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

The effect of prenatal sildenafil administration on postnatal cerebral and renal tissue oxygenation in severe early-onset fetal growth restriction. (#148)

Fieke Terstappen 1 2 , Anne E. Richter 3 , A. Titia Lely 1 , Freek E. Hoebeek 2 , Ayten Elvan 4 , Anouk Pels 5 , Wessel Ganzevoort 5 , Petra M. Lemmers 6 , Elisabeth M.W. Kooi 3
  1. Department of Obstetrics, Wilhelmina Children's Hospital Birth Centre, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
  2. Department for Developmental Origins of Disease, Wilhelmina Children's Hospital and UMC Utrecht Brain Center, Utrecht, The Netherlands
  3. Division of Neonatology, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands
  4. Division of Obstetrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  5. Department of Obstetrics, Amsterdam University Medical Center, Amsterdam, The Netherlands
  6. Department of Neonatology, Wilhelmina Children's Hospital Birth Centre, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

Background: In fetal growth restriction (FGR), sildenafil has been under investigation as a potential agent to improve utero-placental circulation and fetal growth. Potentially, this treatment affects hemodynamic redistribution associated with placental insufficiency. Hereto we investigated the effect of prenatal sildenafil on the neonatal cerebral and renal oxygenation.

Methods: Within the Dutch STRIDER trial, pregnant women with severe early-onset FGR received 25mg tablets of placebo or sildenafil three times daily. In a random subset of neonates admitted to two neonatal intensive care units, cerebral (n=14 vs n=14) and renal (n=5 vs n=6) oxygen saturation (rSO2) was continuously measured with near-infrared spectroscopy during the first 72 hours after birth. Arterial oxygen saturation (SaO2) was used to calculate fractional tissue oxygen extraction (FTOE=(SaO2-rSO2)/SaO2). One hour of good quality measurements per 3-hour intervals was manually selected. A linear mixed model approach was used providing an intercept±slope per 3-hour interval (=r) per group.

Results: Neonates were born with comparable birthweight (707±46g vs 659±48g) and gestational age (28.1±0.4 vs 28.4±0.7wk). Cerebral rSO2 and FTOE levels were similar between the placebo and sildenafil group and had comparable trends over time. Renal rSO2 was similar between groups, but during the first 72 hours renal rSO2 decreased less in the sildenafil group (r: -0.91 vs -0.28; p<0.01). Renal FTOE was elevated in the sildenafil group (intercept: -0.03 vs 0.13; p=0.02) and increased less over time compared with the placebo group (r: 0.015 vs 0.003; p<0.001).

Conclusion: In this small group of neonates born after severe early-onset FGR, we observed a difference in renal but not cerebral oxygenation during the first 72 hours after birth between the sildenafil and placebo group. These data suggest that prenatal sildenafil may not prevent postnatal cerebral redistribution associated with placental insufficiency, wherefore sildenafil affects renal oxygenation by a different mechanism than improved redistribution.

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