Carissa M. Rocheleau

Inter-rater reliability of assessed prenatal maternal occupational exposures to solvents, polycyclic aromatic hydrocarbons, and heavy metals.

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.

Maternal occupational exposure to polycyclic aromatic hydrocarbons and small for gestational age offspring

Objectives While some of the highest maternal exposures to polycyclic aromatic hydrocarbons (PAHs) occur in the workplace, there is only one previous study of occupational PAH exposure and adverse pregnancy outcomes. We sought to extend this literature using interview data combined with detailed exposure assessment. Methods Data for 1997–2002 were analysed from mothers of infants without major birth defects in the National Birth Defects Prevention Study, a large population-based case-control study in the USA. Maternal telephone interviews yielded information on jobs held in the month before conception through delivery. From 6252 eligible control mothers, 2803 completed the interview, had a job, met other selection criteria, and were included in the analysis. Two industrial hygienists independently assessed occupational exposure to PAHs from the interview and reviewed results with a third to reach consensus. Small for gestational age (SGA) was the only adverse pregnancy outcome with enough exposed cases to yield meaningful results. Logistic regression estimated crude and adjusted ORs. Results Of the 2803 mothers, 221 (7.9%) had infants who were SGA. Occupational PAH exposure was found for 17 (7.7%) of the mothers with SGA offspring and 102 (4.0%) of the remaining mothers. Almost half the jobs with exposure were related to food preparation and serving. After adjustment for maternal age, there was a significant association of occupational exposure with SGA (OR=2.2, 95% CI 1.3 to 3.8). Conclusions Maternal occupational exposure to PAHs was found to be associated with increased risk of SGA offspring.

Maternal periconceptional occupational pesticide exposure and neural tube defects

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.

Maternal periconceptional occupational exposure to pesticides and selected musculoskeletal birth defects.

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.

Maternal occupational pesticide exposure and risk of congenital heart defects in the National Birth Defects Prevention Study.

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.

Differences in folic acid use, prenatal care, smoking, and drinking in early pregnancy by occupation.

OBJECTIVE To describe differences in four high risk periconceptional behaviors (lack of folic acid supplementation, lack of early prenatal care, smoking, and drinking) by maternal occupation. METHODS Analyses were conducted among women in the National Birth Defects Prevention Study who delivered liveborn infants without birth defects. Periconceptional occupational data were collected using a computer-assisted telephone interview and occupational coding was performed using the 2000 Standard Occupational Classification System. Logistic regression analyses were conducted to determine whether prevalence of behaviors differed between occupational groups. RESULTS Subjects included 5153 women employed during early pregnancy from 1997 to 2007. Compared to women in management, business, science, and arts occupations, women in other occupations (e.g., service occupations) were significantly more likely to engage in all four high risk behaviors. Specifically, women in food preparation/serving-related occupations were significantly more likely to engage in all four behaviors compared to women in all other occupational groups (odds ratios: 1.8-3.0), while women in education/training/library occupations were significantly less likely to do so (odds ratios: 0.2-0.5). CONCLUSION We identified several occupational groups with an increased prevalence of high-risk maternal behaviors during pregnancy. Our findings could aid in developing interventions targeted towards women in these occupational groups.

Maternal exposure to polychlorinated biphenyls and the secondary sex ratio: an occupational cohort study

BackgroundThough 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.ObjectiveOur objective was to evaluate the association between maternal preconceptional occupational polychlorinated biphenyl exposure and the secondary sex ratio.MethodsWe 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 infants 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).ResultsMaternal body mass index at age 20, smoking status, and race did not vary between those occupationally exposed and those unexposed before the childs 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 mothers age and year of birth found no significant association between the odds of a male birth and mothers cumulative estimated polychlorinated biphenyl exposure to time of conception.ConclusionsBased on these data, we find no evidence of altered sex ratio among children born to primiparous polychlorinated biphenyl-exposed female workers.

Factors associated with employment status before and during pregnancy: Implications for studies of pregnancy outcomes

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.

Shift work and adverse pregnancy outcomes: comments on a recent meta-analysis

Sir, Regarding the recent meta-analysis on shift work and pregnancy outcomes, we disagree that ‘any effects of shift work on preterm delivery are likely to be small’. These conclusions were based on a sensitivity analysis in which the authors excluded studies they deemed to be ‘of lower quality’. Some studies were excluded because shift work and preterm delivery were self-reported on the same instrument, assumed to result in recall bias. However, there is little evidence that women inaccurately report gestational age, especially in broad categories. As Gordis said: Although a potential for recall bias is self-evident in case–control studies, in point of fact, there are few actual examples that demonstrate that recall bias has in fact been a major problem in case–control studies and has led to erroneous conclusions regarding associations. Items that are subjective (e.g. pain intensity), that participants pay little attention to (e.g. minor headache), or that are sensitive (e.g. illicit drugs) might be more prone to recall bias. Preterm birth and shift work do not meet these conditions. Other studies were excluded from the sensitivity analysis of preterm delivery for not controlling for smoking and socio-economic status. This approach ignores variations in study design/population that determine the potential for confounding (e.g. confounding factors such as income and education are unlikely in a cohort of nurses) and the magnitude of potential confounding (resulting from variations in the prevalence of confounding factors). We assert that the potential for uncontrolled confounding does not necessarily mean that confounding occurred. We suggest conducting a subanalysis among the studies that provided both crude and adjusted data, then comparing the pooled odds ratio generated from the crude data with that from the adjusted data. If the difference between the two pooled odds ratios is small, including studies without adjustment may be appropriate. The authors used data from Misra’s study, in which unemployed women were used as the reference group (OR 1.0, 95% CI 0.59–1.69). However, sufficient raw data were available in the paper to calculate a crude odds ratio using employed non-shift workers as a reference group (OR 1.4, 95% CI 0.87–2.32). Given the bias introduced by comparing shift workers with non-workers, we feel using employed non-shift workers would be more comparable with other studies used in the meta-analysis. We are also concerned with the completeness of the literature search: when we duplicated the search as described by the authors, we found additional studies meeting the authors’ inclusion criteria that were not cited by them. In their discussion, the authors note an increased risk of preterm delivery with shift work in countries with weaker support for prenatal leave. The authors could address this quantitatively by stratifying the analysis by whether or not the country where the study occurred supports prenatal leave. A subanalysis examining early and late preterm birth separately should also be considered, as our previous work found that night work was associated with an increased risk of early but not late preterm birth. Because this topic generates considerable public interest, we feel that the interpretation of the results should be reconsidered. j

Maternal occupational exposure to polycyclic aromatic hydrocarbons and craniosynostosis among offspring in the National Birth Defects Prevention Study.

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.