Dietary Calcium Supplementation to Reduce Blood Lead in Pregnancy

Controlled Trial in Pregnancy of Dietary Supplements for Suppression of Bone Resorption and Mobilization of Lead Into Plasma

Lead accumulates in bone. During pregnancy, physiologic changes occur prompting bone resorption in order to provide calcium to the growing fetal skeleton also release the lead stored in bone into a pregnant woman's circulation. We have previously demonstrated that lead stores mobilized into the circulation of pregnant women pose a major threat to fetal development. This is particularly unfortunate since bone lead stores, once accumulated, persist for decades, thereby jeopardizing the pregnancies of women even if their current lead exposures have subsided. What then can be done for the many thousands of women who have had lead exposure while growing up and who want to have healthy children? To address this question, in 2000, this project embarked on a randomized intervention trial to test whether a bedtime nutritional supplement of 1,000 mg of calcium can significantly reduce fetal lead exposure and toxicity by suppressing bone resorption in the pregnant mother.

Study Overview

• Status: Completed
• Conditions: Pregnancy; Bone Resorption; Lead, Blood
• Intervention / Treatment: Dietary supplement: calcium carbonate

Detailed Description

Recent evidence indicates that there is a marked increase in the mobilization of lead from maternal bone stores into circulation during pregnancy and lactation. Furthermore, data from our group and others indicate that this phenomenon carries a significant risk of fetal toxicity in the form of growth (decreased birth weight, head circumference, birth length) and subsequent cognitive development. These findings pose a major public health problem, even among societies with declining lead exposure, given the persistence of pockets of high lead exposure (including some communities living in proximity to hazardous waste) as well as the long residence time of lead in bone (years to decades). One possible strategy for suppressing the mobilization of maternal bone lead stores during pregnancy is nutritional intervention. We are conducting a randomized, double-blinded, placebo-controlled trial of dietary supplements containing 1,200 milligrams of calcium as a means of suppressing bone resorption and the resulting mobilization of lead from bone into plasma during pregnancy, and into breast milk during the postpartum period. We are taking maternal measurements of pre-pregnancy and postpartum bone lead using our K-x-ray fluorescence technology; bone resorption (by assaying N-telopeptide of type I collagen in urine [urinary NTX]), whole blood lead, and plasma lead (using special collection techniques and measured by IDTIMS) during pre-pregnancy, the first, second, third trimesters and at one and four months postpartum; and breast milk lead levels at one and four months postpartum.

We are measuring maternal plasma and breast milk lead levels as these are the most direct sources of fetal and infant lead exposures, and recent research suggests that maternal venous blood lead levels do not adequately reflect either of these parameters. We are testing the hypothesis that supplements will significantly decrease urinary NTX, plasma lead, and breast milk lead levels. We are also exploring the relationship of plasma lead levels to birth anthropometry measures. This research, if successful, may provide a means of preventing secondary toxicity from accumulated lead burdens among women of reproductive age.

• Study Type: Interventional
• Enrollment (Actual): 670
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62100
      • Mauricio Hernandez-Avila

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• being in the first trimester of pregnancy (no more than 14 weeks gestation); not presenting with a high-risk pregnancy; residing and plans to reside in the metropolitan Mexico City area for approximately 5 years; agreeing to participate and signing the informed consent form.

Exclusion Criteria:

• high-risk pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1; Placebo	Dietary supplement: calcium carbonate; daily supplement of 1,200 milligrams calcium (two-600 mg tablets calcium carbonate at bedtime); Other Names: Lederle, Inc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Blood Lead Concentration, Plasma Lead Concentration	2nd, 3rd trimester pregnancy and 1,4,7,12 months postpartum

Secondary Outcome Measures

Outcome Measure	Time Frame
Urinary Cross-linked N-telopeptides (marker of bone resorption)	2nd, 3rd trimester of pregnancy and 1,4,7,12 months postpartum

Collaborators and Investigators

• Sponsor: National Institute of Environmental Health Sciences (NIEHS)
• Collaborators: Brigham and Women's Hospital; University of California, Santa Cruz; Mexican National Institute of Public Health
• Investigators: Principal Investigator: Howard Hu, MD, ScD, Harvard School of Public Health and University of Michigan; Principal Investigator: Mauricio Hernandez-Avila, MD, ScD, National Institute of Public Health and Ministry of Health, Mexico

Publications and helpful links

General Publications

• Perng W, Tamayo-Ortiz M, Tang L, Sanchez BN, Cantoral A, Meeker JD, Dolinoy DC, Roberts EF, Martinez-Mier EA, Lamadrid-Figueroa H, Song PXK, Ettinger AS, Wright R, Arora M, Schnaas L, Watkins DJ, Goodrich JM, Garcia RC, Solano-Gonzalez M, Bautista-Arredondo LF, Mercado-Garcia A, Hu H, Hernandez-Avila M, Tellez-Rojo MM, Peterson KE. Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project. BMJ Open. 2019 Aug 26;9(8):e030427. doi: 10.1136/bmjopen-2019-030427.
• Ettinger AS, Lamadrid-Figueroa H, Mercado-Garcia A, Kordas K, Wood RJ, Peterson KE, Hu H, Hernandez-Avila M, Tellez-Rojo MM. Effect of calcium supplementation on bone resorption in pregnancy and the early postpartum: a randomized controlled trial in Mexican women. Nutr J. 2014 Dec 16;13(1):116. doi: 10.1186/1475-2891-13-116.

Study record dates

Study Major Dates

• Study Start: January 1, 2001
• Study Completion (Actual): April 1, 2005

Study Registration Dates

• First Submitted: November 14, 2007
• First Submitted That Met QC Criteria: November 14, 2007
• First Posted (Estimate): November 15, 2007

Study Record Updates

• Last Update Posted (Estimate): November 15, 2007
• Last Update Submitted That Met QC Criteria: November 14, 2007
• Last Verified: November 1, 2007

More Information

Terms related to this study

• Keywords: randomized trial; pregnancy; dietary supplementation; calcium; bone resorption; lead, blood
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Bone Diseases; Bone Resorption; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Calcium-Regulating Hormones and Agents; Antacids; Calcium; Calcium Carbonate
• Other Study ID Numbers: P10345/9910CONT; NIEHS P42-ES05947 (Project 1)