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Effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early-onset fetal growth restriction: planned subgroup analysis from a multicenter randomized placebo-controlled double-blind trial

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Effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early-onset fetal growth restriction : planned subgroup analysis from a multicenter randomized placebo-controlled double-blind trial. / Khalil, A.; Sharp, A.; Cornforth, C.; Jackson, R.; Mousa, H.; Stock, S.; Harrold, J.; Turner, M. A.; Kenny, L. C.; Baker, P. N.; Johnstone, E. D.; Von Dadelszen, P.; Magee, L.; Papageorghiou, A. T.; Alfirevic, Z.

In: Ultrasound in Obstetrics and Gynecology, Vol. 55, No. 2, 01.02.2020, p. 198-209.

Research output: Contribution to journalArticle

Harvard

Khalil, A, Sharp, A, Cornforth, C, Jackson, R, Mousa, H, Stock, S, Harrold, J, Turner, MA, Kenny, LC, Baker, PN, Johnstone, ED, Von Dadelszen, P, Magee, L, Papageorghiou, AT & Alfirevic, Z 2020, 'Effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early-onset fetal growth restriction: planned subgroup analysis from a multicenter randomized placebo-controlled double-blind trial', Ultrasound in Obstetrics and Gynecology, vol. 55, no. 2, pp. 198-209. https://doi.org/10.1002/uog.20851

APA

Khalil, A., Sharp, A., Cornforth, C., Jackson, R., Mousa, H., Stock, S., ... Alfirevic, Z. (2020). Effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early-onset fetal growth restriction: planned subgroup analysis from a multicenter randomized placebo-controlled double-blind trial. Ultrasound in Obstetrics and Gynecology, 55(2), 198-209. https://doi.org/10.1002/uog.20851

Vancouver

Khalil A, Sharp A, Cornforth C, Jackson R, Mousa H, Stock S et al. Effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early-onset fetal growth restriction: planned subgroup analysis from a multicenter randomized placebo-controlled double-blind trial. Ultrasound in Obstetrics and Gynecology. 2020 Feb 1;55(2):198-209. https://doi.org/10.1002/uog.20851

Author

Khalil, A. ; Sharp, A. ; Cornforth, C. ; Jackson, R. ; Mousa, H. ; Stock, S. ; Harrold, J. ; Turner, M. A. ; Kenny, L. C. ; Baker, P. N. ; Johnstone, E. D. ; Von Dadelszen, P. ; Magee, L. ; Papageorghiou, A. T. ; Alfirevic, Z. / Effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early-onset fetal growth restriction : planned subgroup analysis from a multicenter randomized placebo-controlled double-blind trial. In: Ultrasound in Obstetrics and Gynecology. 2020 ; Vol. 55, No. 2. pp. 198-209.

