Cadmium exposure and risk of adverse pregnancy and birth outcomes: a systematic review and dose–response meta-analysis of cohort and cohort-based case–control studies

Background: There are several inconsistencies in the epidemiological literature on the strength of the association between cadmium exposure and adverse pregnancy and birth outcomes, and the threshold dose of adverse effect. Objectives: We therefore conducted a systematic review and dose–response meta-analysis to evaluate the available evidence to influence clinical decision making and better tailor public health interventions. Methods: PubMed and Scopus databases were searched up to January, 2019. Eighteen prospective studies satisfied the inclusion criteria. Random effects model was used to compute summary-effect estimates. Results: Cadmium exposure resulted in 42.11 g (95% confidence interval [CI]: −69.03, −15.18) reduction in birth weight, and 0.105 cm (95% CI: −0.181, −0.029) reduction in head circumference per 1 µg/l increment in blood/urine cadmium levels. Cadmium exposure also resulted in 21% (RR = 1.21; 95% CI: 1.02, 1.43), 32% (RR = 1.32; 95% CI: 1.05, 1.67) and 10% (RR = 1.10; 95% CI: 0.96, 1.27) increased risk of low birth weight (LBW), preterm birth (PTB), and small-for-gestational age (SGA), respectively. Risk for all outcomes decreased with decreasing exposure. In fixed effects dose–response meta-regression analyses, we found no evidence of association of cadmium exposure with LBW and SGA. For PTB, a 1 µg/l increment in cadmium exposure corresponded to 0.5% (OR = 1.005, 95% CI: 1.003, 1.007) increase in PTB risk. Conclusions: Cadmium exposure was associated with risk of adverse birth outcomes. Regarding PTB, the formal dose–response meta-analyses suggests a causal association.