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研究生:謝佳容
研究生(外文):Chia-Jung Hsieh
論文名稱:母親懷孕期間二手菸暴露對其小孩神經行為發展的基因修飾作用
論文名稱(外文):Gene Modification Effect of Prenatal Environmental Tobacco Smoke on Early Children''s Neurodevelopmental and Behavioral Problems
指導教授:陳保中陳保中引用關係
指導教授(外文):Pau-Chung Chen
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文出版年:2010
畢業學年度:99
語文別:中文
論文頁數:153
中文關鍵詞:基因多型性母親暴露二手菸臍帶血兒童神經發展行為發展
外文關鍵詞:genetic polymorphismsmaternal exposureenvironmental tobacco smokecord blood cotininechildrenneurodevelopmentbehavioral
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背景及目的:已有一些研究指出母親吸菸或二手菸的暴露對於兒童神經行為發展會造成影響,然而基因多型性對兒童健康的修飾作用卻不清楚。此本研究的目的為探討母親懷孕期間二手菸暴露所造成的兒童神經行為發展的基因多型性修飾作用。
方法:本研究對象為2004年4月到2005年1月參與台灣出生長期追蹤研究之孕婦及其嬰兒總計486對。我們在產前即將其納入研究對象,並以結構性問卷進行問卷訪視及收集產婦血液及尿液,生產時亦收集新生兒臍帶血,並進一步分離成血漿與DNA以利後續之暴露量測與基因分析。在出生後三天內以中文版神經行為評估量表由專業人員對新生兒進行評估;並於嬰兒2歲大時,使用嬰幼兒綜合發展測驗與兒童行為量表來評估兒童神經行為發展,並請家長或主要照顧者填寫家庭環境觀察評估量表來瞭解兒童生活家庭環境。臍帶血中可丁寧濃度是以高效能液相層析儀連結串聯質譜儀進行分析,儀器的偵測極限是0.05 ng/mL;此外並分析4個與菸中化學物質有關的代謝基因,包括CYP1A1 Ile462Val、CYP1A1 MspI、GSTT1及GSTM1。並以複迴歸來分析母親懷孕期間二手菸暴露對兒童神經行為發展的關係。
結果:研究的第一部份發現,在未考慮基因之下,母親懷孕期間二手菸暴露並未發現會對新生兒3天大的神經行為發展造成影響。但是考慮了新生兒本身的代謝基因後發現,母懷孕期間二手菸暴露加上新生兒本身是GSTM1 absent type,新生兒在原始反射的表現,特別是抓握及頸部張力明顯的表現較差。研究的第二部份發現,臍帶血中可丁寧濃度與兒童2歲的發展商數有明顯的負相關,包括對發展商數總分、認知、語言、細動作及社會能力都有影響。此外,二手菸暴露加上兒童GSTT1 absent type,對兒童2歲的認知及語言發展商數有更明顯的負相關。此外,二手菸暴露加上兒童GSTT1 absent type及CYP1A1 Ile462Val為變異型,對兒童2歲的發展總分及細動作發展商數有更明顯的負相關。研究的第三份發現,在未考慮基因的影響之下,母親懷孕期間的二手菸暴露即會造成兒童2歲的焦慮行為分數上升。此外,母親懷孕期間的二手菸暴露加上兒童CYP1A1 MspI及CYP1A1 Ile462Val為變異型,會使兒童行為問題總分、兒童內化行為及其次向面情緒分數、焦慮分數,及兒童外化問題及其次向面衝動分數有明顯的上升。
結論:我們的研究指出母親懷孕期間二手菸的暴露對於兒童早期神經行為發展具不良影響,而兒童代謝基因的變異或是缺失,會使影響更加顯著。

