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Background Public trust in the human papilloma virus (HPV) vaccination programme has been challenged by reports of potential severe adverse effects. The reported adverse symptoms were heterogeneous and overlapping with those characterised as chronic fatigue syndrome (CFS) and have been described as CFS-like symptoms. Evidence suggests that CFS is often precipitated by an infection. The aim of the study was to examine if an infection in temporal proximity to HPV vaccination is a risk factor for suspected adverse effects following HPV vaccination. Methods and findings The study was a nationwide register-based cohort study and case-crossover analysis. The study population consisted of all HPV vaccinated females living in Denmark, born between 1974 and 2006, and vaccinated between January 1, 2006 and December 31, 2017. The exposure was any infection in the period ± 1 month around time of first HPV vaccination and was defined as (1) hospital-treated infection; (2) redemption of anti-infective medication; or (3) having a rapid streptococcal test done at the general practitioner. The outcome was referral to a specialised hospital setting (5 national HPV centres opened June 1, 2015) due to suspected adverse effects following HPV vaccination. Multivariable logistic regression was used to estimate the association between infection and later HPV centre referral. The participants were 600,400 HPV-vaccinated females aged 11 to 44 years. Of these, 48,361 (9.7%) females had a hospital-treated infection, redeemed anti-infective medication, or had a rapid streptococcal test ± 1 month around time of first HPV vaccination. A total of 1,755 (0.3%) females were referred to an HPV centre. Having a hospital-treated infection in temporal proximity to vaccination was associated with significantly elevated risk of later referral to an HPV centre (odds ratio (OR) 2.75, 95% confidence interval (CI) 1.72 to 4.40; P < 0.001). Increased risk was also observed among females who redeemed anti-infective medication (OR 1.56, 95% CI 1.33 to 1.83; P < 0.001) or had a rapid streptococcal test (OR 1.45, 95% CI 1.10 to 1.93; P = 0.010). Results from a case-crossover analysis, which was performed to adjust for potential unmeasured confounding, supported the findings. A key limitation of the study is that the HPV centres did not open until June 1, 2015, which may have led to an underestimation of the risk of suspected adverse effects, but stratified analyses by year of vaccination yielded similar results. Conclusions Treated infection in temporal proximity to HPV vaccination is associated with increased risk for later referral with suspected adverse vaccine effects. Thus, the infection could potentially be a trigger of the CFS-like symptoms in a subset of the referred females. To our knowledge, the study is the first to investigate the role of infection in the development of suspected adverse effects after HPV vaccination and replication of these findings are needed in other studies., Author(s): Lene Wulff Krogsgaard 1,*, Irene Petersen 2,3, Oleguer Plana-Ripoll 4, Bodil Hammer Bech 1, Tina Hovgaard Lützen 1, Reimar Wernich Thomsen 2, Dorte Rytter 1 Introduction Human papilloma virus [...]

