ORIGINAL ARTICLE

Year : 2020  |  Volume : 18  |  Issue : 3  |  Page : 227-232

Sildenafil citrate therapy for IUGR and its effect on umbilical artery Doppler

Abdel A.G.E.-D.T El-Darwish¹, Mahmoud A Badawy¹, Sally M.G Farghaly^2
1 Department of Obstetrics and Gynecology, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
² Department of Obstetrics and Gynecology, At Sohag Teaching Hospital, Sohag, Egypt

Correspondence Address:
Sally M.G Farghaly
2012, Alzahraa, Mohammad Abd Elhalim Street, Sohag 28090
Egypt

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/AZMJ.AZMJ_69_19

Background Intrauterine growth restriction (IUGR) occurs when there is deficiency of gas exchange and nutrient delivery to the fetus not allowing it to thrive in utero. This happens because of maternal diseases that decrease oxygen-carrying capacity (e.g. cyanotic heart disease, smoking, and hemoglobinopathy) or by maternal vascular diseases causing a dysfunctional oxygen delivery system or idiopathic causes. Sildenafil (phosphodiesterase-5) inhibitor consists of the citrate salt of sildenafil; it is a selective and specific inhibitor of cyclic guanosine monophosphate. It is primarily used for sexual dysfunction, antidepressant-associated sexual dysfunction, pulmonary hypertension, altitude thickness, and Raynaud’s phenomenon. Herein, the trial is used for improving uteroplacental perfusion by enhancing vasodilatation of myometrial small artery, decreasing peripheral resistance, and boosting flow within the uteroplacental bed.
Aim The aim was to evaluate efficacy and role of sildenafil citrate on the blood flow of uteroplacental circulation and fetal growth in pregnancies accompanied by fetal growth restriction because of dysfunctional oxygen delivery system guided by umbilical Doppler ultrasound.
Patients and methods Our study was a prospective double-blind, randomized, controlled trial. The patients were recruited from women with IUGR attending the emergency ward and outpatient clinic at Sohag teaching Hospital. The study comparing three groups of 150 women. Each group consisted of 50 women. One group received 20 mg of sildenafil citrate orally twice/day, the second received a dose of 40 mg every 12 h vaginally, whereas the last one received a placebo, as a control group.
Results After treatment, improvement of Doppler in the form of S/D, resistance index, and pulsatility index showed highly significant difference between the two sildenafil groups compared with the control one.
Conclusion Sildenafil therapy may offer a new breakthrough in treatment of IUGR-complicated pregnancies, with improvement of the perinatal outcomes.

Keywords: fetal growth restriction, small for gestational age, umbilical artery Doppler, sildenafil citrate therapy

Introduction

Aim

Patients and methods

1. The study protocol was approved by the Local Ethical Committee, Sohag Faculty of Medicine, Sohag University.
2. An informed written consent was taken from all of the pregnant women included in the study.

1. Age: 20–35 years.
2. Regular menstrual history prior pregnancy.
3. Singleton pregnancy.
4. Gestational age (GA) starting 24–36 weeks.
5. IUGR owing to decreased uteroplacental blood flow because of maternal causes.
6. Fetal well-being.

1. Pregnancy before 23 weeks.
2. Maternal cardiovascular morbidity, diabetes, and hypertension.
3. Iatrogenic IUGR.
4. Smoking and/or alcohol or drug abuse.
5. Allergy to sildenafil citrate.
6. Known or suspected fetal anomaly.
7. Constitutionally small fetus.

Methods

1. The first group received 40 mg of sildenafil citrate orally twice.
2. The second group received sildenafil citrate in a dose of 20 mg every 12 h vaginally.
3. The third group received a placebo and is considered as the control group.

1. Full history taking, including past, medical, obstetric, and menstrual history.
2. General and abdominal examination.
3. Investigations included the following:
   1. Laboratory: full urine, blood count analysis, liver and kidney function, and glucose tolerance test.
   2. Ultrasonic measurement to estimate GA, fetal weight, amniotic fluid index, biophysical profile, and placental features (location, thickness, and grading), as well as for ultrasound markers of chromosomal abnormalities.
   3. Umbilical Doppler was done before starting the drug and repeated it after one week, then used for weekly follow-up.

