الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 104 |  |  |
| | | from | 104 | | |
Abstract
Intrauterine growth restriction (IUGR) occurs when fetal full growth potential is not achieved. It is one of the most common and serious complications of pregnancy. The most common etiology for IUGR is placental insufficiency, which is frequently associated with impaired placental blood flow. Growth-restricted fetuses with severe impairment of umbilical artery (UA) blood flow are at increased risk of adverse outcomes such as intrauterine fetal demise and neonatal death, as well as increased neonatal morbidity, including: hypoglycemia, hyperbilirubinemia, hypothermia, intraventricular hemorrhage, necrotizing enterocolitis, seizures, sepsis and respiratory distress syndrome.
Sildenafil citrate is emerging as a potential candidate for the treatment of intra-uterine growth restriction. Sildenafil has also been proposed as a potential therapeutic strategy to maintain placental function in pre-eclampsia. As a nitric oxide donor with vasodilator effects, nitroglycerine has also the potential therapeutic effect as sildenafil and to compare between the two drugs this study was conducted.
This was a prospective randomized double-blind placebo controlled study of 90 singleton pregnancies (gestational age ≥24 weeks) with IUGR and abnormal Ut.A and UA Doppler waveforms. Pregnancies complicated with: multifetal pregnancies, fetal infection, congenital fetal anomalies, maternal medical diseases that contraindicate the use of Glyceryl trinitrate or sildenafil citrate, reversed flow of umbilical artery Doppler and those receiving drugs that interacted with Glyceryl trinitrate or sildenafil citrate; were excluded from the study.
The primary outcome of the study was to evaluate the effects of sildenafil citrate and transdermal nitroglycerin (GTN) on Doppler velocity waveforms of the uterine (Ut.A), umbilical (UA) and fetal middle cerebral (MCA) arteries in pregnancies with intrauterine growth restriction (IUGR). The secondary outcome was comparing the effect of the two drugs on maternal blood pressure.
We compared maternal arterial blood pressure and the pulsatility index (PI) of Ut.A, UA and fetal MCA before and after application of oral sildenafil citrate (50mg), a transdermal GTN patch (average dose, 0.4mg/h), or placebo. Statistical analysis was performed by ANOVA when comparing between more than two means. Paired sample t-test of significance was used when comparing between related samples. Chi-square (x2) test of significance was used in order to compare proportions between two qualitative parameters.
There was a significant decrease in Ut.A PI after application of both sildenafil citrate (16.7%) and GTN (18.7%). UA PI also showed a significant reduction with both sildenafil citrate (17.8%) and GTN (17.03%), with no significant difference between the two drugs. There was no difference in Ut.A- and UA-PI when the GTN and sildenafil groups were compared. No changes in Doppler velocimetry were observed in the placebo group and no significant change in MCA-PI was observed in any group. Maternal arterial blood pressure decreased with administration of both sildenafil citrate and GTN. The use of sildenafil citrate or transdermal GTN in pregnancies with IUGR is associated with a significant reduction in Ut.A and UA Doppler PI, as well as maternal arterial blood pressure. Neither drug affected the MCA-PI.
A significant reduction in MAP, in patients with hypertension and IUGR without compromising Ut.A blood flow, suggests that either sildenafil or GTN may be useful as an antihypertensive drug in the context of placental vascular insufficiency.
Sildenafil citrate has shown a hemodynamic action that is similar to that of GTN with a better therapeutic profile and less side effects. More double-blind randomized controlled trials are recommended with larger sample size, early initiation of medication, evaluation of maternal serum drugs levels, multiple doses and multiple Doppler evaluation, and assessment of perinatal and neonatal outcomes to confirm the therapeutic potential of sildenafil citrate in IUGR.