Background and Objectives: Maternal exposure to environmental tobacco smoke (ETS) has been reported to be associated with children’s neurobehavioral development but there was few studies investigating the genetic susceptibilities to maternal ETS exposure during pregnancy on children’s neurodevelopment. The potential health effect was still unclear. The aim of the study was to explore the modification effect of metabolic gene polymorphisms to cord blood cotinine on early children’s neurodevelopmental and behavioral problems at early childhood.
Methods: The study population was 486 mother-infant pairs who gave births in Taiwan between April 2004 and January 2005 from Taiwan Birth Panel Study. We interviewed them by a structured questionnaire before delivery, collected umbilical cord blood at birth. We followed them by using the Neonatal Neurobehavioral Examination in Chinese Version (NNE-C) after birth within three days and the Developmental Inventory for Infants and Toddlers (CDIIT) and Child Behavior Checklist (CBCL) at two years of age. Cotinine in umbilical cord blood as an indicator of environmental tobacco smoke was analyzed by using HPLC-MS/MS and the detection limited of this method was 0.05 ng/mL. Four metabolic genes, CYP1A1 MspI, CYP1A1 Ile462Val, GSTT1 and GSTM1 were identified. Multiple linear regression models were used to explore the effect of ETS exposure and gene interaction on early children’s neurodevelopmental and behavioral problems.
Results: The first part had shown that maternal ETS exposure during pregnancy was not related to neonatal neurobehavioral development at three days of age when not considering genetic polymorphisms. However, neonates with absent type of GSTM1 were shown adverse effects of ETS exposure on neonatal NNE-C total and primitive reflexes, especially in grasp reflex and tonic neck reflex. The second part had shown that cotinine levels in cord blood were significantly negatively associated with developmental quotients (DQs) of the whole test, and cognitive, language, fine-motor and social subtests of the CDIIT at two years of age. Lower cognitive and language DQs were found in ETS exposed group with absent type of GSTT1. In addition, the lowest scores in fine-motor and whole test DQs were detected in exposed group with CYP1A1 Ile462Val variant type and GSTT1 absent type. The third part had shown that maternal ETS exposure was associated with the anxious score at two years of age. The ETS-exposed group with both the CYP1A1 MspI and CYP1A1 Ile462Val variants had higher scores, as reflected in total CBCL score as well as scores on the internalizing scale and its emotional sub-domain, the anxious scale, and the externalizing scale and its aggressive sub-domain.
Conclusions: Our study shown that gene can modify the effect of maternal ETS exposure during pregnancy on early child neurobehavioral development. Poorer neonatal neurobehavioral development in neonates with absent type GSTM1 was related to maternal ETS exposure during pregnancy. The likely delayed effects of fetal ETS exposure on the child health were also shown in our study. The CYP1A1 Ile462Val and GSTT1 metabolic genes can modify the effect of cord blood cotinine on child neurodevelopment at two year of age especially for language and fine motor development. Furthermore, our results also supported that prenatal ETS exposure may be associated with adverse behavioral development in early childhood, and that this relationship may be modified by CYP1A1 MspI and CYP1A1 Ile462Val metabolic gene polymorphisms.

中文摘要................................................ I
Abstract...............................................III
Table of Contents.......................................VI
List of Tables........................................VIII
List of Figures..........................................X
Chapter 1. The Taiwan Birth Panel Study..................1
1.1 How did the study come about?........................1
1.2 What does it cover?..................................2
1.3 Who is in the sample? ...............................3
1.4 How often have they been followed up?................3
1.5 What has been measured?..............................4
1.6 What has it found? Key findings and publications ....7
1.7 References...........................................8

Chapter 2. Literature Review of the ETS Exposure on Early Child Neurodevelopment...................................15
2.1 Background............................................15
2.2 The Prevalence of Smoking.............................15
2.3 Components of Tobacco Smoke and ETS Exposure, and The Exposure Marker ..........................................16
2.4 Mechanisms ...........................................17
2.5 Children neurodevelopment performance.................18
2.6 Children behavioral problems..........................19
2.7 Metabolic gene polymorphisms..........................20
2.8 References............................................23

Chapter 3. Maternal ETS Exposure and Neonatal Neurodevelopment at Age Three Days........................34
3.1 Introduction..........................................34
3.2 Methods...............................................36
3.3 Results...............................................40
3.4 Discussion............................................42
3.5 Conclusions...........................................46
3.6 References............................................47

Chapter 4. Maternal ETS Exposure and Child Neurodevelopment at Age 2 Years...........................................58
4.1 Introduction.........................................58
4.2 Methods..............................................60
4.3 Results..............................................66
4.4 Discussion...........................................68
4.5 Conclusions..........................................74
4.6 References...........................................75