STUDY QUESTION Do women with endometriosis have higher utilization of primary and secondary healthcare prior to diagnosis compared to women without endometriosis? SUMMARY ANSWER Women with a hospital-based diagnosis of endometriosis had an overall higher utilization of both primary and secondary healthcare in all 10 years prior to diagnosis. WHAT IS KNOWN ALREADY Endometriosis is associated with a diagnostic delay, but only a few studies have investigated the potential consequences of this delay with regard to the utilization of healthcare. To the best of our knowledge, no study has investigated it in a period corresponding to the estimated diagnostic delay. STUDY DESIGN, SIZE, DURATION This national Danish registry-based case–control study included 129 696 women. Cases were women with a first-time hospital-based diagnosis of endometriosis between 1 January 2000 and 31 December 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS We identified 21 616 cases using density sampling. Each case was matched on age at the date of diagnosis (index date) to five women without diagnosed endometriosis (n = 108 080). The utilization of healthcare was assessed for the 10 years before the index. MAIN RESULTS AND THE ROLE OF CHANCE Cases had significantly higher use of healthcare in all 10 years preceding the index. The mean number of yearly contacts with the GP was 9.99 for cases and 7.85 for controls, with an adjusted incidence rate ratio of 1.28 (1.27; 1.29). For hospital contacts, the association increased slightly in the first 9 years and was most profound in the last year preceding index when the adjusted incidence rate ratio was 2.26 (95% CI 2.28; 2.31). LIMITATIONS, REASONS FOR CAUTION We were not able to include women with an endometriosis diagnosis from the general practitioner or private gynaecologist. Therefore, our results are only applicable to hospital-based diagnoses of endometriosis. We do not have information on the specific reasons for contacting the healthcare providers and we can therefore only speculate that the higher utilization of healthcare among cases was related to endometriosis. WIDER IMPLICATIONS OF THE FINDINGS This study is in agreement with the other known studies on the subject. Future studies should include specific reasons for contacting the healthcare system and thereby identify any specific contact patterns for women with endometriosis. With this knowledge, healthcare professionals could be better at relating certain healthcare seeking behaviour to endometriosis earlier and thereby reduce the time from onset of symptoms to diagnosis. STUDY FUNDING/COMPETING INTEREST(S) This study is supported by grants from the project 'Finding Endometriosis using Machine Learning' (FEMaLe/101017562), which has received funding from The European Union's Horizon 2020 research and innovation program and Helsefonden (21-B-0141). K.Z. report grants from Bayer AG, Roche Inc. and Volition, royalties from Oxford-Bayer scientific collaboration in gynaecological therapies, non-financial collaboration with the World Endometriosis Society and World Endometriosis Research Foundation and is a Wellbeing of Women research advisory committee member. All this is outside the submitted work. The other authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Introduction: Exposures in utero are suggested to play a role in the etiology of endometriosis and adenomyosis, although the current evidence is inconclusive. Knowledge about potential prenatal programming and early life exposures that may affect this risk is of high importance, to focus potential preventive strategies for the diseases already during pregnancy. The aim of this study was to review systematically the literature of the association between measures of fetal growth and preterm birth and endometriosis and adenomyosis in adult life. Material and methods: A systematic review according to Preferred Reporting Items for Systematic Reviews and Meta‐analysis (PRISMA) guidelines and by search on PubMed and EMBASE was carried out. We included published case–control and cohort studies. We excluded studies without a reference group, eg case series, case reports as well as commentaries, letters and editorials. The quality of the studies was assessed using the Newcastle–Ottawa Scale. Meta‐analyses using a random‐effect inverse variance weighted model were performed. PROSPERO registration number is CRD42021249322. Results: A total of 11 studies were included. In general, the quality scores of the studies were moderate. We found that the risk of endometriosis was 26% higher in women born with a birthweight <2.5 kg (pooled odds ratio [pOR] 1.26, 95% confidence interval [CI] 1.05–1.52) and 32% higher in women born preterm (pOR 1.32, 95% CI 1.01–1.72) than in the reference groups. The studies on adenomyosis pointed towards no association, but a meta‐analysis was unfeasible due to the small number of studies. Conclusions: This systematic review and meta‐analysis found that low birthweight and being born preterm were associated with endometriosis in adult life, but the results must be interpreted cautiously. No solid conclusion could be made regarding adenomyosis due to a limited number of published studies, but the studies included found no association. The results support the hypothesis of a potential early programming effect of endometriosis. However, the body of evidence is sparse and this hypothesis needs to be investigated further. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to examine the association between multiple health complaints (MHC) in pre-adolescence and prescription redemption in adolescence. Methods: This was a nationwide population-based study based on the Danish National Birth Cohort for an average of 6.9 years (2010–2018). A total of 96,382 children were invited at the age of 11. A modified version of the Health Behaviour in School Children Symptom Checklist was dichotomised into the World Health Organization's definition of MHC (⩾2 complaints, each with a frequency of at least weekly, yes/no). The number of prescriptions was retrieved from Danish registries. Negative binomial regression estimated incidence rate ratios (IRRs) comparing children with MHC to children without. Prescription redemption was further stratified by psychiatric/somatic medication and into subtypes of prescriptions. Results: A total of 47,365 (49.1%) children participated (M age=11.2 years, 52% girls). MHC were reported by 10.3%. The unadjusted IRR (MHC vs. no MHC) of all types of redemptions was 1.57 (95% confidence interval (CI) 1.49–1.64). Results were robust to adjustment for socio-demographic variables and somatic/psychiatric morbidity at baseline (IRR=1.47; 95% CI 1.40–1.54). Associations were especially strong for psychiatric medication (adjusted IRR=3.88; 95% CI 3.43–4.40) and were modified by neither sex nor maternal education. Conclusions: MHC in pre-adolescents predict prescription redemption. This implies that changes in MHC might be indicative of changes in public health. This requires further study, as the cause of a change in reporting of symptoms might also cause a change in treatment response. The latter determines whether prescriptions are treating ill-being or needlessly medicalising subjective symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Due to diagnostic challenges, normalization of symptoms and an overall lack of awareness among both patients and physicians, endometriosis is an underdiagnosed disease. This can result in delayed treatment and potentially worsening of the disease. Despite initiatives, such as patients' support organizations and specialized endometriosis referral centers, differences in awareness, socioeconomic factors and lifestyle, combined with varying distances to specialized referral centers, could result in regional differences in the degree of underdiagnosing. This study aims to explore temporal and regional variations in the incidence of endometriosis based on the Danish hospital discharge register, and shed light on the degree of underdiagnosing of endometriosis in Denmark. Material and methods: This registry‐based cohort study included all women aged 15–55 living in Denmark from 1990–2017. Participants were identified through the Danish Civil Registration system and endometriosis diagnoses received at a hospital were obtained from the Danish National Patient Registry. Incidence rates of diagnosed endometriosis were calculated for each year of the study period and for each municipality in Denmark. A Cox regression analysis, stratified by calendar time and adjusted for ethnic origin, household composition, highest educational level and family socioeconomic status, was performed to estimate the association between residence and likelihood of receiving a hospital‐based diagnosis of endometriosis. Results: The nationwide incidence rate of hospital‐diagnosed endometriosis was 7.89 (95% confidence interval [CI] 7.80–7.99) per 10 000 person‐years and the prevalence in 2017 was 1.63%. The results showed an overall increase in the incidence of diagnosed endometriosis of 46.8% (95% CI 32.9–62.2) during the study period and also displayed significant regional differences. After adjustments, women living in northern Jutland had the highest probability of receiving a hospital‐based diagnosis of endometriosis (hazard ratio 1.13, 95% CI 1.09–1.18), whereas women living in northern Zealand had the lowest probability (hazard ratio 0.63, 95% CI 0.60–0.67) compared with eastern Jutland. These regional differences have become more evident over time. Conclusions: Our results reveal significant regional differences in the incidence of hospital‐diagnosed endometriosis, suggesting that a significant number of women may be left behind without a diagnosis. Further studies are needed to assess the underlying reasons for the significant regional differences. [ABSTRACT FROM AUTHOR]

Purpose: Infertility may affect somatic and mental health later in life. Nevertheless, health status before diagnosed infertility is sparsely studied in women. We aimed to describe healthcare use in primary and secondary care before a first infertility diagnosis and compare use between cases and controls. Materials and Methods: The case–control study was based on register data and used incidence density sampling. From the CROSS-TRACKS Cohort, we included women residing in the Horsens area in Denmark in 2012– 2018 (n = 54,175). Eligible women were aged 18– 40 years, nulliparous, and living in heterosexual relationships. Cases were women with a first infertility diagnosis in the Danish National Patient Registry (index date). Five controls were matched on age, birth year, and calendar time. Through linkage to Danish national health registries, we identified general practitioner (GP) attendance, paraclinical examinations, hospital contacts, diagnoses, and redeemed prescriptions. Healthcare use from one year to five years before index date was compared with conditional logistic regression. Results: We identified 711 cases and 3555 controls. At one year before index date, cases consulted their GP (odds ratio (OR) = 5.2, 95% confidence interval (CI): 3.2, 8.3) and visited hospital (OR = 1.2, 95% CI: 1.0, 1.4) and redeemed prescriptions (OR = 2.3 95% CI: 1.9, 2.7) more often compared to controls. Cases more often had blood and hemoglobin tests performed, redeemed more drugs related to genitourinary and hormonal diseases, and were more often diagnosed with endocrine and genitourinary diseases in the year before a first infertility diagnosis compared to controls. Cases and controls had comparable healthcare use from five years to one year before a first infertility diagnosis. Conclusion: Cases and controls had similar healthcare use from five years to one year before a first infertility diagnosis. However, cases had a higher healthcare use in the year preceding a first infertility diagnosis compared to controls. [ABSTRACT FROM AUTHOR]

