OUTCOMES OF SILDENAFIL CITRATE IN EARLY ONSET OF FETAL GROWTH RESTRICTIONS– A SYSTEMATIC REVIEW
Main Article Content
Keywords
Sildenafil citrate, early-onset fetal growth restriction, uteroplacental blood flow, perinatal outcomes, placental insufficiency, STRIDER trials
Abstract
Background: Early-onset fetal growth restriction (FGR) is a critical obstetric challenge associated with placental insufficiency, resulting in increased perinatal morbidity and mortality. Sildenafil citrate, a phosphodiesterase-5 (PDE-5) inhibitor, has been explored as a therapeutic option to improve uteroplacental blood flow and fetal outcomes. However, its efficacy and safety remain subjects of debate.
Methods: A systematic review was conducted to evaluate the effects of sildenafil citrate in early-onset FGR. Comprehensive literature searches were performed in PubMed, Scopus, Web of Science, and Cochrane Library, including studies published from 2013 to 2023. Studies assessing sildenafil citrate in pregnancies complicated by early-onset FGR (diagnosed before 32 weeks) were included. Outcomes such as fetal growth parameters, uteroplacental blood flow, and neonatal morbidity were analyzed.
Results: The review included 10 studies after screening 2330 articles. Sildenafil citrate showed improvements in uteroplacental blood flow and maternal hemodynamics in some studies, with reductions in uterine artery pulsatility index and arterial stiffness. However, neonatal outcomes, including fetal growth velocity and survival, demonstrated inconsistent improvements. Safety concerns, such as neonatal pulmonary hypertension reported in the Dutch STRIDER trial, raised caution about its routine use. Variations in trial designs and population characteristics contributed to heterogeneity in results.
Conclusion: Sildenafil citrate shows potential to enhance uteroplacental blood flow in early-onset FGR, but its clinical benefits for fetal growth and neonatal outcomes remain inconclusive. Safety concerns warrant careful patient selection and further research to refine its use in this high-risk group. Collaborative efforts through international consortia are essential for advancing evidence-based management of early-onset FGR.
References
2. Sampath, Ananya. Short Term Clinical Profile of Term IUGR. Diss. Rajiv Gandhi University of Health Sciences (India), 2018.
3. Mohammed, Elsayed Elbadawy, et al. "The use of low dose sildenafil citrate in cases of intrauterine growth restriction." Clinical Obstetrics, Gynecology and Reproductive Medicine 3.4 (2017).
4. De Bie, Felix Rafael, et al. "Sildenafil during the 2nd and 3rd Trimester of Pregnancy: Trials and Tribulations." International Journal of Environmental Research and Public Health 19.18 (2022): 11207.
5. Rakhanova, Y., Almawi, W.Y., Aimagambetova, G. et al. The effects of sildenafil citrate on
intrauterine growth restriction: a systematic review and meta-analysis. BMC Pregnancy Childbirth 23, 409 (2023). https://doi.org/10.1186/s12884-023-05747-7
6. Yadav, Rashmi, Amitesh Yadav, and Alka Kumari. "Role of sildenafil citrate therapy in early-onset fetal growth restriction." Journal of South Asian Federation of Obstetrics and Gynaecology 13.6 (2022): 392-395.
7. Pels A, Derks J, Elvan-Taspinar A, et al. Maternal Sildenafil vs Placebo in Pregnant Women With Severe Early-Onset Fetal Growth Restriction: A Randomized Clinical Trial. JAMA Netw Open. 2020;3(6):e205323. doi:10.1001/jamanetworkopen.2020.5323
8. Khalil, Asma, et al. "Effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early‐onset fetal growth restriction: planned subgroup analysis from a multicenter randomized placebo‐controlled double‐blind trial." Ultrasound in Obstetrics & Gynecology 55.2 (2020): 198-209.
9. Abdelshafy, Ahmed, et al. "The role of sildenafil citrate in the treatment of fetal growth restriction: a randomized controlled trial." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 8.5 (2019): 1840-1847.
10. Groom, Katie M., et al. "STRIDER NZAus: a multicentre randomised controlled trial of sildenafil therapy in early‐onset fetal growth restriction." BJOG: An International Journal of Obstetrics & Gynaecology 126.8 (2019): 997-1006.
11. Maged, Mohammed, et al. "Use of sildenafil citrate in cases of intrauterine growth restriction (IUGR); a prospective trial." Taiwanese Journal of Obstetrics and Gynecology 57.4 (2018): 483-486.
12. Sharp, Andrew, et al. "Maternal sildenafil for severe fetal growth restriction (STRIDER): a multicentre, randomised, placebo-controlled, double-blind trial." The Lancet Child & Adolescent Health 2.2 (2018): 93-102.
13. Premalatha, H. L., et al. "Study of effect of sildenafil citrate in pregnant women with intrauterine growth restriction/oligohydramnios." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 5.9 (2016): 3094-3098.
14. Panda, Subrat et al. “Sildenafil citrate in fetal growth restriction.” Journal of reproduction & infertility vol. 15,3 (2014): 168-9.
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Dr. Anupama Ashvini Kumar Deshmukh
Prof and HOD at Dept. Of Obstetrics and Gynecology, Dr Rajendra Gode Medical College Amravati
Dr. Ashvini kumar Deshmukh
Consultant at Dept. Of Obstetrics and Gynecology, Dr. Sudha Deshmukh Hospital, Amravati
Dr. Soniya Wadekar
Consultant at Dept. Of Obstetrics and Gynecology, Suryavanshi Hospital, Amravati
Dr. Jyoti Upadhyay
Consultant at Dept. Of Obstetrics and Gynecology, Upadhyay Hospital, Gwalior
Dr. Bhairavi Deshmukh
Consultant ESIS at Dept. Of Obstetrics and Gynecology, ESIS
Dr. Vijay Patil
Consultant at Dept. Of Obstetrics and Gynecology, Patil Hospital