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Meta-Analysis
. 2019 Jul 24;14(7):e0219732.
doi: 10.1371/journal.pone.0219732. eCollection 2019.

The effects of sildenafil in maternal and fetal outcomes in pregnancy: A systematic review and meta-analysis

Raquel Domingues da Silva Ferreira  1   2 , Romulo Negrini  1   2 , Wanderley Marques Bernardo  3 , Ricardo Simões  3 , Sebastião Piato  1
Affiliations
Meta-Analysis

The effects of sildenafil in maternal and fetal outcomes in pregnancy: A systematic review and meta-analysis

Raquel Domingues da Silva Ferreira et al. PLoS One. .

Retraction in

Abstract

Background: The number of studies associating the use of sildenafil in gestation is increasing. This drug inhibits phosphodiesterase type 5 (PDE5), an enzyme responsible for degradation of nitric oxide, and its efficacy is greater in the placental territory, as the maternal side of the placenta have more PDE5 than other sites. For this reason, promising results have been observed related to the prevention of preeclampsia and intrauterine growth restriction and to improvement of maternal-fetal morbidity in cases of placental insufficiency.

Objective: To evaluate the benefits of using sildenafil in pregnancy.

Searched strategy: MEDLINE, ClinicalTrials.gov, Embase, LILACS and Cochrane databases were searched through September 2018. There was no restriction in language or year of publication. This study was registered in PROSPERO (CRD42017060288).

Selection criteria: Randomized clinical trials which used sildenafil for treatment or prevention of obstetric diseases compared with placebo were selected.

Data collection and analysis: The results were obtained using the inverse variance method for continuous variables and Man-Whitney for categorical variables.

Main results: Among a population of 598 pregnant women from the seven clinical trials included, 139 had pre-eclampsia, 275 had intrauterine growth restriction, and 184 had oligohydramnios. A significant increase of 222.58 grams [27.75 to 417.41] was observed in the fetal weight at birth of patients taking sildenafil. The other outcomes did not show any statistical significance. This may be due to the small number of patients used in each study and the great heterogeneity between the groups.

Conclusions: Sildenafil could be associated with increasing fetal weight at birth in placental insufficiency despite the limitations of this meta-analysis, even though more studies in this field are needed to introduce this drug into obstetric clinical practice.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. PRISMA Flowchart of recovery and selection of studies.
Fig 2
Fig 2. Risk of bias for each study.
Fig 3
Fig 3. Risk of bias for all studies.
Fig 4
Fig 4. Fetal weight at birth: Analysis by the fixed-effects model and funnel plot.
SD: standard deviation; IV: variance inverse; CI: confidence interval.
Fig 5
Fig 5. Fetal weight at birth—Analysis by the random-effects model.
SD: standard deviation; IV: variance inverse; CI: confidence interval.
Fig 6
Fig 6. Gestational age at birth.
SD: standard deviation; IV: variance inverse; CI: confidence interval.
Fig 7
Fig 7. Umbilical artery pulsatility index—Analysis by the fixed-effects model and funnel plots.
SD: standard deviation; IV: variance inverse; CI: confidence interval.
Fig 8
Fig 8. Umbilical artery pulsatility index—Analysis by the random-effects model.
SD: standard deviation; IV: variance inverse; CI: confidence interval.
Fig 9
Fig 9. Indication of delivery due to fetal distress.
SD: standard deviation; M-H: Mann-Whitney; CI: confidence interval.
Fig 10
Fig 10. Indication of labor due to maternal laboratory test abnormality.
SD: standard deviation; M-H: Mann-Whitney; CI: confidence interval.
Fig 11
Fig 11. Indication of delivery due to imminent eclampsia.
SD: standard deviation; M-H: Mann-Whitney; CI: confidence interval.
Fig 12
Fig 12. Neonatal mortality.
SD: standard deviation; M-H: Mann-Whitney; CI: confidence interval.
Fig 13
Fig 13. Headache as a side effect—Analysis by the fixed-effects model and funnel plots.
SD: standard deviation; M-H: Mann-Whitney; CI: confidence interval.
Fig 14
Fig 14. Headache as a side effect—Analysis after removing the outlier.
SD: standard deviation; M-H: Mann-Whitney; CI: confidence interval.
See this image and copyright information in PMC

References

    1. Terrett NK, Bell AS, Brown D, Ellis P. Sildenafil (Viagra™), a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction. Bioorg Med Chem Lett. 1996;6(15):1819–24.
    1. Tan K, Krishnamurthy MB, O’Heney JL, Paul E, Sehgal A. Sildenafil therapy in bronchopulmonary dysplasia-associated pulmonary hypertension: a retrospective study of efficacy and safety. Eur J Pediatr. 2015;174(8):1109–15. 10.1007/s00431-015-2515-7 - DOI - PubMed
    1. Rodway GW, Lovelace AJ, Lanspa MJ, McIntosh SE, Bell J, Briggs B, et al. Sildenafil and exercise capacity in the elderly at moderate altitude. Wilderness Environ Med. 2016;27(2):307–15. 10.1016/j.wem.2016.01.006 - DOI - PubMed
    1. Maharaj CH, O’Toole D, Lynch T, Carney J, Jarman J, Higgins BD, et al. Effects and mechanisms of action of sildenafil citrate in human chorionic arteries. Reprod Biol Endocrinol. 2009;7:34 10.1186/1477-7827-7-34 - DOI - PMC - PubMed
    1. Yallampalli C, Garfield RE. Inhibition of nitric oxide synthesis in rats during pregnancy produces signs similar to those of preeclampsia. Am J Obstet Gynecol. 1993. November;169(5):1316–20. 10.1016/0002-9378(93)90299-x - DOI - PubMed

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