Social selection in cohort studies and later representation of childhood psychiatric diagnoses: The Danish National Birth Cohort.

Aim: This study aimed to estimate the relative representation of childhood psychiatric diagnoses and use of psychotropic medication in the Danish National Birth Cohort (DNBC) compared to the general population. Methods: The general population was identified as all childbirths in Denmark during 1998-2002 (N=344,160). Linking the DNBC (N=91,442) and the general population to the Danish national health registries, all children were followed until they received an ICD-10 psychiatric diagnosis, had a prescription of psychotropic medication or to the end of follow-up in 2013. The prevalence ratios (PRs) with corresponding 95% confidence intervals (CI) were estimated for each psychiatric diagnosis and by sex. Age at first diagnosis presented as means were compared using the one-sample t-test. Results: In the DNBC, the selected childhood psychiatric diagnoses were underrepresented by 3% (PR=0.97, 95% CI 0.94-0.99), ranging from a 20% underrepresentation for schizophrenia (PR=0.80, 95% CI 0.59-1.09) to a 6% over-representation for anxiety disorder or obsessive-compulsive disorder (PR=1.06, 95% CI 0.97-1.17). The majority of the specific diagnoses were modestly underrepresented in the DNBC compared to the general population, while use of psychotropic medication had similar representation. Girls were generally more underrepresented than boys. Depression was on average diagnosed 0.4 years earlier in the DNBC than in the general population (p=0.023). Conclusions: These findings suggest that the social selection may influence the prevalence of diagnosed childhood psychiatric disorders in the DNBC.

[Effects of obesity on global genome DNA methylation and gene imprinting in mouse spermatozoa].

OBJECTIVE: To investigate the influence of high fat diet-induced obesity (HFDIO) on the differentially methylated region (DMR) of the imprinted gene and global genome methylation of sperm DNA. METHODS: We performed bisulfite sequencing on the DMR of the imprinted gene and global genome methylation of sperm DNA in the mouse model of HFDIO. RESULTS: No statistically significant differences were found between the HFDIO model and normal control mice in MEG3-IG (93.73 vs 97.26%, P = 0.252), H19 (98.00 vs 97.83%, P = 0.920), IGF2 (97.34 vs 96.25%, P =0.166), IGF2R (1.43 vs 1.11%, P = 0.695), PEG3 (0.19 vs 0.38%, P = 0.537), MEST (0.23 vs 0.68%, P = 0.315), NNAT (0.31 vs 0.00%, P = 0.134), or SNRPN (1.88 vs 3.13%, P = 0.628). A total of 8 942 DMRs were detected across the sperm genome (P <0.05). Gene functional enrichment analysis indicated that the enriched terms with the largest numbers of genes were the metabolic process (n = 1 482), RNA synthesis (n = 779), and transcription (n = 767). CONCLUSIONS: The methylation level underwent no significant change in the DMRs of the imprinted genes from the mice with HFDIO, but the CG methylation of the genes involved in the metabolic process, RNA synthesis and transcription were significantly altered.

The risk of attention deficit hyperactivity disorder in children exposed to maternal smoking during pregnancy - a re-examination using a sibling design.

BACKGROUND: Conventional cohort studies have consistently shown that exposure to maternal smoking in pregnancy is associated with about twice the risk of attention deficit hyperactivity disorder (ADHD) in the offspring. However, recent studies using alternative designs to disentangle the effect of social and genetic confounders have suggested that confounding may account for the association. In this study we aimed to estimate the association by a sibling design. METHODS: We used a design with half and full siblings in a Danish national register-based cohort on all singletons born between January 1991 and December 2006 and followed until January 2011. Data were available for 90% (N = 968,665) of the singleton live births in the period. We used the combination of the International Classification of Diseases (10th version) diagnosis of hyperkinetic disorder (HKD) and ADHD medication to identify children. We used sibling-matched (conditional) Cox regression to control social and genetic confounding. RESULTS: Using conventional cohort analyses, we found the expected association between pregnancy smoking and offspring ADHD (adjusted HR 2.01, 95% CI 1.94-2.07). In the sibling analysis, however, we did not detect such a strong association (adjusted HR 1.07, 95% CI 0.94-1.22). There was no difference between results for half- and full sibling analyses. The link between pregnancy smoking and low birth weight remained robust in the sibling design (adjusted OR 1.68, 95% CI 1.33-2.12). CONCLUSIONS: We found no support for prenatal smoking as a strong causal factor in ADHD. Our findings suggest that the strong association found in most previous epidemiological studies is likely to be due to a strong link between maternal smoking and maternal ADHD genetics or shared family environment. Pregnant women should still be encouraged to stop smoking because of other risks, but we have no reason to believe that this would reduce the risk of ADHD in the offspring.

