Chronic Maternal Stress and Genetic Variants in the Etiology of Spontaneous Preterm Birth

• Author / Creator

  Christiaens, Inge

• Preterm birth is the leading cause of mortality and morbidity in newborn infants. With an estimated 15 million preterm births annually worldwide, the global burden of preterm birth is enormous. Despite decades of research, its etiology remains elusive. Preterm birth is a complex phenomenon with genes and environmental factors contributing to its risk, both in the mother and the fetus. For this dissertation, we explored the role of chronic maternal stress and genetic variants in the etiology of spontaneous preterm birth. We conducted a case-control study in 622 women in Edmonton. First, we examined the association between lifetime chronic stress and preterm birth. Exposure to two or more adverse childhood experiences was associated with a two-fold risk of preterm birth, regardless of maternal age, smoking status, educational status and a history of miscarriage (OR 2.09, p=0.024) Lifetime physical and emotional abuse was also associated with spontaneous preterm in our study population (OR 1.3, p=0.033) Second, we conducted genomic studies for preterm birth in collaboration with the Preterm Birth Genome Project, the World Health Organization and the March of Dimes. Using a candidate gene approach, we discovered two novel single nucleotide polymorphisms (SNPs), both located in the mineralocorticoid receptor gene that associate with spontaneous preterm birth: rs17484063 (OR 0.50, p=0.038) and rs2883929 (OR 0.49, p=0.017). For each additional effect allele, the risk of preterm birth was halved. In women with ≤1 adverse childhood experiences, the odds ratios of rs17484063 and rs2883929 for preterm birth were further lowered (OR 0.37; p=0.024 and OR 0.37; p=0.013, respectively). Via activation of the maternal-fetal HPA axis, a biological plausibility of the role of these SNPs in the etiology of preterm birth exists.
  This is the first evidence of genetic variations in the mineralocorticoid receptor gene that associate with spontaneous preterm birth. In addition, we discovered a strong relationship between adverse childhood experiences and preterm birth. Taken together, this research confirmed that chronic maternal stress and genes involved in the stress response likely have an impact on the risk of spontaneous preterm birth.

• Subjects / Keywords

  • Single nucleotide polymorphisms
  • Preterm birth
  • Chronic maternal stress

• Graduation date

  Fall 2012

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3ND18

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.