Early-life exposure to cadmium and onset of puberty in girls: a longitudinal mother-child cohort study in Bangladesh

Background and aim: Cadmium is a toxic metal with endocrine disrupting properties, but there are few studies about its impact on puberty onset. We aimed to evaluate if early-life exposure to dietary cadmium is associated with the timing of female puberty. Methods: In a mother-child cohort in rural Bangladesh (n=935), we assessed the exposure to cadmium during pregnancy through concentrations in erythrocytes (half-life 3-4 months) and in the daughters at 5y and 10y through concentrations in urine, a marker of long-term exposure. Cadmium was measured with inductively coupled plasma mass spectrometry. Between the ages of 12 and 15 years, the girls were interviewed twice with a 6-month interval about their date of menarche, and they self-assessed their pubertal development according to Tanner stages. Associations with age at menarche were evaluated with Kaplan-Meier analysis and multivariable-adjusted Cox regression, and associations with pubertal stages with ordered logistic regression. Results: Median age at menarche was 13.0 years. We found no association between maternal exposure to cadmium during pregnancy and the daughters’ age at menarche. Median urinary cadmium concentrations at 10y were 0.25 µg/L. Girls belonging to the highest quartile of urinary cadmium at 10y attained menarche 3.8 months later than girls in the lowest quartile. In multivariable-adjusted analysis, the corresponding hazard ratio of reaching menarche comparing girls in the highest and the lowest quartile of urinary cadmium was 0.77 (95% CI 0.60, 0.98). Similar associations were found for urinary cadmium at 5y. Urinary cadmium at 10y was also associated with delayed breast development; the odds ratio of reaching more advanced breast development stages comparing girls in the highest and the lowest quartile of urinary cadmium was 0.63 (0.40; 0.99). Conclusions: Elevated childhood exposure to cadmium was associated with a pubertal delay in girls. Keywords: Cadmium, early-life, female puberty, menarche, longitudinal