Introduction: Prevalence and consequences of menstrual pain have mainly been studied in younger women. We aimed to describe the prevalence of menstrual pain in mothers and its association with sexual problems. Material and methods: A cross‐sectional study using questionnaire data from the Maternal Follow Up (2013–2014) in the Danish National Birth Cohort (1996–2002). Of 82 569 eligible mothers, 43 639 (53%) completed the follow up. Of these, 24 000 women had a partner, and answered the questions on menstrual pain. Log binomial regression was used to calculate prevalence proportion ratios (PPR) with 95% CI for the association between menstrual pain and specific sexual problems. Results: Menstrual pain was reported by 16 464 women (69%), and severe menstrual pain by 19%. Treatment had previously been requested by 19% of women with menstrual pain. The most common treatment was oral contraceptives, but for 18% of women seeking treatment, no treatment was given. Women with menstrual pain were more likely to report reduced sexual desire (PPR 1.22, 95% CI 1.15–1.29), vaginismus (PPR 1.31, 95% CI 0.96–1.78), and dyspareunia (PPR 1.63, 95% CI 1.47–1.81), in particular deep dyspareunia (PPR 1.92, 95% CI 1.67–2.20). Conclusions: A majority of Danish mothers in mid‐life experienced menstrual pain, and these women more often reported reduced sexual desire, vaginismus, and deep dyspareunia. Few women sought and received treatment for menstrual pain. Healthcare practitioners should be aware that menstrual pain can affect parous women and co‐occurs with sexual problems. Future studies should identify barriers to seeking and receiving adequate treatment for menstrual pain. [ABSTRACT FROM AUTHOR]

Background: A growing body of evidence supports the safety of the human papillomavirus (HPV) vaccines. However, concerns about autonomic dysfunction syndromes and non-specific symptoms continue to linger. These conditions are not easily captured by traditional diagnostic classification schemes and call for innovative approaches to the study of vaccine safety which take more general measures of all-cause morbidity into account.Methods: Taking advantage of the unique Danish registers, including regional registration of absence from school, we conducted a cohort study of 14 068 adolescent Danish girls attending 5th through 9th grade in public schools in the municipality of Copenhagen during 1 August 2013-23 January 2018. We obtained time-varying HPV vaccination status and demographic information from nationwide registers. Using Poisson regression with random effects, we estimated rate ratios (RRs) of absence due to illness, comparing HPV-vaccinated girls with unvaccinated girls with adjustment for grade, season, calendar period, demographic factors and random effects at the individual, class and school levels.Results: Our study included 6 206 188 school days with 213 221 days of absence from school due to illness (absence rate, 3.4%). Comparing absence rates due to illness in HPV-vaccinated and unvaccinated girls yielded an adjusted RR of 1.00 (95% confidence interval [CI], 0.98-1.03).Conclusions: Our study provides an important and novel contribution to HPV vaccine safety. Using absence from school records, we were able to address important safety concerns without relying on medical diagnoses. We conclude that HPV vaccination does not increase the risk of morbidity in any manner that manifests as absence from school due to illness. [ABSTRACT FROM AUTHOR]

Background: Maternal depression has been linked to adverse outcomes in the offspring. Existing literature is mainly based on parental reports, which can be an unreliable source when the parent has depression.Aim: To explore if maternal depression was associated with daily health complaints and low self-assessed health (SAH) in the offspring.Design and Setting: Participants were 45 727 children from the Danish National Birth Cohort recruited between 1996 and 2002. At 11-year follow-up, mothers and their children were invited to complete a questionnaire. Maternal depression was categorised into: no depression, first-time treatment, continued treatment, post-treatment, and relapse.Method: Binomial regression was used to estimate the adjusted prevalence proportion ratio (aPPR) of frequent health complaints and low SAH in children of mothers with depression compared to children of mothers without depression.Results: The prevalence of any daily health complaint was 11.4%, daily somatic complaints 4.1%, daily mental complaints 8.9%, both daily mental and somatic complaints 1.5%, and low SAH 5.3%. Children of mothers with depression (any category) were more likely to report a daily health complaint: first-time treatment aPPR 1.35 (95% confidence interval [CI] = 0.96 to 1.85), continued treatment aPPR 1.59 (95% CI = 1.37 to 1.85), post-treatment aPPR 1.30 (95% CI = 1.20 to 1.41), and relapse aPPR 1.56 (95% CI = 1.35 to 1.79). Children of mothers with depression were also more likely to report low SAH: first-time treatment aPPR 1.58 (95% CI = 0.99 to 2.54), continued treatment aPPR 1.86 (95% CI = 1.51 to 2.28), post-treatment aPPR 1.34 (95% CI = 1.19 to 1.50), and relapse aPPR 1.56 (95% CI = 1.26 to 1.93). Girls had a higher prevalence of mental and somatic health complaints and more often reported low SAH compared to boys.Conclusion: Treatment of maternal depression was associated with higher prevalence of daily health complaints and low SAH in the offspring at age 11 years. The association was strongest for children of mothers with continued depression or relapse. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to describe and compare general practitioner (GP) attendance patterns in the years surrounding HPV-vaccination among cases suspected to experience adverse events and their matched controls in order to determine if a potential larger change in GP attendance among cases was observed in temporal relation to vaccination. Methods: Register-based, matched case–control study. Cases were defined as women referred to specialized hospital settings (HPV-centers) for suspected adverse event between June 1st 2015 and December 31st 2015 (n=1458). Information on referral was obtained from the HPV-centers directly. Each case was matched with five controls on age at vaccination, region, time of first vaccine registration and total number of doses, resulting in a total study population of 8670 girls and women. Negative binomial regression analyses were used (i) to estimate mean yearly GP contacts among cases and controls, and (ii) to further investigate the relative difference in change in GP attendance following vaccination between cases and controls. Results: Overall, cases displayed higher GP attendance than controls from five years before vaccination up until five years after. Compared to controls, cases increased their GP attendance more in the years following HPV vaccination, corresponding to a 40% increase in the incidence rate ratios (IRR) from before to after vaccination (ratio-IRR = 1.40 [1.36; 1.44]). The change occurred in close proximity to vaccination, and the pattern was the same independently of the year of vaccination. However, for the later vaccination years cases displayed an additional increase in their GP attendance around time of extensive media attention. Conclusion: Girls and women being referred for suspected adverse events after HPV-vaccination changed their GP attendance pattern in close proximity to their first HPV-vaccination and not solely in temporal linkage to the onset of public debate. [ABSTRACT FROM AUTHOR]

