Potential exposure to endocrine disrupting chemicals and selected adverse pregnancy outcomes: a follow-up study of pregnant women referred for occupational counselling
- Jessica Bengtsson†1Email authorView ORCID ID profile,
- Pernille Søgaard Thygesen†1,
- Linda Kaerlev2, 3,
- Lisbeth E. Knudsen4 and
- Jens Peter Bonde1, 4
© The Author(s). 2017
Received: 17 August 2016
Accepted: 3 March 2017
Published: 9 March 2017
Experimental evidence indicates that fetal exposure to xenobiotics with the potential to interfere with the endogenous steroid hormone regulation of fetal development may reduce birth weight. However, epidemiological studies are limited. The aim of the study was to investigate whether potential occupational exposure to endocrine disrupting chemicals (EDC) of the mother during pregnancy is associated with preterm birth and low birth weight.
Pregnant women referred to an Occupational Health Clinic (OHC) in two Danish regions (Copenhagen or Aarhus) between 1984 and 2010, suspected of being exposed to occupational reproductive hazards were included in the study. A job exposure matrix enabled estimation of potential occupational exposure to EDC on the basis of job title. Births by women potentially exposed to EDC (n = 582) were compared to births by women referred to an OHC on the suspicion of other exposures than EDC (n = 620), and to a sample of births by all occupationally active women in the same geographical regions (n = 346,544), including 1,077 births of the referred women’s non-referred pregnancies.
No indications of reduced birth weight or increased risk of preterm birth were found among women potentially exposed to EDC. Women potentially exposed to EDC had children with a higher birth weight compared to the sample of occupationally active women but not compared to other women referred to an OHC.
Potential maternal exposure to EDC at Danish workplaces is not related to low birth weight or preterm birth among women referred to occupational counselling. Occupational exposures might be too weak on the average to cause these adverse effects or counselling at the OHCs is effective in preventing them.
KeywordsEndocrine disrupting chemicals Birth weight Gestational age Job exposure matrix Occupational health clinic Work health Prospective study Epidemiology Public health
Endocrine disrupting chemicals (EDC) are exogenous substances that cause adverse health effects through interference with the endocrine system [1, 2]. EDC may affect the endocrine system by mimicking or blocking the action of an endogenous hormone or bind to transport proteins. Furthermore, EDC may interfere with the normal endocrine system by changing the normal hormone level through stimulation or inhibition of the production of hormones [1, 2]. Several epidemiological studies suggest that a range of EDC may actually cause preterm birth and/or low birth weight [3, 4]. Many of these studies are concerned with specific substances, such as phthalates , some pesticides [6, 7] and poly-chlorinated biphenyls (PCB) . For example, exposure to PCB is believed, with increasing evidence, to inhibit fetal growth . Due to methodological restrictions, the complexity of these chemical substances, and due to preventive measures, the effects are often limited and the results inconsistent [9, 10]. Therefore, it is difficult to determine whether associations between EDC and preterm birth and/or low birth weight are causal [11, 12].
Denmark has had regulation on worker protection since 1873. According to the Danish Working Environment Act, the employer is responsible for ensuring a safe and sound working environment (Executive Order no. 1072 of 7 Sept. 2010). If a potentially harmful reproductive risk is present at the workplace, including exposure to EDC, pregnant women may be referred to an Occupational Health Clinic (OHC) by their general practitioner or midwife for reproductive risk assessment. This usually happens between 8 and 12 weeks of gestation. The clinics perform a risk assessment based upon available evidence in order to assess if the pregnant woman may continue in her job or whether there is a case for intervention in terms of actions to reduce or eliminate hazardous exposures, restructuring of job tasks, reassignment of job functions or – as the ultimate and least desirable solution - maternity leave due to reproductive risks that could not be resolved otherwise [13, 14]. Referred pregnant women are relocated or granted sick leave until the potential risk has been determined. However, keeping the pregnant women in their job, if possible, may be beneficial for the women in order to maintain income and attachment to the labor market.
Assuming that pregnant women referred to an OHC have a more hazardous occupational setting compared to pregnant women in general, since they are referred on the basis of a concrete suspicion of a harmful risk factor, these women constitute a relevant population to investigate. The national and complete coverage of the Danish Birth Register enable comparison of birth weight and gestational age of births by women referred to these clinics to all births in the same geographical regions. The aim of the present study was to examine if potential occupational exposure to EDC during pregnancy is related to preterm birth and/or low birth weight.
