Dietary cadmium intake and fecundability in a North American preconception cohort study

Objective To evaluate the association between dietary cadmium intake (D-Cd) and fecundability. Diet is one of the main sources of cadmium, and D-Cd is often used as indicator of cadmium exposure, particularly in non-smoking populations. In a previous preconception cohort study of 501 couples,1 high female cadmium concentrations measured in whole blood were associated with reduced fecundability. Design Prospective cohort study (2013-2018). Materials and Methods Pregnancy Online Study (PRESTO) is a North American prospective preconception cohort of pregnancy planners. At baseline, female participants aged 21-45 years completed a web-based questionnaire on demographic, lifestyle, medical and reproductive factors. Ten days after enrollment, participants completed the National Cancer Institute Dietary History Questionnaire II, a validated food frequency questionnaire (FFQ) of average intake during the previous year. D-Cd (\u3bcg/day) was estimated by combining FFQ responses with US Food and Drug Administration data on food cadmium content. Participants were then followed for up to 12 months or until reported pregnancy, whichever came first. The analysis included 4,768 women attempting to conceive for 646 cycles at study entry and not using fertility treatment. We used a proportional probabilities regression model to estimate fecundability ratios (FR) and 95% confidence intervals (CI), adjusted for age, body mass index (BMI), smoking history, parity, physical activity, last method of contraception, daily use of multivitamins, race/ethnicity, education, income, geographic region, and the 2010 healthy eating index score. We used the nutrient residual approach to adjust for energy intake. Results Median D-Cd was 8.0 \u3bcg/day (interquartile range: 7.0-9.1 \u3bcg/day). The top 5 contributors to D-Cd were nuts and seeds; fried potatoes; dark green lettuce; cooked greens; and white potatoes. Compared with an average D-Cd of <6.8 \u3bcg/day, FRs for D-Cd quintiles of 6.8-7.6, 7.7-8.4, 8.5-9.5, and 659.6 \u3bcg/day were 1.03 (CI: 0.92-1.14), 1.07 (CI: 0.96-1.18), 1.07 (CI: 0.96-1.19), and 1.08 (0.97-1.20), respectively. Results were not appreciably different among never smokers with no current passive smoke exposure, for whom cadmium exposure from other sources (e.g., cigarettes) would be lower (respective FRs: 1.02, 1.05, 1.06 and 1.02). Results did not differ materially by age (<30 vs. 6530 years), BMI (<30 vs. 6530 kg/m2), total fiber intake (<25 vs. 6525 g/day), geographic region of residence (West, Midwest, Northeast, South, Canada), or attempt time at study entry (<3 vs. 653 cycles). Conclusions Dietary intake of cadmium was not appreciably associated with fecundability, though exposure misclassification and confounding could explain the null results. References 1 Buck Louis GM, Sundaram R, Schisterman EF, Sweeney AM, Lynch CD, Gore-Langton RE, Chen Z, Kim S, Caldwell KL, Barr DB. Heavy metals and couple fecundity, the LIFE Study. Chemosphere. 2012 Jun;87(11):1201-7. https://doi.org/10.1016/j.chemosphere.2012.01.017. Epub 2012 Feb 4. PubMed PMID: 22309709; PubMed Central PMCID: PMC3327819

Intake of Lycopene and other Carotenoids and Incidence of Uterine Leiomyomata: A Prospective Ultrasound Study

BACKGROUND: Uterine leiomyomata (UL) are the leading indication for hysterectomy in the United States. Dietary supplementation with lycopene was associated with reduced size and incidence of oviduct leiomyoma in the Japanese quail. Two US prospective cohort studies of women reported little association between intake of lycopene, or other carotenoids, and UL incidence. However, these studies relied on self-reported physician-diagnosed UL, which is prone to misclassification. OBJECTIVE: This study examines the association between dietary intake of carotenoids and UL incidence. DESIGN: Data were derived from the Study of the Environment, Lifestyle, and Fibroids, a prospective cohort study. Women completed self-administered baseline questionnaires on demographic characteristics, reproductive history, and lifestyle, including a 110-item validated food frequency questionnaire, from which dietary intakes of carotenoids-including alpha carotene, beta carotene, cryptoxanthin, lutein-zeaxanthin, and lycopene-and vitamin A were estimated. PARTICIPANTS/SETTING: One thousand two hundred thirty Black women aged 23 to 35 years who did not have a previous diagnosis of UL, cancer, or autoimmune disease were eligible for enrollment (2010-2012). Participants were residents of the Detroit, MI, metropolitan area. MAIN OUTCOME MEASURES: Transvaginal ultrasound was used to assess UL at baseline and 20, 40, and 60 months of follow-up. STATISTICAL ANALYSES PERFORMED: Cox regression was used to estimate hazard ratios and 95% CIs, adjusted for energy intake, age at menarche, education, body mass index, parity, age at first birth, years since last birth, current use of oral contraceptives or progestin-only injectables, alcohol intake, and cigarette smoking. RESULTS: Among 1,230 women without prevalent UL at baseline, 301 incident UL cases during follow-up were identified. Intakes of lycopene, other carotenoids, and vitamin A were not appreciably associated with UL incidence. Hazard ratios comparing quartiles 2 (2,376 to 3,397 μg/day), 3 (3,398 to 4,817 μg/day), and 4 (≥4,818 μg/day) with quartile 1 (\u3c2,376 μg/day) of lycopene intake were 1.03 (95% CI 0.72 to 1.47), 1.22 (95% CI 0.86 to 1.72), and 0.95 (95% CI 0.67 to 1.36), respectively. CONCLUSIONS: Study findings do not support the hypothesis that greater carotenoid intake is associated with reduced UL incidence