Background: Maternal smoking during pregnancy (MSDP) has been associated with a wide range of adverse effects on offspring health, such as low birthweight, behavioural disorders, and asthma. The number of women that smoke during pregnancy in Denmark is still high, making it relevant to study the long-term health outcomes in offspring exposed to maternal smoking in utero.Objective: We investigated whether exposure to MSDP is associated with more frequent use of health care services during the first 10 years of life.Methods: This population-based cohort study included participants enrolled in the Danish National Birth Cohort between 1996 and 2003. Data on MSDP were obtained from two telephone interviews during pregnancy and one interview after pregnancy. The primary outcome was contacts to the health care system. From Danish national registries, we obtained information on number and type of contacts to the general practitioner (GP), and information on the specific types of services provided. Further, we obtained information on hospital admissions, and redemption of prescribed medicine. We fitted negative binomial regression models and Cox proportional hazards regression models to estimate associations. All analyses were adjusted for socio-economic status, birth year, and various maternal factors.Results: We studied 83,905 liveborn singletons and found that offspring exposed to maternal smoking in utero had more contacts to the GP in the first 10 years of life with an incidence rate ratio of 1.05, 95% confidence interval [CI] 1.04, 1.06. A higher rate of admission to hospital in 9 out of 20 categories was found, as was a higher rate of being prescribed psychoanaleptics (hazard ratio [HR] 1.41, 95% CI 1.25, 1.60), drugs for obstructive pulmonary disease (HR 1.14, 95% CI 1.14, 1.20), and antibiotics (HR 1.03, 95% CI 1.01, 1.05).Conclusions: We found that offspring exposed to MSDP had a higher use of health care services than unexposed offspring. [ABSTRACT FROM AUTHOR]

Background: Depression is a common mental illness worldwide. The offspring of a mother with depression has higher risk of developing mental and physical illness.Aim: This study aimed to investigate the association between the timing of maternal depression and the use of primary health care for the offspring.Design and Setting: A population-based birth cohort study in Danish primary care using Danish national registers.Method: All Danish children born between 1 January 2000 and 31 December 2013 (n = 869 140 children) were included in the study. The primary outcome was number and type of annual contacts with the GP. The secondary outcome was specific services used by the GP to assess inflammatory and infectious disease in the children. Exposure was maternal depression of four categories: non-depressed, recent, previous, and past depression. The association was expressed as adjusted incidence rate ratios (IRR) with 95% confidence intervals (CI).Results: Maternal depression was associated with a higher use of primary health care for all three categories of depression. The strongest association was found for children of a mother with recent depression; they had 16% more contacts than children of a non-depressed mother (adjusted IRR = 1.16, 95% CI = 1.15 to 1.17), and 19-24% more positive infectious-related tests were found in this group.Conclusion: Exposure to maternal depression was associated with a significantly higher use of primary health care for the offspring for all exposure categories. These findings reveal that healthcare use is higher for the offspring exposed to maternal depression, even several years after expected remission. The higher ratio of positive tests indicates that exposed children are ill with infectious disease more often. [ABSTRACT FROM AUTHOR]

Background In Denmark, the human papillomavirus (HPV) vaccines have been suspected of adverse events since 2014. However, as no causal associations between the HPV vaccines and numerous diseases have been demonstrated, factors prior to vaccination may influence the risk of suspecting the HPV vaccines of causing symptoms. We studied the associations between individual and parental socioeconomic characteristics and the risk of referral to a diagnostic centre in a female population aged 11–29 years with a first HPV vaccination in January 2008 to June 2015. Methods Individual and parental data from national registries were linked using the unique personal identification number. Logistic regression analyses were used to estimate crude and adjusted odds ratio's according to each individual and parental socioeconomic factor with two-sided 95% 95% CI. Results The cohort consisted of 453 216 individuals of which 1316 (0.29%) were referred to a diagnostic centre in 2015. Having a mother outside the workforce or an unemployed mother was associated with an increased risk of referral, while girls and women who had fathers with a higher educational level were less likely to be referred. In addition, women aged 20–29 years who were unemployed or outside the workforce prior to vaccination had increased odds of being referred to a diagnostic centre. Conclusion We found social inequality in the referral to a diagnostic centre following HPV vaccination. This might be explained by an increased morbidity in girls and women of lower socioeconomic status. [ABSTRACT FROM AUTHOR]

Introduction In Denmark, care and treatment related to epilepsy primarily takes place at specialized hospital departments (neurology and pediatrics). The general practitioner (GP) in contrast is the primary contact and acts as a gatekeeper to the healthcare system for other disorders. The aim of the present study was to describe the utilization of services provided by the GP for children with epilepsy before and after diagnosis of epilepsy and to compare it with that of children without epilepsy. Methods All live born children born in Denmark between 1st of January 1996 and 1st of December 2013 were identified in the Danish National Patient Registry. Information about number and type of contact to the general practitioner was obtained from the Health Insurance Service Register. Information about epilepsy was obtained from the Danish National Patient Registry (n = 10,062). For each child with epilepsy, we sampled 10 children without an epilepsy diagnosis matched on sex and age at the time of diagnosis (n = 100,620). Children were followed up until 31st of December 2013. Multiple negative binomial regression analysis adjusting for relevant confounders was used to estimate the association between epilepsy and the use of GPs both before and after the time of epilepsy diagnosis. Results Children with epilepsy had a higher utilization of services provided by the GP after the diagnosis of epilepsy compared with children without epilepsy (incidence rate ratio (IRR): 1.64 (1.61–1.67)). The IRR for any contacts stayed relatively stable during the follow-up period, whereas the IRR for face-to-face contacts tended to decline and phone contacts tended to increase. The more frequent GP contacts in children with epilepsy were also evident before the time of diagnosis and for both sexes and in all age groups. For the specific services provided, children with epilepsy more often had a blood sample taken and more urine stix and CRP tests performed during the first years following diagnosis. Conclusion Children with epilepsy have a higher use of services provided by the GP both before and after the epilepsy diagnosis compared with children without epilepsy. This is likely due to a higher prevalence of comorbid conditions in children with epilepsy as well as consequences of the underlying condition. [ABSTRACT FROM AUTHOR]

