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Adrienne S. Ettinger,^1,2 Héctor Lamadrid-Figueroa,³ Martha M. Téllez-Rojo,³ Adriana Mercado-García,³ Karen E. Peterson,^1,2 Joel Schwartz,¹ Howard Hu,^1,2,4 and Mauricio Hernández-Avila^3,5

¹Harvard School of Public Health, Boston, Massachusetts, USA; ²University of Michigan School of Public Health, Ann Arbor, Michigan, USA; ³Mexican National Institute of Public Health, Cuernavaca, Morelos, México; ⁴University of Michigan School of Medicine, Ann Arbor, Michigan, USA; ⁵Mexican Ministry of Health, Distrito Federal, México

Abstract
Background: Prenatal lead exposure is associated with deficits in fetal growth and neurodevelopment. Calcium supplementation may attenuate fetal exposure by inhibiting mobilization of maternal bone lead and/or intestinal absorption of ingested lead.

Objective: Our goal was to evaluate the effect of 1,200 mg dietary calcium supplementation on maternal blood lead levels during pregnancy.

Methods: In a double-blind, randomized, placebo-controlled trial conducted from 2001 through 2003 in Mexico City, we randomly assigned 670 women in their first trimester of pregnancy to ingest calcium (n = 334) or placebo (n = 336) . We followed subjects through pregnancy and evaluated the effect of supplementation on maternal blood lead, using an intent-to-treat analysis by a mixed-effects regression model with random intercept, in 557 participants (83%) who completed follow-up. We then conducted as-treated analyses using similar models stratified by treatment compliance.

Results: Adjusting for baseline lead level, age, trimester of pregnancy, and dietary energy and calcium intake, calcium was associated with an average 11% reduction (0.4 µg/dL) in blood lead level relative to placebo (p = 0.004) . This reduction was more evident in the second trimester (–14%, p < 0.001) than in the third (–8%, p = 0.107) and was strongest in women who were most compliant (those who consumed ≥ 75% calcium pills ; –24%, p < 0.001) , had baseline blood lead > 5 µg/dL (–17%, p < 0.01) , or reported use of lead-glazed ceramics and high bone lead (–31%, p < 0.01) .

Conclusion: Calcium supplementation was associated with modest reductions in blood lead when administered during pregnancy and may constitute an important secondary prevention effort to reduce circulating maternal lead and, consequently, fetal exposure.

Key words: calcium, diet, lead, pregnancy, randomized trial, supplementation. Environ Health Perspect 117:26–31 (2009) . doi:10.1289/ehp.11868 available via http://dx.doi.org/ [Online 2 September 2008]

Address correspondence to A.S. Ettinger, Harvard School of Public Health, Landmark Center West, Room 421, 401 Park Dr., Boston, MA 02215 USA. Telephone: (617) 384-8834. Fax: (617) 384-8745. E-mail: aettinge@hsph.harvard.edu. Address reprint requests to H. Hu, University of Michigan, Ann Arbor, MI 48109 USA. Telephone: (734) 764-3188. E-mail: howardhu@umich.edu

We thank the American British Cowdray Hospital in Mexico City for the use of their research facilities.

This study was supported by the U.S. National Institute of Environmental Health Sciences (NIEHS) grants P42-ES05947, R01-ES07821, R01-ES014930, P30-ES00002, and K23-ES000381 ; by Consejo Nacional de Ciencia y Tecnología (CONACyT) grant 4150M9405 ; and by Consejo de Estudios para la Restauración y Valoración Ambiental (CONSERVA) , Department of Federal District, México. A.S.E. was supported by NIEHS K01-ES014907-01A1.

The contents of this study are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS or the National Institutes of Health.

The authors declare they have no competing financial interests.

Received 27 June 2008 ; accepted 2 September 2008.