1. Lead Exposure and Sex Ratio 2. Female Lead Exposure and Fertility

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 4