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Review
. 2023 Dec;30(12):3410-3427.
doi: 10.1007/s43032-023-01287-9. Epub 2023 Jul 14.

The Role of Genetics in Preterm Birth

Elyse C Mead  1 , Carol A Wang  1   2 , Jason Phung  1   2   3 , Joanna Yx Fu  1 , Scott M Williams  4 , Mario Merialdi  5 , Bo Jacobsson  6   7   8 , Stephen Lye  9 , Ramkumar Menon  10 , Craig E Pennell  11   12   13
Affiliations
Review

The Role of Genetics in Preterm Birth

Elyse C Mead et al. Reprod Sci. 2023 Dec.

Abstract

Preterm birth (PTB), defined as the birth of a child before 37 completed weeks gestation, affects approximately 11% of live births and is the leading cause of death in children under 5 years. PTB is a complex disease with multiple risk factors including genetic variation. Much research has aimed to establish the biological mechanisms underlying PTB often through identification of genetic markers for PTB risk. The objective of this review is to present a comprehensive and updated summary of the published data relating to the field of PTB genetics. A literature search in PubMed was conducted and English studies related to PTB genetics were included. Genetic studies have identified genes within inflammatory, immunological, tissue remodeling, endocrine, metabolic, and vascular pathways that may be involved in PTB. However, a substantial proportion of published data have been largely inconclusive and multiple studies had limited power to detect associations. On the contrary, a few large hypothesis-free approaches have identified and replicated multiple novel variants associated with PTB in different cohorts. Overall, attempts to predict PTB using single "-omics" datasets including genomic, transcriptomic, and epigenomic biomarkers have been mostly unsuccessful and have failed to translate to the clinical setting. Integration of data from multiple "-omics" datasets has yielded the most promising results.

Keywords: Epigenetics; Genomics; Gestational duration; Multiple “-omics” analyses; Preterm birth; Transcriptomics.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Mechanisms proposed to underpin spontaneous preterm birth. Figure adapted from [30]
Fig. 2
Fig. 2
Preterm birth (PTB) phenotypes. PTB accounts for approximately 11% of all livebirths and can be subcategorized into medically indicated PTB and spontaneous PTB (sPTB). sPTB includes both preterm prelabor rupture of membranes (PPROM) and idiopathic PTB. PTB can be medically indicated for several reasons involving both mother and baby. Estimates are based off data published by Chawanpaiboon et al. and Morken et al. [11, 31]
Fig. 3
Fig. 3
An overview of basic genetic concepts. The left-hand side of the figure shows a simplified depiction of DNA transcription to protein production. The right-hand side of the figure summarizes the definition of single nucleotide polymorphisms (SNPs) and copy number variants (CNV)
See this image and copyright information in PMC

References

    1. Liu L, Oza S, Hogan D, Chu Y, Perin J, Zhu J, et al. Global, regional, and national causes of under-5 mortality in 2000–15: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet. 2016;388(10063):3027–3035. doi: 10.1016/s0140-6736(16)31593-8. - DOI - PMC - PubMed
    1. Perin J, Mulick A, Yeung D, Villavicencio F, Lopez G, Strong KL, et al. Global, regional, and national causes of under-5 mortality in 2000–19: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet Child Adolesc Health. 2022;6(2):106–115. doi: 10.1016/s2352-4642(21)00311-4. - DOI - PMC - PubMed
    1. Conde-Agudelo A, Romero R, Da Fonseca E, O’Brien JM, Cetingoz E, Creasy GW, et al. Vaginal progesterone is as effective as cervical cerclage to prevent preterm birth in women with a singleton gestation, previous spontaneous preterm birth, and a short cervix: updated indirect comparison meta-analysis. Am J Obstet Gynecol. 2018;219(1):10–25. doi: 10.1016/j.ajog.2018.03.028. - DOI - PMC - PubMed
    1. Dawes L, Groom K, Jordan V, Waugh J. The use of specialised preterm birth clinics for women at high risk of spontaneous preterm birth: a systematic review. BMC Pregnancy Childbirth. 2020;20(1) 10.1186/s12884-020-2731-7. - PMC - PubMed
    1. Medley N, Vogel JP, Care A, Alfirevic Z. Interventions during pregnancy to prevent preterm birth: an overview of Cochrane systematic reviews. Cochrane Database Syst Rev. 2018. 10.1002/14651858.cd012505.pub2. - PMC - PubMed

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