Objective-We investigated self-reported occupational exposure to antineoplastic drugs, anesthetic gases, antiviral drugs, sterilizing agents (disinfectants), and X-rays and the risk of spontaneous abortion in U.S. nurses.Study Design-Pregnancy outcome and occupational exposures were collected retrospectively from 8,461 participants of the Nurses' Health Study II. Of these, 7,482 were eligible for analysis using logistic regression.Results-Participants reported 6,707 live births, and 775 (10%) spontaneous abortions (<20 weeks). After adjusting for age, parity, shift work, and hours worked, antineoplastic drug exposure was associated with a 2-fold increased risk of spontaneous abortion, particularly with early spontaneous abortion before the 12 th week, and 3.5-fold increased risk among nulliparous women. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Exposure to sterilizing agents was associated with a 2-fold increased risk of late spontaneous abortion (12-20 weeks), but not with early spontaneous abortion. HHS Public AccessConclusion-This study suggests that certain occupational exposures common to nurses are related to risks of spontaneous abortion.

Objective To use meta-analytic techniques to synthesize the findings of the current body of published literature regarding the risk of hypospadias resulting from parental exposure to pesticides. Materials and methods A search of Pub Med for original research published in English from January 1966 through March 2008 identified 552 studies, 90 of which were reviewed in detail. Nine studies met all study inclusion criteria. Two reviewers independently abstracted data from each included study. Any disagreements were resolved by consensus. Pooled risk ratios (PRRs) and confidence intervals (CIs) were calculated using both random and fixed effects models, along with statistical tests of homogeneity. Results Elevated but marginally significant risks of hypospadias were associated with maternal occupational exposure (PRR of 1.36, CI = 1.04–1.77), and paternal occupational exposure (PRR of 1.19, CI = 1.00–1.41). Subgroup analyses provided insights into needed designs for future studies. Notably, exposure assessment using a job-exposure matrix resulted in slightly higher estimated risk than agricultural occupation in fathers; but this effect was reversed in mothers, suggesting the importance of indirect and residential pesticide exposures in this group. Conclusions Despite potential exposure misclassification, which would tend to diminish observed associations, the previous literature indicates a modestly increased risk of hypospadias associated with pesticide exposure.

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Background Adverse associations between maternal pesticide exposure and neural tube defects (NTDs) have been suggested but not consistently observed. This study used data from the multisite National Birth Defects Prevention Study to examine associations between maternal periconceptional (1 month preconception through 2 months postconception) occupational pesticide exposure and NTDs. Methods Mothers of 502 NTD cases and 2950 unaffected live-born control infants with estimated delivery dates from 1997 through 2002 were included. Duration, categorical intensity scores, and categorical frequency scores for pesticide classes (e.g., insecticides) were assigned using a modified, literature-based job-exposure matrix and maternal-reported occupational histories. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated based on fitted multivariable logistic regression models that described associations between maternal periconceptional occupational pesticide exposure and NTDs. The aORs were estimated for pesticide exposure (any [yes/no] and cumulative exposure [intensity × frequency × duration] to any pesticide class, each pesticide class, or combination of pesticide classes) and all NTD cases combined and NTD subtypes. Results Positive, but marginally significant or nonsignificant, aORs were observed for exposure to insecticides + herbicides for all NTD cases combined and for spina bifida alone. Similarly, positive aORs were observed for any exposure and cumulative exposure to insecticides + herbicides + fungicides and anencephaly alone and encephalocele alone. All other aORs were near unity. Conclusion Pesticide exposure associations varied by NTD subtype and pesticide class. Several aORs were increased, but not significantly. Future work should continue to examine associations between pesticide classes and NTD subtypes using a detailed occupational pesticide exposure assessment and examine pesticide exposures outside the workplace.

This population-based U.S. study investigated the association between major musculoskeletal malformations and periconceptional maternal occupational pesticide exposure for a wide range of occupations. We conducted a multi-site case–control analysis using data from the National Birth Defects Prevention Study among employed women with due dates from October 1, 1997 through December 31, 2002. Cases included 871 live-born, stillborn, or electively terminated fetuses with isolated craniosynostosis, gastroschisis, diaphragmatic hernia, or transverse limb deficiencies. Controls included 2857 live-born infants without major malformations. Using self-reported maternal occupational information, an industrial hygienist used a job-exposure matrix and expert opinion to evaluate the potential for exposure to insecticides, herbicides or fungicides for each job held during one month pre-conception through three months post-conception. Exposures analyzed included any exposure (yes/no) to pesticides, to insecticides only, to both insecticides and herbicides (I + H) and to insecticides, herbicides and fungicides (I + H + F). We used logistic regression to evaluate the association between exposures and defects, controlling for infant and maternal risk factors. Occupational exposure to I + H + F was associated with gastroschisis among infants of women aged 20 years or older (adjusted odds ratio [aOR] = 1.88; 95% confidence interval [CI]: 1.16–3.05), but not for women under age 20 (aOR = 0.48; 95% CI: 0.20–1.16). We found no significant associations for the other defects. Additional research is needed to validate these findings in a separate population.

Because direct measurements of past occupational exposures are rarely available in population-based case-control studies, exposure assessment of job histories by multiple expert raters is frequently used; however, the subjective nature of this method makes measuring reliability an important quality control step. We evaluated inter-rater reliability of 7729 retrospective jobs reported in the National Birth Defects Prevention Study. Jobs were classified as exposed, unexposed, or exposure unknown by two independent industrial hygienists; exposed jobs were further evaluated for intensity, frequency, and routes. Exposure prevalence ranged from 0.1-9.8%. Inter-rater reliability for exposure (yes/no), assessed by kappa coefficients, was fair to good for cadmium (κ = 0.46), chlorinated solvents (κ = 0.59), cobalt (κ = 0.54), glycol ethers (κ = 0.50), nickel compounds (κ = 0.65), oil mists (κ = 0.63), and Stoddard Solvent (κ = 0.55); PAHs (κ = 0.24) and elemental nickel (κ = 0.37) had poor agreement. After a consensus conference resolved disagreements, an additional 4962 jobs were evaluated. Inter-rater reliability improved or stayed the same for cadmium (κ = 0.51), chlorinated solvents (κ = 0.81), oil mists (κ = 0.63), PAHs (κ = 0.52), and Stoddard solvent (κ = 0.92) in the second job set. Inter-rater reliability varied by exposure agent and prevalence, demonstrating the importance of measuring reliability in studies using a multiple expert rater method of exposure assessment.

Using broad classes of insecticides, herbicides, and fungicides, we found no evidence that low intensity maternal periconceptional occupational pesticide exposure was a risk factor for hypospadias.

Employment status was significantly associated with many common risk factors for adverse pregnancy outcomes. Pregnancy outcome studies should consider adjustment or stratification by employment status. In studies of occupational exposures, these differences may cause uncontrollable confounding if non-employed women are treated as unexposed instead of excluded from analysis. Am. J. Ind. Med. 60:329-341, 2017. © 2017 Wiley Periodicals, Inc.