Bibtex Download

@article{e19b2272ae8f421098042d3bb9f39517,
title = "Effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early-onset fetal growth restriction: planned subgroup analysis from a multicenter randomized placebo-controlled double-blind trial",
abstract = "Objectives: Fetal growth restriction (FGR) is associated with maternal cardiovascular changes. Sildenafil, a phosphodiesterase type-5 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-onset FGR. Methods: This was a cardiovascular substudy within a UK multicenter, placebo-controlled trial, in which 135 women with a singleton pregnancy and severe early-onset FGR (defined as a combination of estimated fetal weight or abdominal circumference below the 10th centile and absent/reversed end-diastolic flow in the umbilical artery on Doppler velocimetry, diagnosed between 22 + 0 and 29 + 6 weeks' gestation) were assigned randomly to receive either 25 mg sildenafil three times daily or placebo until 32 + 0 weeks' 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, 1–2 h and 48–72 h post-randomization, and 24–48 h postnatally. For continuous data, analysis was performed using repeated measures ANOVA methods including terms for timepoint, treatment allocation and their interaction. Results: Included were 134 women assigned randomly to sildenafil (n = 69) or placebo (n = 65) who had maternal BP and HR recorded at baseline. At 1–2 h post-randomization, compared with baseline values, sildenafil increased maternal HR by 4 bpm more than did placebo (mean difference, 5.00 bpm (95{\%} CI, 1.00–12.00 bpm) vs 1.25 bpm (95{\%} CI, –5.38 to 7.88 bpm); P = 0.004) and reduced systolic BP by 1 mmHg more (mean difference, –4.13 mmHg (95{\%} CI, –9.94 to 1.44 mmHg) vs –2.75 mmHg (95{\%} CI, –7.50 to 5.25 mmHg); P = 0.048). Even after adjusting for maternal mean arterial pressure, sildenafil reduced aortic PWV by 0.60 m/s more than did placebo (mean difference, –0.90 m/s (95{\%} CI, –1.31 to –0.51 m/s) vs –0.26 m/s (95{\%} CI, –0.75 to 0.59 m/s); P = 0.001). Sildenafil was associated with a non-significantly greater decrease in SV index after 1–2 h post-randomization than was placebo (mean difference, –5.50 mL/m2 (95{\%} CI, –11.00 to –0.50 mL/m2) vs 0.00 mL/m2 (95{\%} CI, –5.00 to 4.00 mL/m2); P = 0.056). Conclusions: Sildenafil in a dose of 25 mg three times daily increases HR, reduces BP and reduces arterial stiffness in pregnancies complicated by severe early-onset FGR. These changes are short term, modest and consistent with the anticipated vasodilatory effect. They have no short- or long-term clinical impact on the mother.",
keywords = "cardiovascular, endothelium, fetal growth restriction, hemodynamics, nitric oxide, pharmacology, sildenafil, vascular biology",
author = "A. Khalil and A. Sharp and C. Cornforth and R. Jackson and H. Mousa and S. Stock and J. Harrold and Turner, {M. A.} and Kenny, {L. C.} and Baker, {P. N.} and Johnstone, {E. D.} and {Von Dadelszen}, P. and L. Magee and Papageorghiou, {A. T.} and Z. Alfirevic",
year = "2020",
month = "2",
day = "1",
doi = "10.1002/uog.20851",
language = "English",
volume = "55",
pages = "198--209",
journal = "Ultrasound in Obstetrics and Gynecology",
issn = "0960-7692",
publisher = "John Wiley and Sons Ltd",
number = "2",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early-onset fetal growth restriction

T2 - planned subgroup analysis from a multicenter randomized placebo-controlled double-blind trial

AU - Khalil, A.

AU - Sharp, A.

AU - Cornforth, C.

AU - Jackson, R.

AU - Mousa, H.

AU - Stock, S.

AU - Harrold, J.

AU - Turner, M. A.

AU - Kenny, L. C.

AU - Baker, P. N.

AU - Johnstone, E. D.

AU - Von Dadelszen, P.

AU - Magee, L.

AU - Papageorghiou, A. T.

AU - Alfirevic, Z.

PY - 2020/2/1

Y1 - 2020/2/1

N2 - Objectives: Fetal growth restriction (FGR) is associated with maternal cardiovascular changes. Sildenafil, a phosphodiesterase type-5 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-onset FGR. Methods: This was a cardiovascular substudy within a UK multicenter, placebo-controlled trial, in which 135 women with a singleton pregnancy and severe early-onset FGR (defined as a combination of estimated fetal weight or abdominal circumference below the 10th centile and absent/reversed end-diastolic flow in the umbilical artery on Doppler velocimetry, diagnosed between 22 + 0 and 29 + 6 weeks' gestation) were assigned randomly to receive either 25 mg sildenafil three times daily or placebo until 32 + 0 weeks' 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, 1–2 h and 48–72 h post-randomization, and 24–48 h postnatally. For continuous data, analysis was performed using repeated measures ANOVA methods including terms for timepoint, treatment allocation and their interaction. Results: Included were 134 women assigned randomly to sildenafil (n = 69) or placebo (n = 65) who had maternal BP and HR recorded at baseline. At 1–2 h post-randomization, compared with baseline values, sildenafil increased maternal HR by 4 bpm more than did placebo (mean difference, 5.00 bpm (95% CI, 1.00–12.00 bpm) vs 1.25 bpm (95% CI, –5.38 to 7.88 bpm); P = 0.004) and reduced systolic BP by 1 mmHg more (mean difference, –4.13 mmHg (95% CI, –9.94 to 1.44 mmHg) vs –2.75 mmHg (95% CI, –7.50 to 5.25 mmHg); P = 0.048). Even after adjusting for maternal mean arterial pressure, sildenafil reduced aortic PWV by 0.60 m/s more than did placebo (mean difference, –0.90 m/s (95% CI, –1.31 to –0.51 m/s) vs –0.26 m/s (95% CI, –0.75 to 0.59 m/s); P = 0.001). Sildenafil was associated with a non-significantly greater decrease in SV index after 1–2 h post-randomization than was placebo (mean difference, –5.50 mL/m2 (95% CI, –11.00 to –0.50 mL/m2) vs 0.00 mL/m2 (95% CI, –5.00 to 4.00 mL/m2); P = 0.056). Conclusions: Sildenafil in a dose of 25 mg three times daily increases HR, reduces BP and reduces arterial stiffness in pregnancies complicated by severe early-onset FGR. These changes are short term, modest and consistent with the anticipated vasodilatory effect. They have no short- or long-term clinical impact on the mother.