ILEI: a novel marker for epithelial-mesenchymal transition and poor prognosis in colorectal cancer.

AIMS: Accumulating evidence over the past decade has shown that abnormal activation of epithelial to mesenchymal transition (EMT) contributes to tumour progression and metastasis in colorectal cancer (CRC). In this study, we investigated the expression of interleukin-like EMT inducer (ILEI) and EMT-associated markers (E-cadherin, vimentin) in CRC tissues and determined the correlations between ILEI expression and clinicopathological characteristics, prognosis and EMT in CRC. METHODS AND RESULTS: In total, 194 patients diagnosed with CRC based on histopathological evaluation and those subjected to surgical resection at the First Hospital of China Medical University between 2003 and 2005 were examined. Immunohistochemical staining for ILEI, vimentin and E-cadherin was performed for each specimen. Cytoplasmic overexpression of ILEI usually accompanied down-regulation of E-cadherin and positive expression of vimentin. Conversely, ILEI was simultaneously down-regulated with overexpression of E-cadherin and negative expression of vimentin. ILEI overexpression was associated significantly with T-stage, N-stage, TNM stage and EMT phenotype (P = 0.024, <0.001, <0.001 and <0.001, respectively). Multivariate analysis revealed that ILEI expression was an independent prognostic factor for patient survival. CONCLUSIONS: Our findings indicate that cytoplasmic ILEI expression is a potential marker of EMT and tumour progression in CRC. ILEI is an independent predictive factor associated with poor prognosis in CRC.

Social conditions for people with Down syndrome: a register-based cohort study in Denmark.

Today, most persons with Down syndrome (DS) survive into middle age, but information on their social conditions as adults is limited. We addressed this knowledge gap using data from national registers in Denmark. We identified a national cohort of 1,998 persons with DS who were born between 1968 and 2007 (1,852 with standard trisomy 21, 80 with Robertsonian translocations and 66 with mosaicism) using the Danish Cytogenetic Register. We followed this cohort from 1980 to 2007. Information on social conditions (education, employment, source of income, marital status, etc.) was obtained by linkages to national registers, including the Integrated Database for Longitudinal Labor Market Research. For those aged 18 and older, more than 80% of persons with DS attended 10 years of primary school, with about 2% completing secondary or post-secondary education. About 4% obtained a full-time job, whereas the remaining mainly received public support from the government. Only a few (1-2%) of persons with DS were married or had a child. No significant differences in these social conditions were seen between males and females. More persons with mosaic DS attended secondary or post-secondary education, had a full-time job, were married, or had a child (18%, 28%, 15%, and 7%, respectively), compared with persons with standard DS (1%, 2%, 1%, and 1%, respectively). These data may provide families with better insight into social conditions and society with a better understanding of the social support needed for persons with DS.

Survival among people with Down syndrome: a nationwide population-based study in Denmark.

