Hum. Reprod. Advance Access originally published online on August 28, 2007
Human Reproduction 2007 22(10):2751-2757; doi:10.1093/humrep/dem200
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Exposure to organic solvents and adverse pregnancy outcomes
1 Institute of Occupational and Environmental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK 2 Environmental Epidemiology Unit, Department of Public Health, University of Helsinki, Finland
3 Correspondence address. Tel: +44 0121 414 6671; Fax: +44 0121 414 6217; E-mail: j.jaakkola{at}bham.ac.uk,
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Abstract |
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BACKGROUND: Organic solvents are among the most common exposures in the workplace. Our objective was to elaborate the relationship between prenatal occupational solvent exposure and fetal growth as well as duration of pregnancy, and to quantify the impact of occupational organic solvent exposure.
METHODS: We conducted a population-based study of 1670 singleton newborns of women who participated in The Finnish Prenatal Environment and Health Study after their delivery (response rate 94%) and who were working during pregnancy (65%). Exposure information was based on questions about exposure to solvents at work before and during pregnancy. The health outcomes, based on information from a questionnaire and the Finnish Medical Birth Registry, were low birth weight (<3000 g), small-for-gestational-age and preterm delivery (<37 weeks).
RESULTS: In logistic regression analysis, the risk of the baby being small-for-gestational-age was related to any exposure to solvents 3 months before or during pregnancy with an adjusted odds ratio (OR) of 1.67 [95% confidence interval (CI) = 1.02–2.73]. Also the adjusted OR for low birth weight was elevated with exposure, although it did not reach statistical significance (1.17; 95% CI = 0.71–1.93). The population attributable fraction for small-for-gestational-age was 2.3% for all pregnant women.
CONCLUSIONS: Work exposure to organic solvents may reduce intrauterine growth by increasing the risk of the baby being small-for-gestational-age.
Key words: occupational exposure/solvents/low birth weight/preterm delivery/small-for-gestational-age
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionConcluding remarksAcknowledgementsReferences |
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An increasing number of women are working outside the home during pregnancy. In the USA, 57% of first-time mothers in 1996–2000 worked at full-time jobs during their pregnancy, whereas the corresponding figure in 1961–1965 was 40% (Overturf Johnson and Downs, 2005
). Of the women who worked during pregnancy, 57% stopped less than a month before delivery. The percentage of women working during pregnancy in Finland in 1996–1997 was similar, although women started their maternity leave usually at the 36th week of gestation and, thus the percentage of women working during the last month was very low. This increasing trend of women working in pregnancy underlines the need to understand the potential adverse effects of prenatal exposures taking place in workplaces.
Organic solvents are among the most common exposures in the workplace. Few industries are free of solvents, but workers may be particularly exposed in engineering, footwear manufacturing, construction, textile industries, chemical industries, food industries, printing, woodworking, rubber industries, cleaning, dry cleaning, plastics industries and paint, pharmaceutical and ink manufacturing (Health and Safety Executive INDG273, 5/03 C1500). Many organic solvents, such as benzene, toluene and xylene, cross the placenta in pregnant mice (Ghantous and Danielsson, 1986;Donald et al., 1991). Several organic solvents are teratogenic (Laskin et al., 1995), embryotoxic (Ungvary and Tatrai, 1985) and genotoxic (Karacic et al., 1995) in laboratory animals.
Previous epidemiological studies, conducted in laboratory workers (Taskinen et al., 1994), drycleaners (Olsen et al., 1990), pharmacy assistants (Schaumburg and Olsen, 1991) and workers in the petrochemical industry (Ha et al., 2002), have suggested an association between exposure to organic solvents and fetal growth, although other studies conducted in laboratory workers (Axelsson et al., 1984;Wennborg et al., 2000;Zhu et al., 2006) have not supported these findings. There is also some evidence of an increased risk of preterm delivery related to exposure to organic solvents in laboratory work (Wennborg et al., 2002) and work in medicine and science (Savitz et al., 1989). Two population-based studies conducted in California (Lipscomb et al., 1991) and Germany (Seidler et al., 1999) provided suggestive evidence of an increased risk of low birth weight and preterm delivery (Lipscomb et al., 1991) and small-for-gestational-age (Seidler et al., 1999) related to occupational organic solvent exposure.
