This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kajantie, E. Articles by Andersson, S. Search for Related Content PubMed PubMed Citation Articles by Kajantie, E. Articles by Andersson, S.

Circulating Glucocorticoid Bioactivity in the Preterm Newborn after Antenatal Betamethasone Treatment

Hospital for Children and Adolescents (E.K., T.R., P.H., L.D., S.A.); Departments of Obstetrics and Gynecology (S.A.) and Clinical Chemistry (O.A.J.), Helsinki University Central Hospital; and Biomedicum Helsinki, Institute of Biomedicine (T.R., O.A.J.), 00029 HUS Helsinki, Finland; and National Public Health Institute (E.K.), 00300 Helsinki, Finland

Address all correspondence and requests for reprints to: Dr. Eero Kajantie, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland. E-mail eero.kajantie{at}helsinki.fi.

Antenatal glucocorticoid treatment of mothers at risk of premature delivery is highly cost-effective in reducing neonatal mortality and morbidity. However, there is only limited information on the actual glucocorticoid bioactivity (GBA) reaching the fetus. By employing a recently developed recombinant cell bioassay, we studied circulating GBA in preterm newborns exposed to the standard antenatal betamethasone regimen (12 mg betamethasone twice, 24-h interval, for the mother; repeated in 7–10 d if required). Plasma GBA and cortisol concentrations were measured in cord blood of 71 infants (mean gestational age, 28.9 wk; range, 24.6–32 wk; mean birth weight, 1208 g; range, 480-2010 g). The median time between the last administered betamethasone dose and birth was 2.0 d. Cord GBA ranged from less than 15.6 to 170 nmol/liter cortisol equivalents. The level was highly dependent on the time between the last betamethasone dose and birth, i.e. infants born shortly (<12 h) after the last steroid dose displayed on average 4-fold higher GBA than that in the reference group (infants with >7 d since the last betamethasone dose before birth or without treatment; 74 vs. 21 nmol/liter cortisol equivalents; P < 0.0001). By contrast, if more than 72 h had elapsed between the last steroid dose and birth, circulating GBA was strongly dependent on cord cortisol (r = 0.85; P < 0.0001; n = 30). In multiple regression analysis adjusted for cord cortisol concentration and the time since the last steroid dose, increased umbilical artery resistance, a sign of severe fetal distress, was associated with lower cord GBA (P = 0.01). In conclusion, antenatal exposure of preterm fetuses to betamethasone causes a sizeable, but brief, peak of supraphysiological GBA, and approximately 3 d after the last betamethasone dose, circulating GBA derives from cord cortisol concentration.

This work was supported by grants from the Academy of Finland, the Finnish Medical Society Duodecim, Finska Läkaresällskapet, the Foundation for Pediatric Research, Helsinki University Central Hospital Research Fund, the Jalmari and Rauha Ahokas Foundation, the Sigrid Jusélius Foundation, and the Yrjö Jahnsson Foundation.

E.K. and T.R. contributed equally to this work.

Abbreviations: GBA, Glucocorticoid bioactivity; excess GBA, glucocorticoid bioactivity not caused by cortisol; GR, glucocorticoid receptor.

This article has been cited by other articles:

				J. Janer, S. Andersson, E. Kajantie, and P. Lassus Endostatin Concentration in Cord Plasma Predicts the Development of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants Pediatrics, April 1, 2009; 123(4): 1142 - 1146. [Abstract] [Full Text] [PDF]

				M. Neu, M. L. Laudenslager, and J. Robinson Coregulation in Salivary Cortisol During Maternal Holding of Premature Infants Biol Res Nurs, January 1, 2009; 10(3): 226 - 240. [Abstract] [PDF]

				M J J Finken, M G Keijzer-Veen, F W Dekker, M Frolich, F J Walther, J A Romijn, B J van der Heijden, J M Wit, and on behalf of the Dutch POPS-19 Collaborative Study Antenatal glucocorticoid treatment is not associated with long-term metabolic risks in individuals born before 32 weeks of gestation Arch. Dis. Child. Fetal Neonatal Ed., November 1, 2008; 93(6): F442 - F447. [Abstract] [Full Text] [PDF]

				O. Helve, C. Janer, O. Pitkanen, and S. Andersson Expression of the Epithelial Sodium Channel in Airway Epithelium of Newborn Infants Depends on Gestational Age Pediatrics, December 1, 2007; 120(6): 1311 - 1316. [Abstract] [Full Text] [PDF]

				P. Nykanen, T. Raivio, K. Heinonen, O. A Janne, and R. Voutilainen Circulating glucocorticoid bioactivity and serum cortisol concentrations in premature infants: the influence of exogenous glucocorticoids and clinical factors Eur. J. Endocrinol., May 1, 2007; 156(5): 577 - 583. [Abstract] [Full Text] [PDF]