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研究生:林虔睦
研究生(外文):Chien-Muh Lin
論文名稱:一、鉛暴露與性別比二、女性鉛暴露與生育能力
論文名稱(外文):1. Lead Exposure and Sex Ratio2. Female Lead Exposure and Fertility
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:碩士
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
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:英文
論文頁數:55
中文關鍵詞:生育力職業暴露性別比
外文關鍵詞:fertilityleadoccupational exposuresex ratio
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Part I. Lead Exposure and Sex Ratio
Objectives: We used blood lead concentrations (PbBs) to investigate whether exposure to lead at work could influence the sex ratio of offspring.

Methods: The study population consisted of two occupational cohorts—the lead workers identified from occupational blood lead notification database established since July 1993, and those in a battery plant in Taiwan. For the lead workers identified from notification database, we included births whose parental PbBs had to be examined during pregnancy or spermatogenesis prior to conception, or in one year before these two periods. We examined the gender of the children born to the lead workers identified from notification database via linking to Taiwan birth registration database, and that of the battery plant workers’ pregnancies from questionnaires obtained via face-to-face interviews.

Results: There were total 1,637 eligible livebirths born to the lead workers identified from notification database. The sex ratio of offspring born to male (0.98) and female (1.16) lead workers did not differ significantly from the Taiwan population (1.09) and there was no dose-response effect. Even when the both parental PbBs had relatively highly PbBs (³30 mg/dl), the sex ratio did not decline. Among the total 123 reported pregnancies born to the male battery workers, the sex ratio (1.19) was not significantly different from the Taiwan population (1.09). The sex ratio of pregnancies conceived after their fathers’ employment in the battery plant was 1.18, similar to those conceived before (1.22). We found no evidence that the sex ratio decreased with the higher PbBs or time-integrated blood lead concentration. Similar results were found among the pregnancies reported by female workers.

Conclusions: We found no evidence that maternal, paternal or both parental exposure to lead at work can reduce the sex ratio of children.

Part II. Female Lead Exposure and Fertility
Objectives: There is some concern about the association between maternal lead exposure and decreased fertility, but the evidence is limited. The aim of our study was to investigate whether female exposure to lead at work could influence their fertility using time to pregnancy (TTP) and whether the long-term exposure affected the fertility more.

Methods: The study population consisted of 270 female workers ever employed at a lead battery plant in Taiwan from 1987 to November 1998. We obtained TTP and potential confounders from questionnaires by face-to-face interviews. There were total eligible 199 female lead workers with 588 valid pregnancies. Annual records of blood lead concentrations since 1987 to 1997 were acquired from the employer. The fecundability ratios (FRs) were calculated with both the Cox discrete proportional hazard regression model and generalized linear regression model to evaluate the effects of lead exposure.

Results: We found no association between maternal lead exposure and fertility after the potential confounders related to TTP were controlled. The adjusted FRs were 1.00 (95%CI, 0.64-1.63) and 1.17 (0.66-2.08) for concurrent blood lead levels of <30 and ³30mg/dl. Paired self comparison was also performed for 15 couples that had one pregnancy before employment and the next one after lead exposure. There was no TTP prolongation with the increased blood lead. We also found no significant FR decrease with duration of employment more than three years relative to duration less than three years in either of the two blood lead categories.

Conclusions: The data do not support neither of the two hypotheses that female exposure to lead at work is related to decreased fertility and female long-term lead exposure may cause decreased fertility more than short-term exposure in human beings under the condition of similar blood lead level.
Part I . Lead Exposure and Sex Ratio 1
Abstract 2
Introduction 3
Materials and Methods 4
Occupational blood lead notification database 4
The lead workers in a lead battery plant in Taiwan 4
Statistical analysis 5
Results 7
Discussion 9
References 12
Tables and Figures 14
Table 1. Observed sex ratio and relative odds of a boy (OR) among livebirths, born 1993-1997, of the lead workers identified by occupational blood lead notification. 14
Table 2. Observed sex ratio and relative odds of a boy (OR) among all livebirths, born 1993-1997, of the lead workers identified by occupational blood lead notification, in whom either or both of their parents had relatively high PbB. 15
Table 3. Observed sex ratio and relative odds of a boy (OR) among births, born 1987-1998, of the lead workers in a lead battery plant in Taiwan. 16
Figure 1. Selection of study population in the battery plant. Numbers in parentheses indicate numbers of pregnancies.. 17




