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

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.