Pharmacological interventions for the prevention of fetal growth restriction: protocol for a systematic review and network meta-analysis
Introduction Fetal growth restriction (FGR) includes different conditions in which a fetus fails to reach the own full growth, and accounts for 28%–45% of non-anomalous stillbirths. The management of FGR is based on the prolongation of pregnancy long enough for fetal organs to mature while preventin...
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| Format: | Article |
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BMJ Publishing Group
2019-07-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/9/7/e029467.full |
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| author | Alessandra Bettiol Niccolò Lombardi Giada Crescioli Laura Avagliano Alessandro Mugelli Claudia Ravaldi Alfredo Vannacci |
| author_facet | Alessandra Bettiol Niccolò Lombardi Giada Crescioli Laura Avagliano Alessandro Mugelli Claudia Ravaldi Alfredo Vannacci |
| author_sort | Alessandra Bettiol |
| collection | DOAJ |
| description | Introduction Fetal growth restriction (FGR) includes different conditions in which a fetus fails to reach the own full growth, and accounts for 28%–45% of non-anomalous stillbirths. The management of FGR is based on the prolongation of pregnancy long enough for fetal organs to mature while preventing starvation. As for pharmacological management, most guidelines recommend treatment with low-dose aspirin and/or with heparin, although this approach is still controversial and innovative promising therapies are under investigation. As no firm evidence exists to guide clinicians towards the most effective therapeutic intervention, this protocol describes methods for a systematic review and network meta-analysis (NetMA) of pharmacological treatments for FGR prevention.Methods and analysis We will search MEDLINE and Embase for clinical trials and observational studies performed on gestating women with clinically diagnosed risk of FGR. Experimental interventions will include heparin and low-molecular-weight heparin, acetylsalicylic acid, antiplatelet agents, phosphodiesterase type 3 and 5 inhibitors, maternal vascular endothelial growth factor gene therapy, nanoparticles, microRNA, statins, nitric oxide donors, hydrogen sulphide, proton pump inhibitors, melatonin, creatine and N-acetylcysteine, and insulin-like growth factors, compared between each other or to placebo or no treatment. Primary efficacy outcome is FGR. Secondary efficacy outcomes will be preterm birth, fetal or neonatal death and neonatal complications. For the safety outcome, all adverse events reported in included studies and experienced by either mothers, fetuses or newborns will be considered. Two review authors will independently screen title, abstract and full paper text, and will independently extract data from included studies. Where possible and appropriate, for primary and secondary efficacy outcomes, a NetMA will be performed using a random-effects model within a frequentist framework. Adverse events will be narratively described.Ethics and dissemination Results will be disseminated through a peer-reviewed scientific journal, and by scientific congresses and meetings.PROSPERO registration number CRD42019122831. |
| format | Article |
| id | doaj-art-bd07969371ea412da4e08d8d841cdad6 |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2019-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-bd07969371ea412da4e08d8d841cdad62025-08-20T02:03:15ZengBMJ Publishing GroupBMJ Open2044-60552019-07-019710.1136/bmjopen-2019-029467Pharmacological interventions for the prevention of fetal growth restriction: protocol for a systematic review and network meta-analysisAlessandra Bettiol0Niccolò Lombardi1Giada Crescioli2Laura Avagliano3Alessandro Mugelli4Claudia Ravaldi5Alfredo Vannacci6Department of Experimental and Clinical Medicine, University of Florence, Firenze, ItalyDipartimento di Scienze Biomediche Chirurgiche e Odontoiatriche, Universita` degli Studi di Milano, Milan, Italy1 Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy2 Department of Health Sciences, San Paolo Hospital Medical School, Università degli Studi di Milano, Milano, Italy1 Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, ItalyCiaoLapo Foundation for Perinatal Health, Prato, ItalyCiaoLapo Foundation for Perinatal Health, Prato, ItalyIntroduction Fetal growth restriction (FGR) includes different conditions in which a fetus fails to reach the own full growth, and accounts for 28%–45% of non-anomalous stillbirths. The management of FGR is based on the prolongation of pregnancy long enough for fetal organs to mature while preventing starvation. As for pharmacological management, most guidelines recommend treatment with low-dose aspirin and/or with heparin, although this approach is still controversial and innovative promising therapies are under investigation. As no firm evidence exists to guide clinicians towards the most effective therapeutic intervention, this protocol describes methods for a systematic review and network meta-analysis (NetMA) of pharmacological treatments for FGR prevention.Methods and analysis We will search MEDLINE and Embase for clinical trials and observational studies performed on gestating women with clinically diagnosed risk of FGR. Experimental interventions will include heparin and low-molecular-weight heparin, acetylsalicylic acid, antiplatelet agents, phosphodiesterase type 3 and 5 inhibitors, maternal vascular endothelial growth factor gene therapy, nanoparticles, microRNA, statins, nitric oxide donors, hydrogen sulphide, proton pump inhibitors, melatonin, creatine and N-acetylcysteine, and insulin-like growth factors, compared between each other or to placebo or no treatment. Primary efficacy outcome is FGR. Secondary efficacy outcomes will be preterm birth, fetal or neonatal death and neonatal complications. For the safety outcome, all adverse events reported in included studies and experienced by either mothers, fetuses or newborns will be considered. Two review authors will independently screen title, abstract and full paper text, and will independently extract data from included studies. Where possible and appropriate, for primary and secondary efficacy outcomes, a NetMA will be performed using a random-effects model within a frequentist framework. Adverse events will be narratively described.Ethics and dissemination Results will be disseminated through a peer-reviewed scientific journal, and by scientific congresses and meetings.PROSPERO registration number CRD42019122831.https://bmjopen.bmj.com/content/9/7/e029467.full |
| spellingShingle | Alessandra Bettiol Niccolò Lombardi Giada Crescioli Laura Avagliano Alessandro Mugelli Claudia Ravaldi Alfredo Vannacci Pharmacological interventions for the prevention of fetal growth restriction: protocol for a systematic review and network meta-analysis BMJ Open |
| title | Pharmacological interventions for the prevention of fetal growth restriction: protocol for a systematic review and network meta-analysis |
| title_full | Pharmacological interventions for the prevention of fetal growth restriction: protocol for a systematic review and network meta-analysis |
| title_fullStr | Pharmacological interventions for the prevention of fetal growth restriction: protocol for a systematic review and network meta-analysis |
| title_full_unstemmed | Pharmacological interventions for the prevention of fetal growth restriction: protocol for a systematic review and network meta-analysis |
| title_short | Pharmacological interventions for the prevention of fetal growth restriction: protocol for a systematic review and network meta-analysis |
| title_sort | pharmacological interventions for the prevention of fetal growth restriction protocol for a systematic review and network meta analysis |
| url | https://bmjopen.bmj.com/content/9/7/e029467.full |
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