Dataset Information

Metabolomics for predicting fetal growth restriction: protocol for a systematic review and meta-analysis.

ABSTRACT:

Introduction

Fetal growth restriction (FGR) is a relevant research and clinical concern since it is related to higher risks of adverse outcomes at any period of life. Current predictive tools in pregnancy (clinical factors, ultrasound scan, placenta-related biomarkers) fail to identify the true growth-restricted fetus. However, technologies based on metabolomics have generated interesting findings and seem promising. In this systematic review, we will address diagnostic accuracy of metabolomics analyses in predicting FGR.

Methods and analysis

Our primary outcome is small for gestational age infant, as a surrogate for FGR, defined as birth weight below the 10th centile by customised or population-based curves for gestational age. A detailed systematic literature search will be carried in electronic databases and conference abstracts, using the keywords 'fetal growth retardation', 'metabolomics', 'pregnancy' and 'screening' (and their variations). We will include original peer-reviewed articles published from 1998 to 2018, involving pregnancies of fetuses without congenital malformations; sample collection must have been performed before clinical recognition of growth impairment. If additional information is required, authors will be contacted. Reviews, case reports, cross-sectional studies, non-human research and commentaries papers will be excluded. Sample characteristics and the diagnostic accuracy data will be retrieved and analysed. If data allows, we will perform a meta-analysis.

Ethics and dissemination

As this is a systematic review, no ethical approval is necessary. This protocol will be publicised in our institutional websites and results will be submitted for publication in a peer-reviewed journal.

Prospero registration number

CRD42018089985.

SUBMITTER: Leite DFB

PROVIDER: S-EPMC6286473 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Metabolomics for predicting fetal growth restriction: protocol for a systematic review and meta-analysis.

Leite Debora Farias Batista DFB Morillon Aude-Claire AC Melo Júnior Elias F EF Souza Renato T RT Khashan Ali S AS Baker Philip N PN Kenny Louise C LC Cecatti José Guilherme JG

BMJ open 20181206 12

<h4>Introduction</h4>Fetal growth restriction (FGR) is a relevant research and clinical concern since it is related to higher risks of adverse outcomes at any period of life. Current predictive tools in pregnancy (clinical factors, ultrasound scan, placenta-related biomarkers) fail to identify the true growth-restricted fetus. However, technologies based on metabolomics have generated interesting findings and seem promising. In this systematic review, we will address diagnostic accuracy of metab ...[more]

PMID: 30530473

Similar Datasets

Project description:IntroductionFetal 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 analysisWe 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 disseminationResults will be disseminated through a peer-reviewed scientific journal, and by scientific congresses and meetings.Prospero registration numberCRD42019122831.

Project description:BackgroundHyperglycemia in pregnancy (HIP) has been recently differentiated between diabetes in pregnancy (DIP) and gestational diabetes mellitus (GDM). The proposed protocol is relevant, and clinical concern is due to the higher risk of adverse pregnancy outcomes (APO) and long-term effects on both the mother and the fetus. Fasting plasma glucose level (FPG) and oral glucose tolerance test (OGTT) are current diagnostic tools. However, controversy persists concerning diagnostic criteria, cut-off points, and even selective or universal screening. The objective of this systematic review is to assess the performance of metabolomic markers in the prediction of HIP.MethodsThis is a protocol for a systematic review with potential meta-analysis. The primary outcome is GDM, defined as glucose intolerance identified in the second and third trimesters of pregnancy (any FPG ≥ 92 mg/dL and < 126 mg/dL OR when 75-g OGTT shows one altered value among these: FPG ≥ 92 mg/dL or 1-h post glucose load ≥ 180 mg/dL or 2-h post glucose load ≥ 153 mg/dL); the secondary outcome is HIP, defined as hyperglycemia detected in the first trimester of pregnancy (any FPG ≥ 126 mg/dL). A detailed systematic literature search will be carried out in electronic databases and conference abstracts, using the keywords "gestational diabetes mellitus," "metabolomics," "pregnancy," and "screening" (and their variations). We will include original peer-reviewed articles published from Jan 1, 1999, to Dec 31, 2018. Original studies including diabetes diagnosed before pregnancy (T2DM and T1DM), multiple pregnancies, and congenital malformations will be excluded. All results regarding samples, participant characteristics, metabolomic techniques, and diagnostic accuracy measures will be retrieved and analyzed. Since this is a systematic review, no ethical approval is necessary.DiscussionThis systematic review may have the potential to provide significant evidence-based findings on the prediction performance of metabolomics. There are short and long-term repercussions for the mother and the newborn. Therefore, both may benefit from an accurate prediction technique for HIP.Systematic review registrationThis protocol was registered in the PROSPERO platform under number CRD42018100175 .

