University of Oulu

Marttila, S., Rovio, S., Mishra, P.P. et al. Adulthood blood levels of hsa-miR-29b-3p associate with preterm birth and adult metabolic and cognitive health. Sci Rep 11, 9203 (2021).

Adulthood blood levels of hsa-miR-29b-3p associate with preterm birth and adult metabolic and cognitive health

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Author: Marttila, Saara1,2; Rovio, Suvi3,4; Mishra, Pashupati P.1;
Organizations: 1Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, and Finnish Cardiovascular Research Center, Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
2Gerontology Research Center, Tampere University, Tampere, Finland
3Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
4Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
5Division of Medicine, Turku University Hospital and Department of Medicine, University of Turku, Turku, Finland
6Research Unit Molecular Epidemiology, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Munich, Germany
7Vascular Centre, Tampere University Hospital, Tampere, Finland
8Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland
9Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
10Biocenter Oulu, University of Oulu, Oulu, Finland
11NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
12Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA
13Department of Pediatrics, Tampere University and Tampere University Hospital, Tampere, Finland
14Department of Clinical Physiology, Tampere University Hospital, and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
15Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1 MB)
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Language: English
Published: Springer Nature, 2021
Publish Date: 2021-07-07


Preterm birth (PTB) is associated with increased risk of type 2 diabetes and neurocognitive impairment later in life. We analyzed for the first time the associations of PTB with blood miRNA levels in adulthood. We also investigated the relationship of PTB associated miRNAs and adulthood phenotypes previously linked with premature birth. Blood MicroRNA profiling, genome-wide gene expression analysis, computer-based cognitive testing battery (CANTAB) and serum NMR metabolomics were performed for Young Finns Study subjects (aged 34–49 years, full-term n = 682, preterm n = 84). Preterm birth (vs. full-term) was associated with adulthood levels of hsa-miR-29b-3p in a fully adjusted regression model (p = 1.90 × 10–4, FDR = 0.046). The levels of hsa-miR-29b-3p were down-regulated in subjects with PTB with appropriate birthweight for gestational age (p = 0.002, fold change [FC] = − 1.20) and specifically in PTB subjects with small birthweight for gestational age (p = 0.095, FC = − 1.39) in comparison to individuals born full term. Hsa-miR-29b-3p levels correlated with the expressions of its target-mRNAs BCL11A and CS and the gene set analysis results indicated a target-mRNA driven association between hsa-miR-29b-3p levels and Alzheimer's disease, Parkinson's disease, Insulin signaling and Regulation of Actin Cytoskeleton pathway expression. The level of hsa-miR-29b-3p was directly associated with visual processing and sustained attention in CANTAB test and inversely associated with serum levels of VLDL subclass component and triglyceride levels. In conlcusion, adult blood levels of hsa-miR-29b-3p were lower in subjects born preterm. Hsa-miR-29b-3p associated with cognitive function and may be linked with adulthood morbidities in subjects born preterm, possibly through regulation of gene sets related to neurodegenerative diseases and insulin signaling as well as VLDL and triglyceride metabolism.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 11
Issue: 1
Article number: 9203
DOI: 10.1038/s41598-021-88465-4
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
3141 Health care science
Funding: The Young Finns Study has been financially supported by the Academy of Finland: Grants 286284 and 322098 (T.L.), 285902 and 330809 (E.R.), 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi); the Social Insurance Institution of Finland; the Kuopio, Tampere, and Turku University Hospital Medical Funds (Grant X51001 for T.L and 9X047 and 9S054 for E.R); the Juho Vainio Foundation; the Paavo Nurmi Foundation; the Finnish Foundation of Cardiovascular Research (T.L.); the Finnish Cultural Foundation; the Tampere Tuberculosis Foundation (T.L. and N.O.); the Emil Aaltonen Foundation (T.L. and N.O.); and the Yrjö Jahnsson Foundation (T.L., N.O. and E.R.); Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (Grant 755320 for TAXINOMISIS; Grant 848146 for To_Aition); European Research Council (Grant 742927 for MULTIEPIGEN project). M. A-K. is also holding a research Grant from the Sigrid Juselius Foundation, Finland. This work was supported by the Foundation of Clinical Chemistry, Laboratoriolääketieteen edistämissäätiö sr., the Orion-Farmos Research Foundation and the Paulo Foundation.
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