Journal reading

Fajar Akbar Ramadhan

Introduction

↑↑ IUFD
One of major
Intrauterine growth ↑↑ Neonatal
complication of
restriction morbidity&mortality
pregnancy
Childhood sequel

Abnormal Impaired placental

placentation blood circulation
Introduction

Normal pregnancy :
Trophoblast -> Nitric Oxide -> potent vasodilatior

Preeklampsia & IUGR -> decreased release Nitric Oxide

Relaxation of
Nitric Oxide vascular smooth
L-arginine ↑ cGMP
(NO) musce

Sildenafil citrate act by blocking phosphodiesterase-5 inhibitor that breaks down cGMP, vasodilator
effect of NO

There is no evidence of the benefit of using sildenafil citrate in the treatment of IUGR associated with
impaired placental circulation

The studi aim to evaluate the effect of sildenafil citrate in patients with IUGR associated with
impaired placental circulation
Patients and methods
This was a prospective non-randomized study
50 pregnant women
GA 24-32 weeks + Singleton
pregnancy + IUGR
(antenatal)

Inclusion Exclusion
1. Pregnatn women +1 fetus 1. Patient with uncertain GA
with IUGR 2. Patient with known or
2. Age ≥ 19 and ≤ 45 years suspected fetal anomalies
3. Patient with regular 3. Patient with obstetrical
menstrual pattern before complication
pregnancy 4. When urgent delivery is
4. Patient are able to attend indicated
follow up as planned 5. Usage of any vasodilator
medication
6. Multiple pregnancies
7. Smoking, drug or alcohol
abusers

Clinical suspicion+USG+abnormal
IUGR diagnosis
Umbilical artery Doppler indices
 Patients and methods
Outcome
Treatment of sildenafil citrate Each participant
measures

Each participant 1. Fetal movements count 1. UA Doppler indices

( 20mg orally) 2. Biophysical profile 2. Maternal and fetal
3. UA Doppler indices safety
3. GA at delivery
4. Birth weight
Side effect (-) Side effect (+) 5. Neonatal outcomes

The dose was Stop and were considered

increased to 20mg the control group
(3x1tab) until delivery
 Patients and methods
Doppler ultrasonographic measurements Examination of the newborn

All Doppler velocimetric studies were performed in the After resuscitation and establishment of respiration, Apgar score
semi-recumbent position of patient and during fetal quiescence was calculated and the newborn was examined carefully for any
To minimize interobserver errors, all the measurements congenital malformation or any disorder as birth trauma.
in this study were performed by one investigator.
We measured pulsatility index (PI), resistance index (RI) and
systolic/diastolic (S/D) ratio

Statistics

The terms of data description were mean, range, standard deviation

(±SD), frequencies and relative frequencies.
The mean and standard deviation of the collected data were calculated
and the comparison of variables between the two groups in the present
study was done using Student t-test. A probability value (P value)
less than 0.05 was considered statistically significant.
Statistical calculations were done by SPSS (Statistical Package for
the Social Science; SPSS Inc., Chicago, IL, USA) statistical program
Result
Result
 Discussion
• Samangaya et al. = not support the use of sildenafil citrate in patients with pre-eclampsia, but the drug
showed some effect on fetal growth. Sildenafil = an effective intervention for IUGR pregnancies
• The decreased vascular resistance after sildenafil administration = significant decrease in Doppler indices
comparable result were studied by Panda et al., Lin et al., El-Sayed et al., Dastjerdi et al., and Trapani et
al.
• Dadelszen et al. = a significant increase in AC when using sildenafil citrate in pregnancies complicated by
the severe type of IUGR (AC < 5th percentile)
• Mean birth weight at delivery was increased significantly in sildenafil group.
• Headache was the commonest side effect followed by visual disturbance and gastrointestinal tract
symptoms. Overall Sildenafil was well tolerated. In our study, only a few cases stopped sildenafil due to its
side effects. Similar to the findings of Dunn et al.
• Sildenafil is safe with neither increase in fetal morbidity or mortality nor congenital malformations.
 Discussion
• The use of sildenafil doesn't protect from IUFD. Throughout the study, we have seen one case of IUFD in
sildenafil group
• This study was a prospective and focused one including only cases of IUGR associated with impaired
placental circulation. Additionally, they evaluated the effect of sildenafil not only on Doppler but also on
early neonatal outcomes. These issues may add strength to this study.
• On the other hand, we didn't randomize our cases and couldn’t include a large number of cases also
maternal sildenafil concentration was not measured in the serum.
• We recommend larger multicentric studies evaluating the longterm neonatal outcomes to assess the
beneficial effect of sildenafil in IUGR.
• Conclusion, sildenafil citrate treatment may present a new hope towards better perinatal outcomes for
pregnancies complicated by IUGR that may help to decrease neonatal admission to newborn nursery

