Histological outcomes in HPV-screened elderly women in Denmark.

INTRODUCTION: Danish women exit cervical cancer screening at age 65 years, but 23% of cervical cancer cases occur beyond this age. In addition, due to gradual implementation of cervical cancer screening, older women are underscreened by today´s standards. A one-time screening with HPV test was therefore offered to Danish women born before 1948. METHODS: Register based study reporting histology diagnoses and conizations in women found HPV positive in the one-time screening. Number and proportion of women with severe or non-severe histology results were calculated for screened and HPV-positive women by age group or region of residence. Number of women with biopsy and/or conization per case of cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) or CIN3+ were also calculated by age groups and region. RESULTS: 4,479 (4.1% of screened women) had positive HPV test. 94% of these had one or more additional tests. 2,785 (62%) of HPV-positive women had histology results, and conization was performed in 1,076 (24% of HPV-positive and 1% of all screened women). HPV positivity and CIN3+ detection varied little between regions, but the proportions of HPV positive women undergoing histology varied between regions from 40% to 86% and the proportion with conization from 13% to 36%. Correspondingly, the number of histologies and conizations per CIN3+ detected varied from 5.9 to 11.2 and 1.8 to 4.7, respectively. In total, 514 CIN2+ (0.47% of screened women, 11% of HPV-positive) and 337 CIN3+ (0.31% of screened women, 7.5% of HPV-positive) were diagnosed, including 37 cervical cancer cases. DISCUSSION: HPV screening of insufficiently screened birth cohorts can potentially prevent morbidity and mortality from cervical cancer but longer follow-up is needed to see if cancer incidence declines in the screened women in the coming years. Management strategies differed among regions which influenced the proportions undergoing biopsy/conization.

Maternal inflammatory bowel disease and hypospadias in male offspring: a population-based study in Denmark.

BACKGROUND: The occurrence of inflammatory bowel disease (IBD) and hypospadias has been concurrently increasing, possibly through shared environmental risk factors such as endocrine disrupting compounds. Also, maternal IBD may disturb the normal development of the fetal reproductive tract. However, whether maternal IBD increases the risk of hypospadias in male offspring is unknown. We compared hypospadias risk in sons of mothers with and without IBD. METHODS: We used Danish nationwide population-based registries to conduct a longitudinal prevalence study including all live-born boys from 1979 through 2009. We computed HRs, as estimates of prevalence ratios (PRs), with 95% CIs for hypospadias, using Cox proportional hazards regression, while adjusting for measured confounding. RESULTS: Among 966 038 live-born boys, 4688 (0.5%) had a mother with a history of IBD diagnosis before the relevant childbirth. Among the boys with maternal IBD, 36 (0.8%) were diagnosed with hypospadias any time after birth, whereas 6112 (0.6%) sons of mothers without IBD diagnosis had hypospadias (adjusted PR: 1.20, (95% CI 0.86 to 1.67). Adjusted PRs for maternal Crohn's disease and ulcerative colitis were 1.38 (95% CI 0.83 to 2.29) and 1.10 (95% CI 0.71 to 1.68), respectively. Analyses defining hypospadias diagnosis recorded <6 months postpartum showed similar results. CONCLUSIONS: We found no convincing evidence of an association between maternal IBD and hypospadias.

Parental celiac disease and risk of asthma in offspring: a Danish nationwide cohort study.

OBJECTIVE: The incidences of celiac disease (CD) and asthma are increasing and the two conditions are associated in individuals. Risk of asthma may be passed on to the next generation through shared risk factors. We examined whether parental CD is associated with risk of asthma in offspring. METHODS: We conducted a population-based Danish nationwide cohort study, using medical databases, covering the period 1 January 1979 to 31 December 2009. For each child with a parental history of CD, we randomly sampled 100 children without this history from the children born in the same calendar year. We used Cox proportional-hazards regression to estimate incidence rate ratios for asthma, adjusting for measured covariates. RESULTS: We identified 1,107 children with a parental history of CD and 110,700 children without this parental history. During up to 32 years of follow-up, 6,125 children received a hospital diagnosis of asthma. The adjusted incidence rate ratio for asthma associated with a parental history of CD was 1.09 (95% confidence interval: 0.86-1.39) and was similar for maternal and paternal CD. Inclusion of asthma-medication in the definition of asthma did not substantially change the results. CONCLUSION: There was no convincing evidence of an increased risk of asthma among offspring of parents with CD.

Autism spectrum disorders in children of parents with inflammatory bowel disease - a nationwide cohort study in Denmark.

PURPOSE: Inflammatory bowel disease (IBD) and autism spectrum disorders (ASD) may share genetic and environmental risk factors. We examined whether parental IBD is associated with an increased risk of ASD in offspring. METHODS: We conducted a registry-based nationwide cohort study including children born alive in Denmark from January 1, 1994 to December 31, 2009, with follow-up throughout 2010. IBD in parents and ASD in offspring were identified using inpatient and outpatient hospital diagnoses. We computed risk of ASD and crude and adjusted incidence rate ratios (aIRRs) with 95% confidence intervals (CI) using Cox proportional-hazards regression. We evaluated the risk of ASD according to maternal and paternal IBD, and separately for maternal and paternal Crohn's disease (CD) and ulcerative colitis (UC). Children with parents free of IBD were the comparison cohort. RESULTS: We identified 1,005,330 children during the study period. Among them, 11,888 (1.2%) had a parent with IBD and 8,087 (0.8%) had a diagnosis of ASD during up to 17 years of follow-up. The 10-year risks of ASD were 0.7% among children of parents with IBD and 0.9% among children of parents without IBD. The aIRR for ASD among children with parental IBD was 0.8 (95% CI: 0.6-1.0), and results were similar regardless of parent of IBD origin or whether a parent had CD or UC. The estimates were similar for different ASD subtypes. CONCLUSION: We found no evidence of an increased risk of ASD among children born to parents with IBD.