The study population consists of pregnant women referred to an OHC for occupational counselling in two Danish regions (Copenhagen and Aarhus) in the 26 year period from 1984 to 2010. A sample of all occupationally active women giving birth in the same time period and the same geographical regions, constitute an external reference group. We made restrictions as to those who were working at the onset of their pregnancy, mother’s age at delivery 16–45 years, birth weight 1,000–7,000 g and gestational age 154–310 days. Furthermore, one birth was chosen by random sampling among women with two or more deliveries in each of the groups, which left 1,202 women referred to an OHC (261 from Copenhagen, 941 from Aarhus), and 346,544 in the external reference group including 1,077 births of the referred women’s non-referred pregnancies.
Among women receiving occupational counselling, 582 were referred on the basis of suspected exposure to EDC (defined below) and 620 were referred due to other exposures. These 620 pregnancies constitute an internal reference group.
Information about the study population obtained from the OHCs was linked to data from Statistics Denmark  and the Medical Birth Registry . These links enabled comparison of gestational age and birth weight between the women referred to an OHC and the external reference group.
Exposure status of referred women was determined by using a job-exposure matrix (JEM) developed by van Tongeren et al. . The JEM includes 348 job titles according to the Categories of Occupation from 1980 (CO80). When developing the JEM, three occupational hygienists classified the likelihood of exposure to seven different substance groups with suspected endocrine disrupting properties (pesticides, polychlorinated organic compounds, phthalates, alkyl-phenolic compounds, bi-phenolic compounds, heavy metals and other substances) for all job titles independently. The authors defined the likelihood of exposure as unlikely, possible or probable .
Women referred to an OHC have been assigned a Danish occupational code. The code for each woman was translated into one of the job titles in the JEM. All women possibly or probably exposed to EDC in their occupation, according to the JEM, were combined into one group labelled potentially exposed. The seven substance categories in the JEM were combined into one overall group of EDC.
Every person with permanent residence in Denmark is given a unique 10-digit Personal Identification Number (PIN) . In the present study, the PIN enabled linkage between data from the OHCs with data from Statistics Denmark, which provided information on the mothers’ age, year of births, PIN of their children, country of origin, and socioeconomic status (SES) . Linkage to The Medical Birth Registry enabled access to information on birth weight, gestational age, previous pregnancies and smoking status during pregnancy .
Outcome and confounder assessment
We examined the following outcomes: gestational age and birth weight, birth weight at week 40, preterm birth (<37 weeks) and low birth weight (<2500 g). The limits of preterm birth and low birth weight were set according to the WHO definition .
To classify the mothers into four groups of SES, DISCO-88 codes were used . DISCO-88 is the Danish version of the International Standard Classification of Occupation (ISCO) and is divided into 10 main categories based on level of skills. Group 1 (D1-2) refers to top leaders, managers and employees with skills at the highest level. Employees with skills at medium level are classified into group 2 (D3). Group 3 (D4-8) contains employees with skills at basic level, and group 4 (D9-0) contains employees with unspecified working skills. Since the DISCO-88 codes were first registered in our data from 1991, only mothers giving birth hereafter are included in this variable.
Strategy of statistical analysis
We performed linear regression analyses of the effects of potential exposure to EDC (yes/no) on gestational age (days) and birth weight (grams) respectively while adjusting for a fixed set of potential confounding variables defined a priori: maternal age (16–24, 25–34 and 35–45 years), year of birth (1984–1989, 1990–1994, 1995–1999, 2000–2004 and 2005–2010), parity (first, second and third or more), SES (group 1, group 2, group 3, group 4 and unknown), ethnicity (Danish/non-Danish) and smoking at any time during pregnancy (yes/no).
In addition to linear regression of continuous outcomes we computed odds ratios (OR) for preterm birth and low birth weight according to exposure status by logistic regression analyses. We adjusted for maternal age, year of birth, parity, SES, ethnicity and smoking habits during pregnancy.
All calculations were made by the statistical program SAS version 9.3 (SAS Institute Inc, Cary, NC, USA).
Characteristics of women with potential occupational exposure to endocrine disrupting chemicals (EDC), women unexposed to EDC (internal references) and all occupationally active women in Copenhagen and Aarhus in the time period from 1984 to 2010 (external references)
Exposed to EDC
(n = 582)
Internal references (n = 620)
External references (n = 346,544)
Year of birth
Third or more births
Smoking habits during pregnancyb
Crude gestational age (days) with 95% confidence intervals (CI) among referred women potentially exposed to endocrine disrupting chemicals (EDC), and among the internal and the external reference group
Mean difference (95% CI)
Exposed versus internal reference
Exposed versus external reference
Exposed to EDC
276.4 – 278.7
−1.21 (−2.82 – 0.39)
−0.27 (−1.4 – 0.90)
277.7 – 279.9
277.8 – 277.8
Crude birth weight and birth weight at week 40 (grams) with 95% confidence intervals (CI) among referred women potentially exposed to endocrine disrupting chemicals (EDC), and among the internal and the external reference group
Mean difference (95% CI)
Exposed versus internal references
Exposed versus external references
Exposed to EDC
–5.42 (–76,9 – 66,1)
35.0 (−17,2 – 87,2)
Birth weight at week 40
Exposed to EDC
–3.2 (−141 – 136)
−21.5 (−126,4 – 83,5)
In analyses adjusting for gestational age and potential confounders, women potentially exposed to EDC had children with a higher birth weight when compared to the external references (in average 63 g higher, 95% CI: 22–101), but not when compared to internal referents (in average 37 g higher, 95% CI: −19–93).