Background: Depression is a common and potentially debilitating illness worldwide. Attendance to routine childcare appointments is a key point of interest in the effort to improve the health and care for families facing depression.Aim: To evaluate the association between maternal depression and offspring non-attendance to the Danish childcare and vaccination programme (CCP) for children from 0-5 years of age. The CCP consists of seven separate visits and several vaccinations. To investigate if exposure to recent and previous depression may affect attendance differently.Design and Setting: Population-based cohort study using Danish nationwide registers.Method: Participants were all live-born children (n = 853 315) in Denmark in the period from 1 January 2000 until 31 August 2013, and their mothers. The outcome of interest was non-attendance of each one of the seven scheduled childcare visits and two vaccination entities in the CCP. Exposure was maternal (both previous and recent) depression. All information was obtained from Danish national registries.Results: The risk of not attending CCP was higher for children of mothers with depression. For children of mothers with previous depression, the relative risk (RR) was 1.01 (95% confidence interval [CI] = 0.98 to 1.03) at the 5-week childcare visit, and 1.12 (95% CI = 1.09 to 1.14) at the 5-year childcare visit. For children of mothers with recent depression, the RR was 1.07 (95% CI = 1.03 to 1.13) at the 5-week visit, and 1.15 (95% CI = 1.13 to 1.17) at the 5-year visit. Furthermore, the risk of missing at least four of the seven childcare visits was higher for children of females with maternal depression (RR = 1.16, 95% CI = 1.13 to 1.19).Conclusion: Maternal depression seems to compromise CCP attendance. These findings suggest a need for careful clinical attention to these vulnerable families, even years after a diagnosis of depression. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic (AP) medication is increasingly used for many health conditions. Prenatal exposure to AP medication has been associated with several adverse outcomes, but the findings remain inconsistent. Purpose: We aimed to investigate prenatal exposure to AP medication and the use of primary health care system in childhood. Subjects and methods: All live-born singletons in Denmark during 1997-2012 were identified in the nationwide Danish National Patient Register and followed until December 31, 2013 (n = 963,010). Information on prenatal exposure to AP medication was obtained from the Danish Register of Medicinal Product Statistics. Contacts to the general practitioner (GP) were used as a proxy for the overall health of the children. Negative binomial regression was used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between prenatal exposure to AP medication and number and type of GP contacts, excluding routine well-child visits and vaccinations. The models were adjusted for sex and birth date of the child, maternal age, parity, cohabitation status, income, education, smoking status, diagnosis of substance abuse, severe psychiatric disorder, depression and epilepsy as well as the use of antiepileptic drugs, antidepressants, benzodiazepines and insulin. Results: The prenatally AP-exposed children had 7% more GP contacts than unexposed children, IRR: 1.07 (95% CI: 1.03, 1.11). The association was slightly stronger among children of mothers with no diagnosis of severe psychiatric disorder (IRR: 1.08, 95% CI: 1.04-1.13) than among children of mothers with severe psychiatric disorder (IRR: 1.03, 95% CI: 0.96-1.11), but the difference was not statistically significant. We found no difference between prenatally AP-exposed children and their unexposed siblings, IRR: 1.00 (95% CI: 0.97-1.04) for total contacts. Conclusion: Children of women using AP medication in pregnancy had more GP contacts in childhood than children of mothers not using AP medication. However, this might be explained by confounding from maternal behavior and mental illness. [ABSTRACT FROM AUTHOR]

Objective: The Human Papillomavirus (HPV) vaccine has increasingly been suspected of adverse effects in Denmark since 2013. By using consultations with the general practitioner (GP) as an indicator for morbidity, this study aims to examine the association between HPV vaccination and morbidity in girls in the Danish childhood immunization program. Methods: The study is a nationwide register-based cohort study. Both the HPV and the Measles, Mumps and Rubella (MMR) vaccines were offered to 12-year-old girls in Denmark in the study period (2008–2015). Therefore, both vaccines were included as exposures to allow differentiation between potential effects. This resulted in four exposure groups: HPV only vaccinated, HPV+MMR vaccinated, MMR only vaccinated, and Non-vaccinated girls. Outcomes were: daytime consultation rates and frequent GP attendance (> 7 annual GP consultations). We estimated consultation rates by negative binomial regressions analysis and frequent GP attendance by logistic regression analysis. Both analyses were stratified on the years 2008–2013 versus 2014. Results: The study included 214,240 girls born in 1996–2002. All vaccinated groups consulted the GP more often than the non-vaccinated group, both before and after the vaccination. After the vaccination, an increase in consultations was observed for all three vaccinated groups; most distinct for girls vaccinated in 2014. For girls vaccinated before 2014, we found a slightly higher risk of frequent GP attendance after vaccination in the HPV only group compared to the non-vaccinated group, whereas in 2014, frequent GP attendance was seen for all three vaccinated groups; most substantial for the MMR only vaccinated group. Conclusion: In this study, no exclusive increase in health care utilization was detected after HPV vaccination. However, a general difference in the health care utilization pattern was found between vaccinated and non-vaccinated girls, which increased after the time of vaccination, primarily for girls vaccinated after 2013. [ABSTRACT FROM AUTHOR]

Aim: No association between human papilloma virus (HPV) vaccination and numerous diseases has been found. Still, a large number of Danish women are reporting suspected adverse events. Other factors may play a role, and the aim of this study is to examine the association between psychiatric conditions, general practitioner (GP) attendance and indicators of psychological symptoms prior to HPV vaccination and the risk of referral to an HPV center following vaccination. Study design and setting: Register-based, matched case-control study. Cases were identified from five Danish, regional HPV centers, and health data for cases and controls were obtained from national registries. Participants: Cases were defined as women referred to an HPV center between January 1, 2015 and December 31, 2015 (n=1,496). Each case was matched with five controls on age, region and time of first vaccine registration. The total study population consisted of 8,976 women. Results: Overall, women above 18 years who had been referred to an HPV center were more likely to have used psychiatric medication (odds ratio [OR]: 1.88 [95% CI 1.48-2.40]) or to have been hospitalized because of a psychiatric disorder within 5 years prior to the first vaccine registration (OR: 2.13 [95% CI 1.59-2.86]). Specifically, referred women were more likely to have used antipsychotics, antidepressants, attention deficit hyperactivity disorder (ADHD) medication or anxiolytics, and to have been hospitalized for affective disorders or anxiety, but not to have been hospitalized for schizoid, ADHD or eating disorders. In addition, they were more likely to have had talk therapy or psychometric test performed prior to vaccination (OR: 1.72 [95% CI 0.1.35-2.18] and OR: 1.67 [95% CI 1.30-2.13], respectively). Referred women of all ages had higher use of GP before vaccination. Population attributable fraction analyses indicated that psychiatric medication, hospitalization due to a psychiatric disorder and use of talk therapy, or psychometric test "explained" 13%, 10%, 12% and 11% of the referrals, respectively. Results did not change substantially when adjusted for potential confounders. Conclusion: Women referred to HPV centers because of suspected adverse events after vaccination more often had preexisting psychiatric conditions, psychological symptoms or frequent GP attendance prior to HPV vaccination. [ABSTRACT FROM AUTHOR]

