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 (μg/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 ≤6 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 μg/day (interquartile range: 7.0-9.1 μg/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 μg/day, FRs for D-Cd quintiles of 6.8-7.6, 7.7-8.4, 8.5-9.5, and ≥9.6 μg/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. ≥30 years), BMI (<30 vs. ≥30 kg/m2), total fiber intake (<25 vs. ≥25 g/day), geographic region of residence (West, Midwest, Northeast, South, Canada), or attempt time at study entry (<3 vs. ≥3 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.