Maternal Sildenafil vs Placebo in Pregnant Women With Severe Early-Onset Fetal Growth Restriction A Randomized Clinical Trial
| Autor: | Anouk Pels, Janus Christian Jakobsen, Jan B. Derks, Wessel Ganzevoort, Christiana A. Naaktgeboren, Marjon A. de Boer, Sanne J. Gordijn, Hans Duvekot, Christian Gluud, Ayten Elvan-Taspinar, Joris van Drongelen, Judith O E H van Laar, Jim van Eyck, Marieke Sueters, M. Post, Aleid G. van Wassenaer-Leemhuis, Wes Onland, Salwan Al-Nasiry, Ruben G. Duijnhoven, Titia Lely |
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| Přispěvatelé: | Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), Graduate School, ARD - Amsterdam Reproduction and Development, Neonatology, Other Research, Obstetrics and Gynaecology, APH - Quality of Care, APH - Methodology, APH - Digital Health, RS: GROW - R4 - Reproductive and Perinatal Medicine, Obstetrie & Gynaecologie, MUMC+: MA Medische Staf Obstetrie Gynaecologie (9), Obstetrics & Gynecology, Internal Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Middle Cerebral Artery Placenta Diseases medicine.drug_mechanism_of_action diagnosis IMPACT Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] Infant Newborn Diseases Umbilical Arteries CITRATE law.invention chemistry.chemical_compound HEMORRHAGE Pre-Eclampsia Randomized controlled trial Pregnancy law Interquartile range Birth Weight Original Investigation Fetal Growth Retardation Obstetrics infants Obstetrics and Gynecology Gestational age General Medicine Intention to Treat Analysis Online Only Pregnancy Trimester Second Pulsatile Flow Early Termination of Clinical Trials Female Phosphodiesterase 5 inhibitor Adult medicine.medical_specialty hypertension Sildenafil Hypertension Pulmonary Pregnancy Trimester Third childhood neurodevelopment Gestational Age Placebo Sildenafil Citrate preeclampsia All institutes and research themes of the Radboud University Medical Center Double-Blind Method medicine Humans Perinatal Mortality Intention-to-treat analysis business.industry Research Infant Newborn Phosphodiesterase 5 Inhibitors medicine.disease respiratory tract diseases DEFINITION chemistry business |
| Zdroj: | Pels, A, Derks, J, Elvan-Taspinar, A, van Drongelen, J, de Boer, M, Duvekot, H, van Laar, J, van Eyck, J, Al-Nasiry, S, Sueters, M, Post, M, Onland, W, van Wassenaer-Leemhuis, A, Naaktgeboren, C, Jakobsen, J C, Gluud, C, Duijnhoven, R G, Lely, T, Gordijn, S, Ganzevoort, W & Dutch STRIDER Trial Group 2020, ' Maternal Sildenafil vs Placebo in Pregnant Women With Severe Early-Onset Fetal Growth Restriction : A Randomized Clinical Trial ', JAMA network open, vol. 3, no. 6, pp. e205323 . https://doi.org/10.1001/jamanetworkopen.2020.5323 JAMA Network Open, 3, 6 JAMA network open, 3(6). American Medical Association Pels, A, Derks, J, Elvan-Taspinar, A, van Drongelen, J, de Boer, M, Duvekot, H, van Laar, J, van Eyck, J, Al-Nasiry, S, Sueters, M, Post, M, Onland, W, van Wassenaer-Leemhuis, A, Naaktgeboren, C, Jakobsen, J C, Gluud, C, Duijnhoven, R G, Lely, T, Gordijn, S, Ganzevoort, W & Dutch STRIDER Trial Group 2020, ' Maternal Sildenafil vs Placebo in Pregnant Women With Severe Early-Onset Fetal Growth Restriction : A Randomized Clinical Trial ', JAMA Network Open, vol. 3, no. 6, e205323 . https://doi.org/10.1001/jamanetworkopen.2020.5323 Jama network open, 3(6):e205323. AMER MEDICAL ASSOC JAMA Network Open, 3 Jama network open, 3(6):e205323. American Medical Association JAMA network open, 3(6):e205323. American Medical Association JAMA Network Open |
| ISSN: | 2574-3805 |
| DOI: | 10.1001/jamanetworkopen.2020.5323 |
