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. 2004 Mar;112(3):388–391. doi: 10.1289/ehp.6414

In utero pesticide exposure, maternal paraoxonase activity, and head circumference.

Gertrud S Berkowitz 1, James G Wetmur 1, Elena Birman-Deych 1, Josephine Obel 1, Robert H Lapinski 1, James H Godbold 1, Ian R Holzman 1, Mary S Wolff 1
PMCID: PMC1241872  PMID: 14998758

Abstract

Although the use of pesticides in inner-city homes of the United States is of considerable magnitude, little is known about the potentially adverse health effects of such exposure. Recent animal data suggest that exposure to pesticides during pregnancy and early life may impair growth and neurodevelopment in the offspring. To investigate the relationship among prenatal pesticide exposure, paraoxonase (PON1) polymorphisms and enzyme activity, and infant growth and neurodevelopment, we are conducting a prospective, multiethnic cohort study of mothers and infants delivered at Mount Sinai Hospital in New York City. In this report we evaluate the effects of pesticide exposure on birth weight, length, head circumference, and gestational age among 404 births between May 1998 and May 2002. Pesticide exposure was assessed by a prenatal questionnaire administered to the mothers during the early third trimester as well as by analysis of maternal urinary pentachlorophenol levels and maternal metabolites of chlorpyrifos and pyrethroids. Neither the questionnaire data nor the pesticide metabolite levels were associated with any of the fetal growth indices or gestational age. However, when the level of maternal PON1 activity was taken into account, maternal levels of chlorpyrifos above the limit of detection coupled with low maternal PON1 activity were associated with a significant but small reduction in head circumference. In addition, maternal PON1 levels alone, but not PON1 genetic polymorphisms, were associated with reduced head size. Because small head size has been found to be predictive of subsequent cognitive ability, these data suggest that chlorpyrifos may have a detrimental effect on fetal neurodevelopment among mothers who exhibit low PON1 activity.

