Predicting time to relapse in patients with schizophrenia according to patients' relapse history: a historical cohort study using real-world data in Sweden.

BACKGROUND: For patients with schizophrenia, relapse is a recurring feature of disease progression, often resulting in substantial negative impacts for the individual. Although a patient's relapse history (specifically the number of prior relapses) has been identified as a strong risk factor for future relapse, this relationship has not yet been meticulously quantified. The objective of this study was to use real-world data from Sweden to quantify the relationship of time to relapse in schizophrenia with a patient's history of prior relapses. METHODS: Data from the Swedish National Patient Register and Swedish Prescribed Drug Register were used to study relapse in patients with schizophrenia with a first diagnosis recorded from 2006-2015, using proxy definitions of relapse. The primary proxy defined relapse as a psychiatric hospitalisation of ≥7 days' duration. Hazard ratios (HRs) were calculated for risk of each subsequent relapse, and Aalen-Johansen estimators were used to estimate time to next relapse. RESULTS: 2,994 patients were included, and 5,820 relapse episodes were identified using the primary proxy. As the number of previous relapses increased, there was a general trend of decreasing estimated time between relapses. Within 1.52 years of follow-up, 50% of patients with no history of relapse were estimated to have suffered their first relapse episode. 50% of patients with one prior relapse were estimated to have a second relapse within 1.23 years (HR: 1.84 [1.71-1.99]) and time to next relapse further decreased to 0.89 years (HR: 2.77 [2.53-3.03]) and 0.22 years (HR: 18.65 [15.42-22.56]) for 50% of patients with two or ten prior relapses, respectively. Supplementary analyses using different inclusion/exclusion criteria for the study population and redefined proxies of relapse reflected the pattern observed with the primary analyses of a higher number of prior relapses linked with increased risk of/reduced estimated time to the next relapse. CONCLUSIONS: The results suggested a trend of accelerating disease progression in schizophrenia, each relapse episode predisposing an individual to the next within a shorter time period. These results emphasise the importance of providing early, effective, and tolerable treatments that better meet a patient's individual needs.

Perfluoroalkyl and polyfluoroalkyl substances and measures of human fertility: a systematic review.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are found widespread in the environment and humans. The relation of PFASs to fertility has now been examined in a relatively large number of epidemiologic studies and a synthesis is in order. The aim of this study was to assess the current human epidemiologic evidence on the association between exposure to PFASs and measures of human fertility, with particular emphasis on perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Systematic literature searches were initially conducted in MEDLINE and EMBASE and subsequently in references and citations of included papers. Studies were included if they assessed exposure to PFASs in biological samples in relation to reproductive hormones, semen characteristics, or time to pregnancy (TTP). Study characteristics and results were abstracted to predefined forms, and the studies were assessed for the risk of bias and confounding. Sixteen studies investigated the association between PFAS exposure in men and semen parameters, reproductive hormone levels, or TTP. There was a lack of consistent results among the numerous investigated exposure-outcome combinations. However, subtle associations between higher PFOS and lower testosterone or abnormal semen morphology cannot be excluded. Eleven studies assessed the association between PFAS exposure in women and TTP or reproductive hormones levels. Four of eight studies found prolonged TTP with higher PFOS or PFOA, but only one study found an association when restricting to nulliparous women. In men, there is little evidence of an association between PFAS exposure and semen quality or levels of reproductive hormones. For PFOS and PFOA, the literature indicates an association with female fecundability in parous women, which is most likely not causal.

Redemption of asthma pharmaceuticals among stainless steel and mild steel welders: a nationwide follow-up study.

