Abstract
Serum glucocorticoid levels were determined in 20 mothers and 43 premature infants who received prenatal betamethasone therapy for prevention of respiratory distress syndrome (RDS). Maternal betamethasone peaked at 75 microg cortisol equivalents per 100 ml 1 h after injection of 12 mg steroid and declined to half by 6 h. Betamethasone in cord blood was 14.3 microg cortisol equivalents per 100 ml at 1 h, decreased to a level of 4.7 at 20 h, and was not detected 2 days after a second dose at 24 h. After the second dose, the mean level of cortisol in cord blood was 5.9 microg per 100 ml compared with 13.05 microg per 100 ml (p less than 0.001) in untreated premature infants. The unbound glucocorticoid activity in treated infants delivered 1-10 h after the second dose (mean, 8.4 microg per 100 ml) is similar to the unbound cortisol level after birth in untreated premature infants who develop RDS. These findings indicate that (a) serum glucocorticoid levels in the physiologic stress range can induce lung maturation in the human and (b) antenatal treatment with this dose of betamethasone does not expose the human fetus to potentially harmful pharmacologic levels of steroid.
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- Baden M., Bauer C. R., Colle E., Klein G., Taeusch H. W., Jr, Stern L. A controlled trial of hydrocortisone therapy in infants with respiratory distress syndrome. Pediatrics. 1972 Oct;50(4):526–534. [PubMed] [Google Scholar]
- Ballard P. L., Ballard R. A. Cytoplasmic receptor for glucocorticoids in lung of the human fetus and neonate. J Clin Invest. 1974 Feb;53(2):477–486. doi: 10.1172/JCI107581. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ballard P. L., Ballard R. A. Glucocorticoid receptors and the role of glucocorticoids in fetal lung development. Proc Natl Acad Sci U S A. 1972 Sep;69(9):2668–2672. doi: 10.1073/pnas.69.9.2668. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ballard P. L., Carter J. P., Graham B. S., Baxter J. D. A radioreceptor assay for evaluation of the plasma glucocorticoid activity of natural and synthetic steroids in man. J Clin Endocrinol Metab. 1975 Aug;41(2):290–304. doi: 10.1210/jcem-41-2-290. [DOI] [PubMed] [Google Scholar]
- Bauer C. R., Stern L., Colle E. Prolonged rupture of membranes associated with a decreased incidence of respiratory distress syndrome. Pediatrics. 1974 Jan;53(1):7–12. [PubMed] [Google Scholar]
- Beitins I. Z., Bayard F., Ances I. G., Kowarski A., Migeon C. J. The transplacental passage of prednisone and prednisolone in pregnancy near term. J Pediatr. 1972 Nov;81(5):936–945. doi: 10.1016/s0022-3476(72)80547-x. [DOI] [PubMed] [Google Scholar]
- Carson S. H., Taeusch H. W., Jr, Avery M. E. Inhibition of lung cell division after hydrocortisone injection into fetal rabbits. J Appl Physiol. 1973 May;34(5):660–663. doi: 10.1152/jappl.1973.34.5.660. [DOI] [PubMed] [Google Scholar]
- Cotterrell M., Balázs R., Johnson A. L. Effects of corticosteroids on the biochemical maturation of rat brain: postnatal cell formation. J Neurochem. 1972 Sep;19(9):2151–2167. doi: 10.1111/j.1471-4159.1972.tb05124.x. [DOI] [PubMed] [Google Scholar]
- DE MOOR P., HEIRWEGH K., HEREMANS J. F., DECLERCK-RASKIN M. Protein binding of corticoids studied by gel filtration. J Clin Invest. 1962 Apr;41:816–827. doi: 10.1172/JCI104539. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Souza S. W., Adlard B. P. Growth of suckling rats after treatment with dexamethasone or cortisol. Implications for steroid therapy in human infants. Arch Dis Child. 1973 Jul;48(7):519–522. doi: 10.1136/adc.48.7.519. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeLemos R. A., Shermeta D. W., Knelson J. H., Kotas R., Avery M. E. Acceleration of appearance of pulmonary surfactant in the fetal lamb by administration of corticosteroids. Am Rev Respir Dis. 1970 Sep;102(3):459–461. doi: 10.1164/arrd.1970.102.3.459. [DOI] [PubMed] [Google Scholar]
