Post-migration HIV acquisition: A systematic review and meta-analysis.

Migrants in Europe face a disproportionate burden of HIV infection; however, it remains unclear if this can be prevented through public health interventions in host countries. We undertake a systematic review and meta-analysis to estimate post-migration HIV acquisition (PMHA) as a proportion of all HIV cases in European migrants. MEDLINE, EMBASE, Global Health, HMIC, and Cochrane Library were searched with terms capturing 'HIV', 'migration', and 'Europe'. Data relating to the proportion of HIV acquired following migration were extracted and random-effects model (REM) meta-analysis was undertaken to calculate a pooled estimate for the proportion of PMHA in European countries. Subgroup meta-analysis was undertaken for PMHA by migrant demographic characteristics and host country. Fifteen articles were included for systematic review following retrieval and screening of 2,320 articles. A total of 47,182 migrants in 11 European countries were included in REM meta-analysis, showing an overall PMHA proportion of 0.30 (95% CI: 0.23-0.38). Subgroup analysis showed no significant difference in PMHA between host country and migrant demographic characteristics. This work illustrates that migrants continue to be at high risk of HIV acquisition in Europe. This indicates the need for targeted screening and HIV prevention interventions, ensuring resources are appropriately directed to combat the spread of HIV.

Whole-grain intake in mid-life and healthy ageing in the Danish Diet, Cancer and Health cohort.

PURPOSE: Growing elderly populations worldwide have sparked interest in factors promoting healthy aging. Diet and other lifestyle patterns are key factors for healthy ageing; however, evidence is sparse for specific dietary guidelines that are easily implemented in everyday life. Whole grains constitute specific dietary components with unexplored potential in healthy ageing. METHODS: We applied an illness-death multistate model to assess the association between whole-grain intake and life expectancy, both with and without disease, over a 20-year period. Healthy ageing was defined as absence of cancer, ischemic heart disease, stroke, type 2 diabetes, asthma, chronic obstructive pulmonary disease, and dementia during follow-up. RESULTS: Based on information from 22,606 men and 25,468 women in the Danish Diet, Cancer and Health cohort, followed for an average of 13.8 and 17.5 years, respectively, a doubling in whole-grain intake was associated with 0.43 (95% CI: 0.33-0.52) and 0.15 (0.06-0.24) additional years without disease for men and women, respectively. Comparing the highest and lowest quartiles of whole-grain intake, with a special emphasis on men, we found that those with the highest intake lived, on average, one year longer without disease compared to those with the lowest intake. Additionally, although a high intake of whole grains yielded longer life expectancy, the duration of living with disease was shorter. CONCLUSION: Intake of whole grains in mid-life was associated with healthy ageing looking 20 years ahead.

Associations between parenthood and dementia in men and women: biology or confounding?

BACKGROUND: High parity and extremes of age at first birth have been linked with increased dementia risk in women, with exposure to pregnancy-associated physiological changes proposed as an explanation. However, confounding by socioeconomic and lifestyle factors could also produce such associations, whereby men would share similar patterns of association. We investigated whether these associations hold for both sexes. METHODS: In a cohort study including all women (N = 2,222,638) and men (N = 2,141,002) ≥ 40 years of age in 1994-2017 in Denmark, we used Cox regression to evaluate associations between number of children, age at first birth, and dementia risk separately for women and men. RESULTS: During follow-up, 81,413 women and 53,568 men (median age at diagnosis, 83.3 and 80.3 years, respectively) developed dementia. Compared with having one child, having two or more children was associated with modest decreases in overall dementia risk in both sexes (hazard ratio [HR] range 0.82-0.91, Pdifference men vs. women = 0.07). Although the associations between childlessness and overall dementia risk differed statistically for men and women, the association magnitudes differed only slightly (HRmen 1.04, 95% confidence interval [CI] 1.01-1.06; HRwomen 0.99, 95% CI 0.97-1.01; P = 0.002). Associations between age at becoming a parent and overall dementia were also similar for women and men, with the exception of older (≥ 40 years) first-time parents (HRmen 1.00, 95% CI 0.96-1.05; HRwomen 0.92, 95% CI 0.86-0.98; P = 0.01). With few exceptions, sub-analyses by dementia subtype and timing of onset also revealed similar patterns and effect magnitudes for women and men. CONCLUSIONS: Associations between number of children, age at becoming a parent, and dementia risk were similar for both sexes. Lifestyle and socioeconomic factors are more likely to explain the observed associations than normal pregnancy-related physiological changes.