PURPOSE: The purpose was to examine bronchial asthma according to cumulative exposure to fume particulates conferred by stainless steel and mild steel welding through a proxy of redeemed prescribed asthma pharmaceuticals. METHODS: A Danish national company-based historical cohort of 5,303 male ever-welders was followed from 1995 to 2011 in the Danish Medicinal Product Registry to identify the first-time redemption of asthma pharmaceuticals including beta-2-adrenoreceptor agonists, adrenergic drugs for obstructive airway diseases and inhalable glucocorticoids. Lifetime exposure to welding fume particulates was estimated by combining questionnaire data on welding work with a welding exposure matrix. The estimated exposure accounted for calendar time, welding intermittence, type of steel, welding methods, local exhaustion and welding in confined spaces. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a Cox proportional hazards model adjusting for potential confounders and taking modifying effects of smoking into account. RESULTS: The average incidence of redemption of asthma pharmaceuticals in the cohort was 16 per 1,000 person year (95% CI 10-23 per 1,000 person year). A moderate nonsignificant increased rate of redemption of asthma medicine was observed among high-level exposed stainless steel welders in comparison with low-level exposed welders (HR 1.54, 95% CI 0.76-3.13). This risk increase was driven by an increase risk among non-smoking stainless steel welders (HR 1.46, 95% CI 1.06-2.02). Mild steel welding was not associated with increased risk of use asthma pharmaceuticals. CONCLUSION: The present study indicates that long-term exposure to stainless steel welding is related to increased risk of asthma in non-smokers.

Increased risk of rheumatoid arthritis in women with pregnancy complications and poor self-rated health: a study within the Danish National Birth Cohort.

OBJECTIVE: This study assessed the suggested association between pregnancy-associated hypertensive disorders, hyperemesis and subsequent risk of RA using a cohort with information about pre-pregnancy health. METHODS: Self-reported information on pre-pregnancy health, pregnancy course, gestational hypertension, pre-eclampsia and hyperemesis was available from 55 752 pregnant women included in the Danish National Birth Cohort. Information about pregnancy-related factors and lifestyle was obtained by interviews twice during pregnancy and at 6 months post-partum. Women were followed for RA hospitalizations identified in the Danish National Patient Register. Hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards models. Women with RA and non-specific musculoskeletal problems at the time of pregnancy were excluded. RESULTS: On average, women were followed for 11 years after childbirth and 169 cases of RA were identified. The risk of RA was increased in women with pre-eclampsia (n = 11, HR = 1.96, 95% CI 1.06, 3.63), a poor self-rated pregnancy course (n = 32, HR = 1.63, 95% CI 1.11, 2.39) and fair or poor self-rated pre-pregnancy health (fair health: n = 86, HR = 1.52, 95% CI 1.11, 2.09; poor health: n = 14, HR = 3.24, 95% CI 1.82, 5.76). Hyperemesis was not associated with risk of RA. CONCLUSION: We confirmed the previously suggested increased risk of RA in women with pre-eclampsia and also found an inverse association between self-rated pre-pregnancy health and risk of RA. These results suggest that the clinical onset of RA is preceded by a prolonged subclinical phase that may interfere with women's general well-being and pregnancy course or that some women carry a shared predisposition to pre-eclampsia and RA.

Socio-occupational class, region of birth and maternal age: influence on time to detection of cryptorchidism (undescended testes): a Danish nationwide register study.

BACKGROUND: Cryptorchidism (undescended testes) is associated with poor male fertility, but can be alleviated and fertility preserved to some degree by early detection and treatment. Here we assess the influence of socio-occupational class, geographical region, maternal age and birth cohort on time to detection and correction of cryptorchidism. METHODS: All boys born in Denmark, 1981 to 1987 or 1988 to 1994, with a diagnosis of cryptorchidism were identified in nationwide registers. The boys were followed for a diagnosis until their 16th birthday. The age at first diagnosis was noted and used as proxy for time to detection of cryptorchidism. Parental employment in the calendar year preceding birth was grouped into one of five socio-occupational classes. Geographical region was defined by place of birth in one of 15 Danish counties. Detection rate ratios of cryptorchidism were analyzed as a function of parental socio-occupational group, county, maternal age and birth cohort by use of Poisson regression. RESULTS: Some 6,059 boys in the early and 5,947 boys in the late cohort received a diagnosis of cryptorchidism. Time to detection was independent of parental socio-occupational group and maternal age but differed slightly between geographical regions. A similar pattern was obtained for surgical correction after a diagnosis. Age at diagnosis decreased by 2.7 years from the early to the late cohort. CONCLUSIONS: These results indicate that childhood socio-occupational inequality in detection and correction of cryptorchidism would play a negligible role in male infertility in a life course perspective. Geographical region may have exerted some influence, especially for the oldest cohort.

Decreasing risk of colorectal cancer in patients with inflammatory bowel disease over 30 years.

