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Background: Potential reproductive effects of organic solvent exposure during pregnancy remain unclear. We investigated the association between maternal occupational exposure during pregnancy to six chlorinated solvents, three aromatic solvents, and Stoddard solvent, and delivery of preterm infants or those born small‐for‐gestational age (SGA). Methods: In this case–control study of SGA and preterm birth (PTB) nested within the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we analyzed data from 7504 singleton live births without major birth defects and their mothers. Self‐reported information on jobs held in the periconceptional period was assessed for solvent exposure. Unconditional logistic regression was used to estimate the association between maternal occupational exposure (any, none) during early pregnancy to organic solvents and PTB and SGA. Linear regression was used to examine changes in mean birthweight potentially associated with maternal occupational solvent exposure. Results: Maternal occupational exposure to any organic solvents overall was not associated with an increased odds of PTB (adjusted odds ratio [aOR] = 0.94; 95% confidence interval [CI] 0.67–1.33) or SGA (aOR = 0.93; 95% CI 0.65–1.34). Point estimates increased modestly for higher estimated exposure versus lower, but confidence intervals were wide and not statistically significant. Maternal exposure to solvents was not associated with a statistically significant change in term birthweight among infants. Conclusions: Occupational exposure to organic solvents at the frequency and intensity levels found in a population‐based sample of pregnant workers was not associated with PTB or SGA; however, we cannot rule out any effects among pregnant workers with uncommonly high exposure to organic solvents. [ABSTRACT FROM AUTHOR]

Background: Few studies have evaluated birth defects among children of firefighters. We investigated associations between birth defects and paternal work as a firefighter compared to work in non‐firefighting and police officer occupations. Methods: We analyzed 1997–2011 data from the multi‐site case‐control National Birth Defects Prevention Study. Cases included fetuses or infants with major structural birth defects and controls included a random sample of live‐born infants without major birth defects. Mothers of infants self‐reported information about parents' occupations held during pregnancy. We investigated associations between paternal firefighting and birth defect groups using logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Referent groups included families reporting fathers working non‐firefighting and police officer jobs. Results: Occupational groups included 227 firefighters, 36,285 non‐firefighters, and 433 police officers. Twenty‐nine birth defects were analyzed. In adjusted analyses, fathers of children with total anomalous pulmonary venous return (TAPVR; OR = 3.1; 95% CI = 1.1–8.7), cleft palate (OR = 1.8; 95% CI = 1.0–3.3), cleft lip (OR = 2.2; 95% CI = 1.2–4.2), and transverse limb deficiency (OR = 2.2; 95% CI = 1.1–4.7) were more likely than fathers of controls to be firefighters, versus non‐firefighters. In police‐referent analyses, fathers of children with cleft palate were 2.4 times more likely to be firefighters than fathers of controls (95% CI = 1.1–5.4). Conclusions: Paternal firefighting may be associated with an elevated risk of birth defects in offspring. Additional studies are warranted to replicate these findings. Further research may contribute to a greater understanding of the reproductive health of firefighters and their families for guiding workplace practices. [ABSTRACT FROM AUTHOR]

Objective: Nail technicians and hairdressers may be exposed to chemicals with potential reproductive effects. While studies have examined birth defects in children of hairdressers, those in children of nail technicians have not been evaluated. We investigated associations between selected birth defects and maternal occupation as a nail technician or hairdresser versus a non-cosmetology occupation during pregnancy.Methods: We analysed population-based case-control data from the multisite National Birth Defects Prevention Study, 1997-2011. Cases were fetuses or infants with major structural birth defects; controls were live-born infants without major birth defects. Expert raters classified self-reported maternal jobs as nail technician, combination nail technician-hairdresser, hairdresser, other cosmetology work or non-cosmetology work. We used logistic regression to calculate adjusted ORs and 95% CIs for associations between occupation during pregnancy and birth defects, controlling for age, smoking, education and race/ethnicity.Results: Sixty-one mothers worked as nail technicians, 196 as hairdressers, 39 as combination nail technician-hairdressers and 42 810 as non-cosmetologists. The strongest associations among nail technicians included seven congenital heart defect (CHD) groups (ORs ranging from 2.7 to 3.5) and neural tube defects (OR=2.6, CI=0.8 to 8.4). Birth defects most strongly associated with hairdressing included anotia/microtia (OR=2.1, CI=0.6 to 6.9) and cleft lip with cleft palate (OR=2.0, CI=1.1 to 3.7). All oral cleft groups were associated with combination nail technician-hairdresser work (ORs ranging from 4.2 to 5.3).Conclusions: Small samples resulted in wide CIs. Still, results suggest associations between maternal nail technician work during pregnancy and CHDs and between hairdressing work and oral clefts. [ABSTRACT FROM AUTHOR]