Only a few of the previous studies have been population based, and to our knowledge none of the studies provided estimates of population attributable fractions (AF) for adverse pregnancy outcomes due to occupational exposures to solvents. As part of a population-based retrospective cohort study conducted in southeast Finland, we elaborated the relationship between prenatal occupational solvent exposure and fetal growth and duration of pregnancy, and quantified the impact of occupational organic solvent exposure on occurrence of the studied outcomes at a population level.
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Materials and Methods |
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Study population
The Finnish Prenatal Environment and Health Study (Jaakkola et al., 2001
) recruited from a source population of all the 2751 children born from 1 May 1996 to 30 April 1997 in two geographically defined hospital districts in southeast Finland (Kymi and Porvoo Hospital Districts). All mothers were asked after delivery to complete a self-administered questionnaire ‘environment and pregnancy’ (response rate 94.2%). The respondents, 2591 mothers, had 2568 singletons and 23 twin pairs. The present study focused on 1670 singleton newborns of women who were working during pregnancy. The characteristics of the study population are presented in Table 1.
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Data collection
The environment and pregnancy questionnaire administered at the birth clinic inquired about maternal health in general and during pregnancy, parents' education, profession and behavioural factors such as smoking and exercise, and details of the home and other environments. We requested from the maternity health clinics in the two areas the records of these women and received 97% of the records. Additional information on the child's birth weight, gestational age and maternal smoking habits during pregnancy were obtained from the Finnish Medical Birth Registry established in 1987 and run by the National Research and Development Centre for Welfare and Health (STAKES). The study protocol was approved by the Ethical Committees of the Department of Public Health, University of Helsinki, three participating hospitals and the Ministry of Social Affairs and Health.
Health outcomes
The primary health outcomes were fetal growth and duration of pregnancy. We used two measures of fetal growth: low birth weight (<3000 g) and small-for-gestational-age (SGA). A higher than traditional cut-off point for low birth weight, 3000 g, was chosen to increase the number of cases. SGA was defined as birth weight in the lowest 10th percentile according to the week of gestation, which was calculated, separately for boys and girls, from the birth weight distributions of the newborns of non-smoking women in the present source population. Preterm delivery was defined as the length of gestation <37 weeks. We retrieved information on gestational age from maternity health clinic records. Gestational age was practically always verified by ultrasound examination during the 18th week of gestation.
Exposure to solvents
Information on occupational exposure to solvents was based on a question asking about exposure to solvents at work during (i) 3 months before pregnancy, (ii) first trimester, (iii) second trimester and (iv) third trimester. Exposure 3 months before pregnancy was thought to reflect the exposure after conception but before the verification of pregnancy. The questionnaire listed examples of the sources of solvents including paints, lacquers, glues, metal polishers, plastics, printing chemicals and laboratory chemicals. We also asked about the job title and employer. We applied the International Standard Classification of Occupations (ISCO-88) coding for categorizing the occupations (International Labor Organization, 1988).
Covariates
Information on potential confounders was based on the self-administered questionnaire. We used the following potential confounders as the core covariates in the analyses: gender, maternal age, parity, pre-pregnancy BMI, marital status, duration of pregnancy, smoking, exposure to environmental tobacco smoke (ETS) and alcohol consumption during pregnancy. In addition, we adjusted for a combined index of maternal and paternal education as an indicator of socioeconomic status (low: neither parent with vocational education; medium: either one or both parents with vocational school as highest education and high: either one or both parents with college or university education as a reference category).
Statistical methods
We estimated the prevalences (%) of the pregnancy outcomes with 95% confidence intervals (CI) based on the binomial distribution. First, we compared the risks of low birth weight, SGA and preterm delivery in the different categories of exposure. Odds ratio (OR) was the measure of effect. We used logistic regression analysis to estimate adjusted ORs. We adjusted for all the potential determinants of the outcomes listed above. We quantified the impact of occupational organic solvent exposure on occurrence of studied outcomes as an attributable fraction (AFexp) (Greenland, 1988) or etiologic fraction (Miettinen, 1974), which indicates the fraction of cases for which the outcome is attributable to maternal solvent exposure. The AFexp was calculated as follows: AFexp = (OR–1)/OR, where OR is the adjusted OR due to exposure. The OR was obtained from an analysis including any exposure as a dichotomous variable, while adjusting for the core covariates. The 95% CI was calculated using the corresponding interval of OR. The population attributable fraction (Miettinen, 1974) was estimated by: AFpop = p AFexp, where p is the proportion of exposed cases.