Shared environment and colorectal cancer: A Nordic pedigree registry-based cohort study.

Risk of colorectal cancer (CRC) increases in relatives of patients with CRC. The extent to which this is attributable to genetic predisposition or shared environment is unclear. We explored this question using nationwide cohorts from Denmark, Finland and Sweden. From 1977 to 2013, we identified 359 879 individuals with a CRC diagnosis and 2 258 870 of their relatives who we followed for CRC incidence. We calculated standardized incidence ratios (SIR) and 95% confidence intervals (CI) for CRC in individuals with an affected relative. We used nationwide household and pedigree data along with national SIR estimates to calculate risk ratios (RR) for the contribution of shared household environment, childhood environment and genetic relationship to CRC risk in those with an affected relative. SIR of CRC was increased for individuals with an affected relative, across all countries and ages. For those with an affected parent, the SIR was 1.65 (95% CI: 1.61-1.69), 1.98 (95% CI: 1.87-2.09), for those with an affected sibling and 2.14 (95% CI: 1.84-2.49) for those with an affected halfsibling. In those <65 years old, shared childhood (RR: 1.41, 95% CI: 1.26-1.57) and household (RR: 2.08, 95% CI: 1.25-3.46) environments were significantly greater contributors to familial risk of CRC than genetics (RR: 0.88, 95% CI: 0.53-1.46). This large-scale Nordic population-based study of excess risk of CRC among relatives of those with CRC addresses the difficult disentangling of shared environment from genetic predisposition in the heritability of CRC. We found shared environment to be the most important contributor to CRC risk.

Pregnancy duration and ovarian cancer risk: A 50-year nationwide cohort study.

A woman's reproductive history is strongly associated with her risk of ovarian cancer. However, it is unclear how pregnancies of different duration impact a woman's ovarian cancer risk, and therefore, what part of a pregnancy explains the protective effect. Using a cohort of all Danish women followed from 1968 to 2018, with prospectively registered information on reproductive history (eg, gestational duration of pregnancies, tubal ligation and resection and hormonal pharmaceutical use), we investigated the effect of pregnancy duration on ovarian cancer risk. We adjusted for potential confounders, such as age at pregnancy and time since pregnancy, using log-linear Poisson regression to isolate the effect of pregnancy duration on ovarian cancer risk. Among 2.5 million Danish women with 4.4 million pregnancies, a pregnancy was associated with a reduction of ovarian cancer risk of 21% (95% CI, 14%-28%), 26% (95% CI, 21%-31%), 12% (95% CI, 7%-17%) and 3% (95% CI, -5% to 11%) compared to one less, for the first, second, third and fourth pregnancy, respectively (P < .001 for heterogeneity), with similar effects of induced abortions, spontaneous abortions and childbirths. Sensitivity analysis of age at pregnancy, time since pregnancy and other potential confounders did not change these findings. The reduced ovarian cancer risk associated with pregnancy is primarily driven by the first three pregnancies, with similar effects of induced abortion, spontaneous abortions and childbirth, suggesting that mainly exposure to early pregnancy factors, and not pregnancy duration, protect against ovarian cancer.

Postoperative de novo epilepsy after craniotomy: a nationwide register-based cohort study.

