Predicted 25-hydroxyvitamin D Score and Risk of Multiple Sclerosis in U.S. Women

Multiple sclerosis (MS) is a progressive, autoimmune neurodegenerative disorder affecting nearly 350,000 people in the United States and resulting in significant disability. As an immunomodulator, vitamin D may play a role in the development of MS. Previous studies have observed an inverse association of 25-hydroxyvitamin D (25(OH)D) levels and MS risk in younger populations; however, whether this relationship persists in older adults remains unclear. We prospectively investigated the association between predicted 25(OH)D level and incident MS in the Nurses’ Health Study (NHS) (n=121,701) and NHS II (n=116,430). 25(OH)D levels were predicted using validated regression models that include important determinants of vitamin D status, including race, UV-B flux (based on state of residence), physical activity, body mass index, dietary vitamin D intake, alcohol consumption and post-menopausal hormone use. Data on these factors were self-reported on NHS and NHS II questionnaires starting in 1986 and 1991, respectively, and updated every 2-4 years. MS diagnoses were ascertained by self-report and confirmed by medical records. Cox proportional hazards models adjusted for age, ethnicity, latitude of residence at age 15, and BMI at age 18 were used to estimate hazard ratios (HR)s and 95% confidence intervals (CI)s in each cohort. During up to 18 years of follow-up, we documented 179 definite/probable cases of MS with first symptoms after baseline. Multivariable HRs comparing highest and lowest quintiles of predicted 25(OH)D were 1.09 (95% CI: 0.40-2.96) in the NHS and 0.52 (95% CI: 0.28-0.95) in the NHS II. Higher predicted plasma 25(OH)D may be modestly associated with lower risk of MS, primarily in younger women

Vitamin D, Calcium, and Dairy Consumption and Risk of Early Menopause

Early menopause, defined as the cessation of ovarian function before the age of 45, affects roughly 10% of women in Western populations. Current research suggests that women who experience early menopause are at increased risk for cardiovascular disease and other adverse health outcomes. Early menopause may also have substantial financial and psychological consequences for family planning, particularly as women increasingly delay childbearing into the later reproductive years. Emerging research suggests that modifiable lifestyle factors such as diet may play an important role in ovarian aging. According to our review of the current biologic and epidemiologic literature in Chapter 1, vitamin D, calcium, and dairy consumption may be related to the physiologic processes involved in ovarian aging. However, no prior epidemiologic studies have evaluated these exposures with regard to risk of early menopause. Thus, the aim of this dissertation was to evaluate these associations in the prospective Nurses’ Health Study II (NHS2) (n=112,429). In Chapter 2, we evaluated how intakes of vitamin D and calcium are associated with risk of early menopause. Results of this study suggest that high versus low intakes of vitamin D and calcium from food sources, particularly dairy foods, are associated with 17% and 13% lower risk of early menopause, respectively. In Chapter 3, we evaluated how total and free plasma 25-hydroxyvitamin D (25(OH)D) and vitamin D binding protein levels (VDBP) are associated with risk of early menopause. According to our findings, total and free 25(OH)D levels are not associated with risk of early menopause, and VDBP may be positively associated with risk. In Chapter 4, we evaluated how intakes of total, low-fat, high-fat, and individual dairy foods are associated with risk of early menopause. Findings indicate that high versus low intake of low-fat dairy foods is associated with 23% lower risk of early menopause. In particular, intakes of skim milk and yogurt intake were associated with lower risk of early menopause. In conclusion, vitamin D and calcium are not importantly related to early menopause risk. Intake of low-fat dairy foods is associated with lower risk of early menopause, but findings should be replicated in future studies

The Joint Role of Thyroid Function and Iodine Status on Risk of Preterm Birth and Small for Gestational Age: A Population-Based Nested Case-Control Study of Finnish Women

Normal maternal thyroid function during pregnancy is essential for fetal development and depends upon an adequate supply of iodine. Little is known about how iodine status is associated with preterm birth and small for gestational age (SGA) in mildly iodine insufficient populations. Our objective was to evaluate associations of early pregnancy serum iodine, thyroglobulin (Tg), and thyroid-stimulating hormone (TSH) with odds of preterm birth and SGA in a prospective, population-based, nested case-control study from all births in Finland (2012–2013). Cases of preterm birth (n = 208) and SGA (n = 209) were randomly chosen from among all singleton births. Controls were randomly chosen from among singleton births that were not preterm (n = 242) or SGA (n = 241) infants during the same time period. Women provided blood samples at 10–14 weeks’ gestation for serum iodide, Tg and TSH measurement. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for preterm birth and SGA. Each log-unit increase in serum iodide was associated with higher odds of preterm birth (adjusted OR = 1.19, 95% CI = 1.02–1.40), but was not associated with SGA (adjusted OR = 1.01, 95% CI = 0.86–1.18). Tg was not associated with preterm birth (OR per 1 log-unit increase = 0.87, 95% CI = 0.73–1.05), but was inversely associated with SGA (OR per log-unit increase = 0.78, 95% CI = 0.65–0.94). Neither high nor low TSH (versus normal) were associated with either outcome. These findings suggest that among Finnish women, iodine status is not related to SGA, but higher serum iodide may be positively associated with preterm birth

Iodine and thyroid status during pregnancy and risk of stillbirth:a population-based nested case–control study

Abstract Prior research suggests that severe iodine deficiency in pregnancy may be associated with stillbirth. However, the relationship between mild to moderate iodine insufficiency, which is prevalent even in developed countries, and risk of stillbirth is unclear. We thus examined associations of iodine status and risk of stillbirth in a prospective population-based nested case–control study in Finland, a mild to moderately iodine insufficient population. Stillbirth cases (n = 199) and unaffected controls (n = 249) were randomly selected from among all singleton births in Finland from 2012 to 2013. Serum samples were collected between 10 and 14 weeks gestation and analysed for iodide, thyroglobulin (Tg) and thyroid-stimulating hormone (TSH). Odds ratios (ORs) and 95% confidence intervals (CIs) for stillbirth were estimated using logistic regression. After adjusting for maternal age, prepregnancy body mass index, socio-economic status and other factors, neither high nor low serum iodide was associated with risk of stillbirth (Q1 vs. Q2–Q3 OR = 0.92, 95% CI = 0.78–1.09; Q4 vs. Q2–Q3 OR = 0.78; 95% CI = 0.45–1.33). Tg and TSH were also not associated with risk of stillbirth in adjusted models. Maternal iodine status was not associated with stillbirth risk in this mildly to moderately iodine-deficient population. Tg and TSH, which reflect functional iodine status, were also not associated with stillbirth risk. The lack of associations observed between serum iodide, TSH and Tg and risk of stillbirth is reassuring, given that iodine deficiency in pregnancy is prevalent in developed countries