| Popis: | Key Points Question Does sildenafil reduce the risk of perinatal mortality or morbidity in children of pregnant women with severe early onset fetal growth restriction? Findings In this randomized clinical trial including 216 pregnant women, perinatal mortality or major morbidity was not statistically different and occurred in the offspring of 60.2% of participants allocated to sildenafil vs 54.2% of those allocated to placebo. Pulmonary hypertension occurred in 18.8% of neonates in the sildenafil group compared with 5.1% of neonates in the placebo group, which was statistically significantly different. Meaning These findings suggest that treatment of severe early onset fetal growth restriction by maternal sildenafil did not reduce the risk of perinatal mortality or major neonatal morbidity, but increased neonatal pulmonary hypertension was observed. This randomized clinical trial examines whether sildenafil reduces the risk of perinatal mortality or morbidity vs placebo in children of pregnant women with severe early onset fetal growth restriction. Importance Severe early onset fetal growth restriction caused by placental dysfunction leads to high rates of perinatal mortality and neonatal morbidity. The phosphodiesterase 5 inhibitor, sildenafil, inhibits cyclic guanosine monophosphate hydrolysis, thereby activating the effects of nitric oxide, and might improve uteroplacental function and subsequent perinatal outcomes. Objective To determine whether sildenafil reduces perinatal mortality or major morbidity. Design, Setting, and Participants This placebo-controlled randomized clinical trial was conducted at 10 tertiary referral centers and 1 general hospital in the Netherlands from January 20, 2015, to July 16, 2018. Participants included pregnant women between 20 and 30 weeks of gestation with severe fetal growth restriction, defined as fetal abdominal circumference below the third percentile or estimated fetal weight below the fifth percentile combined with Dopplers measurements outside reference ranges or a maternal hypertensive disorder. The trial was stopped early owing to safety concerns on July 19, 2018, whereas benefit on the primary outcome was unlikely. Data were analyzed from January 20, 2015, to January 18, 2019. The prespecified primary analysis was an intention-to-treat analysis including all randomized participants. Interventions Participants were randomized to sildenafil, 25 mg, 3 times a day vs placebo. Main Outcomes and Measures The primary outcome was a composite of perinatal mortality or major neonatal morbidity until hospital discharge. Results Out of 360 planned participants, a total of 216 pregnant women were included, with 108 women randomized to sildenafil (median gestational age at randomization, 24 weeks 5 days [interquartile range, 23 weeks 3 days to 25 weeks 5 days]; mean [SD] estimated fetal weight, 458 [160] g) and 108 women randomized to placebo (median gestational age, 25 weeks 0 days [interquartile range, 22 weeks 5 days to 26 weeks 3 days]; mean [SD] estimated fetal weight, 464 [186] g). In July 2018, the trial was halted owing to concerns that sildenafil may cause neonatal pulmonary hypertension, whereas benefit on the primary outcome was unlikely. The primary outcome, perinatal mortality or major neonatal morbidity, occurred in the offspring of 65 participants (60.2%) allocated to sildenafil vs 58 participants (54.2%) allocated to placebo (relative risk, 1.11; 95% CI, 0.88-1.40; P = .38). Pulmonary hypertension, a predefined outcome important for monitoring safety, occurred in 16 neonates (18.8%) in the sildenafil group vs 4 neonates (5.1%) in the placebo group (relative risk, 3.67; 95% CI, 1.28-10.51; P = .008). Conclusions and Relevance These findings suggest that antenatal maternal sildenafil administration for severe early onset fetal growth restriction did not reduce the risk of perinatal mortality or major neonatal morbidity. The results suggest that sildenafil may increase the risk of neonatal pulmonary hypertension. Trial Registration ClinicalTrials.gov Identifier: NCT02277132 |
| Databáze: | OpenAIRE |
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