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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

Journal of Exposure Science & Environmental Epidemiology volume 31, pages 299–317 (2021)Cite this article

Abstract

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.

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Fig. 1
Fig. 2: Forest plot showing the association of cadmium exposure with birth anthropometric measures.
Fig. 3: Forest plot showing the association of cadmium exposure with adverse birth outcomes.
Fig. 4
Fig. 5: Funnel plot for the association of cadmium exposure with birth anthropometric measures.
Fig. 6: Funnel plot for the association of cadmium exposure with adverse birth outcomes.
Fig. 7: Filled funnel plot for the association between cadmium exposure, and head circumference and adverse birth outcomes.

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Code availability

All the Stata codes and syntax for performing the analyses and generating the results are available upon request from the corresponding author.

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Authors and Affiliations

  1. Public Health Research Group, Department of Biomedical Sciences, University of Cape Coast, Cape Coast, Ghana

    A. Kofi Amegah & Christian Sewor

  2. Center for Environmental and Respiratory Health Research (CERH), University of Oulu, Oulu, Finland

    Jouni J. K. Jaakkola

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Amegah, A.K., Sewor, C. & Jaakkola, J.J.K. 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. J Expo Sci Environ Epidemiol 31, 299–317 (2021). https://doi.org/10.1038/s41370-021-00289-6

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