Parental inflammatory bowel disease and risk of asthma in offspring: a nationwide cohort study in denmark.

OBJECTIVES: Common genetic and environmental risk factors may explain the concurrent increase in the incidence of both inflammatory bowel disease (IBD) and asthma. We examined whether IBD in a parent is associated with an increased asthma risk in offspring. METHODS: This was a registry-based cohort study of all children born alive in Denmark in 1979-2009, followed through 2010. IBD and asthma were identified using hospital diagnoses; antiasthma medication was also used to identify asthma. We computed risk of asthma and estimated adjusted incidence rate ratios (aIRRs) with 95% confidence intervals (CIs) using Cox proportional-hazards regression. We evaluated asthma risk according to maternal and paternal IBD, Crohn's disease (CD), and ulcerative colitis (UC). Children without parental IBD were the comparison cohort for all comparisons. RESULTS: We identified 1,845,281 children, of whom 14,952 (0.8%) had a parent with IBD. The 10-year risk of asthma was 6.9% among offspring of parents with CD, 5.6% among offspring of parents with UC, and 5.0% among offspring of parents without IBD. The aIRR for asthma associated with parental IBD was 0.98 (95% CI: 0.91-1.04). The aIRR was 1.09 (95% CI: 0.98-1.22) for parental CD and 0.92 (95% CI: 0.84-1.00) for parental UC. Results were similar regardless of parent of origin or inclusion of antiasthma medication to define asthma. CONCLUSIONS: Our data do not provide evidence for an increased risk of asthma in offspring with a parental history of IBD.

Use of prescription paracetamol during pregnancy and risk of asthma in children: a population-based Danish cohort study.

PURPOSE: Use of paracetamol during pregnancy may increase the risk of asthma in offspring. The association between prenatal exposure to maternal use of paracetamol and risk of asthma was investigated. METHODS: A cohort study of 197,060 singletons born in northern Denmark in 1996-2008 was conducted, with follow-up until the end of 2009. Maternal paracetamol use during pregnancy was defined as a redeemed prescription. Asthma in offspring was defined as at least two prescriptions of both a ß-agonist and an inhaled glucocorticoid and/or a hospital diagnosis of asthma during follow-up. Absolute risk of asthma in offspring was estimated using the Kaplan-Meier method and incidence rate ratios adjusted for known risk factors were estimated using Cox proportional-hazards regression. RESULTS: Overall, 976 (0.5%) children were exposed prenatally to maternal use of prescription paracetamol. During follow-up, 24,506 (12.4%) children developed asthma. Absolute risk of asthma was 7.5% after 2 years and 14.4% after 10 years among the unexposed children. Corresponding risks were 12.7% and 21.6% among the exposed children. The adjusted incidence rate ratio was 1.35 (95% confidence interval: 1.17-1.57) for exposure in any trimester of pregnancy. A similar association was present for paracetamol exposure in each of the trimesters and for maternal use of prescription nonsteroidal anti-inflammatory drugs. Furthermore, maternal prescription use in the year following the relevant delivery also showed similar associations. CONCLUSION: A robust association was found between prenatal exposure to maternal use of prescription paracetamol and the risk of asthma; however, noncausal explanations could not be ruled out for such association.

Long-term use of zopiclone, zolpidem and zaleplon among Danish elderly and the association with sociodemographic factors and use of other drugs.

PURPOSE: To estimate the degree of long-term use of zopiclone, zolpidem and zaleplon among Danes aged 65 and older and the association with sociodemographic factors and use of other drugs. METHODS: Danish register-based study of 5000 men and 5000 women aged 65 or older on 1 January 2004. Information on sociodemographic factors and drug redemptions were collected for 2003, with follow-up of zopiclone, zolpidem and zaleplon redemptions in 2004. Long-term use was defined as redemptions corresponding to a continuous daily use for more than 4 weeks (based on ½ DDD). The association between long-term use and sociodemographics and drug use was estimated by logistic regression. RESULTS: Ten per cent of all men and 16% of all women had a long-term use for minimum 4 weeks corresponding to 94% of the male and 93% of the female users. Four per cent of the men and 6% of the women had redeemed more than ½ DDD per day in 2004. Long-term use was associated with: Being a woman, high age, widowed or divorced, high education and high gross income. Long-term use was also associated with use of other drugs, the association with ATC group N being the strongest. Restricting the analyses to individuals who had minimum one zopiclone, zolpidem or zaleplon redemption gave similar results. CONCLUSION: The results indicate that the guidance for length of use is not followed. Long-term use of zopiclone, zolpidem and zaleplon is associated with sociodemographic factors and use of other drugs, particularly from ATC group N.