BACKGROUND AND OBJECTIVES: The risks of postoperative risk of epilepsy after a craniotomy is widely believed to be raised. A study is warranted to quantify the risks for any neurosurgical indication. In this unselected register-based nationwide cohort study with virtually complete follow-up, the short-term and long-term cumulative risks of postoperative de novo epilepsy for all major neurosurgical indications were estimated. METHODS: The study was based on 8948 first-time craniotomy patients in Denmark 1 January 2005 to 31 December 2015 with follow-up until 31 December 2016. The patients were classified according to their underlying neurosurgical pathology. Patients with preoperative epilepsy were excluded. The postcraniotomy risks of de novo epilepsy were estimated using the Aalen-Johansen estimator in a multistate model. RESULTS: The overall cumulative 1-year risk of postcraniotomy de novo epilepsy was 13.9% (95% CI 13.2 to 14.6). For patients with intracranial tumour the cumulative 1-year risk was 15.4% (95% CI 14.4 to 16.5), for spontaneous intracranial haemorrhage 11.3% (95% CI 10.1 to 12.6), for traumatic intracranial haemorrhage 11.1% (95% CI 9.6 to 12.9), for cerebral abscess 27.6% (95% CI 22.8 to 33.5) and for congenital malformations 3.8% (95% CI 1.3 to 11.7). The 6-month, 1-year and 5-year risks for all major indications by specific subtypes are provided. CONCLUSIONS: The cumulative risk of de novo epilepsy following craniotomy is high for patients with any indication for craniotomy, as compared with the background population. The results provide comprehensive data to support future recommendations regarding prophylactic antiepileptic treatment and driving restrictions.

Synchronous bilateral breast cancer: a nationwide study on histopathology and etiology.

PURPOSE: The aim of the present study was to describe histopathologic characteristics of synchronous bilateral breast cancer (SBBC), and by comparing SBBC to unilateral breast cancer (UBC), identify possible etiological mechanisms of SBBC. METHODS: Patients with primary SBBC (diagnosed within 4 months) and UBC diagnosed in Denmark between 1999 and 2015 were included. Detailed data on histopathology were retrieved from the Danish Breast Cancer Group database and the Danish Pathology Register. Associations between bilateral disease and the different histopathologic characteristics were evaluated by odds ratios and estimated by multinomial regression models. RESULTS: 1214 patients with SBBC and 59,221 with UBC were included. Patients with SBBC more often had invasive lobular carcinomas (OR 1.29; 95% CI 1.13-1.47), a clinically distinct subtype of breast cancer, than UBC patients. Further, they were older than UBC patients, more often had multifocal cancer (OR 1.13; 95% CI 1.01-1.26), and a less aggressive subtype than UBC patients. Invasive lobular carcinoma was associated with having multiple tumors in breast tissue-both in the form of bilateral disease and multifocal disease, and this association was independent of laterality. No similar pattern was observed for other tumor characteristics. CONCLUSION: We identified two etiological mechanisms that could explain some of the occurrence of SBBC. The high proportion of less aggressive carcinomas and higher age of SBBC compared to UBC patients suggests that many are diagnosed at a subclinical stage as slow-growing tumors have a higher probability of simultaneous diagnosis. The high proportion of invasive lobular carcinoma observed in bilateral and multifocal disease, being independent of laterality, suggests that these patients have an increased propensity to malignant tumor formation in breast tissue.

Prognosis regarding shunt revision and mortality among hydrocephalus patients below the age of 2 years and the association to patient-related risk factors.

