Blood gene transcript signature profiling in pregnancies resulting in preterm birth: A systematic review

Tobias Brummaier; Basirudeen Syed Ahamed Kabeer; Damien Chaussabel; Jürg Utzinger; Rose McGready; Daniel H Paris

doi:10.1016/j.eurox.2020.100118

Blood gene transcript signature profiling in pregnancies resulting in preterm birth: A systematic review

Eur J Obstet Gynecol Reprod Biol X. 2020 Sep 22:8:100118. doi: 10.1016/j.eurox.2020.100118. eCollection 2020 Oct.

Authors

Tobias Brummaier^{1

2

3

4}, Basirudeen Syed Ahamed Kabeer⁵, Damien Chaussabel⁵, Jürg Utzinger^{3

4}, Rose McGready^{1

2}, Daniel H Paris^{3

4}

Affiliations

¹ Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
² Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
³ Swiss Tropical and Public Health Institute, Basel, Switzerland.
⁴ University of Basel, Basel, Switzerland.
⁵ Sidra Medicine, Doha, Qatar.

Abstract

Objective: To pursue a systematic review and summarise the current evidence for the potential of transcriptome molecular profiling in investigating the preterm phenotype.

Study design: We systematically reviewed the literature, using readily available electronic databases (i.e. PubMed/Medline, Embase, Scopus and Web of Science) from inception until March 2020 to identify investigations of maternal blood-derived RNA profiling in preterm birth (PTB). Studies were included if circulating coding or non-coding RNA was analysed in maternal blood during pregnancy and/or at delivery. Interventional trials were not included. The primary outcome was the availability of whole genome expression patterns evaluated in pregnancies resulting in preterm deliveries.

Results: A total of 35 articles were included in the final analysis. Most of the studies were conducted in high-income countries and published in the last decade. Apart from spontaneous PTB, a variety of phenotypes leading to preterm delivery were reported. Differences in sampling methods, target gene selection and laboratory protocols severely limited any quantitative comparisons. Most of the studies revealed that gene expression profiling during pregnancy has high potential for identifying women at risk of spontaneous and/or non-spontaneous PTB as early as in the first trimester.

Conclusion: Assessing maternal blood-derived transcriptional signatures for PTB risk in pregnant women holds promise as a screening approach. However, longitudinally followed, prospective pregnancy cohorts are lacking. These are relevant for identifying causes leading to PTB and whether prediction of spontaneous PTB or co-morbidities associated with PTB is achievable. More emphasis on widely employed standardised protocols is required to ensure comparability of results.

Keywords: ANC, antenatal care; Antenatal screening; DNA, deoxyribonucleic acid; EGA, estimated gestational age; FGR, fetal growth restriction; Gene expression profiling; HIC, high-income country; LIC, low-income country; LMP, last menstrual period; MIC, middle-income country; NGS, next generation sequencing; PCR, polymerase chain reaction; PICo, Population phenomenon of Interest and Context; PPROM, preterm premature rupture of membranes; PROSPERO, Prospective Register of Systematic Reviews; PTB, preterm birth; PTL, preterm labour; PoA, proportion of agreement; Preterm birth; RIN, RNA integrity number; RNA, Ribonucleic acid; SDG, Sustainable Development Goal; SGA, small for gestational age; Systematic review; Transcriptome; WBC, white blood cells; WHO, World Health Organization; mRNA, messenger RNA; miRNA, microRNA; sPTB, spontaneous preterm birth; sPTL, spontaneous preterm labour.

Publication types

Review