Objective: Prenatal exposure to antiepileptic drugs (AEDs) has been associated with adverse outcomes in the offspring such as congenital malformations and neuropsychiatric disorders. The objective of this study was to investigate whether prenatal exposure to AEDs is also associated with more frequent use of primary healthcare during childhood. Design: Population-based cohort study. Setting: Nationwide national registers in Denmark. Participants: All live-born singletons in Denmark during 1997-2012 identified in the Danish National Patient Register and followed until 31 December 2013 (n=963 010). Information on prenatal exposure to AEDs for maternal indication of epilepsy and other neurological conditions was obtained from the Danish Register of Medicinal Product Statistics. Main outcome measures: The primary outcome measure was the number and type of contacts with the general practitioner (GP), excluding routine well-child visits and vaccinations. The secondary outcome measure was specific services provided at the GP contact. The association between prenatal exposure to AEDs and contacts with the GP was estimated by using negative binomial regression adjusting for sex and date of birth of the child, maternal age, cohabitation status, income, education, substance abuse, depression, severe psychiatric disorders and use of antipsychotics, antidepressants and insulin. Results: Children exposed prenatally to AEDs (n=4478) had 3% (95% CI 0 to 5%) more GP contacts during the study period than unexposed children. This was primarily accounted for by the number of phone contacts. Within each year of follow-up, exposed children tended to have more contacts than unexposed children, but the differences were small. We found no difference between exposed and unexposed children with regard to specific services provided at the GP contact. For the individual AEDs, we found that exposure to valproate or oxcarbazepine was associated with more GP contacts. Conclusions: We found only minor differences between prenatally AED-exposed and unexposed children in the number of GP contacts. [ABSTRACT FROM AUTHOR]

Objective: Prenatal exposure to antiepileptic drugs (AEDs) has been associated with adverse outcomes in the offspring such as congenital malformations and neuropsychiatric disorders. The objective of this study was to investigate whether prenatal exposure to AEDs is also associated with more frequent use of primary healthcare during childhood. Design: Population-based cohort study. Setting: Nationwide national registers in Denmark. Participants: All live-born singletons in Denmark during 1997–2012 identified in the Danish National Patient Register and followed until 31 December 2013 (n=963 010). Information on prenatal exposure to AEDs for maternal indication of epilepsy and other neurological conditions was obtained from the Danish Register of Medicinal Product Statistics. Main outcome measures: The primary outcome measure was the number and type of contacts with the general practitioner (GP), excluding routine well-child visits and vaccinations. The secondary outcome measure was specific services provided at the GP contact. The association between prenatal exposure to AEDs and contacts with the GP was estimated by using negative binomial regression adjusting for sex and date of birth of the child, maternal age, cohabitation status, income, education, substance abuse, depression, severe psychiatric disorders and use of antipsychotics, antidepressants and insulin. Results: Children exposed prenatally to AEDs (n=4478) had 3% (95% CI 0 to 5%) more GP contacts during the study period than unexposed children. This was primarily accounted for by the number of phone contacts. Within each year of follow-up, exposed children tended to have more contacts than unexposed children, but the differences were small. We found no difference between exposed and unexposed children with regard to specific services provided at the GP contact. For the individual AEDs, we found that exposure to valproate or oxcarbazepine was associated with more GP contacts. Conclusions: We found only minor differences between prenatally AED-exposed and unexposed children in the number of GP contacts. [ABSTRACT FROM AUTHOR]

Background/Objectives: Vitamin D deficiency is common among pregnant women and since the fetus relies exclusively on maternal supply, deficiency could potentially interfere with fetal development. Vitamin D blood concentrations during pregnancy have been associated with offspring cardio-metabolic health in a few previous studies but the evidence is still inconsistent and only one previous study has followed the offspring into adulthood. The aim of the present study was to investigate the association between maternal serum concentration of vitamin D (25(OH)D) in week 30 of gestation and offspring cardio-metabolic risk factors at 20 years. Subjects/Methods: A follow up study of a Danish birth cohort from 1988–89 (n = 965) was conducted. A blood sample was drawn from the women in week 30 of gestation. In 2008–2009, 95% of the original mother and child dyads could be identified in the central registration registry and were alive and living in Denmark. The offspring were followed up with self-reported anthropometrics (N = 629, 69%) and a clinical examination (N = 410, 45%). Multiple linear regression was used to estimate the association between maternal 25(OH)D and offspring cardio-metabolic risk factors adjusting for potential confounders. Results: No overall association was observed between maternal 25(OH)D in week 30 of gestation and offspring cardio-metabolic risk factors. However, the analyses did suggest a possible inverse association with blood pressure in females. Conclusions: No clear association between maternal 25(OH)D concentration in week 30 of gestation and cardio-metabolic risk factors in the 20 year old offspring was found. [ABSTRACT FROM AUTHOR]

Objective Growing evidence indicates that the metabolic syndrome (MS) is rooted in adverse exposures during fetal life. The aim of this study was to assess the possible associations between biomarkers of inflammation during third trimester of pregnancy and markers of MS in adult offspring. Methods High-sensitive C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleuki-6 (IL-6) were measured in serum samples obtained in gestational week 30. Offspring were clinically examined at age 20 years. Analyses based on 439 mother-offspring dyads were adjusted for maternal smoking during pregnancy, height, prepregnancy body mass index (BMI), education, and offspring's sex. Offspring MS markers included waist circumference, BMI, blood pressure, HOMA insulin resistance, and plasma levels of fasting glucose, triglycerides, cholesterol fractions, insulin, and leptin. Results The median level was 2.8 (interquartile range = 3.3) µg/ml for CRP, for TNF-α: 5.7 (3.2) pg/ml, for IL-1β: 0.5 (0.4) pg/ml, and for IL-6: 1.1 (0.7) pg/ml. Concentrations were not significantly associated with MS markers in the offspring. The results remained essentially unchanged after correction for potential confounding. Conclusion Markers for subclinical inflammation in third trimester in healthy women were not associated with components of MS in their adult offspring. [ABSTRACT FROM AUTHOR]