BACKGROUND & AIMS: The risk for colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) could have changed over time, with changes in treatment options. We studied CRC risk in a nationwide cohort of 47,374 Danish patients with IBD over a 30-year period. METHODS: We determined relative risk (RR) values using Poisson regression-derived incidence rate ratios of CRC from 1 year after IBD diagnosis, adjusted for age, sex, and calendar time. We compared incidence of CRC among patients with IBD vs individuals without IBD. RESULTS: During 178 million person-years of follow-up evaluation, 268 patients with ulcerative colitis (UC) and 70 patients with Crohn's disease (CD) developed CRC. The overall risk of CRC among patients with UC was comparable with that of the general population (RR, 1.07; 95% confidence interval [CI], 0.95-1.21). However, patients diagnosed with UC in childhood or as adolescents, those with long duration of disease, and those with concomitant primary sclerosing cholangitis were at increased risk. For patients with UC, the overall RR for CRC decreased from 1.34 (95% CI, 1.13-1.58) in 1979-1988 to 0.57 (95% CI, 0.41-0.80) in 1999-2008. Among patients with CD, the overall RR for CRC was 0.85 (95% CI, 0.67-1.07), which did not change over time. CONCLUSIONS: A diagnosis of UC or CD no longer seems to increase patients' risk of CRC, although subgroups of patients with UC remain at increased risk. The decreasing risk for CRC from 1979 to 2008 might result from improved therapies for patients with IBD.

Increased risk of inflammatory bowel disease in women with endometriosis: a nationwide Danish cohort study.

BACKGROUND: An association between endometriosis and certain autoimmune diseases has been suggested. However, the impact of endometriosis on risk of inflammatory bowel disease (IBD) remains unknown. OBJECTIVE: To assess the risk of Crohn's disease (CD) and ulcerative colitis (UC) in an unselected nationwide Danish cohort of women with endometriosis. DESIGN: By use of national registers, 37 661 women hospitalised with endometriosis during 1977-2007 were identified. The relative risk of developing IBD after an endometriosis diagnosis was calculated as observed versus expected numbers and presented as standardised incidence ratios (SIRs) with 95% CIs. RESULTS: Women with endometriosis had a increased risk of IBD overall (SIR=1.5; 95% CI 1.4 to 1.7) and of UC (SIR=1.5; 95% CI 1.3 to 1.7) and CD (SIR=1.6; 95% CI 1.3 to 2.0) separately, even 20 years after a diagnosis of endometriosis (UC: SIR=1.5; 95% CI 1.1 to 2.1; CD: SIR=1.8; 95% CI 1.1 to 3.2). Restricting analyses to women with surgically verified endometriosis suggested even stronger associations (UC: SIR=1.8; 95% CI 1.4 to 2.3; CD: SIR=1.7; 95% CI 1.2 to 2.5). CONCLUSION: The risk of IBD in women with endometriosis was increased even in the long term, hence suggesting a genuine association between the diseases, which may either reflect common immunological features or an impact of endometriosis treatment with oral contraceptives on risk of IBD.

Childbirths and risk of female predominant and other autoimmune diseases in a population-based Danish cohort.

To evaluate the possible biological role of pregnancy on the risk of autoimmune diseases we assessed associations between reproductive history and subsequent risk of autoimmune diseases characterized by female predominance and other autoimmune diseases. Our study cohort comprised 4.6 million Danes born since 1935 for whom a complete record of childbirths was available. Cohort members were followed for hospital contacts for 31 autoimmune diseases from 1982 to 2008. Female predominant autoimmune diseases were those with a female:male sex ratio >2:1. Ratios of first hospitalization rates were calculated using Poisson regression, adjusting for potential confounding by age, birth cohort, calendar period and marital status. During 45.5 million person-years of follow-up 102,260 women were hospitalized with one or more autoimmune diseases. Overall, compared with childless women, women with children were at a relative risk of 1.04 (1.02-1.06) for any autoimmune diseases, 1.11 (1.08-1.14) for female predominant and 0.97 (0.95-1.00) for other autoimmune diseases. Possibly biologically related associations with parity were found for Hashimoto thyroiditis (1.11; 1.00-1.24), Graves' disease (1.19; 1.14-1.24), erythema nodosum (1.15; 1.01-1.32), psoriasis (1.08; 1.01-1.15), sarcoidosis (1.17; 1.06-1.28) and systemic lupus erythematosus (0.83; 0.74-0.93). Especially the one-year postpartum period was associated with an increased risk of Hashimoto thyroiditis, Graves' disease and sarcoidosis. Overall, parity was associated with an 11% increased risk of female predominant autoimmune diseases. Pregnancies resulting in liveborn children therefore seem to contribute only little to the general female predominance in autoimmune diseases. However, for a number of autoimmune diseases; especially autoimmune thyroid diseases, erythema nodosum and sarcoidosis parity might somehow be involved in disease development.