Chapter 5. Maternal ETS Exposure and Child Behavioral Problems at Age 2 Years...................................89
5.1 Introduction.........................................89
5.2 Methods..............................................90
5.3 Results..............................................98
5.4 Discussion..........................................103
5.5 Conclusions.........................................110
5.6 References......................................... 111

Appendix...............................................127
Appendix A. Bibliography of My Work-PhD Thesis.........127
Appendix B. Bibliography of My Work-Coauthors..........129
Appendix C. Published Papers...........................136
Appendix D. Paper Under Review.........................153
Appendix E: Paper in Preparation.......................154

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Chapter 3
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8.Stroud LR, Paster RL, Papandonatos GD, Niaura R, Salisbury AL, Battle C, et al. Maternal smoking during pregnancy and newborn neurobehavior: effects at 10 to 27 days. J Pediatr. 2009;154(1):10-16.
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10.Wang X, Zuckerman B, Pearson C, Kaufman G, Chen C, Wang G, et al. Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight. JAMA. 2002;287(2):195-202.
11.Hong YC, Lee KH, Son BK, Ha EH, Moon HS, Ha M. Effects of the GSTM1 and GSTT1 polymorphisms on the relationship between maternal exposure to environmental tobacco smoke and neonatal birth weight. J Occup Environ Med. 2003;45(5):492-498.
12.Wu T, Hu Y, Chen C, Yang F, Li Z, Fang Z, et al. Passive smoking, metabolic gene polymorphisms, and infant birth weight in a prospective cohort study of Chinese women. Am J Epidemiol. 2007;166(3):313-322.
13.Morales E, Sunyer J, Julvez J, Castro-Giner F, Estivill X, Torrent M, et al. GSTM1 polymorphisms modify the effect of maternal smoking during pregnancy on cognitive functioning in preschoolers. Int J Epidemiol. 2009;38(3):690-697.
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15.Jeng SF, Tsao CC, Chen LC, Teng RJ, Yau KI, Jan MH. Reliability of the Neonatal Neurobehavioral Examination--Chinese version. Early Hum Dev. 1996;45(3):191-202.
16.Jeng SF, Yau KI, Teng RJ. Neurobehavioral development at term in very low-birthweight infants and normal term infants in Taiwan. Early Hum Dev. 1998;51(3):235-245.
17.Harth V, Bruning T, Abel J, Koch B, Berg I, Sachinidis A, et al. Real-time genotyping of cytochrome P4501A1 A4889G and T6235C polymorphisms. Mol Cell Probes. 2001;15(2):93-97.
18.Comstock KE, Sanderson BJ, Claflin G, Henner WD. GST1 gene deletion determined by polymerase chain reaction. Nucleic Acids Res. 1990;18(12):3670.
19.Pirkle JL, Flegal KM, Bernert JT, Brody DJ, Etzel RA, Maurer KR. Exposure of the US population to environmental tobacco smoke: the Third National Health and Nutrition Examination Survey, 1988 to 1991. JAMA. 1996;275(16):1233-1240.
20.Ajarem JS, Ahmad M. Prenatal nicotine exposure modifies behavior of mice through early development. Pharmacol Biochem Behav. 1998;59(2):313-318.
21.Slotkin TA. Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates. Toxicol Appl Pharmacol. 2004;198(2):132-151.
22.Suzuki K, Minei LJ, Johnson EE. Effect of nicotine upon uterine blood flow in the pregnant rhesus monkey. Am J Obstet Gynecol. 1980;136(8):1009-1013.
23.Andersen HR, Nielsen JB, Grandjean P. Toxicologic evidence of developmental neurotoxicity of environmental chemicals. Toxicology. 2000;144(1-3):121-127.
24.Sasaki S, Kondo T, Sata F, Saijo Y, Katoh S, Nakajima S, et al. Maternal smoking during pregnancy and genetic polymorphisms in the Ah receptor, CYP1A1 and GSTM1 affect infant birth size in Japanese subjects. Mol Hum Reprod. 2006;12(2):77-83.
25.Infante-Rivard C, Weinberg CR, Guiguet M. Xenobiotic-metabolizing genes and small-for-gestational-age births: interaction with maternal smoking. Epidemiology. 2006;17(1):38-46.
26.Fustinoni S, Soleo L, Warholm M, Begemann P, Rannug A, Neumann HG, et al. Influence of metabolic genotypes on biomarkers of exposure to 1,3-butadiene in humans. Cancer Epidemiol Biomarkers Prev. 2002;11(10 Pt 1):1082-1090.
27.Dejmek J, Solansky I, Benes I, Lenicek J, Sram RJ. The impact of polycyclic aromatic hydrocarbons and fine particles on pregnancy outcome. Environ Health Perspect. 2000;108(12):1159-1164.
28.Nicol CJ, Harrison ML, Laposa RR, Gimelshtein IL, Wells PG. A teratologic suppressor role for p53 in benzo[a]pyrene-treated transgenic p53-deficient mice. Nat Genet. 1995;10(2):181-187.
29.Farah MJ, Shera DM, Savage JH, Betancourt L, Giannetta JM, Brodsky NL, et al. Childhood poverty: specific associations with neurocognitive development. Brain Res. 2006;1110(1):166-174.
30.Benowitz NL. Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev. 1996;18(2):188-204.
31.Wu FY, Chiu HT, Wu HD, Lin CJ, Lai JS, Kuo HW. Comparison of urinary and plasma cotinine levels during the three trimesters of pregnancy. Paediatr Perinat Epidemiol. 2008;22(3):296-301.
32.Wang IJ, Hsieh WS, Wu KY, Guo YL, Hwang YH, Jee SH, et al. Effect of gestational smoke exposure on atopic dermatitis in the offspring. Pediatr Allergy Immunol. 2008;19(7):580-586.