Introduction When it is not possible to capture direct measures of occupational exposure or conduct biomonitoring, retrospective exposure assessment methods are often used. Among the common retrospective assessment methods, assigning exposure estimates by multiple expert rater review of detailed job descriptions is typically the most valid, but also the most time-consuming and expensive. Development of screening protocols to prioritize a subset of jobs for expert rater review can reduce the exposure assessment cost and time requirement, but there is often little data with which to evaluate different screening approaches. We used existing job-by-job exposure assessment data (assigned by consensus between multiple expert raters) from a large, population-based study of women to create and test screening algorithms for polycyclic aromatic hydrocarbons (PAHs) that would be suitable for use in other population-based studies. Methods We evaluated three approaches to creating a screening algorithm: a machine-learning algorithm, a set of a priori decision rules created by experts based on features (such as keywords) found in the job description, and a hybrid algorithm incorporating both sets of criteria. All coded jobs held by mothers of infants participating in National Birth Defects Prevention Study (NBDPS) (n = 35,424) were used in developing or testing the screening algorithms. The job narrative fields considered for all approaches included job title, type of product made by the company, main activities or duties, and chemicals or substances handled. Each screening approach was evaluated against the consensus rating of two or more expert raters. Results The machine-learning algorithm considered over 30,000 keywords and industry/occupation codes (separate and in combination). Overall, the hybrid method had a similar sensitivity (87.1%) as the expert decision rules (85.5%) but was higher than the machine-learning algorithm (67.7%). Specificity was best in the machine-learning algorithm (98.1%), compared to the expert decision rules (89.2%) and hybrid approach (89.1%). Using different probability cutoffs in the hybrid approach resulted in improvements in sensitivity (24–30%), without the loss of much specificity (7–18%). Conclusion Both expert decision rules and the machine-learning algorithm performed reasonably well in identifying the majority of jobs with potential exposure to PAHs. The hybrid screening approach demonstrated that by reviewing approximately 20% of the total jobs, it could identify 87% of all jobs exposed to PAHs; sensitivity could be further increased, albeit with a decrease in specificity, by adjusting the algorithm. The resulting screening algorithm could be applied to other population-based studies of women. The process of developing the algorithm also provides a useful illustration of the strengths and potential pitfalls of these approaches to developing exposure assessment algorithms. [ABSTRACT FROM AUTHOR]

Abstract Background Many epidemiological and public health surveys report increasing difficulty obtaining high participation rates. We conducted a pilot follow-up study to determine whether a mailed or telephone survey would better facilitate data collection in a subset of respondents to an earlier telephone survey conducted as part of the National Birth Defects Prevention Study. Methods We randomly assigned 392 eligible mothers to receive a self-administered, mailed questionnaire (MQ) or a computer-assisted telephone interview (CATI) using similar recruitment protocols. If mothers gave permission to contact the fathers, fathers were recruited to complete the same instrument (MQ or CATI) as mothers. Results Mothers contacted for the MQ, within all demographic strata examined, were more likely to participate than those contacted for the CATI (86.6% vs. 70.6%). The median response time for mothers completing the MQ was 17 days, compared to 29 days for mothers completing the CATI. Mothers completing the MQ also required fewer reminder calls or letters to finish participation versus those assigned to the CATI (median 3 versus 6), though they were less likely to give permission to contact the father (75.0% vs. 85.8%). Fathers contacted for the MQ, however, had higher participation compared to fathers contacted for the CATI (85.2% vs. 54.5%). Fathers recruited to the MQ also had a shorter response time (median 17 days) and required fewer reminder calls and letters (median 3 reminders) than those completing the CATI (medians 28 days and 6 reminders). Conclusions We concluded that offering a MQ substantially improved participation rates and reduced recruitment effort compared to a CATI in this study. While a CATI has the advantage of being able to clarify answers to complex questions or eligibility requirements, our experience suggests that a MQ might be a good survey option for some studies.

