Fetal Glucocorticoid-regulated Pathways Are Not Affected by Inhaled Corticosteroid Use for Asthma during Pregnancy

Rationale: Inhaled corticosteroids (ICS) are currently advised for the control of asthma during pregnancy, despite the lack of evidence regarding potential systemic effects on maternal, placental, and fetal systems. Objectives: To determine maternal plasma concentrations of cortisol, estriol, osteocalcin, and corticotropin-releasing hormone in pregnant women with asthma (n = 156) and without asthma (n = 51). Methods: During each trimester of pregnancy, the use and dose of ICS was recorded and blood samples were collected. Ultrasound was performed at 18 and 30 weeks' gestation, and birth weight and fetal sex were recorded at delivery. Measurements and Main Results: Maternal hormone concentrations were not affected by the presence of asthma; however, they were inhibited by ICS use in a dose-dependent manner. This was dependent on fetal sex: in pregnancies with a female, ICS was inversely associated with maternal cortisol in first trimester and inversely associated with maternal osteocalcin in second and third trimester. When pregnant with a male, no effect of ICS dose was observed on maternal cortisol, estriol, or osteocalcin levels, whereas corticotropin-releasing hormone levels were increased with ICS use only in the first trimester. Conclusions: Maternal glucocorticoid-regulated systems appeared susceptible to ICS only when pregnant with a female. Fetal adrenal function appeared unaffected by ICS in pregnancies of both males and females. This provides clinically important information suggesting that ICS do not exert effects on glucocorticoid-regulated pathways in the fetus, and therefore are unlikely to contribute to adverse effects on fetal growth and development.