Chapter 4

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15.Key AP, Ferguson M, Molfese DL, Peach K, Lehman C, Molfese VJ. Smoking during pregnancy affects speech-processing ability in newborn infants. Environ Health Perspect 2007 Apr;115(4): 623-9.
16.Law KL, Stroud LR, LaGasse LL, Niaura R, Liu J, Lester BM. Smoking during pregnancy and newborn neurobehavior. Pediatrics 2003 Jun;111(6 Pt 1): 1318-23.
17.Orlebeke JF, Knol DL, Verhulst FC. Child behavior problems increased by maternal smoking during pregnancy. Archives of environmental health 1999 Jan-Feb;54(1): 15-9.
18.Rauh VA, Whyatt RM, Garfinkel R, et al. Developmental effects of exposure to environmental tobacco smoke and material hardship among inner-city children. Neurotoxicol Teratol 2004 May-Jun;26(3): 373-85.
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20.Eskenazi B, Castorina R. Association of prenatal maternal or postnatal child environmental tobacco smoke exposure and neurodevelopmental and behavioral problems in children. Environ Health Perspect 1999 Dec;107(12): 991-1000.
21.Infante-Rivard C, Weinberg CR, Guiguet M. Xenobiotic-metabolizing genes and small-for-gestational-age births: interaction with maternal smoking. Epidemiology 2006 Jan;17(1): 38-46.
22.Sasaki S, Kondo T, Sata F, et al. Maternal smoking during pregnancy and genetic polymorphisms in the Ah receptor, CYP1A1 and GSTM1 affect infant birth size in Japanese subjects. Mol Hum Reprod 2006 Feb;12(2): 77-83.
23.Wang X, Zuckerman B, Pearson C, et al. Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight. Jama 2002 Jan 9;287(2): 195-202.
24.Hong YC, Lee KH, Son BK, Ha EH, Moon HS, Ha M. Effects of the GSTM1 and GSTT1 polymorphisms on the relationship between maternal exposure to environmental tobacco smoke and neonatal birth weight. J Occup Environ Med 2003 May;45(5): 492-8.
25.Wu T, Hu Y, Chen C, et al. Passive smoking, metabolic gene polymorphisms, and infant birth weight in a prospective cohort study of Chinese women. Am J Epidemiol 2007 Aug 1;166(3): 313-22.
26.Su FC, Lee MC, Hsieh WS, et al. The Effect of Prenatal and Postnatal Environmental Tobacco Smoke Exposure on Infant Health. Taiwan Journal of Public Health 2007;26: 472-81.
27.Pirkle JL, Flegal KM, Bernert JT, Brody DJ, Etzel RA, Maurer KR. Exposure of the US population to environmental tobacco smoke: the Third National Health and Nutrition Examination Survey, 1988 to 1991. Jama 1996 Apr 24;275(16): 1233-40.
28.Harth V, Bruning T, Abel J, et al. Real-time genotyping of cytochrome P4501A1 A4889G and T6235C polymorphisms. Mol Cell Probes 2001 Apr;15(2): 93-7.
29.Comstock KE, Sanderson BJ, Claflin G, Henner WD. GST1 gene deletion determined by polymerase chain reaction. Nucleic acids research 1990 Jun 25;18(12): 3670.
30.Pemble S, Schroeder KR, Spencer SR, et al. Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 1994 May 15;300 ( Pt 1): 271-6.
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32.Liao HF, Wang TM, Yao G, Lee WT. Concurrent validity of the Comprehensive Developmental Inventory for Infants and Toddlers with the Bayley Scales of Infant Development-II in preterm infants. J Formos Med Assoc 2005 Oct;104(10): 731-7.
33.Liao HF, Pan YL. Test-retest and inter-rater reliability for the Comprehensive Developmental Inventory for Infants and Toddlers diagnostic and screening tests. Early Hum Dev 2005 Nov;81(11): 927-37.
34.Cadwell BM, Bradley RH. Home Observation for Measurement of the Environment. Little Rock, AR: University of Arkansas Press; 1979.
35.Fung YK, Lau YS. Receptor mechanisms of nicotine-induced locomotor hyperactivity in chronic nicotine-treated rats. Eur J Pharmacol 1988 Aug 2;152(3): 263-71.
36.Levin ED, Briggs SJ, Christopher NC, Rose JE. Prenatal nicotine exposure and cognitive performance in rats. Neurotoxicol Teratol 1993 Jul-Aug;15(4): 251-60.
