Comparison of the Effect of Nifedipine Alone and the Combination of Nifedipine and Sildenafil in Delaying Preterm Labor: A Randomized Clinical Trial

Abstract

Objective: Recently, sildenafil as a drug effective in relaxing smooth muscles can be used as an adjunct to delay the onset of uterine contractions and therefore the occurrence of preterm labor. The aim of this study was to evaluate the effect of nifedipine combination with sildenafil on preterm delivery compared with nifedipine alone.
 Materials and methods: This randomized double-blinded clinical trial was performed on pregnant women with a gestational age of 26-34 weeks with singleton pregnancy and symptoms of preterm delivery. The mothers were randomly assigned into two groups receiving nifedipine plus sildenafil or those receiving nifedipine alone. The time of delivery, maternal and neonatal complications were compared between the two groups.
 Results: Mothers who received the combination therapy experienced significantly lower preterm delivery within 72 hours of intervention compared to nifedipine alone (4.5% versus 27.3%, p = 0.002). The rate of delivery during the first 7 days after discharge was 7.6% and 31.8% in nifedipine plus sildenafil and nifedipine alone, respectively (P = 0.001). The prevalence of neonatal respiratory distress syndrome (RDS) as well as mean birth weight was higher in the nifedipine group alone. Treatment protocol with nifedipine and sildenafil compared with nifedipine alone was associated with a significant increase in preterm delivery delay (beta =-5.819, p = 0.001).
 Conclusion: The use of sildenafil in addition to nifedipine causes more delay in delivery in cases of preterm labor, followed by lower risk for RDS, reduces neonatal intensive care unit (NICU) admission, and preserves neonatal birth weight.

Effect of oral nifedipine or combined with sildenafil citrate for management of threatened preterm labour randomized trial

“…In the current study, 40% of the participants in group A had history of preterm birth, whereas; it was 75% in group B. In Elham Mohammadi et al 13 the history of preterm birth was 9.1% in the nifedipine group while it was 21.2% in combination group which was less as compared to our study.…”

“…In the current study, the birth weight was 2090±372.64 in group A and was 2381.67±492.44 grams in group B. Elham Mohammadi et al 13 conducted a randomized study on 139 women in which 1609.0±204.3 and 2154.5±221.3 (grams) were the mean birth weight identified in the nifedipine and combination group which was a decreased mean birth weight compared to our study.…”

The combined uterorelaxant effect of sildenafil and terbutalin in the rat: The potential benefit of co-administration of low doses

“…On the other hand, there is limited clinical knowledge on the effect of sildenafil in pregnancy [ 3 ]. One study suggests that sildenafil-nifedipine combination may be beneficial in preterm birth [ 4 ]. PDE-5 is the main enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP) following the release of nitric oxide (NO) from nitrergic nerves or vascular endothelial cells, leading to smooth muscle relaxation [ 5 ].…”

“…For example, combining Ca-channel blockers and beta-adrenergic receptor agonists are associated with pulmonary hypertension [ 11 ]. Some evidence exists for synergistic effects with sildenafil and nifedipine [ 4 ]. Additionally, we have previously demonstrated in the pregnant rat, that synergistic tocolytic effects are found when combining terbutaline and magnesium sulfate or terbutaline and nifedipine [ 12 , 13 ].…”

Sildenafil during the 2nd and 3rd Trimester of Pregnancy: Trials and Tribulations

“…One clinical trial investigating sildenafil as an add-on therapy to nifedipine, a calcium-antagonist, for threatened preterm labor was retracted due to concerns about the validity of the data [ 46 ]. An Iranian study conducted in 2020 suggested a beneficial effect of adding sildenafil to nifedipine therapy for threatened preterm labor reporting prolonged latency (16 days instead of 10 days), as well as the reduced prevalence of neonatal respiratory distress syndrome (7.6% vs. 25.8%) and higher birth weights (2154 g vs. 1609 g) [ 47 ] ( Table 2 ).…”