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. 2000 Jun;108(6):527–531. doi: 10.1289/ehp.00108527

Effects of lead exposure before pregnancy and dietary calcium during pregnancy on fetal development and lead accumulation.

S Han 1, D H Pfizenmaier 1, E Garcia 1, M L Eguez 1, M Ling 1, F W Kemp 1, J D Bogden 1
PMCID: PMC1638166  PMID: 10856026

Abstract

Millions of women of child-bearing age have substantial bone lead stores due to lead exposure as children. Dietary calcium ingested simultaneously with lead exposure can reduce lead absorption and accumulation. However, the effects of dietary calcium on previously accumulated maternal lead stores and transfer to the fetus have not been investigated. We studied the effects of lead exposure of female rats at an early age on fetal development during a subsequent pregnancy. We gave 5-week-old female Sprague-Dawley rats lead as the acetate in their drinking water for 5 weeks; controls received equimolar sodium acetate. This was followed by a 1-month period without lead exposure before mating. We randomly assigned pregnant rats (n = 39) to diets with a deficient (0.1%) or normal (0.5%) calcium content during pregnancy. A total of 345 pups were delivered alive. Lead-exposed dams and their pups had significantly higher blood lead concentrations than controls, but the concentrations were in the range of those found in many pregnant women. Pups born to dams fed the calcium-deficient diet during pregnancy had higher blood and organ lead concentrations than pups born to dams fed the 0. 5% calcium diet. Pups born to lead-exposed dams had significantly (p<0.0001) lower mean birth weights and birth lengths than controls. There were significant inverse univariate associations between dam or pup organ lead concentrations and birth weight or length. The 0.5% calcium diet did not increase in utero growth. Stepwise regression analysis demonstrated that greater litter size and female sex were significantly associated with reduced pup birth weight and length. However, lead exposure that ended well before pregnancy was significantly (p<0.0001) associated with reduced birth weight and length, even after litter size, pup sex, and dam weight gain during pregnancy were included in the regression analysis. The data demonstrate that an increase in dietary calcium during pregnancy can reduce fetal lead accumulation but cannot prevent lead-induced decreases in birth weight and length. The results provide evidence that dietary nutrients can influence the transfer of toxins to the fetus during pregnancy. If these results are applicable to women, an increase in diet calcium during pregnancy could reduce the transfer of lead from prepregnancy maternal exposures to the fetus.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andrews K. W., Savitz D. A., Hertz-Picciotto I. Prenatal lead exposure in relation to gestational age and birth weight: a review of epidemiologic studies. Am J Ind Med. 1994 Jul;26(1):13–32. doi: 10.1002/ajim.4700260103. [DOI] [PubMed] [Google Scholar]
  2. Ballew C., Khan L. K., Kaufmann R., Mokdad A., Miller D. T., Gunter E. W. Blood lead concentration and children's anthropometric dimensions in the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994. J Pediatr. 1999 May;134(5):623–630. doi: 10.1016/s0022-3476(99)70250-7. [DOI] [PubMed] [Google Scholar]
  3. Barker D. J., Bull A. R., Osmond C., Simmonds S. J. Fetal and placental size and risk of hypertension in adult life. BMJ. 1990 Aug 4;301(6746):259–262. doi: 10.1136/bmj.301.6746.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bogden J. D., Gertner S. B., Christakos S., Kemp F. W., Yang Z., Katz S. R., Chu C. Dietary calcium modifies concentrations of lead and other metals and renal calbindin in rats. J Nutr. 1992 Jul;122(7):1351–1360. doi: 10.1093/jn/122.7.1351. [DOI] [PubMed] [Google Scholar]
