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microRNA signatures associated with fetal growth restriction: a systematic review

European Journal of Clinical Nutrition volume 76, pages 1088–1102 (2022)Cite this article

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Abstract

Placental-origin microRNA (miRNA) profiles can be useful toward early diagnosis and management of fetal growth restriction (FGR) and associated complications. We conducted a systematic review to identify case–control studies that have examined miRNA signatures associated with human FGR. We systematically searched PubMed and ScienceDirect databases for relevant articles and manually searched reference lists of the relevant articles till May 18th, 2021. Of the 2133 studies identified, 21 were included. FGR-associated upregulation of miR-210 and miR-424 and downregulation of a placenta-specific miRNA cluster miRNA located on C19MC (miR-518b, miR-519d) and miR-221-3p was reported by >1 included studies. Analysis of the target genes of these miRNA as well as pathway analysis pointed to the involvement of angiogenesis and growth signaling pathways, such as the phosphatidylinositol 3-kinase- protein kinase B (PI3K-Akt) pathway. Only 3 out of the 21 included studies reported FGR-associated miRNAs in matched placental and maternal blood samples. We conclude that FGR-associated placental miRNAs could be utilized to inform clinical practice towards early diagnosis of FGR, provided enough evidence from studies on matched placental and maternal blood samples become available.

Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42019136762.

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Fig. 1: PRISMA flow diagram.
Fig. 2: Potential role of miRNA and their target genes in fetal growth restriction (FGR).

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Funding

This work was supported by the Women Scientist Scheme, Department of Science & Technology, Government of India to PK (Reference no. SR/WOS-A/LS-669/2016) and the Department of Biotechnology, Government of India grants to AM (Grant sanction nos. BT/PR22326/MED/97/349/2016 and BT/PR30276/MED/97/399/2018).

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Author notes

  1. R. Rajashekhar

    Present address: Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India

Authors and Affiliations

  1. Division of Nutrition, St. John’s Research Institute, A Recognized Research Centre of University of Mysore, Bangalore, India

    P. Kochhar, M. Vukku, R. Rajashekhar & A. Mukhopadhyay

Authors
  1. P. Kochhar
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  2. M. Vukku
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  3. R. Rajashekhar
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  4. A. Mukhopadhyay
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Contributions

All authors planned and designed the study. RR and PK were involved in registering of the study protocol and selection of studies. PK and MV analysed data from the selected studies. PK, MV, and AM drafted and edited the article. All authors read and approved the final version of the systematic review for submission.

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Correspondence to A. Mukhopadhyay.

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Kochhar, P., Vukku, M., Rajashekhar, R. et al. microRNA signatures associated with fetal growth restriction: a systematic review. Eur J Clin Nutr 76, 1088–1102 (2022). https://doi.org/10.1038/s41430-021-01041-x

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  • DOI: https://doi.org/10.1038/s41430-021-01041-x

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