Impact of antenatal glucocorticoid exposure on the activity of the
stress system, cognition and behavior in 8 to 9-year-old children: a
clinical cohort study
Abstract
Objective: To determine stress-sensitivity and neurodevelopmental
outcome in 8- to 9-year-old children following antenatal exposure to
glucocorticoid (GC) prophylaxis for neonatal respiratory distress
syndrome. Design: Clinical cohort study. Setting: University-based
obstetric clinic in Central Germany. Population: 31 term or near-term
born children whose mothers received single or multiple courses of
betamethasone (BM) to induce fetal lung maturation in threatened preterm
birth compared to 39 non-exposed children. Methods: Multi-system
assessment of the individual stress response together with an analysis
of cognitive, behavioral and electrocortical functioning. Main Outcome
Measures: Activity of the hypothalamus-pituitary-adrenal axis (HPAA,
primary outcome domain) and the autonomic nervous system (ANS, secondary
outcome domain) including markers of heart rate variability (HRV).
Additional endpoints were the cognitive performance (IQ) and
attention-deficit/hyperactivity disorder (ADHD) core symptoms. Results:
HPAA activity was not affected by antenatal GC-exposure. ANS activity in
GC-exposed children shifted towards a higher parasympathetic tone
reflected by a higher overall high-frequency band power of HRV (1313 vs.
762 msec2/Hz, p=0.03). BM-exposed children had lower cognitive
performance (IQ 96.9 vs. 108.0, p<0.01) and a marginally
higher ADHD score (FBB-ADHD scale 5.5 vs. 4.6 points, p=0.04). A
monotonic dose-response relationship between GC-exposure and
stress-induced activity of the ANS and IQ was estimated post-hoc.
Conclusions: Antenatal exposure to supraphysiological concentrations of
BM in the context of threatened preterm birth was associated with
multidimensional changes in stress-sensitivity and neurodevelopment in
later life. As these changes may be dose-dependent, antenatal GC
prophylaxis should be used at the minimum effective dose after a careful
risk-benefit assessment.