37.Golub MS, Slotkin TA, Tarantal AF, Pinkerton KE. Visual recognition memory and auditory brainstem response in infant rhesus monkeys exposed perinatally to environmental tobacco smoke. Brain Res 2007 Jun 2;1151: 102-6.
38.Lackmann GM, Salzberger U, Tollner U, Chen M, Carmella SG, Hecht SS. Metabolites of a tobacco-specific carcinogen in urine from newborns. J Natl Cancer Inst 1999 Mar 3;91(5): 459-65.
39.Slotkin TA. Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates. Toxicol Appl Pharmacol 2004 Jul 15;198(2): 132-51.
40.Roy TS, Sabherwal U. Effects of prenatal nicotine exposure on the morphogenesis of somatosensory cortex. Neurotoxicol Teratol 1994 Jul-Aug;16(4): 411-21.
41.Suzuki K, Minei LJ, Johnson EE. Effect of nicotine upon uterine blood flow in the pregnant rhesus monkey. Am J Obstet Gynecol 1980 Apr 15;136(8): 1009-13.
42.Dejmek J, Solansky I, Benes I, Lenicek J, Sram RJ. The impact of polycyclic aromatic hydrocarbons and fine particles on pregnancy outcome. Environ Health Perspect 2000 Dec;108(12): 1159-64.
43.Manchester DK, Gordon SK, Golas CL, Roberts EA, Okey AB. Ah receptor in human placenta: stabilization by molybdate and characterization of binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methylcholanthrene, and benzo(a)pyrene. Cancer Res 1987 Sep 15;47(18): 4861-8.
44.Perera FP, Rauh V, Whyatt RM, et al. Molecular evidence of an interaction between prenatal environmental exposures and birth outcomes in a multiethnic population. Environ Health Perspect 2004 Apr;112(5): 626-30.
45.Anttila S, Tuominen P, Hirvonen A, et al. CYP1A1 levels in lung tissue of tobacco smokers and polymorphisms of CYP1A1 and aromatic hydrocarbon receptor. Pharmacogenetics 2001 Aug;11(6): 501-9.
46.Hayes JD, Strange RC. Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 2000 Sep;61(3): 154-66.
47.Fustinoni S, Soleo L, Warholm M, et al. Influence of metabolic genotypes on biomarkers of exposure to 1,3-butadiene in humans. Cancer Epidemiol Biomarkers Prev 2002 Oct;11(10 Pt 1): 1082-90.
48.Chang TW, Wang SM, Guo YL, Tsai PC, Huang CJ, Huang W. Glutathione S-transferase polymorphisms associated with risk of breast cancer in southern Taiwan. Breast 2006 Dec;15(6): 754-61.
49.Benowitz NL. Biomarkers of environmental tobacco smoke exposure. Environ Health Perspect 1999 May;107 Suppl 2: 349-55.
50.Benowitz NL. Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev 1996;18(2): 188-204.
51.Nafstad P, Kongerud J, Botten G, et al. Fetal exposure to tobacco smoke products: a comparison between self-reported maternal smoking and concentrations of cotinine and thiocyanate in cord serum. Acta Obstet Gynecol Scand 1996 Nov;75(10): 902-7.
52.Pichini S, Basagana XB, Pacifici R, et al. Cord serum cotinine as a biomarker of fetal exposure to cigarette smoke at the end of pregnancy. Environ Health Perspect 2000 Nov;108(11): 1079-83.
53.Benowitz NL, Jacob P, 3rd. Metabolism of nicotine to cotinine studied by a dual stable isotope method. Clinical pharmacology and therapeutics 1994 Nov;56(5): 483-93.
54.Johnson DL, Swank PR, Baldwin CD, McCormick D. Adult smoking in the home environment and children''s IQ. Psychol Rep 1999 Feb;84(1): 149-54.
55.Bauman KE, Flewelling RL, LaPrelle J. Parental cigarette smoking and cognitive performance of children. Health Psychol 1991;10(4): 282-8.
56.Yolton K, Dietrich K, Auinger P, Lanphear BP, Hornung R. Exposure to environmental tobacco smoke and cognitive abilities among U.S. children and adolescents. Environ Health Perspect 2005 Jan;113(1): 98-103.
57.Weitzman M, Byrd RS, Aligne CA, Moss M. The effects of tobacco exposure on children''s behavioral and cognitive functioning: implications for clinical and public health policy and future research. Neurotoxicol Teratol 2002 May-Jun;24(3): 397-406.
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59.Wood D. Effect of child and family poverty on child health in the United States. Pediatrics 2003;112(3 Part 2): 707-11.

