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Sildenafil, a phosphodiesterase type\u20105 inhibitor, potentiates the actions of nitric oxide, and it has been suggested that it alters maternal hemodynamics, potentially improving placental perfusion. Recently, the Dutch STRIDER trial was stopped prematurely owing to excess neonatal mortality secondary to pulmonary hypertension. The main aim of this study was to investigate the effect of sildenafil on maternal hemodynamics in pregnancies with severe early\u2010onset FGR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a cardiovascular substudy within a UK multicenter, placebo\u2010controlled trial, in which 135 women with a singleton pregnancy and severe early\u2010onset FGR (defined as a combination of estimated fetal weight or abdominal circumference below the 10<jats:sup>th<\/jats:sup> centile and absent\/reversed end\u2010diastolic flow in the umbilical artery on Doppler velocimetry, diagnosed between 22\u2009+\u20090 and 29\u2009+\u20096\u2009weeks' gestation) were assigned randomly to receive either 25\u2009mg sildenafil three times daily or placebo until 32\u2009+\u20090\u2009weeks' gestation or delivery. Maternal blood pressure (BP), heart rate (HR), augmentation index, pulse wave velocity (PWV), cardiac output, stroke volume (SV) and total peripheral resistance were recorded before randomization, 1\u20132\u2009h and 48\u201372\u2009h post\u2010randomization, and 24\u201348\u2009h postnatally. For continuous data, analysis was performed using repeated measures ANOVA methods including terms for timepoint, treatment allocation and their interaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Included were 134 women assigned randomly to sildenafil (<jats:italic>n<\/jats:italic>\u2009=\u200969) or placebo (<jats:italic>n<\/jats:italic>\u2009=\u200965) who had maternal BP and HR recorded at baseline. At 1\u20132\u2009h post\u2010randomization, compared with baseline values, sildenafil increased maternal HR by 4\u00a0bpm more than did placebo (mean difference, 5.00\u2009bpm (95%\u2009CI, 1.00\u201312.00\u2009bpm) <jats:italic>vs<\/jats:italic> 1.25\u2009bpm (95%\u2009CI, \u20135.38 to 7.88\u2009bpm); <jats:italic>P<\/jats:italic>\u2009=\u20090.004) and reduced systolic BP by 1\u2009mmHg more (mean difference, \u20134.13\u2009mmHg (95%\u2009CI, \u20139.94 to 1.44\u2009mmHg) <jats:italic>vs<\/jats:italic> \u20132.75\u2009mmHg (95%\u2009CI, \u20137.50 to 5.25\u2009mmHg); <jats:italic>P<\/jats:italic>\u2009=\u20090.048). Even after adjusting for maternal mean arterial pressure, sildenafil reduced aortic PWV by 0.60\u2009m\/s more than did placebo (mean difference, \u20130.90\u2009m\/s (95%\u2009CI, \u20131.31 to \u20130.51\u2009m\/s) <jats:italic>vs<\/jats:italic> \u20130.26\u2009m\/s (95%\u2009CI, \u20130.75 to 0.59\u2009m\/s); <jats:italic>P<\/jats:italic>\u2009=\u20090.001). Sildenafil was associated with a non\u2010significantly greater decrease in SV index after 1\u20132\u2009h post\u2010randomization than was placebo (mean difference, \u20135.50 mL\/m<jats:sup>2<\/jats:sup> (95%\u2009CI, \u201311.00 to \u20130.50\u2009mL\/m<jats:sup>2<\/jats:sup>) <jats:italic>vs<\/jats:italic> 0.00\u2009mL\/m<jats:sup>2<\/jats:sup> (95%\u2009CI, \u20135.00 to 4.00\u2009mL\/m<jats:sup>2<\/jats:sup>); <jats:italic>P<\/jats:italic>\u2009=\u20090.056).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Sildenafil in a dose of 25\u2009mg three times daily increases HR, reduces BP and reduces arterial stiffness in pregnancies complicated by severe early\u2010onset FGR. These changes are short term, modest and consistent with the anticipated vasodilatory effect. They have no short\u2010 or long\u2010term clinical impact on the mother. Copyright \u00a9 2019 ISUOG. Published by John Wiley &amp; Sons Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/uog.20851","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T05:54:02Z","timestamp":1566366842000},"page":"198-209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early\u2010onset fetal growth restriction: planned subgroup analysis from a multicenter randomized placebo\u2010controlled double\u2010blind trial"],"prefix":"10.1002","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2802-7670","authenticated-orcid":false,"given":"A.","family":"Khalil","sequence":"first","affiliation":[{"name":"Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, University of London, London  UK"},{"name":"Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Sharp","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Cornforth","sequence":"additional","affiliation":[{"name":"Liverpool Clinical Trials Unit University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Liverpool Clinical Trials Unit University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Mousa","sequence":"additional","affiliation":[{"name":"Fetal Medicine Unit University of Leicester  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Stock","sequence":"additional","affiliation":[{"name":"The Queen's Medical Research Institute, University of Edinburgh  Edinburgh UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Harrold","sequence":"additional","affiliation":[{"name":"Liverpool Clinical Trials Unit University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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