Hyperemesis, gestational hypertensive disorders, pregnancy losses and risk of autoimmune diseases in a Danish population-based cohort.

The risk of some female predominant autoimmune diseases (ADs) has previously been shown to be higher in women who experience hyperemesis, gestational hypertensive disorders and idiopathic pregnancy losses. This study assessed the association between such pregnancy-related experiences and the subsequent risk of female predominant and other ADs. Our study cohort comprised 1.6 million Danish women born since 1955 for whom we had information about hyperemesis, gestational hypertensive disorders and pregnancy losses and subsequent hospital contacts for 31 ADs between 1982 and 2008. Ratios of first hospitalization rates (RRs) with 95% confidence intervals (CIs) were calculated using Poisson regression, adjusting for age, birth cohort, calendar period, marital status and childbirths. During 27.0 million person-years of follow-up 51,732 women were hospitalized with one or more ADs. Overall, compared with women without the specific pregnancy experiences, the risk of any AD was significantly increased for women with hyperemesis (RR = 1.41; 95% CI 1.30-1.51), gestational hypertensive disorders (1.21; 1.16-1.26), spontaneous abortions (1.10; 1.07-1.14), missed abortions (1.09; 1.04-1.13), stillbirths (1.25; 1.12-1.40), ectopic pregnancies (1.08; 1.02-1.14) and induced abortions (1.07; 1.04-1.09). Associations with female predominant ADs (i.e., ADs with a female:male ratio >2:1) were strongest in the first five years after the studied pregnancy experiences, but overall there was little difference between the RRs for groups of female predominant ADs and other ADs. Strong and potentially biological associations were observed for a number of specific ADs; including systemic lupus erythematosus, Graves' disease, type 1 diabetes mellitus and pernicious anemia, and for some specific ADs associations persisted even more than five years after the abnormal pregnancy experience. Abnormal pregnancies are associated with increased risk of certain ADs, possibly because of underlying immunologic or hormonal factors that predispose to both adverse pregnancy experiences and AD development.

Enteric Salmonella or Campylobacter infections and the risk of inflammatory bowel disease.

OBJECTIVE: Enteric pathogens have been implicated in the aetiology of inflammatory bowel disease (IBD), but increased rates of stool testing of patients with unclear gastrointestinal symptoms might cause detection bias. Hence, the objective of this study was to analyse incidence rates of Crohn's disease and ulcerative colitis among patients with Salmonella- or Campylobacter-positive and negative stool tests and to study the incidence of positive and negative stool tests among patients already diagnosed with IBD. METHODS: The Danish population was followed for 94.3 million person-years during 1992-2008 using national registers to identify persons with positive and negative stool tests and patients with IBD. Using Poisson regression, incidence rate ratios (IRRs) for IBD after positive or negative stool tests and, conversely, IRRs for positive and negative stool tests following IBD, were calculated. RESULTS: IRRs for IBD were significantly high in the first year after Salmonella- or Campylobacter-positive stool tests (IRRs 5.4-9.8), and they remained moderately increased 1-10 years later (IRRs 1.6-2.2), and less so >10 years later (IRRs 0.8-1.8). However, IRRs for IBD <1 year after a negative stool test were several-fold higher (IRRs 53.2-57.5), and a decreasing incidence pattern over time was parallel to that following positive test results. Among patients with IBD, IRRs for subsequent positive and-most notably-negative stool test results were also significantly high. CONCLUSION: Similarities in temporal risk patterns for IBD following positive or negative stool tests indicate that the increased occurrence of Salmonella- or Campylobacter-positive results around the time of first IBD hospitalisation results from detection bias.