1. The umbilical artery: the umbilical artery in the cord was recognized by the characteristic shape of the velocity waveform on the oscilloscope (and sound) and the ability to simultaneous display flow in the umbilical vein in the opposite direction.
2. As waveforms obtained near the placental end of the cord reflect downstream resistance and show higher end-diastolic flow velocity than waveforms obtained near the abdominal cord insertion [4], in the present study to optimize reproducibility, the umbilical artery Doppler was interrogated at the abdominal cord insertion in all cases.
3. The umbilical cord was visualized in cross-section in a free loop and magnified to the maximum possible extent. In most cases, the cord appeared as two arteries and one vein.
4. At least two measurements were made of the cross-sectional area of the artery, if necessary by using different cross-sections of the cord. The ellipse function allowed a directly derived internal cross-sectional area to be obtained for each vessel. Measurements were made in accordance with the manufacturer’s guidelines for this [5] as follows:
   1. Cord vessels were visualized longitudinally in the absence of fetal movements or breathing. In all cases, the angle of insonation was less than 60.
   2. Care was taken to avoid contamination of the waveform with other signals, either above or below the baseline, and only waveforms with a high signal to noise ratio was accepted. The sample volume was adjusted to insonate the whole width of the vessel.
   3. At least three consecutive arterial waveforms were obtained.
   4. Calipers were placed to allow time-averaged velocity measurements to be made with angle correction.

1. Placental and fetal Doppler parameters before and a week after sildenafil administration were taken.
2. Doppler velocimetry: pulsatility index (PI) or resistance index (RI) of the umbilical artery was performed twice, immediately before giving sildenafil dose and after a week of therapy. We took measurements twice for each vessel, and then the mean value was recorded.
3. Blood flow was acquired through using a triplex system (two-dimensional image, color Doppler, and pulsatile Doppler) with color mapping.
4. Scans with a minimum of six uniform waves were analyzed. The volume size of the sample was set according to the vessel diameter to be studied and the angle of insonation was as close to 0° as possible. We froze the image after obtaining a good signal and then automatically measured the Doppler flow velocimetry parameters by the equipment’s software.
5. Velocimetry of the umbilical artery was accomplished at the midpoint between the placental and abdominal insertions of the vessel.

1. The primary outcome was the effect of sildenafil in improving Doppler indices and resultant effect on fetal growth.
2. The secondary outcome was the difference between oral sildenafil in a dose of 20 mg and vaginal sildenafil in a dose of 40 mg every 12 h.

1. For statistical data analysis in the study, we used the Statistical Package for the Social Sciences (IBM-SPSS), version 24 IBM (IBM, Chicago, Illinois, USA) (May 2016).
2. Analysis of variance test was used to compare means between more than two groups.
3. Data were expressed as mean, SD, number, and percentage. Number and percentage were used to describe qualitative data, whereas mean and SD were used as descriptive value for quantitative data.
4. Student t-test was used to compare the means among the three groups. Mann–Whitney test was used instead of Student t-test in case of nonparametric data.
5. The level of significance (P value) was demonstrated as follows:
   1. Significance P less than 0.05.
   2. No significance P greater than 0.05.
   3. High significance P less than 0.001.

Results

Table 1 Demographic and history data of the study groups Click here to view

Table 2 Examination of vital signs Click here to view

Table 3 Gestational age (weeks) among the three groups as assessed by history, symphysis fundal, height, ultrasound, and fetal weight (g) Click here to view

Table 4 Comparison between pre and posttreatment Doppler findings in group I Click here to view

Table 5 Comparison between pre and posttreatment Doppler findings in group II Click here to view

Table 6 comparison between pre and posttreatment Doppler findings in group III Click here to view

Table 7 Doppler examination among the three groups Click here to view

Discussion

References

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