Chronic Maternal Stress and Genetic Variants in the Etiology of Spontaneous Preterm Birth
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".