Modifiable Risk Factors During and After Women's Reproductive Years: From Prenatal Nutrition to Postmenopausal Exposures
Brieger, Katharine
2022
Abstract
This dissertation examines modifiable risk factors during and after women’s reproductive years. The focus is on the investigation of the timing of exposures in vulnerable population, ultimately to provide the possibility of modifying behavioral factors and exposures to promote health. The first aim examines maternal prenatal vitamin use and supplemental folic acid intake during the first month of pregnancy for association with autism spectrum disorder in the Early Autism Risk Longitudinal Investigation, a pregnancy cohort enriched for autism outcomes. Prenatal vitamin use (59.7%) was not significantly reduced odds of autism (OR, 0.70; 95% CI, 0.32 to 1.53). High total folic acid supplementation (>1000 mcg, 9.4% vs 400-1000 mcg, 45.0%) was not significantly associated with odds ASD (OR, 1.64; 95% CI, 0.44 to 5.47). Future work will incorporate dietary sources of folic acid and maternal folate metabolism genetics. The second and third aims transition to studying women in a pooled sample from the international Ovarian Cancer Association Consortium. The second aim examines the association between menopausal hormone therapy (MHT) use and ovarian cancer survival in over 6,000 post-menopausal women. Use of any hormone type (estrogen-only or estrogen + progestin) for at least five years prior to ovarian cancer diagnosis was associated with longer survival (HR, 0.80; 95% CI, 0.74 to 0.87), regardless of recency of use. Those who used MHT were also less likely to have any macroscopic residual disease at the time of primary debulking surgery (ptrend < 0.01 for duration of MHT use). Residual disease mediated some (17%) of the relationship between MHT and ovarian cancer survival. While there is evidence suggesting that MHT use after diagnosis is also beneficial for survival, a large clinical trial is needed to definitively establish the relationship. The third aim more broadly explores factors that influence ovarian cancer survival. While studying over 9,000 women, this work contributes by identifying modifiable pro- and anti-inflammatory risk factors and their cumulative or joint effect on survival. Exposures of interest included environmental cigarette smoke, smoking history, BMI, physical inactivity, and use of acetaminophen, aspirin, NSAIDs, MHT, and alcohol. An inflammatory risk score was created based on a weighted sum of each factor’s association with survival. The most important contributors to the score were smoking and BMI (pro-inflammatory, increased risk of death) and MHT use (anti-inflammatory, decreased risk of death). Risk of death was elevated with increasing inflammatory risk scores (ptrend = 0.026); there was significantly elevated risk of death for women with scores > 90th percentile compared to those with scores < 10th percentile (HR, 1.29; 95% CI, 1.04 to 1.60). Likewise, the odds of residual disease were elevated among women in the with higher inflammatory score (ptrend < 0.001). Odds residual disease were significantly higher for scores > 90th percentile (OR, 2.11; 95% CI, 1.42 to 3.16). Approximately 28% of score’s association with survival was mediated through residual disease. The findings highlight potential biology of disease progression and offer modifiable factors influencing survival. Future work should build upon these findings to investigate post-diagnosis exposures to enhance women’s survival with ovarian cancer. Together, these aims contribute to the understanding of modifiable risk factors during women’s lives and affecting outcomes of public health significance.Deep Blue DOI
Subjects
Autism spectrum disorder Ovarian cancer Epidemiology
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