The timing of antenatal glucocorticoids determines the receptor sensitivity in preterm infants.

Abstract

The global preterm birth rate is about 11%, most of premature (PI) infants receive antenatal glucocorticoids (aGC) to accelerate fetal lung maturation, however, this treatment increases the vulnerability for immune disorders later in life. We hypothesized that aGC given at the "wrong" time of day, determines the vulnerability. We compared the effect of aGCs in PI exposed in the morning (in-phase, IP with the maternal circadian rhythms) and in the evening (out-of-phase, OP) to controls (C). We collected data and blood samples from infants enrolled in a population-based cohort study. Groups are balances in gestational age, birth weight and sex. Infants were divided depending on the time of maternal cortisol peak. Exclusion criteria was established by the cohort, additionally infants born before gestational week 24 and exposed to postnatal GCs were excluded. The study was run in sub-cohorts, GC receptor (GR) sensitivity was assessed on 6 IP and 6OP. RNA sequencing, RNA expression and DNA methylation was assessed in peripheral blood cells from 13 C, 17 IP and 17 OP. All samples were obtained on average 10 days after birth. No interventions were performed. OP infants exhibited reduced GR sensitivity and suppressed expression of genes involved in antibody production, leucocyte migration, antigen presentation. aGCs exposure aligned with the maternal GC rhythms, would be advisable to improve PI's capacity to fight against pathogens in the first weeks of life.