Abstract Background Though commercial production of polychlorinated biphenyls was banned in the United States in 1977, exposure continues due to their environmental persistence. Several studies have examined the association between environmental polychlorinated biphenyl exposure and modulations of the secondary sex ratio, with conflicting results. Objective Our objective was to evaluate the association between maternal preconceptional occupational polychlorinated biphenyl exposure and the secondary sex ratio. Methods We examined primipara singleton births of 2595 women, who worked in three capacitor plants at least one year during the period polychlorinated biphenyls were used. Cumulative estimated maternal occupational polychlorinated biphenyl exposure at the time of the infant's conception was calculated from plant-specific job-exposure matrices. A logistic regression analysis was used to evaluate the association between maternal polychlorinated biphenyl exposure and male sex at birth (yes/no). Results Maternal body mass index at age 20, smoking status, and race did not vary between those occupationally exposed and those unexposed before the child's conception. Polychlorinated biphenyl-exposed mothers were, however, more likely to have used oral contraceptives and to have been older at the birth of their first child than non-occupationally exposed women. Among 1506 infants liveborn to polychlorinated biphenyl-exposed primiparous women, 49.8% were male; compared to 49.9% among those not exposed (n = 1089). Multivariate analyses controlling for mother's age and year of birth found no significant association between the odds of a male birth and mother's cumulative estimated polychlorinated biphenyl exposure to time of conception. Conclusions Based on these data, we find no evidence of altered sex ratio among children born to primiparous polychlorinated biphenyl-exposed female workers.

Background: Previous studies suggested associations between maternal smoking, a source of exposure to polycyclic aromatic hydrocarbons (PAHs) and other chemicals, and central nervous system and face birth defects; however, no previous studies have evaluated maternal occupational PAH exposure itself. Methods: Jobs held in the periconceptional period were retrospectively assigned for occupational PAH exposures. Associations between maternal occupational PAH exposure and selected rare defects of the face (cataracts, microphthalmia, glaucoma, microtia, and choanal atresia) and central nervous system (holoprosencephaly, hydrocephaly, cerebellar hypoplasia, and Dandy‐Walker malformation) were evaluated using data from the National Birth Defects Prevention Study, a population‐based case–control study in the United States. Crude and adjusted odds ratios (ORs) with 95% confidence intervals were calculated to estimate associations between each evaluated defect and PAH exposure using multivariable logistic regression. Results: Food and beverage serving, as well as cooks and food preparation occupations, were among the most frequent jobs held by exposed mothers. Cataracts, microtia, microphthalmia, and holoprosencephaly were significantly associated with PAH exposure with evidence of dose–response (P‐values for trend ≤.05). Hydrocephaly was associated with any PAH exposure, but not significant for trend. Sensitivity analyses that reduced possible sources of exposure misclassification tended to strengthen associations. Conclusions: This is the first population‐based case–control study to evaluate associations between maternal occupational PAH exposures and these rare birth defects of the central nervous system and face. [ABSTRACT FROM AUTHOR]

Much of the literature on the healthy worker effect focuses on studies of chronic disease and mortality; however, when studying pregnancy outcomes, these effects might differ because of the short, defined risk periods of most pregnancy outcomes. Three pregnancy-specific healthy worker effects have also been described, but the structure of these effects has not yet been investigated when occupational exposure, and not employment status, is the exposure of interest. We used directed acyclic graphs to examine healthy worker effects in studies of occupational exposures and pregnancy outcomes: the healthy hire effect, the healthy worker survivor effect, the desperation/privilege effect (differential workforce reentry after pregnancy), the reproductively unhealthy worker effect (women with live births leave the workforce, while women with nonlive births do not), and the insecure pregnancy effect (women with adverse pregnancy outcomes reduce their exposures in subsequent pregnancies). Given our assumptions, we conclude that the healthy hire effect, the desperation/privilege effect, the reproductively unhealthy worker effect, and the insecure pregnancy effect result from confounding that can be addressed if data on measured confounders, such as employment status, are available. The presence of the healthy worker survivor effect, however, varies by study design. Different types of healthy worker effects can be present in studies of occupational exposure and pregnancy outcomes, and many of them are easily addressed analytically. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking is a well‐studied risk factor for orofacial clefts (OFCs). Little is known about which constituents in cigarette smoke contribute to this teratogenicity in humans. One constituent, cadmium, has been associated with OFCs in animal studies; in humans, the role of maternal cadmium exposure on OFCs, independent of cigarette smoke, is unclear. In particular, the relation between maternal occupational cadmium exposure and OFCs is largely unexplored. Methods: Using data from a large, population‐based case‐control study, we compared expert rater assessed maternal occupational cadmium exposure from self‐reported occupational histories during the period 1 month before through 3 months after conception between OFC cases (n = 1,185) and unaffected controls (n = 2,832). Multivariable logistic regression analyses were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals for any (yes/no) and cumulative (no, low, high exposure) occupational cadmium exposures and all OFCs, cleft lip ± cleft palate (CL/P) and cleft palate (CP). Results: Overall, 45 mothers (cases = 13, controls = 32) were rated as having occupational cadmium exposure. Comparing all OFCs to controls, we observed inverse, nonsignificant aORs for any or low exposure, and positive, nonsignificant aORs for high exposure. Where data were available, aORs for CL/P and CP tended to parallel those for all OFCs. Conclusion: To our knowledge, this is the first study to specifically examine maternal occupational cadmium exposure and OFCs, using expert rater exposure assessment. The small numbers of exposed mothers observed, however, led to imprecise estimates. Continued research using more detailed occupational exposure assessment and increased sample sizes is recommended. [ABSTRACT FROM AUTHOR]