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Selected References

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  1. Aviram M., Hardak E., Vaya J., Mahmood S., Milo S., Hoffman A., Billicke S., Draganov D., Rosenblat M. Human serum paraoxonases (PON1) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions: PON1 esterase and peroxidase-like activities. Circulation. 2000 May 30;101(21):2510–2517. doi: 10.1161/01.cir.101.21.2510. [DOI] [PubMed] [Google Scholar]
  2. Bellinger D. C., Stiles K. M., Needleman H. L. Low-level lead exposure, intelligence and academic achievement: a long-term follow-up study. Pediatrics. 1992 Dec;90(6):855–861. [PubMed] [Google Scholar]
  3. Berkowitz Gertrud S., Obel Josephine, Deych Elena, Lapinski Robert, Godbold James, Liu Zhisong, Landrigan Philip J., Wolff Mary S. Exposure to indoor pesticides during pregnancy in a multiethnic, urban cohort. Environ Health Perspect. 2003 Jan;111(1):79–84. doi: 10.1289/ehp.5619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brophy V. H., Jampsa R. L., Clendenning J. B., McKinstry L. A., Jarvik G. P., Furlong C. E. Effects of 5' regulatory-region polymorphisms on paraoxonase-gene (PON1) expression. Am J Hum Genet. 2001 May 2;68(6):1428–1436. doi: 10.1086/320600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Busch C. P., Ramdath D. D., Ramsewak S., Hegele R. A. Association of PON2 variation with birth weight in Trinidadian neonates of South Asian ancestry. Pharmacogenetics. 1999 Jun;9(3):351–356. doi: 10.1097/00008571-199906000-00010. [DOI] [PubMed] [Google Scholar]
  6. Castellanos F. Xavier, Lee Patti P., Sharp Wendy, Jeffries Neal O., Greenstein Deanna K., Clasen Liv S., Blumenthal Jonathan D., James Regina S., Ebens Christen L., Walter James M. Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA. 2002 Oct 9;288(14):1740–1748. doi: 10.1001/jama.288.14.1740. [DOI] [PubMed] [Google Scholar]
  7. Chanda S. M., Pope C. N. Neurochemical and neurobehavioral effects of repeated gestational exposure to chlorpyrifos in maternal and developing rats. Pharmacol Biochem Behav. 1996 Apr;53(4):771–776. doi: 10.1016/0091-3057(95)02105-1. [DOI] [PubMed] [Google Scholar]
  8. Chang M. J., Lin C. Y., Lo L. W., Lin R. S. Biological monitoring of exposure to chlorpyrifos by high performance liquid chromatography. Bull Environ Contam Toxicol. 1996 Mar;56(3):367–374. doi: 10.1007/s001289900053. [DOI] [PubMed] [Google Scholar]
  9. Chen Jia, Germer Søren, Higuchi Russell, Berkowitz Gertrud, Godbold James, Wetmur James G. Kinetic polymerase chain reaction on pooled DNA: a high-throughput, high-efficiency alternative in genetic epidemiological studies. Cancer Epidemiol Biomarkers Prev. 2002 Jan;11(1):131–136. [PubMed] [Google Scholar]
  10. Chen Jia, Kumar Madhu, Chan Wendy, Berkowitz Gertrud, Wetmur James G. Increased influence of genetic variation on PON1 activity in neonates. Environ Health Perspect. 2003 Aug;111(11):1403–1409. doi: 10.1289/ehp.6105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Costa L. G., McDonald B. E., Murphy S. D., Omenn G. S., Richter R. J., Motulsky A. G., Furlong C. E. Serum paraoxonase and its influence on paraoxon and chlorpyrifos-oxon toxicity in rats. Toxicol Appl Pharmacol. 1990 Mar 15;103(1):66–76. doi: 10.1016/0041-008x(90)90263-t. [DOI] [PubMed] [Google Scholar]
  12. Dam K., Garcia S. J., Seidler F. J., Slotkin T. A. Neonatal chlorpyrifos exposure alters synaptic development and neuronal activity in cholinergic and catecholaminergic pathways. Brain Res Dev Brain Res. 1999 Aug 5;116(1):9–20. doi: 10.1016/s0165-3806(99)00067-x. [DOI] [PubMed] [Google Scholar]
  13. Dam K., Seidler F. J., Slotkin T. A. Chlorpyrifos exposure during a critical neonatal period elicits gender-selective deficits in the development of coordination skills and locomotor activity. Brain Res Dev Brain Res. 2000 Jun 30;121(2):179–187. doi: 10.1016/s0165-3806(00)00044-4. [DOI] [PubMed] [Google Scholar]
  14. Davis D. L., Ahmed A. K. Exposures from indoor spraying of chlorpyrifos pose greater health risks to children than currently estimated. Environ Health Perspect. 1998 Jun;106(6):299–301. doi: 10.1289/ehp.98106299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Eskenazi B., Bradman A., Castorina R. Exposures of children to organophosphate pesticides and their potential adverse health effects. Environ Health Perspect. 1999 Jun;107 (Suppl 3):409–419. doi: 10.1289/ehp.99107s3409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Furlong C. E., Richter R. J., Seidel S. L., Motulsky A. G. Role of genetic polymorphism of human plasma paraoxonase/arylesterase in hydrolysis of the insecticide metabolites chlorpyrifos oxon and paraoxon. Am J Hum Genet. 1988 Sep;43(3):230–238. [PMC free article] [PubMed] [Google Scholar]