PURPOSE: Several studies have shown substantially longer survival among persons with Down syndrome in recent decades. We examined survival patterns among Danish persons with Down syndrome by karyotype. METHODS: A national cohort of 3,530 persons with Down syndrome identified from the Danish Cytogenetic Register and a reference cohort of persons without Down syndrome randomly selected from the general population were followed from 1 April 1968 to 15 January 2009 by linkages to the Register of Causes of Death and the Civil Registration System. RESULTS: Overall, persons with Down syndrome had higher mortality than the reference cohort but to a lesser degree for persons with mosaic trisomy 21 than for persons with standard trisomy 21 or with Robertsonian translocations (hazard ratio 4.98 (95% confidence interval 3.51-7.08), 8.94 (8.32-9.60), and 10.23 (7.50-13.97), respectively). Among persons with Down syndrome born after April 1968, more recent birth cohorts had lower mortality rates than older birth cohorts, which was largely due to declining mortality among persons with Down syndrome who also had congenital heart defects. CONCLUSION: Recent birth cohorts of persons with Down syndrome experienced declining mortality, likely due to treatment for congenital heart defects, and persons with mosaic trisomy 21 had better survival than persons with other Down syndrome karyotypes.

The clinical significance of mesenchyme forkhead 1 (FoxC2) in gastric carcinoma.

AIMS: Mesenchyme forkhead 1 (FoxC2) is an epithelial-mesenchymal transition (EMT)-inducing factor. Previous studies have demonstrated that FoxC2 binds directly to the promoter region of p120-catenin (p120ctn). The aim of this study was to investigate the clinical significance of FoxC2 expression and the inter-relationship between FoxC2 and p120ctn, in gastric cancer. METHODS AND RESULTS: Immunohistochemistry was used to examine the expression of FoxC2 and p120ctn proteins in 325 gastric cancer samples. Staining for FoxC2 in cancer tissues was markedly stronger than in normal tissues. High FoxC2 expression was associated significantly with differentiation, invasion depth, lymph node metastasis and tumour stage. Patients with high FoxC2 expression or low p120ctn expression had a poor prognosis. In the high p120ctn expression group, the prognosis for patients with low FoxC2 expression was better than for the high FoxC2 group. Moreover, stepwise Cox regression showed that p120ctn was an independent prognostic factor, but FoxC2 in combination with p120ctn was not correlated significantly with survival. CONCLUSIONS: We found that FoxC2 and p120ctn play important roles in the progression and prognosis of gastric cancer. Moreover, FoxC2 and p120ctn should be evaluated further as novel biomarkers and therapeutic targets for gastric cancer treatment.

Hospitalizations among people with Down syndrome: a nationwide population-based study in Denmark.

Most persons with Down syndrome (DS) now survive to adulthood, but their health care needs beyond childhood are not well described. We followed a national cohort of 3,212 persons with DS and a reference cohort of persons without DS through the Danish National Hospital Register from January 1, 1977, to May 31, 2008. Poisson regression was used to calculate rate ratios for numbers of overnight hospital admissions and hospital days. During the study period, persons with DS had more than twice the rate of hospital admissions and nearly three times as many bed-days as the population as a whole. Malformations, diseases of the respiratory system, and diseases of the nervous system or sensory organs were the principal indications for hospital admissions. The higher rate ratios for hospital admissions were seen especially among persons less than 20 years of age. Hospitalizations for neoplasms or for diseases of the musculoskeletal system or connective tissue were much less frequent among adults with DS. As survival among persons with DS continues to improve, these findings are likely to be useful for health care planning, although the potential utility may be different for different health care systems.

Cancer risks in parents who had a child with a congenital malformation.

Cancer risk in parents may be related to congenital malformations (CMs) in their children if they share genetic susceptibility or environmental exposure that may be teratogenic and carcinogenic. We conducted a population-based cohort study based on Danish register data. We identified 795,607 mothers and 781,424 fathers who had all their children between 1977 and 2007 in Denmark. Information on CM was obtained from the Danish Hospital Registry and information on cancer was obtained from the Danish Cancer Registry. Parents were followed from the birth of their first child until the diagnosis of cancer, death, emigration, or December 31, 2007. We used Cox regression models to estimate hazard ratios (HRs) for cancer including cancer in specific organs in mothers and fathers. Overall, 75,701 (9.5%) mothers and 72,724 (9.3%) fathers had at least one child diagnosed with CMs within the first year of life. Neither mothers (HR=1.04; 95% CI: 0.99-1.04) nor fathers (HR=1.03; 95% CI: 0.98-1.09) who had a child with a CM had a higher overall risk of cancer. Mothers (HR=0.76, 95% CI: 0.58-1.00) or fathers (HR=0.89, 95% CI: 0.66-1.19) who had a child with a chromosomal malformation had a lower overall cancer risk. The findings also showed a higher risk for some specific types of cancer in parents who had children with a CM in the specific system. Some, or perhaps all, of these findings may be due to chance caused by multiple comparisons. We present all results on paper or online to provide clues for further research and to avoid publication bias.