BACKGROUND: Little is known about the prognosis regarding shunt revision and mortality among hydrocephalus patients below 2 years of age. The aims of this study were to investigate (1) the cumulative risks of shunt revision (SR) and mortality and (2) the potential associations between prematurity, low weight for gestational age (LWGA), underlying aetiology, sex, age of the child at shunt placement, and the risk of SR. METHOD: This was a purely register-based cohort study including all shunted hydrocephalic infants in Denmark 1996-2015. The cumulative risks of SR and mortality were estimated using the Aalen-Johansen and Kaplan-Meier estimators, respectively. A multivariable Cox-regression model was used to estimate hazard ratios (HRs) for SR according to the listed patient-related risk factors. RESULTS: Among 374 shunted infantile hydrocephalus patients accounting for 1047 SRs, the 3-month and 1-year cumulative risks of SR were 36% and 50%, respectively. The overall 10-year cumulative mortality was 12%, and for non-tumour subgroups 7-16% (isolated hydrocephalus 7%). The 10-year cumulative mortality for children born with LWGA was 21%. Except for aetiology, we observed no strong overall associations between the investigated risk factors and the risk of SR but interaction analyses for aetiology showed that patients with Dandy-Walker malformation born with LWGA had a higher risk of SR compared to patients of similar aetiology with normal WGA (HR 2.47, 95% CI: 1.39-4.40). CONCLUSIONS: We found very high cumulative risks of SR and mortality among this youngest group of hydrocephalus patients, disregarding aetiology, but none of them were strongly related to the investigated risk factors.

Vasectomy and Prostate Cancer Risk: A 38-Year Nationwide Cohort Study.

BACKGROUND: A man's risk of prostate cancer has been linked to his prior reproductive history, with low sperm quality, low ejaculation frequency, and a low number of offspring being associated with increased prostate cancer risk. It is, however, highly controversial whether vasectomy, a common sterilization procedure for men, influences prostate cancer risk. METHODS: We established a cohort of all Danish men (born between 1937 and 1996) and linked information on vasectomy, doctor visits, socioeconomic factors, and cancer from nationwide registries using unique personal identification numbers. Incidence risk ratios for prostate cancer by time since vasectomy and age at vasectomy during the follow-up were estimated using log-linear Poisson regression. RESULTS: Overall, 26 238 cases of prostate cancer occurred among 2 150 162 Danish men during 53.4 million person-years of follow-up. Overall, vasectomized men had an increased risk of prostate cancer compared with nonvasectomized men (relative risk = 1.15, 95% confidence interval = 1.10 to 1.20). The increased risk of prostate cancer following vasectomy persisted for at least 30 years after the procedure and was observed regardless of age at vasectomy and cancer stage at diagnosis. Adjustment for the number of visits to the doctor and socioeconomic factors did not explain the association. CONCLUSIONS: Vasectomy is associated with a statistically significantly increased long-term risk of prostate cancer. The absolute increased risk following vasectomy is nevertheless small, but our finding supports a relationship between reproductive factors and prostate cancer risk.

Pregnancy duration and endometrial cancer risk: nationwide cohort study.

OBJECTIVE: To explore the association between pregnancy duration and risk of endometrial cancer. DESIGN: Nationwide register based cohort study. SETTING: Denmark. PARTICIPANTS: All Danish women born from 1935 to 2002. MAIN OUTCOME MEASURES: Relative risk (incidence rate ratio) of endometrial cancer by pregnancy number, type, and duration, estimated using log-linear Poisson regression. RESULTS: Among 2 311 332 Danish women with 3 947 650 pregnancies, 6743 women developed endometrial cancer during 57 347 622 person years of follow-up. After adjustment for age, period, and socioeconomic factors, a first pregnancy was associated with a noticeably reduced risk of endometrial cancer, whether it ended in induced abortion (adjusted relative risk 0.53 (95% confidence interval 0.45 to 0.64) or childbirth (0.66, 0.61 to 0.72). Each subsequent pregnancy was associated with an additional reduction in risk, whether it ended in induced abortion (0.81, 0.77 to 0.86) or childbirth (0.86, 0.84 to 0.89). Duration of pregnancy, age at pregnancy, spontaneous abortions, obesity, maternal birth cohort, fecundity, and socioeconomic factors did not modify the results. CONCLUSIONS: The risk of endometrial cancer is reduced regardless of whether a pregnancy ends shortly after conception or at 40 weeks of gestation. This reduction in risk could be explained by a biological process occurring within the first weeks of pregnancy, as pregnancies ending in induced abortions were associated with similar reductions in risk as pregnancies ending in childbirth.