  17. Gurunathan S., Robson M., Freeman N., Buckley B., Roy A., Meyer R., Bukowski J., Lioy P. J. Accumulation of chlorpyrifos on residential surfaces and toys accessible to children. Environ Health Perspect. 1998 Jan;106(1):9–16. doi: 10.1289/ehp.981069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hill R. H., Jr, Shealy D. B., Head S. L., Williams C. C., Bailey S. L., Gregg M., Baker S. E., Needham L. L. Determination of pesticide metabolites in human urine using an isotope dilution technique and tandem mass spectrometry. J Anal Toxicol. 1995 Sep;19(5):323–329. doi: 10.1093/jat/19.5.323. [DOI] [PubMed] [Google Scholar]
  19. Jacobson J. L., Jacobson S. W. Intellectual impairment in children exposed to polychlorinated biphenyls in utero. N Engl J Med. 1996 Sep 12;335(11):783–789. doi: 10.1056/NEJM199609123351104. [DOI] [PubMed] [Google Scholar]
  20. Landrigan P. J., Claudio L., Markowitz S. B., Berkowitz G. S., Brenner B. L., Romero H., Wetmur J. G., Matte T. D., Gore A. C., Godbold J. H. Pesticides and inner-city children: exposures, risks, and prevention. Environ Health Perspect. 1999 Jun;107 (Suppl 3):431–437. doi: 10.1289/ehp.99107s3431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lasky R. E., Klein R. E., Yarbrough C., Engle P. L., Lechtig A., Martorell R. The relationship between physical growth and infant behavioral development in rural Guatemala. Child Dev. 1981 Mar;52(1):219–226. [PubMed] [Google Scholar]
  22. Lemons J. A., Schreiner R. L., Gresham E. L. Relationship of brain weight to head circumference in early infancy. Hum Biol. 1981 Sep;53(3):351–354. [PubMed] [Google Scholar]
  23. Leng G., Leng A., Kühn K. H., Lewalter J., Pauluhn J. Human dose-excretion studies with the pyrethroid insecticide cyfluthrin: urinary metabolite profile following inhalation. Xenobiotica. 1997 Dec;27(12):1273–1283. doi: 10.1080/004982597239859. [DOI] [PubMed] [Google Scholar]
  24. Mueller R. F., Hornung S., Furlong C. E., Anderson J., Giblett E. R., Motulsky A. G. Plasma paraoxonase polymorphism: a new enzyme assay, population, family, biochemical, and linkage studies. Am J Hum Genet. 1983 May;35(3):393–408. [PMC free article] [PubMed] [Google Scholar]
  25. Nolan R. J., Rick D. L., Freshour N. L., Saunders J. H. Chlorpyrifos: pharmacokinetics in human volunteers. Toxicol Appl Pharmacol. 1984 Mar 30;73(1):8–15. doi: 10.1016/0041-008x(84)90046-2. [DOI] [PubMed] [Google Scholar]
  26. Ounsted M., Moar V. A., Scott A. Head circumference and developmental ability at the age of seven years. Acta Paediatr Scand. 1988 May;77(3):374–379. doi: 10.1111/j.1651-2227.1988.tb10663.x. [DOI] [PubMed] [Google Scholar]
  27. Qiao Dan, Seidler Frederic J., Tate Charlotte A., Cousins Mandy M., Slotkin Theodore A. Fetal chlorpyrifos exposure: adverse effects on brain cell development and cholinergic biomarkers emerge postnatally and continue into adolescence and adulthood. Environ Health Perspect. 2003 Apr;111(4):536–544. doi: 10.1289/ehp.5828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Roy A. C., Loke D. F., Saha N., Viegas O. A., Tay J. S., Ratnam S. S. Interrelationships of serum paraoxonase, serum lipids and apolipoproteins in normal pregnancy. A longitudinal study. Gynecol Obstet Invest. 1994;38(1):10–13. doi: 10.1159/000292435. [DOI] [PubMed] [Google Scholar]
  29. Shih D. M., Gu L., Xia Y. R., Navab M., Li W. F., Hama S., Castellani L. W., Furlong C. E., Costa L. G., Fogelman A. M. Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature. 1998 Jul 16;394(6690):284–287. doi: 10.1038/28406. [DOI] [PubMed] [Google Scholar]
  30. Slotkin T. A. Developmental cholinotoxicants: nicotine and chlorpyrifos. Environ Health Perspect. 1999 Feb;107 (Suppl 1):71–80. doi: 10.1289/ehp.99107s171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Smolen A., Eckerson H. W., Gan K. N., Hailat N., La Du B. N. Characteristics of the genetically determined allozymic forms of human serum paraoxonase/arylesterase. Drug Metab Dispos. 1991 Jan-Feb;19(1):107–112. [PubMed] [Google Scholar]
  32. Song X., Violin J. D., Seidler F. J., Slotkin T. A. Modeling the developmental neurotoxicity of chlorpyrifos in vitro: macromolecule synthesis in PC12 cells. Toxicol Appl Pharmacol. 1998 Jul;151(1):182–191. doi: 10.1006/taap.1998.8424. [DOI] [PubMed] [Google Scholar]
  33. Uhl S., Schmid P., Schlatter C. Pharmacokinetics of pentachlorophenol in man. Arch Toxicol. 1986 Feb;58(3):182–186. doi: 10.1007/BF00340979. [DOI] [PubMed] [Google Scholar]
  34. Whitney K. D., Seidler F. J., Slotkin T. A. Developmental neurotoxicity of chlorpyrifos: cellular mechanisms. Toxicol Appl Pharmacol. 1995 Sep;134(1):53–62. doi: 10.1006/taap.1995.1168. [DOI] [PubMed] [Google Scholar]
  35. Whyatt Robin M., Camann David E., Kinney Patrick L., Reyes Andria, Ramirez Judy, Dietrich Jessica, Diaz Diurka, Holmes Darrell, Perera Frederica P. Residential pesticide use during pregnancy among a cohort of urban minority women. Environ Health Perspect. 2002 May;110(5):507–514. doi: 10.1289/ehp.02110507. [DOI] [PMC free article] [PubMed] [Google Scholar]

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