  5. Bogden J. D., Kemp F. W., Han S., Murphy M., Fraiman M., Czerniach D., Flynn C. J., Banua M. L., Scimone A., Castrovilly L. Dietary calcium and lead interact to modify maternal blood pressure, erythropoiesis, and fetal and neonatal growth in rats during pregnancy and lactation. J Nutr. 1995 Apr;125(4):990–1002. doi: 10.1093/jn/125.4.990. [DOI] [PubMed] [Google Scholar]
  6. Bogden J. D., Oleske J. M., Louria D. B. Lead poisoning--one approach to a problem that won't go away. Environ Health Perspect. 1997 Dec;105(12):1284–1287. doi: 10.1289/ehp.105-1470406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Factor-Litvak P., Graziano J. H., Kline J. K., Popovac D., Mehmeti A., Ahmedi G., Shrout P., Murphy M. J., Gashi E., Haxhiu R. A prospective study of birthweight and length of gestation in a population surrounding a lead smelter in Kosovo, Yugoslavia. Int J Epidemiol. 1991 Sep;20(3):722–728. doi: 10.1093/ije/20.3.722. [DOI] [PubMed] [Google Scholar]
  8. Factor-Litvak P., Wasserman G., Kline J. K., Graziano J. The Yugoslavia Prospective Study of environmental lead exposure. Environ Health Perspect. 1999 Jan;107(1):9–15. doi: 10.1289/ehp.991079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. González-Cossío T., Peterson K. E., Sanín L. H., Fishbein E., Palazuelos E., Aro A., Hernández-Avila M., Hu H. Decrease in birth weight in relation to maternal bone-lead burden. Pediatrics. 1997 Nov;100(5):856–862. doi: 10.1542/peds.100.5.856. [DOI] [PubMed] [Google Scholar]
  10. Gulson B. L., Jameson C. W., Mahaffey K. R., Mizon K. J., Korsch M. J., Vimpani G. Pregnancy increases mobilization of lead from maternal skeleton. J Lab Clin Med. 1997 Jul;130(1):51–62. doi: 10.1016/s0022-2143(97)90058-5. [DOI] [PubMed] [Google Scholar]
  11. Gulson B. L., Mahaffey K. R., Jameson C. W., Patison N., Law A. J., Mizon K. J., Korsch M. J., Pederson D. Impact of diet on lead in blood and urine in female adults and relevance to mobilization of lead from bone stores. Environ Health Perspect. 1999 Apr;107(4):257–263. doi: 10.1289/ehp.99107257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Han S., Qiao X., Kemp F. W., Bogden J. D. Lead exposure at an early age substantially increases lead retention in the rat. Environ Health Perspect. 1997 Apr;105(4):412–417. doi: 10.1289/ehp.97105412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Harlan W. R., Landis J. R., Schmouder R. L., Goldstein N. G., Harlan L. C. Blood lead and blood pressure. Relationship in the adolescent and adult US population. JAMA. 1985 Jan 25;253(4):530–534. doi: 10.1001/jama.253.4.530. [DOI] [PubMed] [Google Scholar]
  14. Hertz-Picciotto I., Croft J. Review of the relation between blood lead and blood pressure. Epidemiol Rev. 1993;15(2):352–373. doi: 10.1093/oxfordjournals.epirev.a036125. [DOI] [PubMed] [Google Scholar]
  15. Hessol N. A., Fuentes-Afflick E., Bacchetti P. Risk of low birth weight infants among black and white parents. Obstet Gynecol. 1998 Nov;92(5):814–822. doi: 10.1016/s0029-7844(98)00310-x. [DOI] [PubMed] [Google Scholar]
  16. Hu H., Aro A., Payton M., Korrick S., Sparrow D., Weiss S. T., Rotnitzky A. The relationship of bone and blood lead to hypertension. The Normative Aging Study. JAMA. 1996 Apr 17;275(15):1171–1176. [PubMed] [Google Scholar]
  17. Kerper L. E., Hinkle P. M. Cellular uptake of lead is activated by depletion of intracellular calcium stores. J Biol Chem. 1997 Mar 28;272(13):8346–8352. doi: 10.1074/jbc.272.13.8346. [DOI] [PubMed] [Google Scholar]