Breast cancer mortality in synchronous bilateral breast cancer patients.

BACKGROUND: Evidence suggests that patients with synchronous bilateral breast cancer (SBBC), diagnosed within 4 months, have an inferior prognosis compared to unilateral breast cancer (UBC) patients. Using data from nationwide Danish clinical databases, this cohort study investigated whether the inferior prognosis could be explained by SBBC patients having a more aggressive disease, or whether the prognosis could be explained by the fact that they have two simultaneous cancers. METHODS: Patients were diagnosed from 1999-2015. The main outcome was excess mortality, subtracting background population mortality from observed mortality. Differences between SBBC and UBC patients were evaluated by rate ratios (RR) and estimated by Poisson regression. RESULTS: In total, 1214 SBBC and 59 177 UBC patients were included. SBBC patients had a significantly higher excess mortality than UBC patients after adjustment for age and period (RR = 1.73; 95% CI:1.44-2.08; p < 0.01) and after adjusting for characteristics of the worst tumour as traditionally done (RR = 1.31; 95% CI:1.08-1.57; p = 0.01). However, adjusting for characteristics of both tumours, using a more advanced competing risks model, no difference was observed (RR = 1.01; 95% CI:0.83-1.22; p = 0.93). CONCLUSIONS: Our study does not support that the inferior prognosis in SBBC patients is due to having more aggressive tumours per se, but rather the combined effect of having two simultaneous cancers.

Male hormone-interfering drugs and meningioma development.

BACKGROUND: Extremely strong associations between male hormone-interfering drugs and meningiomas have been reported in two previous studies, but these findings are limited by small size of the study populations and possibly by surveillance- and selection bias. Thus, such possible and indeed very interesting association must be investigated in a large, unselected cohort. Accordingly, the aim of this study was to determine whether patients exposed to male hormone-interfering drugs had a higher risk of meningioma development in a nationwide cohort study. METHODS: A retrospective Danish nationwide cohort study with follow-up from January 1, 1996 to December 31, 2016. Exposure was use of male hormone-interfering drugs (5-α-reductase-inhibitors, luteinizing hormone-releasing hormone agonist, steroidal antiandrogen, and nonsteroidal antiandrogen). Hazard ratio of first-time diagnosis of meningioma according to drug use was estimated using Cox proportional hazards model with adjustment for age and birth year. RESULTS: The cohort included 244,696 men of which 64,047 had used male hormone-interfering drugs. Overall 444 meningiomas occurred during follow-up. No significant association was observed between use of male hormone-interfering drugs and the occurrence of meningioma (hazard ratio 1.02, 95% confidence interval 0.82-1.27). Similar results were observed 0-1, 2-4, and 5+ years after first use. In explorative analyses, no elevated risk association was observed for specific drugs (5-α-reductase-inhibitors, luteinizing hormone-releasing hormone agonist, steroidal antiandrogen, and nonsteroidal antiandrogen). CONCLUSION: As opposed to previous studies, we found no evidence of an increased risk of meningioma in men treated with male hormone-interfering drugs.

Pregnancy duration and breast cancer risk.

Full-term pregnancies reduce a woman's long-term breast cancer risk, while abortions have been shown to have no effect. The precise minimal duration of pregnancy necessary to lower a woman's breast cancer risk is, however, unknown. Here we provide evidence which point to the protective effect of pregnancy on breast cancer risk arising precisely at the 34th pregnancy week. Using a cohort of 2.3 million Danish women, we found the reduction in breast cancer risk was not observed for pregnancies lasting 33 weeks or less, but restricted to those pregnancies lasting 34 weeks or longer. We further found that parity, socioeconomic status, and vital status of the child at birth did not explain the association, and also replicated our finding in data from 1.6 million women in Norway. We suggest that a distinct biological effect introduced around week 34 of pregnancy holds the key to understand pregnancy-associated breast cancer protection.

