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ToolsSharp, Andrew, Cornforth, Christine, Jackson, Richard, Harrold, Jane, Turner, Mark A., Kenny, Louise C., Baker, Philip N., Johnstone, Edward D., Khali, Asma, von Dadelszen, Peter, Papageorghiou, Aris T., Alfirevic, Zarko and Vollmer, Brigitte and STRIDER group (2025) Neurodevelopmental outcomes at 2 years in children who received sildenafil therapy in utero: The STRIDER randomized controlled trial. Obstetrical and Gynecological Survey, 80 (5). pp. 280-282. ISSN 0029-7828
Full text not available from this repository. (Request a copy)Abstract
Fetal growth restriction (FGR) occurs when a fetus grows slower than expected for gestational age. Severe early-onset cases are associated with stillbirth, neonatal death, and developmental disorders. With no current treatment, management focuses on balancing the risks of prematurity against fetal demise from intrauterine hypoxia. One cause of FGR is inadequate maternal vessel remodeling around the placenta, reducing uteroplacental circulation while preserving vessel responsiveness to nitric oxide. Sildenafil, a phosphodiesterase type 5 inhibitor and vasodilator, has been studied as a potential therapy to improve fetal blood flow. This study evaluates sildenafil’s effectiveness in prolonging pregnancy and reducing adverse perinatal outcomes and neurological impairment at 2-year follow-up. This double-blind randomized controlled trial recruited participants from 19 UK tertiary obstetric units between 2014 and 2016. Eligible women had a singleton pregnancy between 22 and 30 weeks with severe early-onset FGR, defined as an estimated fetal weight or abdominal circumference <10th percentile and absent or reversed end-diastolic flow in the umbilical artery, with an expectant management plan. Exclusions included maternal age <16 years, contraindications to sildenafil, cocaine use, suspected chromosomal or structural anomaly, and likelihood of delivering within 72 hours. Participants received either 25 mg of oral sildenafil or a placebo 3 times daily. The primary outcome—time from treatment initiation to delivery—was previously reported. This study assessed 2-year follow-up outcomes, including cognitive, language, and motor development (Bayley Scales of Infant and Toddler Development, third edition), neurological status (Hempel Neurological Examination), overall health (Health Status Classification System—Preschool Version), behavior (Child Behavior Checklist 1.5–5), and executive function (Behavior Rating Inventory of Executive Function—Preschool). The primary follow-up outcome was survival without cerebral palsy or neurosensory impairment and a Bayley-III composite score >85. The study enrolled a total of 135 participants, with 70 in the sildenafil group and 65 in the placebo group. At 2 years, 81% of surviving infants completed follow-up. As previously reported, median gestational age at delivery did not differ between groups (sildenafil: 29.2 weeks, placebo: 29.9 weeks). The only significant physical difference at 2 years was a slightly larger head circumference in the sildenafil group (mean difference, 2.02 cm; 95% confidence interval, 0.11–3.93). BSID-III results showed no differences in cognitive, language, or motor development. Cerebral palsy prevalence, as well as assessments of executive function, behavior, and overall health, was similar between groups. Hempel Neurological Assessment could not be recorded due to the nature of the patient population, which prevented direct comparison of neurological function. However, medical records indicated no difference in cerebral palsy rates. These findings confirm that sildenafil does not improve pregnancy duration, perinatal outcomes, or long-term neurodevelopmental, behavioral, or emotional outcomes in severe early-onset FGR cases. Similar results have been reported in Australian and New Zealand studies. Additionally, a Dutch study suggests sildenafil may increase the risk of persistent pulmonary hypertension and neonatal death. Limitations include the lack of direct neurological and cardiovascular assessments and insufficient statistical power for follow-up outcomes.
| Item Type: | Article |
|---|---|
| Additional Information: | Publisher Copyright: Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved. |
| Uncontrolled Keywords: | obstetrics and gynaecology ,/dk/atira/pure/subjectarea/asjc/2700/2729 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 02 Jul 2025 16:30 |
| Last Modified: | 14 Jul 2025 12:31 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/99820 |
| DOI: | 10.1097/OGX.0000000000001401 |
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