Superfund Research Program
The Harvard-Mexico Project on Maternal-Fetal Lead Exposure, Risks, and Prevention
Despite years of regulatory efforts and attention from public health authorities, lead remains a toxin of great concern. It is widespread in our nation's toxic waste sites, homes, and workplaces, with many opportunities for people to be exposed through water, food, and air. With respect to children, research shows lead has adverse effects on intelligence and other neurobehavioral attributes, even at very modest levels of exposure. Recent research has also demonstrated that these effects are not readily reversible, even with medical treatment, and are accompanied by effects that extend into adulthood, such as an increased risk of hypertension or kidney impairment.
A newly recognized but poorly understood aspect of lead toxicity stems from the fact that lead exposure results in large deposits of lead in bone (i.e., throughout the skeleton). These deposits persist for many years, even after exposure has ceased and blood lead levels have returned to normal. During pregnancy, the physiologic changes that prompt a pregnant woman's bones to resorb (i.e., partially dissolve) in order to provide calcium to the growing fetal skeleton also release the lead stored in bone into a pregnant woman's circulation.
To address questions regarding the potential impact of maternal bone lead on the fetus and lactating infant, Superfund Basic Research investigators led by Howard Hu at the Harvard School of Public Health have partnered with investigators at the National Institute of Public Health in Mexico and created the Harvard-Mexico Project on Maternal-Fetal Lead Exposure, Risks, and Prevention (the "Harvard-Mexico Project"). Mexico City was chosen as the location for this research because its unique environmental lead exposure profile - leaded gasoline was phased out beginning in 1992 - left many women with low blood lead levels but high bone lead levels.
To conduct these studies, the project team developed and validated new analytical techniques including:
- K-x-ray fluorescence - a non-invasive and rapid method for measuring lead in bone
- A new method for estimating rates of bone resorption
- A new technique for measuring the ultra-low levels of lead that appear in blood plasma
The Harvard-Mexico Project has made a number of critical discoveries. Among these are:
- The bone lead levels of most women of reproductive age are easily measurable and are not low.
- These maternal bone lead levels are a major driving force of lead that appears in blood, plasma, and breast milk (luckily, despite this influence, most breast milk lead levels are low).
- Maternal bone lead levels can be used as biomarkers to predict lower newborn weight, head circumference, and body length.
- Maternal bone lead levels can be used as biomarkers to predict smaller weight gains from birth to one month of age, and lower measures of intelligence at age 2 years. This finding that further confirms the importance of addressing lead exposure during pregnancy.
- Women who breast feed continue to have enhanced mobilization of lead from their bones into their blood, making potential lead toxicity an important issue to study in breast-feeding as well as pregnant women.
This SBRP-funded project has demonstrated that lead stores mobilized into the circulation of pregnant women pose a major threat to fetal development. Because bone lead stores, once accumulated, persist for decades, lead exposure can jeopardize the pregnancies of women even if their current lead exposures have subsided.
To address the public health challenge represented by the many thousands of women who have had lead exposure while growing up and who want to have healthy children, the Harvard-Mexico Project investigators have implemented a randomized trial of calcium supplementation as a low-cost strategy for reducing the toxic effects of maternal bone lead. Although the trial is still in progress, preliminary studies provide evidence that calcium supplements reduce bone resorption rates during pregnancy as well as maternal blood lead levels during lactation.
Because there is no known method to reduce bone lead stores, the successful identification of a safe and easily implemented dietary intervention would constitute a major advance in our ability to minimize damage caused by lead. The ultimate significance of these studies will be the optimization of the care of pregnant women who have had exposure to lead and to minimize risk to their babies.
This research, which won a Progress and Achievement Award from the National Institute for Environmental Health Sciences in 1999, is a good example of a productive international research collaboration. Such collaborations will continue to become more important as globalization of industry and science continues to expand.
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To learn more about this research, please refer to the following sources:
- Hernandez-Avila M, Gonzalez-Cossio T, Hernandez-Avila JE, Romieu I, Peterson KE, Aro A, Palazuelos E, Hu H. 2003. Dietary calcium supplements to lower blood lead levels in lactating women: a randomized placebo-controlled trial. Epidemiology 14(2):206-212. doi:10.1097/01.EDE.0000038520.66094.34 PMID:12606887
- Hu H, Hernandez-Avila M. 2002. Invited commentary: lead, bones, women, and pregnancy--the poison within?. Am J Epidemiol 156(12):1088-1091. PMID:12480652
- Tellez-Rojo MM, Hernandez-Avila M, Gonzalez-Cossio T, Romieu I, Aro A, Palazuelos E, Schwartz J, Hu H. 2002. The impact of breastfeeding on the mobilization of lead from bone. Am J Epidemiol 155(5):420-428. PMID:11867353
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