Poster Presentation & Flash Talk 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

Antenatal glucocorticoids and the female postnatal advantage: possible mechanisms underlying early- and long-term vascular adaptations following preterm birth (#115)

Rebecca M Dyson 1 , Max J Berry 1 , Ashlina Kanji 1 , Ryan P Sixtus 1 , Janna L Morrison 2 , Vicki L Clifton 3 , Clint L Gray 1
  1. Perinatal & Developmental Physiology Group, Department Of Paediatrics & Child Health, University of Otago Wellington, Newtown, Wellington, New Zealand
  2. Early Origins of Adult Health Research Group, School of Pharmacy & Medical Sciences, University of South Australia, Adelaide, South Australia, Australia
  3. Mater Medical Research Institute, University of Queensland, Brisbane, Queensland, Australia

It is debated whether many of the short- and long-term cardiovascular consequences of preterm birth may be a result of shortened gestation per se or common perinatal treatments, such as exposure to antenatal glucocorticoids (GC). Differential placental GR isoforms in males and females are upregulated following exposure to GC, resulting in specific GC responses that activate various downstream pathways. In females, these downstream pathways appear to regulate growth, aid in heart maturation, and promote the production of pro-vasoconstrictive factors and inhibition of pro-vasodilatory factors in the fetus.

Our aim was to determine if GC exposure improves microvascular control and haemodynamic stability in females, possibly explaining some of their “survival benefit”. We used our guinea pig model of perinatal insult. Guinea pigs delivered equivalent to human preterm infants requiring steroids cannot survive without GC exposure, we administered vehicle (saline) or betamethasone (1mg/kg) at GA60 and GA61, (preterm-equivalent developmental window), and delivered at term (GA69). On day of delivery, pups underwent cardiovascular assessment (NIBP, ECG, laser Doppler flowmetry) and were allocated to neonatal (0d) or juvenile (28d) tissue collection. Females in the neonatal group underwent vascular pressure myography studies and all juveniles underwent repeat cardiovascular assessment at 28d.

Diameter:pressure relationship, EDHF and prostanoid-induced pathways appeared unchanged between groups. However, vascular responsiveness in resistance vessels was significantly impaired in GC pups. Nitric oxide-induced vasodilation in GC pups was significantly decreased (P<0.005 Fig.1). In contrast, peripheral microvascular dilatation as assessed by laser Doppler flowmetry was not different in pups exposed to GC (P=0.08) immediately after birth. However, flow increased in females, but decreased in males at 28d postnatal age (P=0.03 for treatment).

GC may diminish NO-mediated dilatation in the initial extrauterine period in females, potentially contributing to their greater cardiovascular stability and improved outcomes. Further work is underway to fully understand the mechanisms involved.5d2853534bc78-PG+tram34+Lgdose+vs+response.jpg