Maternal occupational exposure to endocrine-disrupting chemicals and urogenital anomalies in the offspring.

STUDY QUESTION: Is there an association between maternal occupational exposure to endocrine-disrupting chemicals (EDCs) early in pregnancy and subgroups of congenital anomalies of kidney and urinary tract (CAKUT), and hypospadias? SUMMARY ANSWER: Exposure to specific EDCs can increase the risk of CAKUT and no association with hypospadias was observed. WHAT IS KNOWN ALREADY: Previous studies showed an association between maternal occupational exposure to EDCs and hypospadias. However, little is known about the effect of these chemicals on the development of CAKUT, especially subgroups of urinary tract anomalies. STUDY DESIGN, SIZE, DURATION: For this case-control study, cases with urogenital anomalies from the European Concerted Action on Congenital Anomalies and Twins Northern Netherlands (Eurocat NNL) registry and non-malformed controls from the Lifelines children cohort (living in the same catchment region as Eurocat NNL) born between 1997 and 2013 were selected. This study included 530 cases with CAKUT, 364 cases with hypospadias, 7 cases with both a urinary tract anomaly and hypospadias and 5602 non-malformed controls. Cases with a genetic or chromosomal anomaly were excluded, and to avoid genetic correlation, we also excluded cases in which a sibling with the same defect was included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information on maternal occupation held early in pregnancy was collected via self-administered questionnaires. Job titles were translated into occupational exposure to EDCs using a job-exposure matrix (JEM). Adjusted odds ratios (aORs) and 95% CIs were estimated to assess the association between maternal occupational exposure to EDCs (and to specific types of EDCs) and CAKUT and hypospadias. MAIN RESULTS AND THE ROLE OF CHANCE: For CAKUT and hypospadias, 23.1% and 22.9% of the cases were exposed to EDCs, respectively, whereas 19.8% of the controls were exposed. We found an association between maternal occupational exposure to organic solvents/alkylphenolic compounds and CAKUT (aOR 1.41, 95% CI 1.01-1.97) that became stronger when combinations of urinary tract anomalies co-occurred with other defects (aOR 7.51, 95% CI 2.41-23.43). An association was also observed for exposure to phthalates/benzophenones/parabens/siloxanes and CAKUT (aOR 1.56, 95% CI 1.06-2.29), specifically urinary collecting system anomalies (aOR 1.62, 95% CI 1.03-2.54) and combinations of urinary tract anomalies (aOR 2.90, 95% CI 1.09-7.71). We observed no association between EDC exposure and hypospadias. LIMITATIONS, REASONS FOR CAUTION: The different study designs of Eurocat NNL and Lifelines could have introduced differential information bias. Also, exposure misclassification could be an issue: it is possible that the actual exposure differed from the exposure estimated by the JEM. In addition, women could also have been exposed to other exposures not included in the analysis, which could have resulted in residual confounding by co-exposures. WIDER IMPLICATIONS OF THE FINDINGS: Women, their healthcare providers, and their employers need to be aware that occupational exposure to specific EDCs early in pregnancy may be associated with CAKUT in their offspring. An occupational hygienist should be consulted in order to take exposure to those specific EDCs into consideration when risk assessments are carried out at the workplace. STUDY FUNDING/COMPETING INTEREST(S): N.S. was paid by the Graduate School of Medical Sciences (MD/PhD programme), University Medical Center Groningen (UMCG), Groningen, the Netherlands. Eurocat Northern Netherlands is funded by the Dutch Ministry of Health, Welfare and Sports. The Lifelines Biobank initiative has been made possible by subsidy from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG the Netherlands), University Groningen and the Northern Provinces of the Netherlands. The authors report no conflict of interest. TRIAL REGISTRATION NO: N/A.

Congenital anomalies in the offspring of occupationally exposed mothers: a systematic review and meta-analysis of studies using expert assessment for occupational exposures.

STUDY QUESTION: Is there an association between maternal occupational exposure to solvents, pesticides and metals as assessed by expert-based assessment and congenital anomalies in the offspring? SUMMARY ANSWER: There is an association between maternal occupational exposure to solvents and congenital anomalies in the offspring, including neural tube defects, congenital heart defects and orofacial clefts. WHAT IS KNOWN ALREADY: One important environmental risk factor for development of congenital anomalies is maternal occupational exposure to chemicals in the workplace prior to and during pregnancy. A number of studies have assessed the association with often conflicting results, possibly due to different occupational exposure assessing methods. STUDY DESIGN, SIZE, DURATION: For this systematic review with meta-analysis, the search terms included maternal occupation, exposure, congenital anomalies and offspring. Electronic databases MEDLINE and EMBASE were searched for English studies up to October 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two reviewers independently screened all citations identified by the search. Case-control studies and cohort studies were included if (I) they reported on the association between maternal occupational exposure to solvents, pesticides or metals and congenital anomalies, and (II) assessment of occupational exposure was performed by experts. Data on study characteristics, confounders and odds ratios (ORs) were extracted from the included studies for four subgroups of congenital anomalies. Methodological quality was assessed using the Newcastle-Ottawa Scale. In the meta-analysis, random effects models were used to pool estimates. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 2806 titles and abstracts and 176 full text papers were screened. Finally, 28 studies met the selection criteria, and 27 studies could be included in the meta-analysis. Our meta-analysis showed that maternal occupational exposure to solvents was associated with neural tube defects (OR: 1.51, 95%CI: 1.09-2.09) and congenital heart defects (OR: 1.31, 95%CI:1.06-1.63) in the offspring. Also maternal occupational exposure to glycol ethers, a subgroup of solvents, was associated with neural tube defects (OR: 1.93, 95%CI: 1.17-3.18) and orofacial clefts (OR: 1.95, 95%CI: 1.38-2.75) in the offspring. Only one study investigated the association between maternal occupational exposure to solvents and hypospadias and found an association (OR: 3.63, 95%CI: 1.94-7.17). Results of the included studies were consistent. In our meta-analysis, we found no associations between occupational exposure to pesticides or metals and congenital anomalies in the offspring. LIMITATIONS, REASONS FOR CAUTION: A limited number of studies was included, which made it impossible to calculate pooled estimates for all congenital anomalies, analyse individual chemicals or calculate exposure-response relations. Bias could have been introduced because not all included studies corrected for potentially confounding factors. WIDER IMPLICATIONS OF THE FINDINGS: Employers and female employees should be aware of the possible teratogenic effects of solvent exposure at the workplace. Therefore, is it important that clinicians and occupational health specialist provide women with preconception advice on occupational solvent exposure, to reduce the congenital anomaly risk. STUDY FUNDING/COMPETING INTEREST(S): NSp was paid by the Graduate School of Medical Sciences (MD/PhD program), UMCG, Groningen, the Netherlands. EUROCAT Northern Netherlands is funded by the Dutch Ministry of Health, Welfare and Sports. There are no competing interests. REGISTRATION NUMBER: CRD42017053943.