- Fargier P., Salle B., Baud, Gagnaire J. C., Arnaud P., Magnin P. Prévention du syndrome de détresse respiratoire chez le prématuré. Intérêt du traitement antepartum par les glucocorticoïdes. Nouv Presse Med. 1974 Jun 22;3(25):1595–1597. [PubMed] [Google Scholar]
- Fitzhardinge P. M., Eisen A., Lejtenyi C., Metrakos K., Ramsay M. Sequelae of early steroid administration to the newborn infant. Pediatrics. 1974 Jun;53(6):877–883. [PubMed] [Google Scholar]
- Giannopoulos G. Variations in the levels of cytoplasmic glucocorticoid receptors in lungs of various species at different developmental stages. Endocrinology. 1974 Feb;94(2):450–458. doi: 10.1210/endo-94-2-450. [DOI] [PubMed] [Google Scholar]
- Gumbinas M., Oda M., Huttenlocher P. The effects of corticosteroids on myelination of the developing rat brain. Biol Neonate. 1973;22(5):355–366. doi: 10.1159/000240568. [DOI] [PubMed] [Google Scholar]
- Hardie G., Harrison V. C., Kench J. E. Further observations on serum proteins in respiratory distress syndrome of the newborn. Arch Dis Child. 1968 Aug;43(230):471–474. doi: 10.1136/adc.43.230.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kotas R. V., Mims L. C., Hart L. K. Reversible inhibition of lung cell number after glucocorticoid injection into fetal rabbits to enhance surfactant appearance. Pediatrics. 1974 Mar;53(3):358–361. [PubMed] [Google Scholar]
- Liggins G. C., Howie R. N. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics. 1972 Oct;50(4):515–525. [PubMed] [Google Scholar]
- Motoyama E. K., Orzalesi M. M., Kikkawa Y., Kaibara M., Wu B., Zigas C. J., Cook C. D. Effect of cortisol on the maturation of fetal rabbit lungs. Pediatrics. 1971 Oct;48(4):547–555. [PubMed] [Google Scholar]
- Murphy B. E. Cortisol and cortisone levels in the cord blood at delivery of infants with and without the respiratory distress syndrome. Am J Obstet Gynecol. 1974 Aug 15;119(8):1112–1120. doi: 10.1016/0002-9378(74)90268-3. [DOI] [PubMed] [Google Scholar]
- Murphy B. E. Some studies of the protein-binding of steroids and their application to the routine micro and ultramicro measurement of various steroids in body fluids by competitive protein-binding radioassay. J Clin Endocrinol Metab. 1967 Jul;27(7):973–990. doi: 10.1210/jcem-27-7-973. [DOI] [PubMed] [Google Scholar]
- Perey D. Y., Herdman R. C., Good R. A. Polycystic renal disease: a new experimental model. Science. 1967 Oct 27;158(3800):494–496. doi: 10.1126/science.158.3800.494. [DOI] [PubMed] [Google Scholar]
- Reynolds J. W. Serum total corticoid and cortisol levels in premature infants with respiratory distress syndrome. Pediatrics. 1973 May;51(5):884–890. [PubMed] [Google Scholar]
- Trapp G. A., West C. D. Determination of corticosteroid-binding proteins by an adsorption method. J Lab Clin Med. 1969 May;73(5):861–871. [PubMed] [Google Scholar]
- Weichsel M. E., Jr Glucocorticoid effect upon thymidine kinase in the developing cerebellum. Pediatr Res. 1974 Oct;8(10):843–847. doi: 10.1203/00006450-197410000-00005. [DOI] [PubMed] [Google Scholar]
- de Fencl M., Tulchinsky D. Total cortisol in amniotic fluid and fetal lung maturation. N Engl J Med. 1975 Jan 16;292(3):133–136. doi: 10.1056/NEJM197501162920304. [DOI] [PubMed] [Google Scholar]