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Metabolomics for predicting fetal growth restriction: protocol for a systematic review and meta-analysis
  1. Debora Farias Batista Leite1,2,
  2. Aude-Claire Morillon3,
  3. Elias F Melo Júnior1,
  4. Renato T Souza2,
  5. Ali S Khashan3,4,
  6. Philip N Baker5,
  7. Louise C Kenny3,6,
  8. José Guilherme Cecatti2
  1. 1 Department of Maternal and Child Health, Clinics Hospital of Federal University of Pernambuco, Recife, Brazil
  2. 2 Department of Gynaecology and Obstetrics, University Campinas, Sao Paulo, Brazil
  3. 3 Irish Centre for Fetal and Neonatal Translational Research (INFANT), University College Cork, Cork, Ireland
  4. 4 School of Public Health, University College Cork, Cork, Ireland
  5. 5 College of Life Sciences, University of Leicester, Leicester, UK
  6. 6 Department of Women’s and Children’s Health, Faculty of Health and Life Sciences, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
  1. Correspondence to Professor José Guilherme Cecatti; cecatti{at}


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.

  • fetal growth restriction
  • intrauterine growth restriction
  • small for gestational age infant
  • metabolomics
  • prediction

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  • Contributors DFBL (the guarantor of the review) and A-CM developed the systematic review protocol and will perform the literature search, study selection, data extraction and risk of bias assessment. ASK, PNB, RTS, EFMJ and JGC supervised protocol elaboration and the latter three will resolve any discrepancy about methodology. ASK, DFBL and A-CM will deal with statistics procedures. PNB and LCK performed the last amendments of protocol and will revise the final systematic review draft. All authors have read this manuscript and have agreed with this submission.

  • Funding This research was supported by Brazilian National Research Council (grant number 401636/2013-5) and Bill and Melinda Gates Foundation (grant number OPP1107597-Grand Challenges Brazil: Reducing the burden of preterm birth, Fiotec number 05/2013), which provided funding to PRETERM-SAMBA project ( DFBL was granted a scholarship (process number 88881.134512/2016-01) from the Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES) and developed part of her doctoral studies as a visiting student at University College Cork, Ireland. RTS has also awarded a scholarship from CAPES (process number 88881.134095/2016-01). A-CM was granted a scholarship from Science Foundation Ireland, for her doctoral thesis. Our sponsors have not intervened in authors’ decision to write the systematic review protocol or to submit this paper.

  • Competing interests DFBL and A-CM are studying this technology in predicting FGR. JGC, LCK and PNB have presented conference talks about this field. LCK and PNB are principal investigators of Metabolomic Diagnostics.

  • Patient consent Not required.

  • Ethics approval As this is a systematic review protocol, no ethics committee approval is necessary.

  • Provenance and peer review Not commissioned; externally peer reviewed.