Clinicopathological significance of claudin-4 in gastric carcinoma.

BACKGROUND: Aberrant expression of claudin proteins has been reported in a variety of cancers. Previous studies have demonstrated that overexpression of claudin may promote tumorigenesis and metastasis through increased invasion and survival of tumor cells. However, the prognostic significance of claudin-4 in gastric cancer remains unclear. METHODS: Immunohistochemistry was used to analyze the expression of claudin-4 in 329 clinical gastric cancer specimens and 44 normal stomach samples, 21 intestinal metaplasia samples, and 21 adjacent precursor lesions dysplasia samples. Statistical analysis methods were used to evaluate the relationship between claudin-4 expression and various clinicopathological parameters. Univariate and multivariate analyses were performed, respectively, to detect the independent predictors of survival. RESULTS: Claudin-4 expression was present in only 7(15.9%) normal gastric samples, but expression of claudin-4 in the intestinal metaplasia lesions and dysplasia lesions was 90.5% and 95.2%, respectively. The expression of claudin-4 was significantly associated with histological differentiation (P < 0.001) and tumor growth patterns (P < 0.001) but not associated with patient survival. However, intermediate type staining of claudin-4 exhibited a trend of correlation with patients' survival (P = 0.023). The five-year survival rate with low expression of claudin-4 in intermediate type (76.4%) was similar to expanding type (64.5%), while the high expression group (46.6%) was closer to infiltrative type (50.7%). CONCLUSIONS: The findings in this study demonstrate claudin-4 aberrant expression in gastric cancer and precursor lesions. The expression of claudin-4 could serve as a basis for identifying gastric cancer of the intermediate type.

Association Between Night Shift and Hypertension: A Cross-Sectional Study in Chinese Adults.

OBJECTIVE: The purpose of this study was to explore the effect of night-shift work on the risk of hypertension for improving workers' health. METHODS: A total of 10,038 Chinese participants were constituted in the cross-sectional study. Logistic regression and restricted cubic spline were used to estimate the effect of night shift on hypertension. RESULTS: There were higher odds of having hypertension in any night-shift workers (odds ratio [OR], 1.16 [95% confidence interval, 1.03-1.30]) when compared with day workers. Having 5 to 10 night shifts per month were significantly more likely to be hypertensive (OR, 1.19 [95% confidence interval, 1.03-1.38]). The OR for hypertension increased as the number of night shifts increased as the result of the restricted cubic spline. CONCLUSIONS: Our results support the hypothesis that night shift is associated with an elevated risk of hypertension.

Associations of non-metastatic cells 1 gene polymorphisms with lymph node metastasis risk of gastric cancer in Northern Chinese population.