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Results |
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Characteristics of the study population
The characteristics of the study population of 1670 singleton newborns are shown in Table 1 according to any occupational exposure to solvents. The characteristics of exposed women and their newborns did not differ substantially from the reference group.
A total of 147 women (8.8%) reported exposure to solvents at work 3 months before or during pregnancy and 125 women (7.5%) reported exposure during any of the trimesters (Table 2). The number of exposed during pregnancy was 100 (6.0%) during the first, 102 (6.1%) the second and 63 (3.8%) during the third trimester. Table 3 displays the exposed women according to occupational categories based on the ISCOs coding (International Labor Organization 1988). The largest group was life science and health associated professionals (22.0%), which includes technicians, pharmacist and nurses. The second largest group was craft and related trades workers (10.6%) followed by hospital, domestic and kitchen helpers and cleaners (9.2%).
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Effect of organic solvent exposure on low birth weight
There were 234 newborns (14.0%) with birth weight <3000 g, as shown in Table 2. The prevalence of low birth weight was 17.7% among the exposed and 13.7% among the unexposed, yielding a crude OR of 1.39 (95% CI = 0.87–2.13) for the effect of solvent exposure (Table 4). The highest prevalence of low birth weight was among those exposed during the second trimester. In a logistic regression analysis, adjusting for potential confounders, the adjusted OR for any exposure 3 months before or during pregnancy was 1.17 (95% CI = 0.71–1.93), and 1.26 (95% CI = 0.71–2.24) for exposure during the second trimester.
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Effect of organic solvent exposure on SGA
There were 198 newborns (12.7%) who were SGA. The prevalence of SGA was 18.2% among exposed and 11.5% among the reference group resulting in an OR of 1.71 (95% CI = 1.08–2.69) (Table 5). The corresponding adjusted OR was 1.67 (95% CI = 1.02–2.73). The highest effect estimate was for exposure during the second trimester, 1.54 (95% CI = 0.86–2.76). The attributable fraction for any exposure was 40.1% (95% CI = 2.0—63.4). The population attributable fraction was 2.3% for all pregnant women and 3.2% for those working during pregnancy.
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Effect of organic solvent exposure on preterm delivery
There were 83 children (5.0%) born premature, before 37 weeks of gestation, as shown in Table 2. There was no indication that the risk of preterm delivery would be related to solvent exposure, as shown in Table 6. The prevalence of preterm delivery was 5.4% among the exposed and 4.9% in the reference group and the corresponding crude OR was 1.11 (95% CI = 0.53–2.35). However, adjustment for confounding factors reduced the OR to 0.46 (95% CI = 0.14–1.50).
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionConcluding remarksAcknowledgementsReferences |
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This population-based study provided evidence that exposure to organic solvents during pregnancy reduce intrauterine growth resulting in an increased risk of a SGA newborn. In this population, almost two-thirds of pregnant women (66%) were working during pregnancy, and of these, 8.9% were exposed to organic solvents, which means that 5.7% of all pregnant women were exposed. There was no evidence that the duration of pregnancy is affected by solvent exposure. The adjusted OR of SGA was 1.67, which translates to an attributable fraction of 40.1% (95% CI = 2.0–63.4). The population attributable fraction was 2.3% for all pregnant women and 3.2% for those working during pregnancy. The effect estimate for low birth weight was also elevated, although 95% CI included unity.
Validity of the results
The source population included all children born in the designated geographic region during the course of 12 months in 1996–1997. A high proportion of women participated in the study (94%). The population-based approach of the study and high participation rate minimized the potential influence of selection bias.
The outcome information was based on measurements of birth weight after delivery, which are conducted in a standardized manner and estimated duration of pregnancy in most cases is based on definition of gestational age using ultrasound. Birth weight and gestational age information was verified from two sources, study project data collection and from the Finnish Birth Registry data. SGA was based on the sex-specific birth weight distributions of the non-smoking women in the study population. Exposure information was based on questions answered after the delivery. Examples of the potentials sources of solvent emissions were given to help women remember possible exposures of interest. The study did not focus on organic solvent exposures in particular and, thus there was no special attention that could generate information bias. However, exposure assessment based on self-administered questionnaire have several limitations. Participants may not have identified relevant sources of exposure or sometimes they may have falsely reported exposure in settings where no relevant exposure was experienced. This type of exposure misclassification was not likely related to the outcomes of interest and therefore would probably have resulted in underestimation of the effect. Further, we were not able to assess the level of exposure.