AB - Objectives: Fetal growth restriction (FGR) is associated with maternal cardiovascular changes. Sildenafil, a phosphodiesterase type-5 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-onset FGR. Methods: This was a cardiovascular substudy within a UK multicenter, placebo-controlled trial, in which 135 women with a singleton pregnancy and severe early-onset FGR (defined as a combination of estimated fetal weight or abdominal circumference below the 10th centile and absent/reversed end-diastolic flow in the umbilical artery on Doppler velocimetry, diagnosed between 22 + 0 and 29 + 6 weeks' gestation) were assigned randomly to receive either 25 mg sildenafil three times daily or placebo until 32 + 0 weeks' 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, 1–2 h and 48–72 h post-randomization, and 24–48 h postnatally. For continuous data, analysis was performed using repeated measures ANOVA methods including terms for timepoint, treatment allocation and their interaction. Results: Included were 134 women assigned randomly to sildenafil (n = 69) or placebo (n = 65) who had maternal BP and HR recorded at baseline. At 1–2 h post-randomization, compared with baseline values, sildenafil increased maternal HR by 4 bpm more than did placebo (mean difference, 5.00 bpm (95% CI, 1.00–12.00 bpm) vs 1.25 bpm (95% CI, –5.38 to 7.88 bpm); P = 0.004) and reduced systolic BP by 1 mmHg more (mean difference, –4.13 mmHg (95% CI, –9.94 to 1.44 mmHg) vs –2.75 mmHg (95% CI, –7.50 to 5.25 mmHg); P = 0.048). Even after adjusting for maternal mean arterial pressure, sildenafil reduced aortic PWV by 0.60 m/s more than did placebo (mean difference, –0.90 m/s (95% CI, –1.31 to –0.51 m/s) vs –0.26 m/s (95% CI, –0.75 to 0.59 m/s); P = 0.001). Sildenafil was associated with a non-significantly greater decrease in SV index after 1–2 h post-randomization than was placebo (mean difference, –5.50 mL/m2 (95% CI, –11.00 to –0.50 mL/m2) vs 0.00 mL/m2 (95% CI, –5.00 to 4.00 mL/m2); P = 0.056). Conclusions: Sildenafil in a dose of 25 mg three times daily increases HR, reduces BP and reduces arterial stiffness in pregnancies complicated by severe early-onset FGR. These changes are short term, modest and consistent with the anticipated vasodilatory effect. They have no short- or long-term clinical impact on the mother.

KW - cardiovascular

KW - endothelium

KW - fetal growth restriction

KW - hemodynamics

KW - nitric oxide

KW - pharmacology

KW - sildenafil

KW - vascular biology

UR - http://www.scopus.com/inward/record.url?scp=85078870524&partnerID=8YFLogxK

U2 - 10.1002/uog.20851

DO - 10.1002/uog.20851

M3 - Article

C2 - 31432556

AN - SCOPUS:85078870524

VL - 55

SP - 198

EP - 209

JO - Ultrasound in Obstetrics and Gynecology

JF - Ultrasound in Obstetrics and Gynecology

SN - 0960-7692

IS - 2

ER -

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