Association of blood cadmium and lead levels with self-reported reproductive lifespan and pregnancy loss: The national health and nutrition examination survey 1999–2018

Cadmium and lead are known to interfere with the endocrine function. Thus, hormonally regulated processes such as menarche, menopause and pregnancy are likely influenced by chronic exposure to these metals. In US post-menopausal women, who already completed their reproductive lifespan, we evaluated the association between blood cadmium and lead levels with self-reported reproductive lifespan and personal history of pregnancy loss. We selected 5317 post-menopausal women participating in the National Health and Nutrition Examination Survey (NHANES), 1999–2018. Blood cadmium and lead levels were measured by inductively coupled plasma mass spectrometry. Reproductive lifespan was defined as the number of years between self-reported age at menarche and menopause. Personal history of pregnancy loss was defined as number of self-reported pregnancy losses out of the self-reported number of pregnancies. The fully adjusted mean difference in reproductive lifespan (95% confidence interval [CI]) comparing the 80th to the 20th percentiles of blood cadmium and lead distributions was, respectively, 0.50 (0.10, 0.91) and 0.72 (0.41, 1.03) years. Ever smoker showed stronger association of blood lead with reproductive lifespan. For self-reported pregnancy loss, the corresponding fully adjusted relative prevalence (95% CI) was 1.10 (0.93, 1.31) for cadmium and 1.10 (1.00, 1.21) for lead, and remained similar after additional adjustment for reproductive lifespan. In never smokers, the relative prevalence was 1.07 (1.04, 1.11) and 1.16 (1.05, 1.28) for blood cadmium and lead, respectively. These findings suggest that blood cadmium and lead exposures increase reproductive lifespan and prevalence of pregnancy loss in the general population. Additional studies are needed to improve the understanding of mechanisms and prevention potential of metals-related pregnancy outcomes.