Odds ratio with 95% confidence interval (CI) for preterm birth among women potentially exposed to endocrine disrupting chemicals (EDC) compared to the internal and external references respectively
Exposed to EDC
Odds ratio with 95% confidence intervals (CI) for low birth weight among women potentially exposed to endocrine disrupting chemicals (EDC) compared to the internal and external references respectively
Low birth weight
Normal birth weight
Exposed to EDC
A sensitivity analysis only including first births did not show any differences of importance for gestational age and birth weight between the three exposure groups (data not shown).
In this prospective follow-up study of pregnant women referred to an OHC for counselling, we found no indications of reduced birth weight or increased risk of preterm birth among women potentially exposed to EDC. Women potentially exposed to EDC had children with a higher birth weight when compared to the external references. This might reflect an anabolic effect of EDC (for instance an estrogenic effect), but without consistent findings in analyses using the internal references, we consider this a chance or spurious result.
Women referred to an OHC are presumed to represent a high risk group, and constitute thereby a preferable basis for investigation compared to a population based study. The present study design enables comparison between women referred to an OHC potentially exposed to EDC and women referred to an OHC but unexposed to EDC. These two groups are highly comparable, since they are expected to be similar in most aspects except exposure status. Furthermore, use of register data provides a large study population contributing to enhanced statistical power.
These reassuring results can be understood in several ways. First of all, Denmark has a long tradition of worker protection regulation and the Danish Working Environment Authorities regularly performs inspections at Danish workplaces. Thus, potentially harmful chemical exposures of pregnant women at Danish workplaces are in general considered well controlled and chemically induced birth defects are rarely notified to the National Board of Industrial Injuries . Therefore, the women defined as potentially exposed to EDC in the present study might not have been exposed to EDC to an extent that is strong enough to cause detectable adverse effects on gestational age and birth weight. A second explanation of the findings might be that the risk imposed by EDC is reduced by occupational risk assessment and counselling. If the risk assessment indicates a harmful exposure, actions to reduce or eliminate the exposure are recommended. Finally, awareness of potential harmful exposure, induced by the referral to an OHC, might cause a behavior change to a more protective lifestyle during pregnancy . However, human embryo development is most vulnerable to toxic substances and endocrine disruption in the early embryonic period during the first 8 weeks of gestation, while counselling at an OHC usually takes place between 8 and 12 weeks of gestation.
One limitation of this study concerns the determination of exposure to EDC. The risk of EDC might go undetected in the present study due to misclassification associated with determination of exposure status. Using a JEM does not necessarily give an accurate picture of exposure since exposure might vary within job titles .
The JEM of van Tongeren et al. divides the chemical substances into seven substance categories . In the present study all substances were combined into one group of EDC. By doing so, some accuracy in relation to potential differences between substances is lost. However, these reductions of categories were made to address the purpose of the present study - to investigate the general potential effects of EDC on gestational age and birth weight.
Finally and importantly, EDC are also found in many consumer products and the exposure besides the occupationally induced might be profound which would diminish the association in the present study. We know very little about what factors pregnant women are exposed to at home .
Pregnant women with potential occupational exposure to EDC were not at increased risk of delivering preterm or low birth weight babies. Findings may reflect that exposure levels are low without impact on the studied reproductive outcomes or that occupational counseling result in effective preventive actions.
Categories of occupation
Endocrine disrupting chemicals
International standard classification of occupation
Occupational health clinic
Personal identification number
This study has no external funding.
Availability of data and materials
The data that support the findings of this study are available from the OHC in Copenhagen and Aarhus but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from author JPB (email@example.com) upon reasonable request and with permission of the OHC in Copenhagen and Aarhus.