Antipsychotic treatment patterns in Alzheimer's disease patients with agitation: a cohort study using the UK clinical practice research datalink.

OBJECTIVES: There is a lack of robust epidemiological evidence on antipsychotic (AP) use in patients with agitation in Alzheimer's disease (AD). Authors studied AP use in patients with AD and agitation and compared their use with patients with other or no neuropsychiatric symptoms (NPS). METHODS: A retrospective cohort study in the UK Clinical Practice Research Datalink, included patients with AD between January 1st, 2015, and December 31st, 2017. AP use was compared between patients with agitation, other types of NPS and no NPS. RESULTS: There were 24,464 patients with AD, median follow-up of 1.1 years (interquartile range [IQR] 0.5-2.1), and median age 83 years (78-88). A larger percentage of patients with agitation (n = 2432) were prescribed APs (38.2%) than other NPS (n = 13,076, 20.4%) and no NPS (n = 11,816, 12.2%). Compared to patients with no NPS, adjusted hazard ratios for AP use were 3.45 (95% CI 2.86-4.17) for patients with agitation and 1.31 (95% CI 1.19-1.44) for patients with other NPS. Among users of APs, the treatment discontinuation rate at six months was 44.8% in patients with agitation (other NPS 57.1%; no NPS 63.5%). CONCLUSIONS: Patients with AD and agitation were frequently prescribed APs and for long periods in routine clinical practice in the UK. The high real-life usage of APs suggests that physicians prefer using APs for the treatment of agitation despite recommendations against their long-term use. These data support a need for AP therapies that better address known safety concerns with currently used APs to treat agitation in elderly patients with AD.

Transdiagnostic individualized clinically-based risk calculator for the automatic detection of individuals at-risk and the prediction of psychosis: external replication in 2,430,333 US patients.

The real-world impact of psychosis prevention is reliant on effective strategies for identifying individuals at risk. A transdiagnostic, individualized, clinically-based risk calculator to improve this has been developed and externally validated twice in two different UK healthcare trusts with convincing results. The prognostic performance of this risk calculator outside the UK is unknown. All individuals who accessed primary or secondary health care services belonging to the IBM® MarketScan® Commercial Database between January 2015 and December 2017, and received a first ICD-10 index diagnosis of nonorganic/nonpsychotic mental disorder, were included. According to the risk calculator, age, gender, ethnicity, age-by-gender, and ICD-10 cluster diagnosis at index date were used to predict development of any ICD-10 nonorganic psychotic disorder. Because patient-level ethnicity data were not available city-level ethnicity proportions were used as proxy. The study included 2,430,333 patients with a mean follow-up of 15.36 months and cumulative incidence of psychosis at two years of 1.43%. There were profound differences compared to the original development UK database in terms of case-mix, psychosis incidence, distribution of baseline predictors (ICD-10 cluster diagnoses), availability of patient-level ethnicity data, follow-up time and availability of specialized clinical services for at-risk individuals. Despite these important differences, the model retained accuracy significantly above chance (Harrell's C = 0.676, 95% CI: 0.672-0.679). To date, this is the largest international external replication of an individualized prognostic model in the field of psychiatry. This risk calculator is transportable on an international scale to improve the automatic detection of individuals at risk of psychosis.

Risk of congenital malformations among children of construction painters in Denmark: a nationwide cohort study.

OBJECTIVES: Painters' occupational exposure is classified as a group 1 carcinogen by the International Agency for Research on Cancer (IARC). Previous studies have shown increased risk of congenital malformations among children of women exposed to organic solvents and paint emissions during pregnancy. In Denmark, women comprise half of those enrolled in vocational paint training. We investigated the association between maternal and paternal occupational painting, respectively, and the risk of congenital malformations among children. METHODS: National register data were used to link childbirths, malformations, and parental occupation. The cohort included >1,300,000 children born to occupationally active women in Denmark 1980-2010. Cases were hospital-diagnosed with malformations within the first year of life. Odds ratios (OR) with 95% confidence intervals (95% CI) were estimated using multiple logistic regression with adjustment for potential confounders. RESULTS: Among 3444 children of female construction painters, we found no increased risk of malformations overall (126 cases, OR 0.88, 95% CI 0.74-1.05) or in organ-specific subgroups compared to children of women in all other occupations (55 045 cases). Sensitivity analyses restricted to severe malformations, children of maternal painters with ≥2 years of pre-pregnancy exposure, and firstborn children, and analyses with maternal healthcare assistants and kitchen workers as reference supported the main results. Also, no associations were found when including diagnoses within the first 10 years of life, when stratifying by maternal age, birth year, and sex, or for paternal construction painters. CONCLUSIONS: This nationwide cohort study is reassuring with no indications of increased risk of congenital malformations among children of male or of female construction painters.

