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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.

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