THE GENETICS OF PRETERM
LABOR
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Genetics of Preterm Labor: Risk Factors, Complications, and Genetic Approaches, Slides of Pediatrics
An overview of preterm labor, including its definition, risk factors, complications, and genetic approaches for understanding its causes. Risk factors for preterm labor include twin pregnancy, pre-eclampsia, and various spontaneous factors such as infection, stress, poor nutrition, and genetic factors. Complications of preterm labor include immature lungs, brain, immune system, and digestive system. Genetic approaches to understanding preterm labor include linkage analysis, association studies, and direct resequencing of candidate genes. Several studies have identified specific genes associated with preterm labor, including those in the inflammatory cytokine pathway and the complement-coagulation pathway.
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2011/2012
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THE GENETICS OF PRETERM
LABOR
TERM & PRETERM DELIVERY
- Term delivery is typically 40 weeks postmenstrual age
- Preterm delivery is defined as delivery before the completion of 37 weeks
- Preterm delivery is associated with high mortality rate during the first month of life, as well as high morbidity
EVIDENCE FOR GENETIC
FACTORS
- Positive maternal family history
- Previous birth of a premature child
- Associated with an odds ratio: 4.
- Maternal inbreeding
- 50 fold increase in coefficient of kinship of maternal grandparents of preterm infants
- Twin studies
- Heritability 0.27 – 0.
OTHER FACTORS
- Early spontaneous pregnancy loss
- Substance abuse
- Low socio-economic status
- Low serum cholesterol
- Extremes of maternal age
- Maternal infections
GENETIC APPROACHES
- Linkage analysis; genome-wide
- Families
- Preferably inbred
- Association studies; genome-wide
- Case – control
- Families (trios)
- Direct resequencing of candidate genes
GENES & PRETERM LABOR
- 2004 : 22 SNPs in 8 genes in the inflammatory cytokine pathway; case- control 200 mothers - IL-1,-4,-6,-10, TGFB1, TNFA, FAS, MBL - weak significance (p~0.02) with IL4, IL10, TNFA and MBL - MBL2 has shown significance in an independent study
GENES & PRETERM LABOR
- 2007 : a large-scale candidate gene association study examining 1536 SNP in 130 candidate genes
- Maternal : complement-coagulation pathway including Factor V, Factor VII and Plasminogen activator
- Fetal : Interleukin-10 receptor antagonist