Effect of maternal asthma, inhaled glucocorticoids and cigarette use during pregnancy on the newborn insulin-like growth factor axis

Abstract

Background Fetal growth varies in a sex-specific manner in response to maternal asthma during pregnancy, but the mechanisms are unclear. Objective We examined the influence of maternal asthma severity and associated exposures, inhaled glucocorticoid treatment, maternal cigarette use, and fetal sex on fetal growth and placental function during pregnancy and on the newborn insulin-like growth factor (IGF) axis. Study subjects and design Fetal growth was assessed in a prospective cohort of asthmatic and non-asthmatic women ( n = 145). At delivery, umbilical vein plasma was collected from male ( n = 61, controls n = 16 and asthmatic n = 45) or female ( n = 84, controls n = 22 and asthmatic n = 62) fetuses. Cord plasma insulin-like growth factor (IGF) binding protein (BP)-1, IGFBP-3, IGF-1 and IGF-2 were measured by radioimmunoassay and ELISA. Results Cord plasma IGF-1 was the main component of the neonatal IGF axis altered by asthma and cigarette use. IGF-1 was increased in the presence of mild asthma and a male fetus and decreased in the presence of a female fetus and maternal asthma with cigarette use. IGFBP-3 was also decreased in the female fetuses of pregnancies complicated by asthma and cigarette use. Inhaled glucocorticoid use for the treatment of asthma did not affect the IGF axis. The strongest overall predictor of female birth weight after accounting for asthma severity, inhaled glucocorticoid treatment and cigarette use was IGF-1. For males, the strongest predictor of birth weight was IGFBP-3. Conclusion The data suggest male and female fetuses institute different strategies in response to adverse pregnancy conditions such as asthma and cigarette use.