The wide variety of jobs encountered in population-based studies makes retrospective exposure assessment challenging in occupational epidemiology. In this analysis, two methods for estimating exposure intensity to chlorinated solvents are compared: rated (assigned by an expert rater) and modeled (assigned using statistical models). Estimates of rated and modeled intensities were compared for jobs held by mothers participating in the National Birth Defects Prevention Study with possible exposure to six chlorinated solvents: carbon tetrachloride, chloroform, methylene chloride, perchloroethylene, 1,1,1-trichloroethane, and trichloroethylene. For each possibly exposed job, an industrial hygienist assigned (1) an exposure intensity (rated intensity) and (2) determinants of exposure to be used in a statistical model of exposure intensity (modeled intensity). Of 12,326 reported jobs, between 31 (0.3%) and 746 (6%) jobs were rated as possibly exposed to each of the six solvents. Agreement between rated and modeled intensities was low overall (Spearman correlation coefficient range: −0.09 to 0.28; kappa range: −0.23 to 0.43). Although no air measurements were available to determine if rated or modeled estimates were more accurate, review of participants' job titles showed that modeled estimates were often unexpectedly high given the low-exposure tasks found in these jobs. Differences between the high-exposure jobs used to create the statistical models (obtained from air measurements in the published literature) and the low-exposure jobs in the actual study population is a potential explanation for the disagreement between the two methods. Investigators should be aware that statistical models estimating exposure intensity using existing data from one type of worker population might not be generalizable to all populations of workers. [ABSTRACT FROM PUBLISHER]

Background Because of persistent concerns over the association between pesticides and spina bifida, we examined the role of paternal and combined parental occupational pesticide exposures in spina bifida in offspring using data from a large population-based study of birth defects. Methods Occupational information from fathers of 291 spina bifida cases and 2745 unaffected live born control infants with estimated dates of delivery from 1997 to 2002 were collected by means of maternal report. Two expert industrial hygienists estimated exposure intensity and frequency to insecticides, herbicides, and fungicides. Multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for exposure to any pesticide and to any class of pesticide (yes/no; and by median), and exposure to combinations of pesticides (yes/no) and risk of spina bifida. Adjusted odds ratios were also estimated by parent exposed to pesticides (neither, mother only, father only, both parents). RESULTS Joint parental occupational pesticide exposure was positively associated with spina bifida (aOR, 1.5; 95% CI, 0.9-2.4) when compared with infants with neither maternal nor paternal exposures; a similar association was not observed when only one parent was exposed. There was a suggested positive association between combined paternal insecticide and fungicide exposures and spina bifida (aOR, 1.5; 95% CI, 0.8-2.8), however, nearly all other aORs were close to unity. Conclusion Overall, there was little evidence paternal occupational pesticide exposure was associated with spina bifida. However, the small numbers make it difficult to precisely evaluate the role of pesticide classes, individually and in combination. Birth Defects Research (Part A) 106:963-971, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background Evidence in animal models and humans suggests that exposure to polycyclic aromatic hydrocarbons (PAHs) may lead to birth defects. To our knowledge, this relationship has not been evaluated for craniosynostosis, a birth defect characterized by the premature closure of sutures in the skull. We conducted a case-control study to examine associations between maternal occupational exposure to PAHs and craniosynostosis. Methods We used data from craniosynostosis cases and control infants in the National Birth Defects Prevention Study (NBDPS) with estimated delivery dates from 1997 to 2002. Industrial hygienists reviewed occupational data from the computer-assisted telephone interview and assigned a yes/no rating of probable occupational PAH exposure for each job from 1 month before conception through delivery. We used logistic regression to assess the association between occupational exposure to PAHs and craniosynostosis. Results The prevalence of exposure was 5.3% in case mothers (16/300) and 3.7% in control mothers (107/2,886). We observed a positive association between exposure to PAHs during the 1 month before conception through the third month of pregnancy and craniosynostosis (odds ratio [OR] = 1.75; 95% confidence interval [CI], 1.01-3.05) after adjusting for maternal age and maternal education. The number of cases for each craniosynostosis subtype limited subtype analyses to sagittal craniosynostosis; the odds ratio remained similar (OR = 1.76, 95% CI, 0.82-3.75), but was not significant. Conclusion Our findings support a moderate association between maternal occupational exposure to PAHs and craniosynostosis. Additional work is needed to better characterize susceptibility and the role PAHs may play on specific craniosynostosis subtypes. Birth Defects Research (Part A) 106:55-60, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND Congenital heart defects (CHDs) are common birth defects, affecting approximately 1% of live births. Pesticide exposure has been suggested as an etiologic factor for CHDs, but previous results were inconsistent. METHODS We examined maternal occupational exposure to fungicides, insecticides, and herbicides for 3328 infants with CHDs and 2988 unaffected control infants of employed mothers using data for 1997 through 2002 births from the National Birth Defects Prevention Study, a population-based multisite case-control study. Potential pesticide exposure from 1 month before conception through the first trimester of pregnancy was assigned by an expert-guided task-exposure matrix and job history details self-reported by mothers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. RESULTS Maternal occupational exposure to pesticides was not associated with CHDs overall. In examining specific CHD subtypes compared with controls, some novel associations were observed with higher estimated pesticide exposure: insecticides only and secundum atrial septal defect (OR = 1.8; 95% CI, 1.3-2.7, 40 exposed cases); both insecticides and herbicides and hypoplastic left heart syndrome (OR = 5.1; 95% CI, 1.7-15.3, 4 exposed cases), as well as pulmonary valve stenosis (OR = 3.6; 95% CI, 1.3-10.1, 5 exposed cases); and insecticides, herbicides, and fungicides and tetralogy of Fallot (TOF) (OR = 2.2; 95% CI, 1.2-4.0, 13 exposed cases). CONCLUSION Broad pesticide exposure categories were not associated with CHDs overall, but examining specific CHD subtypes revealed some increased odds ratios. These results highlight the importance of examining specific CHDs separately. Because of multiple comparisons, additional work is needed to verify these associations. Birth Defects Research (Part A) 103:823-833, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

