The evidence that lead increases the risk for spontaneous abortion

Reports from a period spanning more than a century, and covering occupationally exposed women in several countries, support an increase in pregnancy loss from high maternal lead exposures. Nevertheless, most studies conducted among populations with low/moderate exposures have provided little evidence of an association with pregnancy loss, or in particular, spontaneous abortions.

A critique of these low/moderate level studies reveals small sample sizes, problems in definition or ascertainment of outcome, lack of control for confounding, and/or deficiencies in the exposure assessment. For estimating exposure, either an ecologic measure was used, or individual biologic specimens were taken but attention was not paid to the timing of measurement of lead levels in these samples. A prospective study that overcame most of the deficiencies of previous studies enrolled pregnant women in Mexico City with low-to-moderate-level lead exposures, collected blood specimens during their first trimester, and ascertained spontaneous abortions by week 20. A key design element of this study was the use of incidence-density-matched controls in order to achieve comparable opportunity for the outcome and comparable timing of exposure measurements. The latter is especially important because blood lead levels are altered by pregnancy.

In the prospective Mexico City Study, a striking dose-response relation between blood lead and risk of spontaneous abortion was found: the odds ratio for spontaneous abortion was 1.8 (95% confidence interval = 1.1-3.1) for every 5 microg/dL increase in blood lead.

Low-to-moderate lead exposures may increase the risk for spontaneous abortion at exposures comparable to U.S. general population levels during the 1970s and to many populations worldwide today; these are far lower than exposures encountered in some occupations. Further research is needed to confirm the association, to delineate the role of maternal vs. paternal exposures, and to assess increases in menstrual variability as an explanation for this finding.