Part II Female Lead Exposure and Fertility 18
Abstract 19
Introduction 20
Materials and Methods 21
Study design 21
Study population 21
Exposure assessment 21
Questionnaires 22
Statistical analysis 22
Results 24
Discussion 25
References 28
Tables and Figures 30
Table 1. Pregnancy outcomes by blood lead levels in the year when TTP started 30
Table 2. Distribution of TTP and potential confounders by blood lead level in the year when TTP started. 31
Table 3. Crude fecundability ratios according to lead exposure and potential confounders; univariate Cox discrete proportional hazard models 32
Table 4. Adjusted fecundability ratio according to lead exposure and confounders; multivariable Cox discrete proportional hazard models 33
Figure 1. Selection of study population. Numbers in parentheses indicate numbers of pregnancies. 34
Figure 2. The relation between TTP difference and blood lead levels in women. Solid line represents the linear regression and the number indicates methods of birth control in the later pregnancy (1, none; 2, safe period; 3, condom; 4, intrauterine device; 5, oral contraceptives). 35

Part III Appendix 36
Appendix A. Literature review 37
Appendix B. Certificate of birth 46
Appendix C. Questionnaire used in the lead battery plant 47
Part I.
1. James WH. Evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels at the time of conception. J Theor Biol 1996; 180(4):271-286.
2. Mocarelli P, Gerthoux PM, Ferrari E, Patterson DG, Jr., Kieszak SM, Brambilla P et al. Paternal concentrations of dioxin and sex ratio of offspring. Lancet 2000; 355(9218):1858-1863.
3. del RG, I, Marshall T, Tsai P, Shao YS, Guo YL. Number of boys born to men exposed to polychlorinated byphenyls. Lancet 2002; 360(9327):143-144.
4. Rogan WJ, Gladen BC, Guo YL, Hsu CC. Sex ratio after exposure to dioxin-like chemicals in Taiwan. Lancet 1999; 353(9148):206-207.
5. Saadat M, Ansari-Lari M, Bahaoddini A. Sex ratio at birth in Masjid-i-Sulaiman (Khozestan province, Iran). Occup Environ Med 2002; 59(12):853.
6. Fukuda M, Fukuda K, Shimizu T, Moller H. Decline in sex ratio at birth after Kobe earthquake. Hum Reprod 1998; 13(8):2321-2322.
7. Fukuda M, Fukuda K, Shimizu T, Andersen CY, Byskov AG. Parental periconceptional smoking and male: female ratio of newborn infants. Lancet 2002; 359(9315):1407-1408.
8. Dickinson H, Parker L. Do alcohol and lead change the sex ratio? J Theor Biol 1994; 169(3):313-315.
9. Maconochie N, Roman E, Doyle P, Davies G, Smith PG, Beral V. Sex ratio of nuclear industry employees'' children. Lancet 2001; 357(9268):1589-1591.
10. Saadat M. No change in sex ratio in Ramsar (north of Iran) with high background of radiation. Occup Environ Med 2003; 60(2):146-147.
11. Winther JF, Boice JD, Jr., Thomsen BL, Schull WJ, Stovall M, Olsen JH. Sex ratio among offspring of childhood cancer survivors treated with radiotherapy. Br J Cancer 2003; 88(3):382-387.
12. Wilcox AJ, Weinberg CR, Baird DD. Timing of sexual intercourse in relation to ovulation. Effects on the probability of conception, survival of the pregnancy, and sex of the baby. N Engl J Med 1995; 333(23):1517-1521.
13. Irgens A, Kruger K, Skorve AH, Irgens LM. Reproductive outcome in offspring of parents occupationally exposed to lead in Norway. American Journal of Industrial Medicine 1998; 34(5):431-437.
14. Needleman HL, Rabinowitz M, Leviton A, Linn S, Schoenbaum S. The relationship between prenatal exposure to lead and congenital anomalies. JAMA 1984; 251(22):2956-2959.
15. Liou SH, Yang GY, Wu TN, Ko YC, Lee CC, Ho ST et al. Assessment of interlaboratory performance on the measurement of blood lead levels in Taiwanese adults. Ind Health 1995; 33(4):181-190.
16. Wu TN, Shen CY, Liou SH, Yang GY, Ko KN, Chao SL et al. The epidemiology and surveillance of blood lead in Taiwan (ROC): a report on the PRESS-BLL project. Int Arch Occup Environ Health 1997; 69(6):386-391.
17. HELLER CG, CLERMONT Y. Spermatogenesis in man: an estimate of its duration. Science 1963; 140:184-186.
18. Roels H, Konings J, Green S, Bradley D, Chettle D, Lauwerys R. Time-integrated blood lead concentration is a valid surrogate for estimating the cumulative lead dose assessed by tibial lead measurement. Environ Res 1995; 69(2):75-82.
19. Pan IJ, Wang JD, Chen PC. Parental exposure to lead and small for gestational age [accepted]. Am J Ind Med 2005.
20. Mocarelli P, Gerthoux PM, Ferrari E, Patterson DG, Jr., Kieszak SM, Brambilla P et al. Paternal concentrations of dioxin and sex ratio of offspring. Lancet 2000; 355(9218):1858-1863.
21. del RG, I, Marshall T, Tsai P, Shao YS, Guo YL. Number of boys born to men exposed to polychlorinated byphenyls. Lancet 2002; 360(9327):143-144.
22. Kelada SN, Shelton E, Kaufmann RB, Khoury MJ. Delta-aminolevulinic acid dehydratase genotype and lead toxicity: a HuGE review. Am J Epidemiol 2001; 154(1):1-13.