Occupational lifting, fetal death and preterm birth: findings from the Danish National Birth Cohort using a job exposure matrix.

OBJECTIVE: We examined the association between occupational lifting during pregnancy and risk of fetal death and preterm birth using a job exposure matrix (JEM). METHODS: For 68,086 occupationally active women in the Danish National Birth Cohort, interview information on occupational lifting was collected around gestational week 16. We established a JEM based on information from women, who were still pregnant when interviewed. The JEM provided mean total loads lifted per day within homogeneous exposure groups as informed by job and industry codes. All women were assigned an exposure estimate from the JEM. We used Cox regression models with gestational age as underlying time variable and adjustment for covariates. RESULTS: We observed 2,717 fetal deaths and 3,128 preterm births within the study cohort. No exposure-response relation was observed for fetal death, but for women with a prior fetal death, we found a hazard ratio (HR) of 2.87 (95% CI 1.37, 6.01) for stillbirth (fetal death ≥22 completed gestational weeks) among those who lifted >200 kg/day. For preterm birth, we found an exposure-response relation for primigravid women, reaching a HR of 1.43 (95% CI 1.13, 1.80) for total loads >200 kg per day. These findings correspond to an excess fraction of 11% for stillbirth and 10% for preterm birth. CONCLUSION: We found an increased risk of stillbirth among women with a prior fetal death, who lifted >200 kg/day, and an exposure-response relationship between occupational lifting and preterm birth among primigravid women. The study adds to a large body of prospective studies on occupational lifting and adverse pregnancy outcomes by refined exposure assessment.

Risk of cryptorchidism among sons of horticultural workers and farmers in Denmark.

OBJECTIVES: Previous studies indicate an increased risk of cryptorchidism, incomplete testicular descent, among sons of women working with pesticides. This study assessed the risk of cryptorchidism among boys of parents employed as horticultural workers and farmers using nationwide registers on occupation and cryptorchidism. METHODS: The cohort consisted of >600 000 boys born in Denmark from 1980-2007 with a parent in employment during pregnancy. These boys were followed for cryptorchidism from 1980-2009 comparing risks among sons of horticultural workers and farmers with sons of parents in other occupations. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox regression adjusting for parental age, birth years, parity, and geographical region. RESULTS: Sons of maternal farmers were at increased risk of cryptorchidism (157 cases; HR 1.31, 95% CI 1.12-1.53) compared to boys of mothers in other occupations (15 511 cases). Paternal occupation as farmer was unrelated to the risk among sons. Maternal occupation as a horticultural worker was associated with a non-significantly increased risk (72 cases; HR 1.20, 95% CI 0.95-1.52). A similar association was found for paternal horticultural workers. Sons of maternal farmers or horticultural workers who likely worked in the first trimester were not at increased risk of cryptorchidism. CONCLUSIONS: This nationwide cohort study found a slightly increased risk of cryptorchidism in sons of maternal horticultural workers and farmers. However, subgroup analyses indicated similar findings for paternal horticultural workers, and no association for women likely working in the first trimester. The main findings should therefore be interpreted with caution.

Risk of inflammatory bowel disease according to self-rated health, pregnancy course, and pregnancy complications: a study within the Danish National Birth Cohort.