.
Thank you
Critical Appraisal

 Patient : Pregnant women who were 24-32 years of age having singleton pregnancy + IUGR
attending the antenatal clinic in Mansoura University Hospitals ( March 2016-October 2017)

 Intervention : Receive Sildenafil citrate

 Comparison : Not receive Sildenafil citrate

 Outcome : better perinatal outcomes for pregnancies complicated by IUGR

Reference of Article

 Authors : Mohammed Maged, Alaa Wageh, Maher Shams, Abdlgawad

Elmetwally
 Affiliation : Resident of Obstetrics and Gynecology at Mansoura University
Hospitals & Faculty of Medicine, Mansoura University, Egypt
 Title : Use of sildenafil citrate in cases of intrauterine growth restriction
(IUGR); a prospective trial
 Journal : Taiwanese Journal of Obstetrics & Gynecology
 Volume and page number : Taiwanese Journal of Obstetrics & Gynecology 57
483-486
 Year of publication : 2018
 General Methodological Issues
Criteria Y S N NC NR NA NQ Comments Type of Study Check Instructions
Assessment of a diagnostic procedure [ ] Fill in sections D to F
A priori hypothesis clearly stated [ ] [ ] [ ] [ V] [ ] [ ] [ ]
Controlled trial of intervention [ V] Fill in sections G to I

Source population identified [ V] [ ] [ ] [ ] [ ] [ ] [ ] Cohort or prognostic study [ ] Fill in sections J to L

Inclusion criteria described and Case-control study [ ] Fill in sections M to O

appropriate (same in all groups)
[V] [ ] [ ] [ ] [ ] [ ] [ ]
Cross-sectional study [ ] Fill in sections P to R
Exclusion criteria described and
appropriate (same in all groups)
[V] [ ] [ ] [ ] [ ] [ ] [ ] Clinical or descriptive study [ ] Fill in section S

Number of excluded or refusal Other, specify ___________________________________ [ ] Fill in section S

(before study) reported
[ ] [ ] [V] [ ] [ ] [ ] [ ]

Withdrawals (during study) reported,

explained, and reasonable
[ ] [ ] [ ] [V] [ ] [ ] [ ]

Withdrawals equal in groups [ ] [ ] [ ] [ ] [ V] [ ] [ ]

Sample size preplanned to provide
adequate statistical power
[ ] [ ] [V] [ ] [ ] [ ] [ ]

Statistical analysis appropriate [ ] [V] [ ] [ ] [ ] [ ] [ ]

Adjustment for multiple comparisons [ ] [ ] [ ] [ ] [ ] [ ] [ ]

Adjustment for important variables [ ] [ ] [ ] [ ] [ ] [ ] [ ]

Results verifiable from raw data [ ] [ ] [V] [ ] [ ] [ ] [ ]

Specific methodological issues
Criteria Y S N NC NR NA NQ Comments

Randomization properly done [ ] [ ] [V] [ ] [ ] [ ] [ ]

Baseline comparability reported [ V] [ ] [ ] [ ] [ ] [ ] [ ]

Same data collection for all arms [ V] [ ] [ ] [ ] [ ] [ ] [ ]

Subjects blinded to treatment

assignment
[ ] [ ] [ ] [ ] [V] [ ] [ ]

Care givers blinded to treatment

assignment
[ ] [ ] [ ] [ ] [V] [ ] [ ]

Treatments clearly described [ V] [ ] [ ] [ ] [ ] [ ] [ ]

Co interventions monitored [ ] [ ] [ ] [ ] [ ] [ V] [ ]
Compliance monitored and equal in
all groups
[ ] [ ] [ ] [ ] [ ] [V] [ ]

Side effects assessed [ V] [ ] [ ] [ ] [ ] [ ] [ ]

Outcomes defined, measurable, and

valid
[V] [ ] [ ] [ ] [ ] [ ] [ ]

Blind assessment of outcomes [ ] [ ] [ ] [ ] [ V] [ ] [ ]

Author’s key results and conclusions

 Sildenafil citrate treatment may present a new hope towards

better perinatal outcomes for pregnancies complicated by
IUGR that may help to decrease neonatal admission to
newborn nursery
Conclusions and assessment of the
article
 Strengths of the paper : This study was a prospective and focused one including only cases of IUGR
associated with impaired placental circulation. The authors didn't include IUGR cases with normal
Doppler as they consider small for gestational age with good perinatal morbidity and mortality. They also
excluded IUGR cases from other causes due to the unpredictable course of the pathology. Additionally,
they evaluated the effect of sildenafil not only on Doppler but also on early neonatal outcomes

 Weaknesses of the paper : The authors didn’t reported clearly how to divide the participant into two
groups (randomization), so that it can increase selection and confounding bias.
 no randomization
 Small sample size, no preplanned sample size to achieve adequate statistical power
 maternal sildenafil concentration was not measured in the serum

 Clinical relevance : Relevant

 Scientific merit : Good