Genetics in preterm birth

Several observations support the hypothesis that preterm birth is influenced by genetics(1). First, evidence from two twin studies suggests a genetic predisposition of PTB with heritability from almost 20% to almost 40%(2;3). Other observations that support the idea of a genetic factors affecting risk of preterm birth are:

   1) The leading risk factor for preterm birth is a previous preterm birth(4;5)
   2) Association between ethnicity/race and preterm birth persists in some instances,
       even if corrected for socio-economic status(6) and
   3) Mothers who were preterm themselves have an increased risk of delivering preterm(5).

These factors have led investigators in the last few years to begin examining associations between single nucleotide polymorphisms (SNPs) and preterm birth(7-10). The numbers of different SNPs investigated are still relatively few and primarily concentrated around SNPs that have been found to be associated with other diseases that could potentially be related to PTB. Special emphasis has been placed on SNPs in the coding regions of genes or those previously hypothesized to have regulatory function, especially in the cytokine genes. Several of those studies have been able to identify genetic associations with PTB, but the results do not always translate across ethnic populations and will require replication in order to demonstrate their usefulness in predicting pregnancies at risk. It is our intension to increase the numbers of SNPs investigated in relevance to PTB specifically. In order to do this we will propose a systematic approach that uses candidate and non-candidate SNPs in a large array of genes. We will also discuss the ways that these data can be analyzed in order to better understand genetic risks for PTB.


1. Varner MW, Esplin MS. Current understanding of genetic factors in preterm birth. BJOG. 2022;112 Suppl 1:28-31.
2. Clausson B, Lichtenstein P, Cnattingius S. Genetic influence on birthweight and gestational length determined by studies in offspring of twins. BJOG. 2000;107:375-81.
3. Treloar SA, Macones GA, Mitchell LE, Martin NG. Genetic influences on premature parturition in an Australian twin sample. Twin.Res. 2000;3:80-82.
4. Carr-Hill RA, Hall MH. The repetition of spontaneous preterm labour. Br.J.Obstet.Gynaecol. 1985;92:921-28.
5. Porter TF, Fraser AM, Hunter CY, Ward RH, Varner MW. The risk of preterm birth across generations. Obstet.Gynecol. 1997;90:63-67.
6. Goldenberg RL, Cliver SP, Mulvihill FX, Hickey CA, Hoffman HJ, Klerman LV et al. Medical, psychosocial, and behavioral risk factors do not explain the increased risk for low birth weight among black women. Am.J.Obstet.Gynecol. 1996;175:1317-24.
7. Genc MR, Gerber S, Nesin M, Witkin SS. Polymorphism in the interleukin-1 gene complex and spontaneous preterm delivery. Am.J.Obstet.Gynecol. 2002;187:157-63.
8. Hao K, Wang X, Niu T, Xu X, Li A, Chang W et al. A candidate gene association study on preterm delivery: application of high-throughput genotyping technology and advanced statistical methods. Hum.Mol.Genet. 2004;13:683-91.
9. Landau R, Xie HG, Dishy V, Stein CM, Wood AJ, Emala CW et al. beta2-Adrenergic receptor genotype and preterm delivery. Am.J.Obstet.Gynecol. 2002;187:1294-98.
10. Wang X, Zuckerman B, Pearson C, Kaufman G, Chen C, Wang G et al. Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight. JAMA 2002;287:195-202.
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