose regimen of cortisol achieves higher fetal corticoid levels. However, a double-dose trial of betamethasone by Liggins and Howie’ did not improve the efficacy of treatment, and physiologic stress levels of corticoids are suflicient to induce lung maturation in animals.” Thus, there is no evidence to suggest that a larger dose of steroid would be more effective, and the adverse effects of pharmac,ologic doses of steroid in both newborn animals and human infants are of concern in the use of this cortisol regimen.” While I agree with the authors that the benefits of prenatal betamethasone therapy for prevention of RDS greatly outweigh the risks, I do not feel that clinical trials of large doses of cortisol are warranted with the data presently available. Furthermore, sitlce the therapeutic effectiveness of high doses of cortisol is “neither supported nor negated by this study,” it should be re-emphasized that this regimen should not be considered for routine prenatal therapy. Philip L. Hrrlkud. M.D.. Ph.D. Department of Pediatrics University of Cal$ornia at San Frrcrwi.vo San Francisco, Cahfornia 94143 REFERENCES
Ballard, P. L., Granberg, P., and Ballard, R. A.: Glucocorticoid levels in maternal and cord serum after prenatal betamethasone therapy to prevent respiratory distress syndrome, J. Clin. Invest. 56: 1548, 1975. Liz-gins, G. C., and Howie, R. N.: The prevention of RDS by-maternal steroid therapy, in Gluck. i,., editor: Modern Perinatal Medicine. Chicano. 1974, Year Book Medical Publishers, Inc., pp. 415-4i4. Platzker, A. C. G., Kitterman, J. A., Meschrr, E. J., Clemerits. J. A., and Tooley, W. H.: Surfactant in the lung and tracheal fluid of the fetal lamb and acceleration of its appearance by dexamethasone, Pediatrics 56: 554, 1975. Fitzhardinge, P. M., Eisen, A., Leitenvi, C., Mrtrakos. K., ” and Ramsay, M.: Sequelae of early steroid adminictration to the newborn infant, Pediatrics 53: 877, 1974.
2. I)ray. niotic
F., and Frvdman, fluid in pregnancy
()BS,‘t.I‘.
GYNECOL.
R.: Primary prostaglandins and spontaneous labor,
126:
13,
in amAM. J.
1976.
3 K&se.
M. J. N. C., Flint, A. P. F.. and Turnbull, A. C.: F prostaglandins in amniotic Huid during pregnancy and labour. ,J. Obstet. Gvnaecol. Br. 81: 131, 1974.
Reply to Dr. Keirse 7‘0 thr Editors: Using a sensitive and specific radioimmunoassay, my colleagues and I’, ’ have been able to measure primary prostaglandins at levels ~0.2 ng. per milliliter. In our study, we” found a level of PGE, in amniotic fluid 11hich increased significantly from 140 pg. per milliliter at 33 to 3.5 weeks to 318 pg. per milliliter at 36 weeks and showed a further slight (and not significant) increase at term (370 pg. per milliliter). Keirse and Turnbull’l reported that “neither PGE, nor PGF,Z rvas detected in 10 of 12 amniotic fluid samples” and gave the range found as
F. Dray, M.D.
REFERENCES
I. Dray. F.. munoassay
Charbonnel. B.. and Maclouf, J.: Radioimof prostaglandins Fez. E,. EP, Eur. J. Clin. Invest. 5: 311. 1975. 2. Maclouf, J., Andrieu, J. M., and Dray, F.: Validity of PG El tradioimmunoassay by using PC El antisera with differenti,d binding. parameters, FEBS Lett. 56: 273. 1975. 3. Dray, F.. and Frydman, R.: Primary prostaglandins in amniotic fuid in pregnant and spontaneous labour, AM. J. ORSTET. GYNECOL. 126: 13. 1976. 4. Keirsc, M. 1. N. C., and Turnbull. A. C.: E prostaglandins in amniotic’ fluid during late pregnancy and labour, Br. J. Ohster
Gvnaecol.
80:
970.
1973.
Betamethasone and cortisol in prevention of respiratory distress syndrome 7-U the Edi/o,lc: In their March 1, 1976, article, “A comparison of two glucocor~icoid regimens for acceleration of fetal lung maturation in premature labor.” Whitt and associates reported that 1 Gm. of intravenous cortisol adminisrcred
to pregnant
women
suppresses
maternal
estriol
475
levels more extensively and more rapidly than an intramuscular dose of 12 mg. of betamethasone. They concluded that cortisol at this dose reaches the fetal circulation more rapidly and achieves higher plasma levels and also suggested that the cortisol regimen may be better suited for lung maturation and prevention of respiratory distress syndrome (RDS). I would point out that this latter conclusion is not justified by the data presented and indeed may increase the risk of adverse effects from prenatal glucocorticoid therapy. Betamethasone reaches peak levels in both the maternal and fetal circulations by one hour after intramuscular injection.’ Thus, there is no significant regimen parison required
delay in therapy with the betamethasone of Liggins and Howie,’ particularly in COIIE with the minimum time of 24 hours which is to observe a beneficial effect on the incidence
of RDS. The indirect measurements by the authors do suggest that the large dose regimen of cortisol achieves higher fetal corticoid levels. However, a double-dose trial of betamethasone by Liggins and Howie’ did not improve the efficacy of treatment, and physiologic stress levels of corticoids are suflicient to induce lung maturation in animals.” Thus, there is no evidence to suggest that a larger dose of steroid would be more effective, and the adverse effects of pharmac,ologic doses of steroid in both newborn animals and human infants are of concern in the use of this cortisol regimen.” While I agree with the authors that the benefits of prenatal betamethasone therapy for prevention of RDS greatly outweigh the risks, I do not feel that clinical trials of large doses of cortisol are warranted with the data presently available. Furthermore, sitlce the therapeutic effectiveness of high doses of cortisol is “neither supported nor negated by this study,” it should be re-emphasized that this regimen should not be considered for routine prenatal therapy. Philip L. Hrrlkud. M.D.. Ph.D. Department of Pediatrics University of Cal$ornia at San Frrcrwi.vo San Francisco, Cahfornia 94143 REFERENCES
Ballard, P. L., Granberg, P., and Ballard, R. A.: Glucocorticoid levels in maternal and cord serum after prenatal betamethasone therapy to prevent respiratory distress syndrome, J. Clin. Invest. 56: 1548, 1975. Liz-gins, G. C., and Howie, R. N.: The prevention of RDS by-maternal steroid therapy, in Gluck. i,., editor: Modern Perinatal Medicine. Chicano. 1974, Year Book Medical Publishers, Inc., pp. 415-4i4. Platzker, A. C. G., Kitterman, J. A., Meschrr, E. J., Clemerits. J. A., and Tooley, W. H.: Surfactant in the lung and tracheal fluid of the fetal lamb and acceleration of its appearance by dexamethasone, Pediatrics 56: 554, 1975. Fitzhardinge, P. M., Eisen, A., Leitenvi, C., Mrtrakos. K., ” and Ramsay, M.: Sequelae of early steroid adminictration to the newborn infant, Pediatrics 53: 877, 1974.