  18. Kosnett M. J., Becker C. E., Osterloh J. D., Kelly T. J., Pasta D. J. Factors influencing bone lead concentration in a suburban community assessed by noninvasive K x-ray fluorescence. JAMA. 1994 Jan 19;271(3):197–203. [PubMed] [Google Scholar]
  19. Lai A., Kiyomi-Ito M., Komatsu K., Niiyama Y. Effects of various levels of dietary calcium during pregnancy on maternal calcium utilization and fetal growth in rats. J Nutr Sci Vitaminol (Tokyo) 1984 Jun;30(3):285–295. doi: 10.3177/jnsv.30.285. [DOI] [PubMed] [Google Scholar]
  20. Langley-Evans S., Jackson A. Intrauterine programming of hypertension: nutrient-hormone interactions. Nutr Rev. 1996 Jun;54(6):163–169. doi: 10.1111/j.1753-4887.1996.tb03923.x. [DOI] [PubMed] [Google Scholar]
  21. Law C. M., de Swiet M., Osmond C., Fayers P. M., Barker D. J., Cruddas A. M., Fall C. H. Initiation of hypertension in utero and its amplification throughout life. BMJ. 1993 Jan 2;306(6869):24–27. doi: 10.1136/bmj.306.6869.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mahaffey K. R., Gartside P. S., Glueck C. J. Blood lead levels and dietary calcium intake in 1- to 11-year-old children: the Second National Health and Nutrition Examination Survey, 1976 to 1980. Pediatrics. 1986 Aug;78(2):257–262. [PubMed] [Google Scholar]
  23. Mahaffey K. R., Goyer R., Haseman J. K. Dose-response to lead ingestion in rats fed low dietary calcium. J Lab Clin Med. 1973 Jul;82(1):92–100. [PubMed] [Google Scholar]
  24. Miller G. D., Massaro T. F., Massaro E. J. Interactions between lead and essential elements: a review. Neurotoxicology. 1990 Spring;11(1):99–119. [PubMed] [Google Scholar]
  25. Min Y. I., Correa-Villaseñor A., Stewart P. A. Parental occupational lead exposure and low birth weight. Am J Ind Med. 1996 Nov;30(5):569–578. [PubMed] [Google Scholar]
  26. O'Flaherty E. J. Physiologically based models for bone-seeking elements. V. Lead absorption and disposition in childhood. Toxicol Appl Pharmacol. 1995 Apr;131(2):297–308. doi: 10.1006/taap.1995.1072. [DOI] [PubMed] [Google Scholar]
  27. Philion J. J., Schmitt N., Rowe J., Gelpke P. M. Effect of lead on fetal growth in a Canadian smelter city, 1961-1990. Arch Environ Health. 1997 Nov-Dec;52(6):472–475. doi: 10.1080/00039899709602226. [DOI] [PubMed] [Google Scholar]
  28. Ronis M. J., Badger T. M., Shema S. J., Roberson P. K., Templer L., Ringer D., Thomas P. E. Endocrine mechanisms underlying the growth effects of developmental lead exposure in the rat. J Toxicol Environ Health A. 1998 May 22;54(2):101–120. doi: 10.1080/009841098158944. [DOI] [PubMed] [Google Scholar]
  29. Silbergeld E. K., Schwartz J., Mahaffey K. Lead and osteoporosis: mobilization of lead from bone in postmenopausal women. Environ Res. 1988 Oct;47(1):79–94. doi: 10.1016/s0013-9351(88)80023-9. [DOI] [PubMed] [Google Scholar]
  30. West W. L., Knight E. M., Edwards C. H., Manning M., Spurlock B., James H., Johnson A. A., Oyemade U. J., Cole O. J., Westney O. E. Maternal low level lead and pregnancy outcomes. J Nutr. 1994 Jun;124(6 Suppl):981S–986S. doi: 10.1093/jn/124.suppl_6.981S. [DOI] [PubMed] [Google Scholar]
  31. Zambrana R. E., Dunkel-Schetter C., Collins N. L., Scrimshaw S. C. Mediators of ethnic-associated differences in infant birth weight. J Urban Health. 1999 Mar;76(1):102–116. doi: 10.1007/BF02344465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ziegler E. E., Edwards B. B., Jensen R. L., Mahaffey K. R., Fomon S. J. Absorption and retention of lead by infants. Pediatr Res. 1978 Jan;12(1):29–34. doi: 10.1203/00006450-197801000-00008. [DOI] [PubMed] [Google Scholar]

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