Article - Association between female circulating heavy metal concentration and abortion: a systematic review and meta-analysis.

Plain Language Summary

The causes of spontaneous abortion (SA) and recurrent pregnancy loss (RPL) are complex, with endocrine disrupting pollutants being a risk factor for both SA and RPL. The aim of this systematic review and meta-analysis was to investigate the association between SA and RPL and levels of zinc (Zn), copper (Cu), lead (Pb) and cadmium (Cd) in pregnant women. 24 case-control and 4 cross-sectional studies were included in the meta-analysis, 14 on Zn and Cu, 15 on Pb and 8 on Cd. All of the studies had adequate quality scores. Meta-analysis showed that Zn level was negatively associated with RPL but not SA, whilst Cu level was negatively associated with both SA and RPL. Both high levels of Pb and Cd increased the risk for SA and RPL. There was significant heterogeneity amongst studies across all associations investigated. The authors concluded that low levels of Zn and Cu and high levels of Pb and Cd may increase the risk of SA and RPL and that this may be mediated through endocrine dysfunction such as insulin resistance, vitamin D insufficiency, and disruption of thyroid and sex hormone balance.

Expert Review

Reviewer: Chloe Steele

6th Feb 2025

Conflict of interest

None

Take home message

High toxic metals and low essential metal levels may have a role to play in RPL and SA.
However, this study was based on observational studies and mechanisms linking essential and heavy metal levels and RPL and SA need to be determined before causal relationships can be made.

Evidence category

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

Summary review

Introduction

Spontaneous abortion (SA) is the involuntary loss of a foetus before 28 weeks gestation (prevalence 10-15%).
Recurrent pregnancy loss (RPL) occurs in significantly less women, however, is still a concerning reproductive condition.
Whilst the aetiology is complex, exposure to heavy metals and a deficiency in essential metals may play a role.
This systematic review/meta-analysis aimed to determine the role of the heavy metals cadmium (Cd) and lead (Pb), and the essential metals zinc (Zn) and copper (Cu) in endocrine disruption, RPL and SA.

Methods

Studies were observational.
These involved pregnant women without obstetric disease and who had experienced SA or RPL.
Control groups were healthy pregnant women with normal pregnancy or delivery.

Results

28 studies were included in the analysis (from 1979-2023).
The quality of the studies were deemed to be fair or good quality based on the Newcastle-Ottawa Scale. None were poor quality.
Compared to those who had a normal delivery, women with RPL had lower Zn (SMD = −3.44, 95% CI: −5.01 to −1.87, p<0.001) and copper levels −3.92 (95% CI: −6.97, −0.87, p = 0.012).
They also had higher circulating Pb (SMD = 8.19, 95% CI: 4.52–11.85, p<0.001) and Cd (SMD = 2.45, 95% CI: 0.85–4.04, p = 0.003).
Women with SA had lower copper levels (SMD= −0.97 (95% CI: −1.47, −0.48, p <0.001) and higher PB (SMD = 0.33, 95% CI: 0.12–0.55, p = 0.002) and Cd levels SMD = 0.42, 95% CI: 0.02–0.82, p = 0.040) but no differences were seen in Zn levels compared to healthy controls.

Conclusion

It was concluded that higher blood PB and Cd and lower Zn and Cu may be associated with SA and RPL.
It was also concluded that endocrine dysfunction may play a role in this, however the study did not look at any endocrine parameters.

Clinical practice applications

Clinicians should consider testing Pb, Cd, Cu and Zn levels as part of investigations in women who are experiencing RPL and SA.
However until causal relationships are determined it cannot be said with certainty that adjusting these levels may aid reproductive health but should aid overall health.

Considerations for future research

Understanding the relationship between high heavy metals and low essential metals may influence reproductive health.
Research investigating toxic metal exposure, sex hormone levels and essential metals may be of benefit in high risk groups.

Expert reviews are written by nutrition professionals and academics with advanced qualifications to provide a critical appraisal of the article and implications for practice. Each review is peer-reviewed by a member of the NED Editorial Board. Find out more about our NED Expert Reviewers here.

Abstract

OBJECTIVE

This study aimed to evaluate the association between blood heavy metal (zinc (Zn), copper (Cu), lead (Pb), and cadmium (Cd)) concentrations and spontaneous abortion (SA) and recurrent pregnancy loss (RPL) and explore the possible endocrine dysfunction associated with it.

METHODS

A literature search was performed in the PubMed, Embase, Cochrane Library, and Web of Science databases up to April 2023. The overall effects were expressed as the standard mean difference (SMD). Subgroup analysis was performed according to the type of abortion (SA or RPL). Stata 16.0 was utilized for data analysis.

RESULTS

Based on the integrated findings, abortion women showed significantly lower Zn (SMD = -1.05, 95% CI: -1.74 to -0.36, = 0.003) and Cu concentrations (SMD = -1.42, 95% CI: -1.97 to -0.87, 0.001) and higher Pb (SMD = 1.47, 95% CI: 0.89-2.05, 0.001) and Cd concentrations (SMD = 1.15, 95% CI: 0.45-1.85, = 0.001) than normal pregnant women. Subgroup analysis showed that Zn and Cu deficiency and Cd and Pb exposure were significantly (0.05) associated with RPL, whereas Cu deficiency and Cd and Pb exposure were significantly (0.05) associated with SA.

CONCLUSION

Zn and Cu deficiencies and Pb and Cd exposure were associated with abortion. Endocrine dysfunction, such as insulin resistance, vitamin D insufficiency, and abnormal thyroid and sex hormone concentrations, is thought to be involved in heavy metal-related abortion.