Chapter 5

1.Stroud LR, Paster RL, Papandonatos GD, et al. Maternal smoking during pregnancy and newborn neurobehavior: effects at 10 to 27 days. J Pediatr 2009 Jan;154(1): 10-6.
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4.Leonardi-Bee J, Smyth A, Britton J, Coleman T. Environmental tobacco smoke and fetal health: systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2008 Sep;93(5): F351-61.
5.Eskenazi B, Castorina R. Association of prenatal maternal or postnatal child environmental tobacco smoke exposure and neurodevelopmental and behavioral problems in children. Environmental Health Perspectives 1999 Dec;107(12): 991-1000.
6.Ernst M, Moolchan ET, Robinson ML. Behavioral and neural consequences of prenatal exposure to nicotine. J Am Acad Child Adolesc Psychiatry 2001 Jun;40(6): 630-41.
7.Ashford J, van Lier PA, Timmermans M, Cuijpers P, Koot HM. Prenatal smoking and internalizing and externalizing problems in children studied from childhood to late adolescence. J Am Acad Child Adolesc Psychiatry 2008 Jul;47(7): 779-87.
8.Carter S, Paterson J, Gao W, Iusitini L. Maternal smoking during pregnancy and behaviour problems in a birth cohort of 2-year-old Pacific children in New Zealand. Early Human Development 2008 Jan;84(1): 59-66.
9.Gatzke-Kopp LM, Beauchaine TP. Direct and passive prenatal nicotine exposure and the development of externalizing psychopathology. Child Psychiatry Hum Dev 2007 Dec;38(4): 255-69.
10.Mansi G, Raimondi F, Pichini S, et al. Neonatal urinary cotinine correlates with behavioral alterations in newborns prenatally exposed to tobacco smoke. Pediatr Res 2007 Feb;61(2): 257-61.
11.Grandjean P. [Effect of industrial chemicals on development of the nerve system--secondary publication]. Ugeskr Laeger 2007 Aug 20;169(34): 2782-4.
12.Wang X, Zuckerman B, Pearson C, et al. Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight. Jama 2002 Jan 9;287(2): 195-202.
13.Sasaki S, Kondo T, Sata F, et al. Maternal smoking during pregnancy and genetic polymorphisms in the Ah receptor, CYP1A1 and GSTM1 affect infant birth size in Japanese subjects. Molecular Human Reproduction 2006 Feb;12(2): 77-83.
14.Hsieh CJ, Liao HF, Wu KY, et al. CYP1A1 Ile462Val and GSTT1 modify the effect of cord blood cotinine on neurodevelopment at 2 years of age. Neurotoxicology 2008 Sep;29(5): 839-45.
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24.Orlebeke JF, Knol DL, Verhulst FC. Child behavior problems increased by maternal smoking during pregnancy. Archives of environmental health 1999 Jan-Feb;54(1): 15-9.
25.Stene-Larsen K, Borge AI, Vollrath ME. Maternal smoking in pregnancy and externalizing behavior in 18-month-old children: results from a population-based prospective study. J Am Acad Child Adolesc Psychiatry 2009 Mar;48(3): 283-9.
