Clinicians should stop prescribing sildenafil for fetal growth restriction (FGR): comment from the STRIDER Consortium

Groom, Katie; Ganzevoort, Wessel; Alfirević, Z̄arko; Lim, Kenneth; Papageorghiou, Aris T.

doi:10.1002/uog.19186

Cited by 83 publications

(75 citation statements)

References 12 publications

(11 reference statements)

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“…) or in the case of the Dutch trial, have been halted due to an increased risk of poor fetal outcomes (Groom et al . ). However, before commencement of these human trials, Sildenafil treatment in a sheep model of IUGR was found to be detrimental to uteroplacental perfusion and fetal wellbeing (Miller et al .…”

Section: Discussionmentioning

confidence: 97%

“…Improving fetal substrate supply has been previously attempted in IUGR pregnancies. Clinical trials of maternal treatment with the vasodilator Sildenafil have shown either no improvement in fetal outcome measures (Groom et al 2019;Sharp et al 2019) or in the case of the Dutch trial, have been halted due to an increased risk of poor fetal outcomes (Groom et al 2018). However, before commencement of these human trials, Sildenafil treatment in a sheep model of IUGR was found to be detrimental to uteroplacental perfusion and fetal wellbeing (Miller et al 2009).…”

Section: Discussionmentioning

confidence: 99%

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Subcutaneous maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe and increases fetal but not cardiac growth

Darby

Saini

Soo

et al. 2019

The Journal of Physiology

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Key points Substrate restriction during critical developmental windows of gestation programmes offspring for a predisposition towards cardiovascular disease in adult life. This study aimed to determine the effect of maternal resveratrol (RSV) treatment in an animal model in which chronic fetal catheterisation is possible and the timing of organ maturation reflects that of the human. Maternal RSV treatment increased uterine artery blood flow, fetal oxygenation and fetal weight. RSV was not detectable in the fetal circulation, indicating that it may not cross the sheep placenta. This study highlights RSV as a possible intervention to restore fetal substrate supply in pregnancies affected by placental insufficiency. Abstract Suboptimal in utero environments with reduced substrate supply during critical developmental windows of gestation predispose offspring to non‐communicable diseases such as cardiovascular disease (CVD). Improving fetal substrate supply in these pregnancies may ameliorate the predisposition these offspring have toward adult‐onset CVD. This study aimed to determine the effect of maternal resveratrol (RSV) supplementation on uterine artery blood flow and the direct effects of RSV on the fetal heart in a chronically catheterised sheep model of human pregnancy. Maternal RSV treatment significantly increased uterine artery blood flow as measured by phase contrast magnetic resonance imaging, mean gestational fetal PnormalaO2 and SnormalaO2 as well as fetal weight. RSV was not detectable in the fetal circulation, and mRNA and protein expression of the histone/protein deacetylase SIRT1 did not differ between treatment groups. No effect of maternal RSV supplementation on AKT/mTOR or CAMKII signalling in the fetal left ventricle was observed. Maternal RSV supplementation is capable of increasing fetal oxygenation and growth in an animal model in which cardiac development parallels that of the human.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Subcutaneous maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe and increases fetal but not cardiac growth

Darby

Saini

Soo

et al. 2019

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…We read with interest the Physician Alert of Groom et al . published following interim analysis of the Dutch STRIDER trial investigating the effect of sildenafil on fetal growth restriction (FGR).…”

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confidence: 99%

Antenatal therapy with sildenafil: don't throw the baby out with the bathwater

Russo

Hooper

Tibboel

et al. 2019

Ultrasound in Obstet & Gyne

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“…Unfortunately, the attention on SC trials raised globally when a Dutch trial using SC to correct FGR has been halted after 11 babies died unexpectedly . A review by a committee of the STRIDER trial declared that lung complications were more common in the babies born to women given SC, of whom 17 had lung problems, and 11 died, while only three babies in the placebo group developed lung complications, and none of them died, suggesting a potential causal association.…”

mentioning

confidence: 99%

Perinatal deaths after sildenafil treatment of fetal growth restriction raise the issue of safety in randomised clinical trials

Lombardi

Crescioli

Bettiol

et al. 2019

Pharmacoepidemiology and Drug

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Clinicians should stop prescribing sildenafil for fetal growth restriction (FGR): comment from the STRIDER Consortium

Cited by 83 publications

References 12 publications

Subcutaneous maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe and increases fetal but not cardiac growth

Subcutaneous maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe and increases fetal but not cardiac growth

Antenatal therapy with sildenafil: don't throw the baby out with the bathwater

Perinatal deaths after sildenafil treatment of fetal growth restriction raise the issue of safety in randomised clinical trials

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