Epidemiologic methods for prospective assessment of menstrual cycle and reproductive characteristics in female semiconductor workers.

Methods were developed to assess potential adverse effects of semiconductor fabrication work in a prospective study of reproductive health. All women aged 18-44 years who worked in seven silicon-wafer fabrication sites in five companies and a frequency-matched sample of women in nonfabrication jobs were included. Among 3,480 selected for screening, 2,639 (75%) completed a self-administered questionnaire to identify women at risk of pregnancy. Among the 739 (28%) eligible women, 481 (65%) completed baseline interviews and 402 (83.6%) completed at least one menstrual cycle of follow-up by providing daily diaries and daily urine samples. Menstrual cycle characteristics were assessed from questionnaires and diaries. Urine samples were assayed for reproductive hormones to identify conceptions. The usual cycle length recalled at baseline was 28 days. The mean cycle length (MCL) recorded in diaries was 29 days, with greater dispersion than at baseline. The median of the MCL from diary data was 28 days for women reporting regular cycles at baseline but 34 days for women reporting irregular cycles at baseline, and the median standard deviation in cycle length per woman was 2.5 days and 7.5 days, respectively. The prospective method, while expensive and labor intensive, showed good compliance. Nevertheless, recall also provided reasonably accurate estimates and distinguished women with regular and irregular cycles.

Prospectively assessed menstrual cycle characteristics in female wafer-fabrication and nonfabrication semiconductor employees.

Women aged 18-44 years in silicon-wafer fabrication-room (fab) jobs and frequency-matched women in nonfab jobs were screened for a prospective study of reproductive health (n = 2,639). Among the 739 (28%) eligible women, 481 (65%) completed a baseline interview; 402 completed at least one menstrual cycle of follow-up with daily diaries and urinary assays to exclude conceptive cycles. Adjusted mean cycle lengths (MCL) did not differ between fab and nonfab women (p = 0.97). Women working in thin film and ion implantation (TFII) had the highest adjusted MCL (34.8 +/- 1.7 days) compared with nonfab workers (32.5 +/- 1.4 days, p = 0.07). Among women working exclusively in one group, TFII women had significantly higher MCL (36.1 +/- 2.04 days) than nonfab women (32.0 +/- 1.38 days, p = 0.017). TFII women were also more likely to have all cycles > 35 days (adjusted relative risk [RR] = 2.45; 95% CI = 0.85-6.06). Variability was assessed by logarithmic transformation of the mean standard deviation (MLSD) in cycle length per woman and adjusted for age and ethnicity (4.5 days for fab vs. 4.0 days for nonfab, p = 0.16). Women working exclusively in TFII or photolithography (PHOTO) had significantly higher adjusted MLSD in cycle length (6.68 +/- 1.28 and 5.72 +/- 1.24 days, respectively) than women in nonfab (4.1 +/- 1.16 days, p = 0.013 and 0.019, respectively). Fab and nonfab women did not differ significantly in mean days of bleeding or risk of having cycles > 35 or < 24 days. However, elevated risks of having cycles < 24 days were seen in supervisor engineers (adjusted RR = 2.46, 95% CI = 1.19-3.63) and PHOTO women (adjusted RR = 1.83, 95% CI = 0.94-2.88).

Prospective assessment of fecundability of female semiconductor workers.

To investigate a possible effect of reduced fecundability (probability of conception per menstrual cycle) among women who fabricate silicon wafers, 152 fabrication-room (fab) and 251 nonfab workers were followed for an average of five menstrual cycles. Daily urine samples were analyzed to confirm clinical spontaneous abortions (SABs) and early fetal losses (EFLs). Adjusted fecundability odds ratios (FRs) for fab workers ranged from 0.59 to 0.72 (p = 0.09-0.28 vs. nonfab). For clinical pregnancies only, the adjusted FR ranged from 0.43-0.50 (p = 0.04-0.09 vs. nonfab). This lower fecundability was most pronounced among dopants and thin-film workers [adjusted FR = 0.61, 95% confidence interval (CI) = 0.27-1.40 for all pregnancies; adjusted FR = 0.22, 95% CI = 0.05-0.96 for clinical pregnancies] and in workers exposed to ethylene-based glycol ethers (adjusted FR = 0.37, 95% CI = 0.11-1.19).

Prospective monitoring of early fetal loss and clinical spontaneous abortion among female semiconductor workers.

Women who work in silicon wafer fabrication rooms (fabs) have been reported to have an increased risk of spontaneous abortion (SAB). Although previous studies have included only clinically recognized SABs, more than two-thirds of SABs may be clinically unrecognized. To determine whether fab work is associated with SAB, we recruited 152 fab and 251 nonfab workers, who collected urine samples for a 6-month period. Samples were analyzed by immunoradiometric assay for the presence of human chorionic gonadotropin to detect early fetal losses. Approximately 63% of fab and 46% of nonfab pregnancies ended in SAB [adjusted relative risk (RR) = 1.25; 95% confidence interval (CI) = 0.63-1.76]. Similar RR were seen for women who worked in dopant and thin-film processes (adjusted RR = 1.30; 95% CI = 0.51-1.96) or in masking (adjusted RR = 1.30; 95% CI = 0.59-1.84). The four pregnancies among women who worked with ethylene-based glycol ethers ended in SAB.