Background: Previous findings suggest that developmental exposures to persistent organochlorine pollutants (POPs) may be detrimental for the development of the immune system in the offspring. Whether these suspected immunoregulatory effects persist beyond early childhood remains unclear. Objectives: The objective of this study was to evaluate the association between maternal serum concentrations of POPs and the risk of asthma in offspring after 20 years of follow-up. Methods: A birth cohort with 965 women was formed in 1988-1989 in Aarhus, Denmark. Concentrations of six polychlorinated biphenyls (PCBs) (congeners 118, 138, 153, 156, 170, 180), hexachlorobenzene (HCB), and dichlorodiphenyldichloroethylene (p,p´-DDE) were quantified in maternal serum (n = 872) collected in gestation week 30. Information about offspring use of asthma medications was obtained from the Danish Registry of Medicinal Product Statistics. Results: Maternal serum concentrations of HCB and dioxin-like PCB-118 were positively associated with offspring asthma medication use after 20 years of follow-up (p for trend < 0.05). Compared with subjects in the first tertile of maternal concentration, those in the third tertile of PCB-118 had an adjusted hazard ratio (HR) of 1.90 (95% CI: 1.12, 3.23). For HCB the HR for the third versus the first tertile of maternal concentration was 1.92 (95% CI: 1.15, 3.21). Weak positive associations were also estimated for PCB-156 and the non-dioxin-like PCBs (PCBs 138, 153, 170, 180). No associations were found for p,p´-DDE. Conclusions: Maternal concentrations of PCB-118 and HCB were associated with increased risk of asthma in offspring followed through 20 years of age. [ABSTRACT FROM AUTHOR]

The intake of marine n-3 PUFA has been shown to decrease the risk of CVD in a number of studies. Since the development of CVD is often a lifelong process, marine n-3 PUFA intake early in life may also affect the development of later CVD. The aim of the present study was to investigate the association between maternal intake of marine n-3 PUFA during the second trimester of pregnancy and factors associated with cardiometabolic risk in the 20-year-old offspring. The study was based on the follow-up of the offspring of a Danish pregnancy cohort who participated in a study conducted from 1988 to 1989. A total of 965 pregnant women were originally included in the cohort and detailed information about the intake of marine n-3 PUFA during the second trimester was collected. In 2008–9, the offspring were invited to participate in a clinical examination including anthropometric, blood pressure (BP) and short-term heart rate variability measurements. Also, a fasting venous blood sample was drawn from them. Multiple linear regression modelling, using the lowest quintile of marine n-3 PUFA intake as the reference, was used to estimate the association with all outcomes. A total of 443 offspring participated in the clinical examination. No association between the intake of marine n-3 PUFA during the second trimester of pregnancy and offspring adiposity, glucose metabolism, BP or lipid profile was found. In conclusion, no association between the intake of marine n-3 PUFA during the second trimester of pregnancy and the factors associated with cardiometabolic risk in the 20-year-old offspring could be detected. [ABSTRACT FROM PUBLISHER]

Objective: Growing evidence indicates that metabolic syndrome is rooted in fetal life with a potential key role of nutrition during pregnancy. The objective of the study was to assess the possible associations between the dietary glycemic index (GI) and glycemic load (GL) during pregnancy and biomarkers of the metabolic syndrome in young adult offspring. Methods: Dietary GI and GL were assessed by questionnaires and interviews in gestation week 30 and offspring were clinically examined at the age of 20 years. Analyses based on 428 mother-offspring dyads were adjusted for maternal smoking during pregnancy, height, pre-pregnancy body mass index (BMI), education, energy intake, and the offspring’s ambient level of physical activity. In addition, possible confounding by gestational diabetes mellitus was taken into account. Outcome Measures: Waist circumference, blood pressure, HOMA insulin resistance (HOMA-IR) and plasma levels of fasting glucose, triglycerides, HDL cholesterol, LDL cholesterol, total cholesterol, insulin, and leptin were measured in the offspring. Results: Significant associations were found between dietary GI in pregnancy and HOMA-IR (the relative increase in HOMA-IR per 10 units’ GI increase was 1.09 [95% CI: 1.01, 1.16], p = 0.02), insulin (1.09 [95% CI: 1.02, 1.16], p = 0.01) and leptin (1.21 [95% CI: 1.06, 1.38], p = 0.01) in the offspring; whereas no associations were detected for GL. Conclusions: Our data suggests that high dietary GI in pregnancy may affect levels of markers for the metabolic syndrome in young adult offspring in a potentially harmful direction. [ABSTRACT FROM AUTHOR]

Studies in experimental animals and human subjects have suggested that intake of n-3 fatty acids in early life can affect cardiovascular risk factors in adult life. Therefore, the aim of the present study was to investigate the effect of fish oil (FO) supplementation during the third trimester of pregnancy on blood pressure (BP), heart rate (HR) and HR variability (HRV) in the 19-year-old offspring. The study was based on follow-up of a randomised, controlled trial from 1990, in which 533 pregnant women were randomised to FO, olive oil (OO) or no oil (NO) during the last trimester of pregnancy. The offspring was invited to a physical examination including BP, HR and HRV measurements. A subgroup consisting of the offspring of mothers with a low baseline fish intake also had 24 h HRV determined. The OO group was used as reference and multiple linear regression modelling was used to compare the FO and OO groups. A total of 180 of the offspring from the FO and OO groups agreed to participate in the study (45 %). The adjusted difference between the FO and OO groups was 2 (95 % CI − 1, 4) mmHg in systolic and 1 (95 % CI 0, 3) mmHg in diastolic BP. The difference in HR was 1 (95 % CI − 2, 4). Also, HRV indices did not differ significantly between groups. Hence, FO supplementation during late pregnancy was not associated with offspring BP, HR and HRV during adolescence. [ABSTRACT FROM PUBLISHER]