Exposure to tetrachloroethylene-contaminated drinking water and time to pregnancy

BackgroundThe synthetic solvent tetrachloroethylene (PCE), commonly used in dry cleaning operations, is a human neurotoxicant and carcinogen. However, its effect on reproduction is poorly understood, as prior studies have been limited to small occupational cohorts. We examined the association between PCE exposure from contamination of the public drinking water supply and time-to-pregnancy (TTP) in a cohort of mothers from Cape Cod, Massachusetts.MethodsThe Cape Cod Family Health Study is a retrospective cohort study designed to examine the reproductive and developmental health effects of exposure to PCE-contaminated drinking water. Our analysis included 1565 women who reported 3826 planned pregnancies from 1949 to 1990. Women completed self-administered questionnaires that ascertained TTP for each of her pregnancies, regardless of the outcome, as well as residential history and demographic information. We utilized EPANET water distribution system modeling software and a leaching and transport model to assess PCE exposure for each pregnancy. We used log-binomial regression models to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for potential confounders. We performed a probabilistic bias analysis to examine the effect of outcome misclassification on our results.ResultsAny cumulative PCE exposure before pregnancy was associated with a 15% reduction in risk of TTP > 12 months (RR = 0.85, 95% CI: 0.70, 1.03). However, women with the highest average monthly PCE exposure around the time of the pregnancy attempt (≥ 2.5 g) had increased risk of TTP > 12 months (RR = 1.36, 95% CI: 1.06, 1.76).ConclusionsWe found little evidence for long-term, cumulative adverse effects of PCE exposure on TTP, but high levels of PCE exposure around the time of the pregnancy attempt were associated with longer TTP. These associations may be underestimated due to the exclusion of unsuccessful pregnancy attempts from our study population, and may be biased by outcome and exposure misclassification given the long-term recall of TTP and use of a leaching and transport model to estimate PCE exposure

Dietary Fat Intake and Risk of Uterine Leiomyomata: A Prospective Ultrasound Study

Uterine leiomyomata (UL) are associated with severe reproductive morbidity and are the primary indication for hysterectomy in the United States. A recent prospective cohort study of Black women reported positive associations between intakes of marine-sourced omega-3 fatty acids and UL risk. We examined whether intakes of dietary fat were associated with UL incidence in a 5-year prospective study of premenopausal Black women living in Detroit who underwent serial ultrasound. At baseline (2010-2012) and 20, 40, and 60 months of follow-up, participants underwent transvaginal ultrasound. Among 1,171 UL-free women at baseline, incident UL were detected in 277 women. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of dietary fat and UL incidence. Intakes of total fat and saturated, monounsaturated, polyunsaturated (PUFA), and trans-fat were not appreciably associated with UL incidence. Intake of the marine omega-3 PUFA, docosahexaenoic acid, was associated with 49% higher UL incidence (quartile 4 vs. 1: HR 1.49, 95% CI: 1.04, 2.14; P trend=0.01). Intakes of total marine omega-3 PUFAs were similarly associated with elevated UL incidence (HR 1.35, 95% CI: 0.94, 1.93; P trend=0.03). It remains unclear whether the fatty acids or persistent environmental pollutants drive the association

Glycemic load, dietary fiber, and added sugar and fecundability in 2 preconception cohorts

BACKGROUND: Glycemic load (GL) reflects the quantity and quality of carbohydrates in the diet; dietary fiber and added sugar are components of GL. Few epidemiologic studies have assessed the association between these dietary factors and fecundability. OBJECTIVE: We prospectively evaluated the associations of GL, total carbohydrates, dietary fiber, and added sugar with fecundability. METHODS: Snart Foraeldre (SF) and Pregnancy Study Online (PRESTO) are parallel web-based prospective preconception cohorts of couples attempting to conceive in Denmark and North America. At baseline, female participants completed a web-based questionnaire on demographic and lifestyle factors and a validated FFQ. We calculated GL, total carbohydrate intake, total dietary fiber, carbohydrate-to-fiber ratio, and added sugar based on reported frequencies for individual foods, standard recipes for mixed foods, and average serving sizes. The analysis included 2709 SF participants and 4268 PRESTO participants. We used proportional probabilities regression models to estimate fecundability ratios (FR) and 95% CIs. RESULTS: Compared with an average daily GL of ≤100, FRs for an average daily GL of ≥141 were 0.89 (95% CI: 0.73, 1.08) in SF and 0.87 (95% CI: 0.77, 0.98) in PRESTO participants. Compared with consuming ≤16 g/d of dietary fiber, FRs for consuming ≥25 g/d were 0.99 (95% CI: 0.81, 1.22) in SF and 1.06 (95% CI: 0.94, 1.20) in PRESTO. Compared with a carbohydrate-to-fiber ratio of ≤8, FRs for a ratio of ≥13 were 0.86 (95% CI: 0.73, 1.01) in SF and 0.87 (95% CI: 0.78, 0.98) in PRESTO. Compared with ≤27 g/d of added sugar, FRs for ≥72 g/d were 0.87 (95% CI: 0.68, 1.10) in SF and 0.86 (95% CI: 0.75, 0.99) in PRESTO participants. CONCLUSIONS: Among women attempting to conceive in Denmark and North America, diets high in GL, carbohydrate-to-fiber ratio, and added sugar were associated with modestly reduced fecundability