Use of medical records and questionnaire information allowed us to take into account an extensive number of potential confounders as displayed in Table 1. The exposed and unexposed were relatively similar with respect to measured determinants of the outcomes. A larger proportion of exposed pregancies produced girls (57.1%) compared with the reference group (49.2%). This could be due to chance (X2(1 df) = 3.37, P = 0.06), or unknown factors. In the present study, this is a confounding issue, because newborns sex is a known determinant of the studied pregnancy outcomes. The hypothesis needs further elaboration, which is beyond the present study. Exposed were more often single (X2(1 df) = 2.14, P = 0.14) and reported use of alcohol during pregnancy more common in exposed (42.7%) than unexposed (37.7%) women (X2(1 df) = 1.38, P = 0.24).
Synthesis with previous knowledge
Animal studies have shown fetotoxic and embryotoxic effects for a number of different solvents, often including growth retardation. Maternal toluene exposures at levels close to occupational exposures have been found to cause intrauterine growth retardation (Donald et al., 1991). N-hexane and methyl-ethyl ketone mixtures have been found to cause embryotoxic and fetotoxic effects as well as fetal growth retardation in rats (Stoltenburg-Didinger et al., 1990). Benzene can cause embryotoxicity and reduced fetal growth in mice (Maropon, 1987).
Most of the epidemiologic evidence of the effects of organic solvent exposure on fetal growth and duration of pregnancy comes from studies focusing on specific occupational groups including laboratory workers (Axelsson et al., 1984; Taskinen et al., 1994; Wennborg et al., 2000,2002; Zhu et al., 2006), drycleaners (Olsen et al., 1990), pharmacy assistants (Schaumburg and Olsen, 1991), hairdressers (Kersemaekers et al., 1997) and workers in petrochemical industry (Ha et al., 2002). The results of these studies are inconsistent. Consistent with the present study, two previous population-based epidemiological studies reported associations between solvent exposure and indicators of fetal growth retardation, although the findings did not reach statistical significance (Lipscomb et al., 1991; Seidler et al., 1999). Lipscomb and colleagues (1991) conducted a cross-sectional study in four census tracts in the San Jose area. They identified 1038 women aged 15–49 years who were pregnant any time between 1980 and 1985. Occupational exposure information was based on occupational history including job title, type of industry, type of work activity and months of employment 3 months before and during the pregnancy. Solvent exposure parameters were determined using both job titles and self-reports. The risk of low birth weight was elevated among newborns of exposed mothers with an adjusted OR of 2.00 (95% CI = 0.55–7.19) and the corresponding effect estimate for preterm delivery was 1.90 (95% CI = 0.30–3.99). The risk of spontaneous abortion was significantly elevated with an adjusted OR of 3.34 (1.42–7.81). Seidler et al. (1999) conducted a cohort study originally designed for assessing effects of the Chernobyl accident. They recruited a sample of pregnant women through 591 obstetric practices constituting 3946 pregnant women of whom 1865 were employed and with complete information forming the study population. Exposure assessment was based on a job-exposure matrix developed by Pannett et al. (1985). Estimated intensity and probability of exposure weighted by working hours/day were used to form an exposure score and ordinal scale exposure categories of no, low, moderate and high exposure. There were no observations in the high exposure category and the adjusted OR of SGA was 1.3 (95% CI = 0.6–2.5) for low versus no exposure and 2.2 (95% CI = 0.8–6.1) for medium versus no exposure. The P-value for the trend was 0.13. In summary, three population-based studies now provide consistent evidence that exposure to solvent may influence fetal growth, but the evidence of the effect on duration of pregnancy remains inconsistent.
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Concluding remarks |
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Our findings strengthen the evidence that work exposure to organic solvents may reduce intrauterine growth by increasing the risk of a SGA baby, but does not influence the duration of pregnancy. Given the extent of these exposures, the population impact is substantial and could be avoided by focused protection of pregnant women.
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Acknowledgements |
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We are grateful to the physicians and nurses in the Kymi and Porvoo Hospital Districts for their help and support that made this study possible. This study was supported by the Ministry of Social Affairs and Health, Finland and the West Midlands Levy Board, UK.
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