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

The effects of maternal sildenafil treatment on the developing lung: potential insights into poor postnatal outcomes.  (#121)

Ishmael Inocencio 1 , Graeme R Polglase 1 2 , Amy E Sutherland 1 , Ilias Nitsos 1 , Suzie L Miller 1 2 , Beth Allison 1
  1. Hudson Institute of Medical Research, Clayton, VIC, Australia
  2. Obstetrics & Gynaecology Monash Health, Monash University, Clayton, Vic, Australia

Background:Fetal growth restriction (FGR) commonly occurs due to placental insufficiency. Recent clinical trials have investigated the potential of sildenafil citrate (SC) to promote growth in FGR fetuses via improved placental blood flow. However, antenatal SC treatment has been associated with increased rates of persistent pulmonary hypertension in neonates. Here, we aimed to investigate the effect of maternal SC treatment on fetal lung development in growth restricted and appropriately grown (AG) fetal sheep.

Methods:  Preterm fetal sheep (88d gestation, term is 150d) underwent single umbilical artery ligation (SUAL) to induce fetal growth restriction (FGR). Ewes were randomly allocated to receive saline or sildenafil (SC) commencing at ~92d. At 127d fetuses underwent post-mortem for collection of lungs. Lung parenchyma and vasculature were assessed for markers of lung development.

Results: Antenatal SC treatment increased secondary crests and elastin abundance (P<0.05) in both FGR and AG lambs. Cell proliferation and alpha smooth muscle abundance were also increased following SC treatment in FGR (p<0.05), but not AG fetuses. Crucially, antenatal SC treatment resulted in increased blood vessel size as well as hypertrophy of perivascular smooth muscle (corrected for vessel size) (Figure 1).

Conclusions: Maternal SC treatment altered the parenchyma and blood vessels of fetal lungs. Our findings offer potential mechanistic links between maternal SC treatment and increased risk of pulmonary hypertension postnatally in FGR offspring.

 

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