The effects of maternal sildenafil treatment on vascular function and physiology in growth restricted fetal sheep

Mikee Inocencio, Graeme Roger Polglase, Amy E. Sutherland, Jamie Mihelakis, Ilias Nitsos, Suzanne Miller, Beth Allison

Research output: Contribution to journalMeeting Abstractpeer-review

Abstract

Background Fetal growth restriction (FGR) commonly occurs due to inadequate delivery of nutrients to the fetus. Recent clinical trials have investigated the potential of sildenafil citrate (SC) to promote growth in FGR fetuses via improved placental blood flow. However, the effect that fetal exposure to SC has on developing cardiovascular system remain unknown. We aimed to investigate the effect of maternal SC treatment on fetal physiology and vascular function. Methods Preterm fetuses (0.6 gestation) underwent single umbilical artery ligation (SUAL) to induce FGR. Ewes were randomly allocated to receive saline or sildenafil (SC). Ewes and fetuses were instrumented to record in vivo physiology. At 0.83 gestation lambs underwent post‐mortem for in vitro analysis of cerebral and femoral artery functional. Results SUAL caused 25% reduction in weight compared to appropriately grown (AG) (P = 0.03), growth deficits were exacerbated following SC treatment (FGRSC, 50% reduction, P < 0.01). Despite a similar degree of hypoxia in both FGR and FGRSC fetuses compared to AG (P < 0.05) only FGR fetuses increased carotid to femoral blood flow indicative of brain sparing (P < 0.01). In‐vitro assessment of vascular function revealed preservation of function in the cerebral circulation in FGR and AG fetuses, as compared to FGRSC fetuses where significant cerebral vascular dysfunction was observed. Conclusions Maternal SC treatment resulted in fetal hypoxia and an exacerbation of growth deficits. SC impaired the fetal ability to mount cardiovascular adaptations to hypoxia and also impaired vascular function. Our findings inform the mechanisms by which SC may impair development in severely growth restricted fetuses.
Original languageEnglish
Pages (from-to)26-27
Number of pages2
JournalJournal of Paediatrics and Child Health
Volume55
Issue numberSupp 1
Publication statusPublished - 18 Mar 2019
EventAnnual Congress of the Perinatal-Society-of-Australia-and-New-Zealand 2019 - Gold Coast Convention and Exhibition Centre, Gold Coast, Australia
Duration: 17 Mar 201920 Mar 2019
https://psanz.com.au/meetings-and-events/psanz-annual-congress/

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