26.Ruckinger S, Rzehak P, Chen CM, et al. Prenatal and Postnatal Tobacco Exposure and Behavioral Problems in 10-Year-Old Children: Results from the GINI-plus Prospective Birth Cohort Study. Environ Health Perspect 2010 Jan;118(1): 150-4.
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28.Andersen HR, Nielsen JB, Grandjean P. Toxicologic evidence of developmental neurotoxicity of environmental chemicals. Toxicology 2000 Apr 3;144(1-3): 121-7.
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30.Paus T. Primate anterior cingulate cortex: where motor control, drive and cognition interface. Nat Rev Neurosci 2001 Jun;2(6): 417-24.
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33.Anttila S, Tuominen P, Hirvonen A, et al. CYP1A1 levels in lung tissue of tobacco smokers and polymorphisms of CYP1A1 and aromatic hydrocarbon receptor. Pharmacogenetics 2001 Aug;11(6): 501-9.
34.Fustinoni S, Soleo L, Warholm M, et al. Influence of metabolic genotypes on biomarkers of exposure to 1,3-butadiene in humans. Cancer Epidemiol Biomarkers Prev 2002 Oct;11(10 Pt 1): 1082-90.
35.Hong YC, Lee KH, Son BK, Ha EH, Moon HS, Ha M. Effects of the GSTM1 and GSTT1 polymorphisms on the relationship between maternal exposure to environmental tobacco smoke and neonatal birth weight. Journal of Occupational & Environmental Medicine 2003 May;45(5): 492-8.
36.Infante-Rivard C, Weinberg CR, Guiguet M. Xenobiotic-metabolizing genes and small-for-gestational-age births: interaction with maternal smoking. Epidemiology 2006 Jan;17(1): 38-46.
37.Nukui T, Day RD, Sims CS, Ness RB, Romkes M. Maternal/newborn GSTT1 null genotype contributes to risk of preterm, low birthweight infants. Pharmacogenetics 2004 Sep;14(9): 569-76.
38.Wu T, Hu Y, Chen C, et al. Passive smoking, metabolic gene polymorphisms, and infant birth weight in a prospective cohort study of Chinese women. American Journal of Epidemiology 2007 Aug 1;166(3): 313-22.
39.Chen D, Hu Y, Yang F, et al. Cytochrome P450 gene polymorphisms and risk of low birth weight. Genet Epidemiol 2005 May;28(4): 368-75.
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41.Chiu HT, Isaac Wu HD, Kuo HW. The relationship between self-reported tobacco exposure and cotinines in urine and blood for pregnant women. Sci Total Environ 2008 Nov 15;406(1-2): 331-6.
42.Wu FY, Chiu HT, Wu HD, Lin CJ, Lai JS, Kuo HW. Comparison of urinary and plasma cotinine levels during the three trimesters of pregnancy. Paediatr Perinat Epidemiol 2008 May;22(3): 296-301.
43.Thapar A, Harold G, Rice F, Langley K, O''Donovan M. The contribution of gene-environment interaction to psychopathology. Dev Psychopathol 2007 Fall;19(4): 989-1004.

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