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. Birth Defects Research (Part A) 100:877-886, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

: Background: Many antineoplastic (chemotherapeutic) drugs are known or probable human carcinogens, and many have been shown to be reproductive toxicants in cancer patients. Evidence from occupational exposure studies suggests that health care workers who have long-term, low-level occupational exposure to antineoplastic drugs have an increased risk of adverse reproductive outcomes. It's recommended that, at minimum, nurses who handle or administer such drugs should wear double gloves and a nonabsorbent gown to protect themselves. But it's unclear to what extent nurses do., Purpose: This study assessed glove and gown use by female pregnant and nonpregnant nurses who administer antineoplastic drugs in the United States and Canada., Methods: We used data collected from more than 40,000 nurses participating in the Nurses' Health Study 3. The use of gloves and gowns and administration of antineoplastic drugs within the past month (among nonpregnant nurses) or within the first 20 weeks of pregnancy (among pregnant nurses) were self-reported via questionnaire., Results: Administration of antineoplastic drugs at any time during their career was reported by 36% of nonpregnant nurses, including 27% who reported administering these drugs within the past month. Seven percent of pregnant nurses reported administering antineoplastic drugs during the first 20 weeks of pregnancy. Twelve percent of nonpregnant nurses and 9% of pregnant nurses indicated that they never wore gloves when administering antineoplastic drugs, and 42% of nonpregnant nurses and 38% of pregnant nurses reported never using a gown. The percentage of nonpregnant nurses who reported not wearing gloves varied by type of administration: 32% of those who administered antineoplastic drugs only as crushed pills never wore gloves, compared with 5% of those who administered such drugs only via infusion., Conclusion: Despite longstanding recommendations for the safe handling of antineoplastic and other hazardous drugs, many nurses-including those who are pregnant-reported not wearing protective gloves and gowns, which are considered the minimum protective equipment when administering such drugs. These findings underscore the need for further education and training to ensure that both employers and nurses understand the risks involved and know which precautionary measures will minimize such exposures.

Background: Potential confounding or effect modification by employment status is frequently overlooked in pregnancy outcome studies., Methods: To characterize how employed and non-employed women differ, we compared demographics, behaviors, and reproductive histories by maternal employment status for 8,343 mothers of control (non-malformed) infants in the National Birth Defects Prevention Study (1997-2007) and developed a multivariable model for employment status anytime during pregnancy and the 3 months before conception., Results: Sixteen factors were independently associated with employment before or during pregnancy, including: maternal age, pre-pregnancy body mass index, pregnancy intention, periconceptional/first trimester smoking and alcohol consumption, and household income., Conclusions: 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., (© 2017 Wiley Periodicals, Inc.)