Single nucleotide polymorphisms (SNPs) in the promoter regions of non-metastatic cells 1 gene (NME1) may attribute to the changing of promoter activities. In addition, high NME1 protein levels are correlated with negative lymph node metastasis in gastric cancer. This study evaluated possible associations between SNPs in NME1 gene and gastric cancer susceptibility, clinicopathological parameters, or survival. We obtained formalin-fixed paraffin-embedded tissues from 404 gastric cancer patients and blood samples from 404 controls. SNPs were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A significant correlation between SNPs and lymph node metastases risk was found. Patients carrying TT genotype in rs16949649, AA genotype in rs3760468, TT genotype in rs3760469, CC genotype in rs2302254, and GG genotype in rs34214448 were correlated to greater numbers of lymph node metastases (P = 0.023 in rs16949649; P = 0.015 in rs3760468; P = 0.043 in rs3760469; P = 0.008 in rs2302254; and P = 0.021 in rs34214448, respectively). Moreover, the haplotype TATCG were associated with positive lymph node metastasis (P = 0.039) and lymphovascular invasion (P = 0.048) compared to the haplotype CTGTT carriers. Furthermore, patients carrying AA genotype in rs3760468 or the haplotype TATCG had poor survival in T4 subgroup (P = 0.038 in univariate and P = 0.014 in multivariate analysis for rs3760468, and P = 0.017 in univariate and P = 0.012 in multivariate analysis for TATCG, respectively). In conclusion, SNPs in NME1 gene may play an important role in regulating lymph node metastasis and, thus, affect survival in T4 subgroup of gastric cancer in a Northern Chinese population.

Risk for developmental coordination disorder correlates with gestational age at birth.

BACKGROUND: Studies suggest that children born very preterm have a high risk of developmental coordination disorder (DCD). We examined the relation between the larger spectrum of gestational age at birth and the risk of DCD. METHODS: We used the 7-year follow-up data from 22898 singletons in the Danish National Birth Cohort. We calculated a total score from the Developmental Coordination Disorder Questionnaire (DCDQ), incorporated in the 7-year follow-up, and defined children with a score of 46 or below as having probable DCD. Information on gestational age was obtained from the Medical Birth Register. RESULTS: Gestational age at birth was inversely associated with the risk of DCD; a decline in gestational age by a week was associated with a 19% [95% confidence interval 14%, 25%] increased risk of DCD screening positive among children delivered before 40 weeks. No significant increased risk of DCD was seen for children born post-term. CONCLUSION: Our data indicate that short gestational age at birth in a range up to gestational week 37 is related to an increased risk of DCD.

Time to pregnancy among women with rheumatoid arthritis.

OBJECTIVE: To assess whether onset of rheumatoid arthritis (RA) prior to conception is associated with a delayed time to pregnancy (TTP). METHODS: The study included pregnant women from across Denmark who enrolled in the Danish National Birth Cohort between 1996 and 2002 and had planned or partly planned the cohort pregnancy. RA diagnosis was identified using the Danish National Hospital Discharge Registry. Self-reported data, including TTP, maternal age, parity, prepregnancy height and weight, maternal occupational status, smoking, and alcohol consumption, were collected using a detailed computer-assisted telephone interview at ∼16 weeks of gestation. We used logistic regression analyses as well as a complementary log regression model to examine whether TTP was influenced by RA, adjusting for the abovementioned variables. RESULTS: Overall, compared with women with no recorded RA (n=74,255), women with prevalent RA (onset prior to conception) (n=112) were slightly older (mean±SD age 30.8±4.3 years versus 29.7±4.1 years), were more likely to have been treated for infertility (9.8% versus 7.6%), and were more likely to have taken>12 months to conceive (25.0% versus 15.6%). The association between RA and TTP was borderline significant after adjusting for covariates in the regression analyses (odds ratio 1.6 [95% confidence interval 1.0-2.4]). Similar results were obtained after restricting the analyses to women who had planned the pregnancy or those who were nulliparous before the cohort pregnancy. CONCLUSION: Women with RA onset prior to conception had a slightly longer TTP compared with those who did not have RA, indicating a slight reduction in fecundity.

Infertility, infertility treatment and behavioural problems in the offspring.