Project description:Background and Objective: Fetal growth restriction (FGR) is a pathological condition in which the fetus cannot reach its expected growth potential. When it is diagnosed as a suspected FGR, it remains an unsolved problem whether to direct induction or continue expectant management. To effectively reduce the incidence of neonatal adverse outcomes, we aimed to evaluate whether either method was associated with a lower incidence of neonatal adverse outcomes. Methods: We searched the relevant literature through the PubMed, Web of Science, and Cochrane Library from inception to January 10, 2020. We defined induction as the experimental group and expectant management as the control group. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models owing to heterogeneity. Furthermore, we conducted a sensitivity analysis to explore the robustness of the included literature. We used the Newcastle-Ottawa scale (NOS) to evaluate the quality of the available studies. We applied the funnel plot to describe the publication bias. Additionally, subgroup analysis based on the study method, sample size, area, NOS score, Apgar score <7 at 5 min, definition of suspected FGR, severity, and neonatal adverse outcomes were performed to further evaluate the differences between the induction and expectant management. Results: Our study included a total of eight articles with 6,706 patients, which consisted of four randomized controlled trials (RCTs), three retrospective cohort studies, and one prospective cohort study. The total pooled OR and 95% CI between the induction group and the expected management group was 1.38 (95% CI, 0.84-2.28) in the random model. The heterogeneity was I 2 = 84%, P < 0.01. The sensitivity analysis showed that the neonatal adverse outcomes of induction vs. expectant management still presented similar outcomes after omitting of any one of these studies. The funnel plot and linear regression equation showed that there was no publication bias in our study (P = 0.75). Subgroup analysis showed that induction increased the neonatal adverse outcome risks of hypoglycemia and respiratory insufficiency (ORneonatal hypoglycaemia = 8.76, 95% CI: 2.57-29.90; ORrespiratory insufficiency = 1.74, 95% CI: 1.35-2.24, respectively). However, no significant differences were observed based on the other subgroups (all P > 0.05). Conclusion: Regardless of induction or expectant management of a suspected FGR, the neonatal adverse outcomes showed no obvious differences. More studies should be conducted and confounding factors should be taken into consideration to elucidate the differential outcomes of the two approaches for suspected FGR.

Project description:BackgroundEarly onset fetal growth restriction secondary to placental insufficiency can lead to severe maternal and neonatal morbidity and mortality. Pre-clinical studies and a few small randomised clinical trials have suggested that phosphodiesterase type 5 (PDE-5) inhibitors may have protective effects against placental insufficiency in this context; however, robust evidence is lacking. The STRIDER Consortium conducted four randomised trials to investigate the use of a PDE-5 inhibitor, sildenafil, for the treatment of early onset fetal growth restriction. We present a protocol for the pre-planned systematic review with individual participant data meta-analysis, aggregate meta-analysis, and trial sequential analysis of these and other eligible trials. The main objective of this study will be to evaluate the effects of PDE-5 inhibitors on neonatal morbidity compared with placebo or no intervention among pregnancies with fetal growth restriction.MethodsWe will search the following electronic databases with no language or date restrictions: OVID MEDLINE, OVID EMBASE, the Cochrane Controlled Register of Trials (CENTRAL), and the clinical trial registers Clinicaltrials.gov and World Health Organisation International Clinical Trials Registry Platform (ICTRP). We will identify randomised trials of PDE-5 inhibitors in singleton pregnancies with growth restriction. Two reviewers will independently screen all citations, full-text articles, and abstract data. Our primary outcome will be infant survival without evidence of serious adverse neonatal outcome. Secondary outcomes will include gestational age at birth and birth weight z-scores. We will assess bias using the Cochrane Risk of Bias 2 tool. We will conduct aggregate meta-analysis using fixed and random effects models, Trial Sequential Analysis, and individual participant data meta-analysis using one- and two-stage approaches. The certainty of evidence will be assessed with GRADE.DiscussionThis pre-defined protocol will minimise bias during analysis and interpretation of results, toward the goal of providing robust evidence regarding the use of PDE-5 inhibitors for the treatment of early onset fetal growth restriction.Systematic review registrationPROSPERO (CRD42017069688).

Project description:Introduction: Fetal growth restriction (FGR) is associated with a higher risk of perinatal morbidity and mortality, as well as long-term health issues in newborns. Currently, there is no effective medicine for FGR. Phosphodiesterase-5 (PDE-5) inhibitors have been shown in pre-clinical studies to improve FGR. This study aimed to evaluate the latest evidence about the clinical outcomes and safety of PDE-5 inhibitors for the management of FGR. Methods: Eight databases (PubMed, Embase, Medline, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Database and WangFang Database) were searched for English and Chinese articles published from the database inception to December 2023. Randomized controlled trials (RCTs) reporting the use of PDE-5 inhibitors in FGR were included. The quality of the RCTs was assessed using the Cochrane Risk of Bias Tool. Odds ratio and mean difference (MD) (95% confidence intervals) were pooled for meta-analysis. Results: From 253 retrieved publications, 16 studies involving 1,492 pregnant women met the inclusion criteria. Only sildenafil (15 RCTs) and tadalafil (1 RCT) were studied for FGR. Compared with the control group (placebo, no treatment, or other medication therapies), sildenafil increased birth weight, pregnancy prolongation and umbilical artery pulsatility indices. However, it also increased the risk of pulmonary hypertension in newborns, as well as headache and flushing/rash in mothers. There were no significant differences in gestation age, perinatal mortality or major neonatal morbidity, stillbirth, neonate death, infants admitted to neonatal intensive care unit, intraventricular hemorrhage and necrotizing enterocolitis in infants, as well as pregnancy hypertension and gastrointestinal side effects in mothers between the treatment and the control groups. Discussion: Sildenafil was the most investigated PDE-5 inhibitors for FGR. Current evidence suggests that sildenafil can improve birth weight and duration of pregnancy but at the same time increase the risk of neonatal pulmonary hypertension. It remains uncertain whether the benefits of sildenafil in FGR outweigh the risks and further high-quality RCTs are warranted. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=325909.

Dataset Information

Metabolomics for predicting fetal growth restriction: protocol for a systematic review and meta-analysis.

Introduction

Methods and analysis

Ethics and dissemination

Prospero registration number

Publications

Metabolomics for predicting fetal growth restriction: protocol for a systematic review and meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets