Impact of low-level gestational exposure to organophosphate pesticides on neurobehavior in early infancy: a prospective study

Kimberly Yolton, Yingying Xu, Heidi Sucharew, Paul Succop, Mekibib Altaye, Ann Popelar, M Angela Montesano, Antonia M Calafat, Jane C Khoury, Kimberly Yolton, Yingying Xu, Heidi Sucharew, Paul Succop, Mekibib Altaye, Ann Popelar, M Angela Montesano, Antonia M Calafat, Jane C Khoury

Abstract

Background: National data suggest widespread gestational exposure to organophosphate pesticides (OPs) based on the detection of OP metabolites in the urine of pregnant women. Associations with early infant neurobehavior are largely understudied, with only two studies reporting abnormal reflexes in newborns in association with gestational exposure to OPs. Our objective was to utilize biological markers of OP metabolites in pregnant women and a comprehensive assessment of infant neurobehavior to determine the association of gestational exposure to OPs with neurobehavioral outcomes during early infancy.

Methods: Among a cohort of 350 mother/infant pairs, we measured six common dialkylphosphate metabolites of OP pesticides in maternal urine, at two times during pregnancy (16 w & 26 w gestation), then calculated aggregate concentrations of diethylphosphate, dimethylphosphate, and total dialkyphosphate metabolites. We measured infant neurobehavior at about five weeks of age using the NICU Network Neurobehavioral Scale (NNNS), a comprehensive assessment of neurobehavior in young infants. Analyses of associations between gestational exposure to OPs and neurobehavior at five weeks included multiple linear and logistic regression.

Results: After adjustment for covariates, higher creatinine-corrected urinary concentrations of diethylphosphate metabolites were associated with improved attention and reduced lethargy and hypotonia in young infants. Higher creatinine-corrected urinary concentrations of total dialkylphosphate metabolites were associated with fewer signs of autonomic stress. Women who were white, married, had advanced education, and reported more frequent consumption of fresh fruits and vegetables had higher concentrations of OP metabolites during pregnancy.

Conclusions: In this sample of pregnant women whose urinary concentrations of dialkylphosphate metabolites are representative of national exposure levels, we found no detrimental effects of gestational exposure to OPs on neurobehavioral outcomes among young infants. These results are important as they suggest there may be minimal to no detectable adverse impact of low level prenatal OP exposure on the neurobehavior of young infants.

References

    1. Woodruff TJ, Zota AR, Schwartz JM. Environmental chemicals in pregnant women in the United States: NHANES 2003–2004. Environ Health Perspect. 2011;12:878. doi: 10.1289/ehp.1002727.
    1. Engel SM, Wetmur J, Chen J, Zhu C, Barr DB, Canfield RL, Wolff MS. Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood. Environ Health Perspect. 2011;12:1182. doi: 10.1289/ehp.1003183.
    1. Eskenazi B, Marks AR, Bradman A, Harley K, Barr DB, Johnson C, Morga N, Jewell NP. Organophosphate pesticide exposure and neurodevelopment in young Mexican-American children. Environ Health Perspect. 2007;12:792. doi: 10.1289/ehp.9828.
    1. Rauh VA, Garfinkel R, Perera FP, Andrews HF, Hoepner L, Barr DB, Whitehead R, Tang D, Whyatt RW. Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children. Pediatrics. 2006;12:e1845–e1859. doi: 10.1542/peds.2006-0338.
    1. Bouchard MF, Chevrier J, Harley KG, Kogut K, Vedar M, Calderon N, Trujillo C, Johnson C, Bradman A, Barr DB. Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children. Environ Health Perspect. 2011;12:1189. doi: 10.1289/ehp.1003185.
    1. Rauh V, Arunajadai S, Horton M, Perera F, Hoepner L, Barr DB, Whyatt R. Seven-year neurodevelopmental scores and prenatal exposure to chlorpyrifos, a common agricultural pesticide. Environ Health Perspect. 2011;12:1196. doi: 10.1289/ehp.1003160.
    1. Marks AR, Harley K, Bradman A, Kogut K, Barr DB, Johnson C, Calderon N, Eskenazi B. Organophosphate pesticide exposure and attention in young Mexican-American children: the CHAMACOS study. Environ Health Perspect. 2010;12:1768. doi: 10.1289/ehp.1002056.
    1. Liu J, Bann C, Lester B, Tronick E, Das A, Lagasse L, Bauer C, Shankaran S, Bada H. Neonatal neurobehavior predicts medical and behavioral outcome. Pediatrics. 2010;12:e90–e98. doi: 10.1542/peds.2009-0204.
    1. Sucharew H, Khoury JC, Xu Y, Succop P, Yolton K. NICU Network Neurobehavioral Scale profiles predict developmental outcomes in a low-risk sample. Paediatric Perinatal Epidemiol. 2012;12:344. doi: 10.1111/j.1365-3016.2012.01288.x.
    1. Brazelton T, Nugent J. Neonatal behavioral assessment scale. 3. London: MacKeith Press; 1995.
    1. Lester B, Tronick E. NICU Network Neurobehavioral Scale (NNNS) manual. Baltimore, MD: Paul H Brookes Pub Co; 2005.
    1. Coles CD, Platzman KA, Smith I, James ME, Falek A. Effects of cocaine and alcohol use in pregnancy on neonatal growth and neurobehavioral status. Neurotoxicol Teratol. 1992;12:23–33. doi: 10.1016/0892-0362(92)90025-6.
    1. Cotes CD, Smith I, Fernhoff PM, Fatek A. Neonatal neurobehavioral characteristics as correlates of maternal alcohol use during gestation. Alcohol Clin Exp Res. 2008;12:454–460.
    1. Ernhart CB, Wotf AW, Linn PL, Sokol RJ, Kennard MJ, Filipovich HF. Alcohol-Related Birth Defects: Syndromal Anomalies, Intrauterine Growth Retardation, and Neonatal Behavioral Assessment. Alcohol Clin Exp Res. 2008;12:447–453.
    1. Jacobson SW, Fein GG, Jacobson JL, Schwartz PM, Dowler JK. Neonatal correlates of prenatal exposure to smoking, caffeine, and alcohol. Infant Behav Dev. 1984;12:253–265.
    1. Smith L. NICU Network Neurobehavioral Scale Manual. J Dev Behav Pediatr. 2005;12:68.
    1. Streissguth AP, Barr HM, Martin DC. Maternal alcohol use and neonatal habituation assessed with the Brazelton scale. Child Dev. 1983;12:1118.
    1. Lester BM, Tronick EZ, LaGasse L, Seifer R, Bauer CR, Shankaran S, Bada HS, Wright LL, Smeriglio VL, Lu J. The maternal lifestyle study: effects of substance exposure during pregnancy on neurodevelopmental outcome in 1-month-old infants. Pediatrics. 2002;12:1182. doi: 10.1542/peds.110.6.1182.
    1. Napiorkowski B, Lester BM, Freier MC, Brunner S, Dietz L, Nadra A, Oh W. Effects of in utero substance exposure on infant neurobehavior. Pediatrics. 1996;12:71–75.
    1. Richardson GA, Hamel SC, Goldschmidt L, Day NL. The effects of prenatal cocaine use on neonatal neurobehavioral status. Neurotoxicol Teratol. 1996;12:519–528. doi: 10.1016/0892-0362(96)00062-1.
    1. Singer LT, Arendt R, Minnes S, Farkas K, Salvator A. Neurobehavioral outcomes of cocaine-exposed infants. Neurotoxicol Teratol. 2000;12:653–666. doi: 10.1016/S0892-0362(00)00092-1.
    1. Smith LM, LaGasse LL, Derauf C, Grant P, Shah R, Arria A, Huestis M, Haning W, Strauss A, Della Grotta S. Prenatal methamphetamine use and neonatal neurobehavioral outcome. Neurotoxicol Teratol. 2008;12:20. doi: 10.1016/j.ntt.2007.09.005.
    1. Tronick EZ, Frank DA, Cabral H, Mirochnick M, Zuckerman B. Late dose–response effects of prenatal cocaine exposure on newborn neurobehavioral performance. Pediatrics. 1996;12:76–83.
    1. Law KL, Stroud LR, LaGasse LL, Niaura R, Liu J, Lester BM. Smoking during pregnancy and newborn neurobehavior. Pediatrics. 2003;12:1318. doi: 10.1542/peds.111.6.1318.
    1. Mansi G, Raimondi F, Pichini S, Capasso L, Sarno M, Zuccaro P, Pacifici R, Garcia-Algar Ó, Romano A, Paludetto R. Neonatal urinary cotinine correlates with behavioral alterations in newborns prenatally exposed to tobacco smoke. Pediatr Res. 2007;12:257–261. doi: 10.1203/pdr.0b013e31802d89eb.
    1. Stroud LR, Paster RL, Goodwin MS, Shenassa E, Buka S, Niaura R, Rosenblith JF, Lipsitt LP. Maternal smoking during pregnancy and neonatal behavior: a large-scale community study. Pediatrics. 2009;12:e842–e848. doi: 10.1542/peds.2008-2084.
    1. Yolton K, Khoury J, Xu Y, Succop P, Lanphear B, Bernert J, Lester B. Low-level prenatal exposure to nicotine and infant neurobehavior. Neurotoxicol Teratol. 2009;12:356–363. doi: 10.1016/j.ntt.2009.07.004.
    1. Lonky E, Reihman J, Darvill T, Mather J Sr, Daly H. Neonatal behavioral assessment scale performance in humans influenced by maternal consumption of environmentally contaminated Lake Ontario fish. J Great Lakes Res. 1996;12:198–212. doi: 10.1016/S0380-1330(96)70949-8.
    1. Stewart P, Reihman J, Lonky E, Darvill T, Pagano J. Prenatal PCB exposure and neonatal behavioral assessment scale (NBAS) performance. Neurotoxicol Teratol. 2000;12:21–29. doi: 10.1016/S0892-0362(99)00056-2.
    1. Steuerwald U, Weihe P, Jørgensen PJ, Bjerve K, Brock J, Heinzow B, Budtz-Jørgensen E, Grandjean P. Maternal seafood diet, methylmercury exposure, and neonatal neurologic function. J Pediatr. 2000;12:599–605. doi: 10.1067/mpd.2000.102774.
    1. Emory E, Pattillo R, Archibold E, Bayorh M, Sung F. Neurobehavioral effects of low-level lead exposure in human neonates. Am J Obstet Gynecol. 1999;12:S2–S11. doi: 10.1016/S0002-9378(99)70465-5.
    1. Rothenberg SJ, Schnaas L, Cansino-Ortiz S, Perroni-Hernández E, De La Torre P, Neri-Méndez C, Ortega P, Hidalgo-Loperena H, Svendsgaard D. Neurobehavioral deficits after low level lead exposure in neonates: the Mexico City pilot study. Neurotoxicol Teratol. 1989;12:85–93. doi: 10.1016/0892-0362(89)90046-9.
    1. Engel SM, Zhu C, Berkowitz GS, Calafat AM, Silva MJ, Miodovnik A, Wolff MS. Prenatal phthalate exposure and performance on the Neonatal Behavioral Assessment Scale in a multiethnic birth cohort. Neurotoxicology. 2009;12:522–528. doi: 10.1016/j.neuro.2009.04.001.
    1. Yolton K, Xu Y, Strauss D, Altaye M, Calafat AM, Khoury J. Prenatal exposure to bisphenol A and phthalates and infant neurobehavior. Neurotoxicol Teratol. 2011;12:558. doi: 10.1016/j.ntt.2011.08.003.
    1. Rogan WJ, Gladen BC, McKinney JD, Carreras N, Hardy P, Thullen J, Tinglestad J, Tully M. Neonatal effects of transplacental exposure to PCBs and DDE. J Pediatr. 1986;12:335–341. doi: 10.1016/S0022-3476(86)80397-3.
    1. Sagiv SK, Nugent JK, Brazelton TB, Choi AL, Tolbert PE, Altshul LM, Korrick SA. Prenatal organochlorine exposure and measures of behavior in infancy using the Neonatal Behavioral Assessment Scale (NBAS) Environ Health Perspect. 2008;12:666. doi: 10.1289/ehp.10553.
    1. Engel SM, Berkowitz GS, Barr DB, Teitelbaum SL, Siskind J, Meisel SJ, Wetmur JG, Wolff MS. Prenatal organophosphate metabolite and organochlorine levels and performance on the Brazelton Neonatal Behavioral Assessment Scale in a multiethnic pregnancy cohort. Am J Epidemiol. 2007;12:1397–1404. doi: 10.1093/aje/kwm029.
    1. Young JG, Eskenazi B, Gladstone EA, Bradman A, Pedersen L, Johnson C, Barr DB, Furlong CE, Holland NT. Association between in utero organophosphate pesticide exposure and abnormal reflexes in neonates. Neurotoxicology. 2005;12:199–209. doi: 10.1016/j.neuro.2004.10.004.
    1. Geraghty SR, Khoury JC, Morrow AL, Lanphear BP. Reporting individual test results of environmental chemicals in breastmilk: potential for premature weaning. Breastfeed Med. 2008;12:207–213. doi: 10.1089/bfm.2008.0120.
    1. Bravo R, Caltabiano LM, Weerasekera G, Whitehead RD, Fernandez C, Needham LL, Bradman A, Barr DB. Measurement of dialkyl phosphate metabolites of organophosphorus pesticides in human urine using lyophilization with gas chromatography-tandem mass spectrometry and isotope dilution quantification. J Expo Sci Environ Epidemiol. 2004;12:249–259. doi: 10.1038/sj.jea.7500322.
    1. Beck AT, Steer RA, Brown GK. Beck Depression Inventory. 2. San Antonio, TX: The Psychological Corporation; 1996.
    1. SAS Institute. SAS Institute, Inc. Cary, NC: SAS 9.3; 2011.
    1. Centers for Disease Control and Prevention. Department of Health and Human Services, Centers for Disease Control and Prevention. Atlanta, GA: Division of Laboratory Sciences; 2009. Fourth national report on human exposure to environmental chemicals.
    1. Lu C, Bravo R, Caltabiano L, Irish R, Weerasekera G, Barr D. The presence of dialkylphosphates in fresh fruit juices: implication for organophosphorus pesticide exposure and risk assessments. J Toxicol Environ Health A. 2005;12:209–227. doi: 10.1080/15287390590890554.
    1. Pesticides and Food. What the Pesticide Residue Limits are on Food. .
    1. Choi AL, Cordier S, Weihe P, Grandjean P. Negative confounding in the evaluation of toxicity: the case of methylmercury in fish and seafood. Crit Rev Toxicol. 2008;12:877–893. doi: 10.1080/10408440802273164.
    1. Ramón R, Ballester F, Iñiguez C, Rebagliato M, Murcia M, Esplugues A, Marco A, de la Hera MG, Vioque J. Vegetable but not fruit intake during pregnancy is associated with newborn anthropometric measures. J Nutr. 2009;12:561–567. doi: 10.3945/jn.108.095596.
    1. Bunin GR, Kuijten RR, Buckley JD, Rorke LB, Meadows AT. Relation between maternal diet and subsequent primitive neuroectodermal brain tumors in young children. N Engl J Med. 1993;12:536–541. doi: 10.1056/NEJM199308193290804.
    1. Orjuela MA, Titievsky L, Liu X, Ramirez-Ortiz M, Ponce-Castaneda V, Lecona E, Molina E, Beaverson K, Abramson DH, Mueller NE. Fruit and vegetable intake during pregnancy and risk for development of sporadic retinoblastoma. Cancer Epidemiol Biomarkers Prev. 2005;12:1433–1440. doi: 10.1158/1055-9965.EPI-04-0427.
    1. Kim H, Hwang J-Y, Ha E-H, Park H, Ha M, Lee S-H, Hong Y-C, Chang N. Fruit and vegetable intake influences the association between exposure to polycyclic aromatice hydrocarbons and a marker of oxidative stress in pregnant women. Eur J Clin Nutr. 2011;12:1118–1125. doi: 10.1038/ejcn.2011.77.
    1. Guxens M, Aguilera I, Ballester F, Estarlich M, Fernández-Somoano A, Lertxundi A, Lertxundi N, Mendez MA, Tardón A, Vrijheid M. Prenatal exposure to residential air pollution and infant mental development: modulation by antioxidants and detoxification factors. Environ Health Perspect. 2012;12:144.

Source: PubMed

3
Předplatit