Behavioural patterns in children of infertile couples may be influenced by both the underlying causes of infertility and stress in the couples. Treatment procedures, such as culture media and manipulation of gametes and embryos, may also result in developmental problems. We examined behavioural problems in children as a function of infertility and infertility treatment, using data from three population-based birth cohorts in Denmark (Aalborg-Odense Birth Cohort, Aarhus Birth Cohort and Danish National Birth Cohort). Information on time to pregnancy and infertility treatment was collected during pregnancy. Children aged between 7 and 21 years were assessed using the Strengths and Difficulties Questionnaire (SDQ). The SDQ was completed by mothers in all cohorts and, in addition, by teachers in the Aarhus cohort and by children themselves in the Aalborg-Odense cohort. Children born after a time to pregnancy of >12 months and no infertility treatment had a behavioural pattern similar to children of fertile parents. Teachers reported a higher total difficulties score for children born after infertility treatment, but no significant differences were seen on any subscales of the teachers' report, and neither the mothers nor the children reported any differences on the total difficulties score and the prosocial behaviour score. Our results are thus overall reassuring regarding behavioural problems in children born to infertile couples, regardless of infertility treatment.

Has fertility declined in recent decades?

OBJECTIVE: Increasing use of infertility treatment and a decline in demographic fertility in some countries have raised concern whether human fecundity is declining or has declined over time. A dramatic decline in semen quality over the past half-century has been proposed and widely discussed, but none of the existing studies provide data good enough for coming to any firm conclusion. RESULTS: Results from 19 articles published during the last 5 years on semen quality and fecundity, covering data from the Nordic countries since the year 2000, do not indicate an ongoing decline in fertility. CONCLUSION: We will probably never know, whether semen quality and fecundity has declined over time, but we may be able to monitor biological fecundity and semen quality over time from now on. There are both research initiatives and interest from official channels that could provide more funding for infertility research.

Unemployment and pregnancy outcomes: a study within the Danish National Birth Cohort.

AIMS: To explore the relation between employment status, type of unemployment and pregnancy outcomes. METHODS: A cohort study of 7,282 pregnancies of unemployed women and 56,014 pregnancies among women in paid jobs was performed within the Danish National Birth Cohort. Pregnancy outcomes were ascertained and information about lifestyle, occupational, medical, and obstetric factors was obtained. Logistic regression was used to calculate odds ratios (OR) for fetal loss, congenital anomalies, multiple births, sex ratio, preterm and very preterm birth and small for gestational age status, adjusting for lifestyle, medical and obstetric factors. RESULTS: There were no differences in pregnancy outcomes between employed and unemployed women but women receiving unemployment benefit had an increased risk of preterm birth (adjusted OR (aOR) 1.16, 95% confidence interval (95% CI) 1.03-1.31) and having a small for gestational age child (aOR 1.08, 95% CI 1.00-1.19) compared with employed women. Women receiving sickness or maternity benefit had an increased risk of multiple birth (aOR 1.70, 95% CI 1.43-2.04), preterm (aOR 1.47, 95% CI 1.22-1.77) and very preterm birth (aOR 1.88, 95% CI 1.22-2.89), while those receiving an unreported type of support had an increased risk of preterm birth (aOR 1.40, 95% CI 1.02-1.93). CONCLUSIONS: We found no indication that being unemployed during pregnancy benefits or endangers the health of the child. Within the subgroups of unemployed women, we observed that women receiving unemployment and sickness or maternity benefits were at higher risk for some adverse pregnancy outcomes.

Multiple metal exposure and obesity: A prospective cohort study of adults living along the Yangtze River, China.

Association between long-term exposure to multiple metals and obesity remains inconclusive, and prospective evidence on the region along the Yangtze River was limited. Thus, our study aimed to examine the association of multiple metal exposure and obesity. We measured baseline urine levels of 22 metals of 982 adults living along the Yangtze River, incidence of obesity was calculated from body mass index (BMI) and waist circumference (WC) measured at follow-up survey. Cox proportional hazards models were used to examine the hazard ratios (HR) and 95% confidence interval (CI) for the association between urinary metals and obesity, and the mixing effect of metals on obesity was estimated by using quantile g-computation. In multiple-metal models, arsenic was significantly associated with BMI/obesity, with the HR in the highest quartiles of 0.33 (95% CI: 0.16, 0.69; p-trend = 0.004). The HRs for WC/obesity of arsenic and molybdenum were 0.49 (95% CI: 0.32, 0.75 for the fourth vs. first quartile; p-trend = 0.002) and 1.83 (95% CI: 1.25, 2.70; p-trend = 0.001), respectively. Quantile g-computation mixtures approach showed a significantly negative joint effect of multiple metals on WC/obesity, with the HR of 0.26 (95% CI: 0.14, 0.47; p < 0.001) when increasing all seventeen metals by one quartile. Our study suggests that all seventeen metal mixed exposure may be negatively associated with obesity. Further cohort studies are needed to confirm these findings and clarify the underlying biological mechanisms.