BACKGROUND: Poor self-rated health (SRH) has been connected to immunological changes, and pregnancy complications have been suggested in the etiology of autoimmune diseases including inflammatory bowel disease (IBD). We evaluated the impact of self-rated pre-pregnancy health and pregnancy course, hyperemesis, gestational hypertension, and preeclampsia on risk of IBD. METHODS: Information was collected by questionnaires from The Danish National Birth Cohort (enrolment 1996-2002) at 16(th) and 30(th) week of pregnancy and 6 months postpartum. A total of 55,699 women were followed from childbirth until development of IBD (using validated National Hospital Discharge Register diagnoses), emigration, death, or end of follow-up, 31(st) of October, 2011. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards models adjusting for age and evaluating pre-pregnancy BMI, parity, alcohol and tobacco consumption, and socio-occupational status as potential confounders. RESULTS: Risk of IBD increased with decreasing level of self-rated pre-pregnancy health (p = 0.002) and was elevated in women with poor self-rated pregnancy course (HR, 1.61, 95% CI 1.22-2.12). Associations persisted for more than 5 years postpartum. Hyperemesis and preeclampsia were not significantly associated with risk of IBD. CONCLUSIONS: This is the first prospective observational study to suggest that poor self-rated health--in general and in relation to pregnancy--is associated with increased risk of IBD even in the long term though results needs further confirmation. Symptoms of specific pregnancy complications were, on the other hand, not significantly associated with risk of IBD.

Miscarriage and occupational activity: a systematic review and meta-analysis regarding shift work, working hours, lifting, standing, and physical workload.

OBJECTIVE: Previous studies have indicated that shift work, long working hours, and prevalent workplace exposures such as lifting, standing, and physical workload increase the risk of miscarriage, but the evidence is conflicting. We conducted a systematic review of original research reports. METHODS: A search in Medline and EMBASE 1966-2012 identified 30 primary papers reporting the relative risk (RR) of miscarriage according to ≥1 of 5 occupational activities of interest. Following an assessment of completeness of reporting, confounding, and bias, each risk estimate was characterized as more or less likely to be biased. Studies with equivalent measures of exposure were pooled to obtain a weighted common risk estimate. Sensitivity analyses excluded studies most likely to be biased. RESULTS: Working fixed nights was associated with a moderately increased risk of miscarriage (pooled RR 1.51 [95% confidence interval (95% CI) 1.27-1.78, N=5), while working in 3-shift schedules, working for 40-52 hours weekly, lifting >100 kg/day, standing >6-8 hours/day and physical workload were associated with small risk increments, with the pooled RR ranging from 1.12 (3-shift schedule, N=7) to 1.36 (working hours, N=10). RR for working hours and standing became smaller when analyses were restricted to higher quality studies. CONCLUSIONS: These largely reassuring findings do not provide a strong case for mandatory restrictions in relation to shift work, long working hours, occupational lifting, standing, and physical workload. Considering the limited evidence base, however, it may be prudent to advise women against work entailing high levels of these exposures and women with at-risk pregnancies should receive tailored individual counseling.

Risk of cryptorchidism and hypospadias among boys of maternal hairdressers - a Danish population-based cohort study.

OBJECTIVES: Pregnant hairdressers may be exposed to a mixture of chemicals in their working environment. The possible relationship between these chemical agents and male reproductive tract malformations has raised concern that the working environment of hairdressers might have adverse effects on fetal development. This study assessed the risk of cryptorchidism and hypospadias among boys of maternal hairdressers. METHODS: National population-based registers were used to determine maternal occupation and identify cases of cryptorchidism and hypospadias. The cohort comprised all children born in Denmark from 1980-2007. Using Cox regression, we estimated hazard ratios (HR) with 95% confidence intervals (95% CI) for hospitalization for cryptorchidism and hypospadias from 1980-2009. RESULTS: Boys of hairdressers were not at increased risk of cryptorchidism (134 cases, HR 0.91; 95% CI 0.77-1.08) or hypospadias (33 cases, HR 1.27; 95% CI 0.90-1.79) compared to children of mothers in other occupations (14 988 and 2556 cases of cryptorchidism and hypospadias, respectively). Additional analyses using children of shop assistants and receptionists as controls and restricted to (i) firstborns, (ii) cryptorchidism cases with corrective surgery, (iii) specific birth years, and (iv) women without social benefit payments in gestational weeks 8-14 produced consistent results of no increased risk. CONCLUSION: Our nationwide cohort study shows that, despite exposure to a complex chemical milieu, hairdressers do not have an increased risk of having boys with cryptorchidism and hypospadias.