Part II. Female Lead Exposure and Fertility
1. Hertz-Picciotto I. The evidence that lead increases the risk for spontaneous abortion. [Review] [33 refs]. American Journal of Industrial Medicine 38(3):300-9, 2000.
2. Irgens A, Kruger K, Skorve AH, Irgens LM. Reproductive outcome in offspring of parents occupationally exposed to lead in Norway. American Journal of Industrial Medicine 1998; 34(5):431-437.
3. Andrews KW, Savitz DA, Hertz-Picciotto I. Prenatal lead exposure in relation to gestational age and birth weight: a review of epidemiologic studies. American Journal of Industrial Medicine 26(1):13-32, 1994.
4. Needleman HL, Rabinowitz M, Leviton A, Linn S, Schoenbaum S. The relationship between prenatal exposure to lead and congenital anomalies. JAMA 1984; 251(22):2956-2959.
5. Sallmen M, Anttila A, Lindbohm ML, Kyyronen P, Taskinen H, Hemminki K. Time to pregnancy among women occupationally exposed to lead. J Occup Environ Med 1995; 37(8):931-934.
6. Ronis MJ, Badger TM, Shema SJ, Roberson PK, Shaikh F. Reproductive toxicity and growth effects in rats exposed to lead at different periods during development. Toxicol Appl Pharmacol 1996; 136(2):361-371.
7. Borman SM, Christian PJ, Sipes IG, Hoyer PB. Ovotoxicity in female Fischer rats and B6 mice induced by low-dose exposure to three polycyclic aromatic hydrocarbons: comparison through calculation of an ovotoxic index. Toxicol Appl Pharmacol 2000; 167(3):191-198.
8. Mattison DR, Thorgeirsson SS. Ovarian aryl hydrocarbon hydroxylase activity and primordial oocyte toxicity of polycyclic aromatic hydrocarbons in mice. Cancer Res 1979; 39(9):3471-3475.
9. Liou SH, Yang GY, Wu TN, Ko YC, Lee CC, Ho ST et al. Assessment of interlaboratory performance on the measurement of blood lead levels in Taiwanese adults. Ind Health 1995; 33(4):181-190.
10. Roels H, Konings J, Green S, Bradley D, Chettle D, Lauwerys R. Time-integrated blood lead concentration is a valid surrogate for estimating the cumulative lead dose assessed by tibial lead measurement. Environ Res 1995; 69(2):75-82.
11. Scheike TH, Jensen TK. A discrete survival model with random effects: an application to time to pregnancy. Biometrics 1997; 53(1):318-329.
12. Baird DD, Wilcox AJ, Weinberg CR. Use of time to pregnancy to study environmental exposures. Am J Epidemiol 1986; 124(3):470-480.
13. Baird DD, Weinberg CR, Rowland AS. Reporting errors in time-to-pregnancy data collected with a short questionnaire. Impact on power and estimation of fecundability ratios. Am J Epidemiol 1991; 133(12):1282-1290.
14. Joffe M, Villard L, Li Z, Plowman R, Vessey M. Long-term recall of time-to-pregnancy. Fertil Steril 1993; 60(1):99-104.
15. Chen PC, Hsieh GY, Wang JD, Cheng TJ. Prolonged time to pregnancy in female workers exposed to ethylene glycol ethers in semiconductor manufacturing. Epidemiology 2002; 13(2):191-196.
16. Shiau CY, Wang JD, Chen PC. Decreased fecundity among male lead workers. Occup Environ Med 2004; 61(11):915-923.
17. Weinberg CR, Baird DD, Wilcox AJ. Sources of bias in studies of time to pregnancy. Stat Med 1994; 13(5-7):671-681.
18. Liu J, Larsen U, Wyshak G. Prevalence of primary infertility in China: in-depth analysis of infertility differentials in three minority province/autonomous regions. J Biosoc Sci 2005; 37(1):55-74.
19. Larsen U. Primary and secondary infertility in sub-Saharan Africa. Int J Epidemiol 2000; 29(2):285-291.
20. Doyle P, Roman E, Maconochie N, Davies G, Smith PG, Beral V. Primary infertility in nuclear industry employees: report from the nuclear industry family study. Occup Environ Med 2001; 58(8):535-539.
21. Wyshak G. Infertility in American college alumnae. Int J Gynaecol Obstet 2001; 73(3):237-242.
22. Axmon A, Rylander L, Stromberg U, Dyremark E, Hagmar L. Polychlorinated biphenyls in blood plasma among Swedish female fish consumers in relation to time to pregnancy. J Toxicol Environ Health A 2001; 64(6):485-498.
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