Thyroid hormones in relation to polybrominated diphenyl ether and metals exposure among rural adult residents along the Yangtze River, China.

Although several studies indicate that exposure to polybrominated diphenyl ethers (PBDEs) and metals may influence thyroid function, the evidence is limited and inconsistent in general population. The current study was conducted to determine the levels of plasma PBDEs and urinary metals and evaluate the associations of co-exposure to both with thyroid hormones (THs) among rural adult residents along the Yangtze River, China. A total of 329 subjects were included in current analyses, and 8 PBDEs congeners and 14 urinary metals were measured to reflect the levels of environmental exposure. Multiple linear regression models were used to evaluate the association between PBDEs, metals and THs levels. Bayesian Kernel Machine Regression (BKMR) was used to examine PBDEs and metals mixtures in relation to THs. The geometric mean (GM) and 95% confidence interval (CI) of total measured PBDEs was 65.10 (59.96, 70.68) ng/g lipid weights (lw). BDE-209 was the most abundant congener, with a GM (95% CI) of 47.91 (42.95, 53.26) ng/g lw, accounting for 73.6% of the total PBDEs. Free thyroxine (FT4) was significantly negatively associated with BDE-28, 47, 99, 100, 154, and 183, and urinary strontium [ß (95% CI): -0.04 (-0.07, -0.02)], but positively associated with selenium [ß (95% CI): 0.04 (0.02, 0.06)]. Free triiodothyronine (FT3) was negatively associated with BDE-28 [ß (95% CI): -0.03 (-0.05, -0.01)] and urinary arsenic [ß (95% CI): -0.01 (-0.02, -0.001)]. The current study did not observe a statistically significant association of thyroid-stimulating hormone (TSH) with PBDEs and urinary metals. BKMR analyses showed similar trends when these chemicals were taken into consideration simultaneously. We found no significant interaction in the association between individual chemical at the 25th versus 75th percentiles and THs estimates, comparing the results when other chemicals were set at their 10th, 50th, and 90th percentile levels. Further study is required to confirm these findings and determine potential mechanisms.

Associations of exposure to multiple trace elements with the risk of goiter: A case-control study.

Goiter is one of common endocrine diseases, and its etiology has not been fully elucidated. The changes in trace elements' levels have an important impact on the thyroid. We designed a case-control study, which involved 383 goiter cases and 383 matched controls. We measured these elements in the urine of participants by inductively coupled plasma optical emission spectrometry (ICP-OES), graphite furnace atomic absorption spectrometry (GFAAS) and As3+-Ce4+ catalytic spectrophotometry. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to select the elements into multi-element models, conditional logistic regression models were applied to analyze the association between elements and goiter risk. Bayesian kernel machine regression (BKMR) model was used to depict elements' mixtures and evaluate their joint effects. Finally, 7 elements were included in the multi-element model. We found that the concentrations of lithium (Li), strontium (Sr) and barium (Ba) had a negative effect with goiter risk, and lead (Pb) and iodine (I) showed an extreme positive effect. Additionally, compared with the lowest levels, patients with highest quartiles of I and Pb were 6.49 and 1.94 times more likely to have goiter, respectively. On the contrary, in its second and third quartiles, arsenic (As) showed a negative effect (both OR<1). BKMR model showed a certain interaction among Pb, As, Sr and Li on goiter risk. Further large sample studies are needed to confirm these findings in the future.