Background: Previous findings suggest that developmental exposures to persistent organochlorine pollutants (POPs) may be detrimental for the development of the immune system in the offspring. Whether these suspected immunoregulatory effects persist beyond early childhood remains unclear. Objectives: The objective of this study was to evaluate the association between maternal serum concentrations of POPs and the risk of asthma in offspring after 20 years of follow-up. Methods: A birth cohort with 965 women was formed in 1988–1989 in Aarhus, Denmark. Concentrations of six polychlorinated biphenyls (PCBs) (congeners 118, 138, 153, 156, 170, 180), hexachlorobenzene (HCB), and dichlorodiphenyldichloroethylene (p,p´-DDE) were quantified in maternal serum (n = 872) collected in gestation week 30. Information about offspring use of asthma medications was obtained from the Danish Registry of Medicinal Product Statistics. Results: Maternal serum concentrations of HCB and dioxin-like PCB-118 were positively associated with offspring asthma medication use after 20 years of follow-up (p for trend < 0.05). Compared with subjects in the first tertile of maternal concentration, those in the third tertile of PCB-118 had an adjusted hazard ratio (HR) of 1.90 (95% CI: 1.12, 3.23). For HCB the HR for the third versus the first tertile of maternal concentration was 1.92 (95% CI: 1.15, 3.21). Weak positive associations were also estimated for PCB-156 and the non-dioxin-like PCBs (PCBs 138, 153, 170, 180). No associations were found for p,p´-DDE. Conclusions: Maternal concentrations of PCB-118 and HCB were associated with increased risk of asthma in offspring followed through 20 years of age. Citation: Hansen S, Strøm M, Olsen SF, Maslova E, Rantakokko P, Kiviranta H, Rytter D, Bech BH, Hansen LV, Halldorsson TI. 2014. Maternal concentrations of persistent organochlorine pollutants and the risk of asthma in offspring: results from a prospective cohort with 20 years of follow-up. Environ Health Perspect 122:93–99; http://dx.doi.org/10.1289/ehp.1206397

Background: This systematic review and meta-analysis summarizes the evidence for the association between endometriosis and adverse pregnancy outcome, including gestational hypertension, pre-eclampsia, low birth weight, and small for gestational age, preterm birth, placenta previa, placental abruption, cesarean section, stillbirth, postpartum hemorrhage, spontaneous hemoperitoneum in pregnancy, and spontaneous bowel perforation in pregnancy. Methods: We performed the literature review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), by searches in PubMed and EMBASE, until 1 November 2020 (PROSPERO ID CRD42020213999). We included peer-reviewed observational cohort studies and case-control studies and scored them according to the Newcastle–Ottawa Scale, to assess the risk of bias and confounding. Results: 39 studies were included. Women with endometriosis had an increased risk of gestational hypertension, pre-eclampsia, preterm birth, placenta previa, placental abruption, cesarean section, and stillbirth, compared to women without endometriosis. These results remained unchanged in sub-analyses, including studies on spontaneous pregnancies only. Spontaneous hemoperitoneum in pregnancy and bowel perforation seemed to be associated with endometriosis; however, the studies were few and did not meet the inclusion criteria. Conclusions: The literature shows that endometriosis is associated with an increased risk of gestational hypertension, pre-eclampsia, preterm birth, placenta previa, placental abruption, cesarean section, and stillbirth. [ABSTRACT FROM AUTHOR]

Abstract Background The human papillomavirus vaccine (HPV vaccine) was introduced into the Danish Childhood Vaccination Programme in 2009. Following a national debate questioning the safety of the vaccine, the coverage decreased from an uptake of >90% for the first dose of the HPV vaccine to an uptake of 52% in girls born in 2003. The aim of this study was to identify changes in determinants for HPV vaccine hesitancy in the period when the debate spiraled and to identify determinants for specific hesitancy towards the HPV vaccine among girls who received the second dose of the measles, mumps and rubella vaccine. Methods We included girls born in the period 1999–2003 who were residing in Denmark between their 12th and 13th birthday (n = 161,528). Data from the Danish Vaccination Register were linked with demographic data from the Danish Civil Registration System. We used multiple logistic regression models to identify associations between determinants and the uptake of the first dose of the HPV vaccine (HPV1). Results For girls born in 1999–2000, low uptake was seen in children of increasing birth order, young or old age of mother, non-Danish origin, low uptake of other childhood vaccines, and in girls living with one parent. For girls born in 2001–2003, most of these determinants of low uptake became less significant. Birth order and origin showed different tendencies when comparing birth cohorts 1999–2000 with birth cohorts 2001–2003. Conclusions We found demographic disparities in the uptake of HPV1 that were generally in line with existing literature. More importantly, the results indicate that determinants for hesitancy towards the HPV vaccines changed during a period of intense public debate regarding the safety of the HPV vaccine. This may indicate that the public concerns over safety disproportionally affect those who trusted vaccines prior to the debate. [ABSTRACT FROM AUTHOR]

The article focuses on an observational cohort study on capillary refill time (CRT) as a predictor of 30-day mortality. The researchers observed patients from the medical admission unit at Sydvestjysk Sygehus, Esbjerg, Denmark from October 2, 2008 to February 19, 2009. The study found that CRT is a poor vital sign and it should not be used in the clinical setting.

Previous studies have indicated that girls experiencing suspected adverse events (AE) following HPV vaccination were more vulnerable prior to vaccination. However, no study has previously investigated differences in vulnerability using prospectively collected self-reported measures of vulnerability. The objective of this study therefore was to describe the distribution of biological and psychosocial indicators of vulnerability in girls referred to a hospital setting due to suspected adverse events and compare it with a sample of non-referred HPV vaccinated girls. The study was conducted as a case control study based within the Danish National Birth Cohort. Cases were defined as HPV vaccinated girls referred to a hospital setting between 2015 and 2017 due to suspected adverse events (n = 80), and 5 controls were randomly selected from the remaining source population, matched to cases on age at vaccination, region of residence and year of vaccination. The final study population consisted of 480 girls. Prior exposures were based on information gathered from an 11 year follow up of the DNBC and included information on self-rated health, frequent health complaints, medication use, bullying, stressful life events and physical activity. Conditional logistic regression analysis was used to estimate the association between each exposure and referral. The percentage of individuals in the exposed category of each exposure was generally higher for cases than controls. Particularly, the odds of being referred were higher for those with low self-rated health compared to high (OR [95%-CI] 2.43 [1.07–5.5]1), those being bullied (OR 3.19 [1.17–8.73]), and those who had taken medication (OR 2.22 [1.32–3.67]). Overall, these results indicated that girls experiencing suspected AE following HPV vaccination were more vulnerable prior to vaccination. [ABSTRACT FROM AUTHOR]