Impact of Antenatal Synthetic Glucocorticoid Exposure on Endocrine Stress Reactivity in Term-Born Children

Abstract

The present study provides the first evidence for long-lasting effects of antenatal synthetic GC exposure on HPA-axis reactivity in term-born children. These findings may bear important implications regarding the vulnerability for stress-related physical and psychiatric disorders, for which dysregulation of the HPA-axis has been discussed as a potential causal factor.

Prenatal Treatment of Congenital Adrenal Hyperplasia: Long-Term Effects of Excess Glucocorticoid Exposure

“…Furthermore, there seems to be evidence that treated girls are more susceptible to altered programming. A follow-up of children who had been exposed to late prenatal GC treatment showed an increase in cortisol responses to psychosocial stress, with a greater effect in girls [38]. A similar effect was also observed in neonatal DEX treatment in children at risk of bronchopulmonary dysplasia [82].…”

“…In a follow-up study of children who had been treated prenatally with GCs but were born full term, there was an increased cortisol response to psychosocial stress, indicating an imprinting effect on the hypothalamic–pituitary–adrenal (HPA) axis and with a greater effect seen in girls [38]. Effects on cognition have also been studied in preterm infants exposed to synthetic GCs, but there are difficulties in defining the exact cause of the negative effects since adversities directly related to the preterm birth are also of importance [39].…”

“…Effects on cognition have also been studied in preterm infants exposed to synthetic GCs, but there are difficulties in defining the exact cause of the negative effects since adversities directly related to the preterm birth are also of importance [39]. The situation is difficult to assess and further complicated by the fact that there seem to be individual differences in the vulnerability to GC exposure, due to genetic differences in both the GC receptor and in the enzyme 11-beta-HSD type 1 as well as to sex differences where girls seem to be more vulnerable than boys [38, 40, 41]. …”

The Hypothalamic-Pituitary-Adrenal Axis and the Fetus

“…Ascertainment bias likely occurs as well. Since pregnancy complications such as threatened preterm delivery are stressful for mothers, Alexander et al [38, 39] used an innovative experimental approach to separate the consequences of maternal stress and sGC use. They recruited three distinct groups of term infants: group 1 consisted of infants of mothers with a complicated pregnancy who had received a single course of sGC (PP/GC); group 2 consisted of infants of mothers with a complicated pregnancy who had not received sGC (PP/non-GC); and group 3 were infants of mothers without pregnancy complications.…”

“…Post hoc testing showed slightly lower birth weights, birth lengths, and shorter gestations in the PP/GC infants. Using the paradigm of an acute psychosocial stress situation, 6- to 11-year-old term-born children exposed to antenatal sGC manifested significantly increased cortisol reactivity compared to both the control children and the maternally stressed group that did not receive sGC; this effect was more pronounced in females [38]. After controlling for potentially confounding factors, IQ scores were lower in both the PP/GC and PP/non-GC groups; this finding was primarily driven by the results in males and suggests that the stress of threatened preterm delivery independent of sGC exposure can have deleterious consequences on postnatal cognitive function [39].…”