JB and PST have contributed equally to the analysis of data and in writing the manuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Ethics approval and consent to participate
The Danish Data Protection Agency approved the study. Evaluation by a scientific ethical committee is in Denmark not requested for registry-based studies where participants are not contacted.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Van Tongeren M, Nieuwenhuijsen MJ, Gardiner K, Armstrong B, Vrijheid M, Dolk H, et al. A job-exposure matrix for potential endocrine-disrupting chemicals developed for a study into the association between maternal occupational exposure and hypospadias. Ann Occup Hyg. 2002;46:465–77.PubMedGoogle Scholar
- Schug TT, Janesick A, Blumberg B, Heindel JJ. Endocrine disrupting chemicals and disease susceptibility. J Steroid Biochem Mol Biol. 2011;127:204–15.View ArticlePubMedPubMed CentralGoogle Scholar
- Triche EW, Hossain N. Environmental factors implicated in the causation of adverse pregnancy outcome. Semin Perinatol. 2007;31:240–2.View ArticlePubMedGoogle Scholar
- Caserta D, Mantovani A, Marci R, Fazi A, Ciardo F, La Rocca C, et al. Environment and women’s reproductive health. Hum Reprod Update. 2011;17:418–33.View ArticlePubMedGoogle Scholar
- Wolff MS, Engel SM, Berkowitz GS, Ye X, Silva MJ, Zhu C, et al. Prenatal phenol and phthalate exposures and birth outcomes. Environ Health Perspect. 2008;116:1092–7.View ArticlePubMedPubMed CentralGoogle Scholar
- Wohlfahrt-Veje C, Main KM, Schmidt IM, Boas M, Jensen TK, Grandjean P, et al. Lower birth weight and increased body fat at school age in children prenatally exposed to modern pesticides: a prospective study. Environ Health Glob Access Sci Source. 2011;10:79.Google Scholar
- Burdorf A, Nieuwenhuijsen MJ. Endocrine disrupting chemicals and human reproduction: fact or fiction? Ann Occup Hyg. 1999;43:435–7.View ArticlePubMedGoogle Scholar
- Govarts E, Nieuwenhuijsen M, Schoeters G, Ballester F, Bloemen K, de Boer M, et al. Birth weight and prenatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE): a meta-analysis within 12 European Birth Cohorts. Environ Health Perspect. 2012;120:162–70.View ArticlePubMedGoogle Scholar
- Figà-Talamanca I. Occupational risk factors and reproductive health of women. Occup Med Oxf Engl. 2006;56:521–31.View ArticleGoogle Scholar
- Suárez-Varela MMM, Kaerlev L, Zhu JL, Bonde JP, Nøhr E-A, Llopis-González A, et al. Hospital work and pregnancy outcomes: a study in the Danish national birth cohort. Int J Occup Environ Health. 2009;15:402–9.View ArticlePubMedGoogle Scholar
- Meeker JD. Exposure to environmental endocrine disruptors and child development. Arch Pediatr Adolesc Med. 2012;166:952–8.View ArticlePubMedGoogle Scholar
- DiVall SA. The influence of endocrine disruptors on growth and development of children. Curr Opin Endocrinol Diabetes Obes. 2013;20:50–5.View ArticlePubMedGoogle Scholar
- Kaerlev L, Jacobsen LB, Olsen J, Bonde JP. Long-term sick leave and its risk factors during pregnancy among Danish hospital employees. Scand J Public Health. 2004;32:111–7.View ArticlePubMedGoogle Scholar
- Bonde JP, Johansen JP. [The occupational environment and pregnancy. Occupational medicine advice to pregnant women in potentially high-risk occupational environments]. Ugeskr. Laeger. 1987;149:677–80.Google Scholar
- Statistics Denmark [Internet]. [cited 2015 Apr 22]. Available from: http://dst.dk/en
- Knudsen LB, Olsen J. The Danish medical birth registry. Dan Med Bull. 1998;45:320–3.PubMedGoogle Scholar
- Pedersen CB. The Danish civil registration system. Scand J Public Health. 2011;39:22–5.View ArticlePubMedGoogle Scholar
- WHO | Preterm birth [Internet]. WHO. [cited 2015 Apr 3]. Available from: http://www.who.int/mediacentre/factsheets/fs363/en/
- DISCO-88. Statistics Denmark’s standard classification of occupation. Copenhagen: Statistics Denmark; 1996.Google Scholar
- Arbejdsskader - årsopgørelser - Arbejdstilsynet [Internet]. [cited 2017 Feb 7]. Available from: http://arbejdstilsynet.dk/da/statistik/arbejdsskader/arbejdsskader-arsopgorelser
- Morales-Suárez-Varela M, Kaerlev L, Zhu JL, Bonde JP, Nohr EA, Llopis-González A, et al. Unemployment and pregnancy outcomes: a study within the Danish national birth cohort. Scand J Public Health. 2011;39:449–56.View ArticlePubMedGoogle Scholar