DOI: http://dx.doi.org/10.18203/2320-1770.ijrcog20191929

The role of sildenafil citrate in the treatment of fetal growth restriction: a randomized controlled trial

Ahmed Abdelshafy, Khaled Ibrahim Abdullah, Sherif Ashoush, Heba E. Hosni

Abstract


Background: This study was aimed to evaluate the effect of sildenafil citrate on Doppler velocity indices in patients with fetal growth restriction (FGR) associated with impaired placental circulation.

Methods: A double-blinded, parallel group randomized clinical trial (clinicaltrials.gov NCT02590536) was conducted in Ain Shams Maternity Hospital, in the period between October 2015 and June 2017. Ninety pregnant women with documented intrauterine growth retardation at 24-37 weeks of gestation were randomized to either sildenafil citrate 25 mg orally every 8 hours or placebo visually-identical placebo tablets with the same regimen. The primary outcome of the study was the change in umbilical artery and fetal middle cerebral artery indices.

Results: There was a significant improvement in umbilical and middle cerebral artery indices after sildenafil administration p<0.001. Present study observed that, sildenafil group, in comparison to placebo, has a significantly higher mean neonatal birth weight. 1783±241g vs 1570±455g (p<0.001). There was a significantly higher mean gestational age at delivery in women in sildenafil group 35.3±1.67 weeks, whereas it was lower in the placebo group 33.5±1.7 weeks. The side effects as headache, palpitation and facial flushing were significantly higher in sildenafil group compared to placebo group.

Conclusions: The use sildenafil citrate in pregnancies with fetal growth restriction (FGR) improved the feto-placental Doppler indices (pulsatility index of umbilical artery and middle cerebral artery) and improved neonatal outcomes.


Keywords


Fetal growth restriction (FGR), Middle cerebral artery doppler, Sildenafil citrate, Umbilical artery doppler

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References


Bilardo CM, Wolf H, Stigter RH, Ville Y, Baez E, Visser GH, et al. Relationship between monitoring parameters and perinatal outcome in severe, early intrauterine growth restriction. Ultrasound Obstet Gynecol. 2004;23(2):119-25.

Manning E, Corcoran P, Meaney S, Greene RA. On behalf of the perinatal mortality group: perinatal mortality in Ireland Annual Report 2011. National Perinat Epidemiol Centre Cork. 2013.

Turan S, Miller J, Baschat AA. Integrated testing and management in fetal growth restriction. In Seminars Perinatol. 2008:32(3):194-200.

Baschat AA, Cosmi E, Bilardo CM, Wolf H, Berg C, Rigano S, et al. Predictors of neonatal outcome in early-onset placental dysfunction. Obstet Gynecol. 2007;109(2):253-61.

Unterscheider J, Daly S, Geary MP, Kennelly MM, McAuliffe FM, O'donoghue K, et al. Optimizing the definition of intrauterine growth restriction: the multicenter prospective PORTO Study. Am J Obstet Gynecol. 2013; 208(4):290-e1.

Lees C, Marlow N, Arabin B, Bilardo CM, Brezinka C, Derks JB, et al. Perinatal morbidity and mortality in early‐onset fetal growth restriction: cohort outcomes of the trial of randomized umbilical and fetal flow in Europe (Truffle). Ultrasound Obstetr Gynecol. 2013;42(4):400-8.

Lin CS, Lin G, Xin ZC, Lue TF. Expression, distribution and regulation of phosphodiesterase 5. Current Pharm Design. 2006;12(27):3439-57.

Wareing M, Myers JE, O’hara M, Baker PN. Sildenafil citrate (Viagra) enhances vasodilatation in fetal growth restriction. J Clinic Endocrinol Metabol. 2005;90(5):2550-5.

Von Dadelszen P, Dwinnell S, Magee LA, Carleton BC, Gruslin A, Lee B, et al. Sildenafil citrate therapy for severe early‐onset intrauterine growth restriction. BJOG: Int J Obstetr Gynaecol. 2011;118(5):624-8.

El-Sayed MA, Saleh SA, Maher MA, Khidre AM. Utero-placental perfusion Doppler indices in growth restricted fetuses: effect of sildenafil citrate. J Maternal Fetal Neonat Med. 2018;31(8):1045-50.

Trapani Jr A, Gonçalves LF, Trapani TF, Franco MJ, Galluzzo RN, Pires MM. Comparison between transdermal nitroglycerin and sildenafil citrate in intrauterine growth restriction: effects on uterine, umbilical and fetal middle cerebral artery pulsatility indices. Ultrasound Obstet Gynecol.2016;48(1):61-5.

Maged AM, Hashem AM, Gad Allah SH, Mahy ME, Mostafa WA, Kotb A. The effect of loading dose of magnesium sulfate on uterine, umbilical, and fetal middle cerebral arteries Doppler in women with severe preeclampsia: a case control study. Hypertens Pregancy. 2016;35(1):91-9.

Levine RJ, Karumanchi SA. Circulating angiogenic factors in preeclampsia. Clinic Obstet Gynecol. 2005;48(2):372-86.

Villanueva-Garcia D, Mota-Rojas D, Hernandez-Gonzalez R, Sanchez-Aparicio P, Alonso-Spilsbury M, Trujillo-Ortega ME, et al. A systematic review of experimental and clinical studies of sildenafil citrate for intrauterine growth restriction and pre-term labour. J Obstet Gynaecol. 2007;27(3):255-9.

Samangaya RA, Mires G, Shennan A, Skillern L, Howe D, McLeod A, et al. A randomised, double-blinded, placebo-controlled study of the phosphodiesterase type 5 inhibitor sildenafil for the treatment of preeclampsia. Hypertension Pregnancy. 2009;28(4):369-82.

Sharp A, Cornforth C, Jackson R, Harrold J, Turner MA, Kenny LC, et al. Maternal sildenafil for severe fetal growth restriction (STRIDER): a multicentre, randomised, placebo-controlled, double-blind trial. Lancet Child Adolesc Health. 2018;2(2):93-102.

Nurnberg HG, Hensley PL, Heiman JR, Croft HA, Debattista C, Paine S. Sildenafil treatment of women with antidepressant-associated sexual dysfunction: a randomized controlled trial. JAMA. 2008;300(4):395-404.