Incidence of sialolithiasis in Denmark: a nationwide population-based register study.

Sialolithiasis is a frequent disorder affecting the salivary glands. The incidence rate (IR) has been reported to be 2.9-5.5 per 100,000 person-years, but all previous studies have been based on selected hospital data. In this study, we conducted a population-based study evaluating the IR of sialolithiasis and the IR variation according to age, gender and geography in Denmark. We included data from hospitals as well as from private ear, nose and throat (ENT) clinics. The study was based on registry data on all sialolithiasis cases in Denmark between 2003 and 2009 extracted from the Danish National Patient Registry (hospital cohort) and the Danish Regions Centre for Healthcare Statistics (private ENT clinic cohort). To validate the diagnosis, the proportion of visually confirmed cases was estimated based on patient records from subsamples of the two cohorts. The IR was 7.27 and 14.10 per 100,000 person-years based on visually confirmed cases only and on all cases, respectively. The highest IR was observed among 60- to 70-year-olds, in the North Denmark region and among females. In the validation subsamples, 35% of assumed sialoliths were visually confirmed in the private ENT clinic cohort and 59% in the hospital cohort. In this first population-based study of IR on sialolithiasis, we found a substantially higher IR. With respect to both visually confirmed cases and all cases, this is higher than previously reported from studies based on selected hospital data.

Associations of parity-related reproductive histories with ER± and HER2± receptor-specific breast cancer aetiology.

Background: Associations of reproductive history with breast cancer risk differ by oestrogen receptor (ER±) status and possibly by the joint expression of ER and the human epidermal growth factor receptor-2 (ER±/HER2±). However, large sample sizes are needed to establish ER-specific risks by HER2± expression. Methods: We linked a cancer registry covering nearly 95% of the primary breast cancer diagnoses in Denmark with a research parity database to assess associations for parity, number of live births and age at first live birth (AFLB) with receptor-specific risk. Relative risks (RRs) for associations were estimated with Poisson regression models. Results: With nearly 31 million women-years of follow-up, 45 786 Danish women aged 20-84 years developed invasive breast cancer during 1992-2011. ER± expression was available for the entire study period and HER2± after 2006. Of the breast cancers with known ER expression, 79% were ER+. Most breast cancers with known ER and HER2 were HER2- (90% of ER+ cancers and 65% of ER- cancers). RRs differed by ER± expression for all reproductive variables ( p -homogeneity < 0.001). Associations were stronger for ER+ than ER- cancers and for those diagnosed before age 50. Parity and early [not later] AFLB showed a protective association with ER+/HER2- and risk association with ER-/HER2- cancers. Conclusion: Associations of reproductive history with breast cancer risk varied among Danish women by ER± and ER±/HER2± expression and age-at-diagnosis, consistent with receptor-specific and age-related etiological heterogeneity. Further stratification by HER2 status demonstrated dual (or opposite) effects for ER+/HER2- and ER-/HER2- cancers.

Cervical cancer screening in Greenland, 1997-2011: Screening coverage and trends in the incidence of high-grade cervical lesions.

OBJECTIVE: In spite of the high incidence of cervical cancer in Greenland, no assessment has been made of the impact of organized cervical screening, introduced in 1998, in relation to occurrence of high-grade cervical lesions. The objectives of the present study were to estimate coverage of the screening program and to examine possible changes in cervical intraepithelial neoplasia (CIN3) incidence in Greenland during 1997-2011 according to calendar period and age. METHODS: Using nationwide registries, we calculated age-standardized incidence rates for all women born and living in Greenland. To investigate whether possible variation in the incidence of CIN3 were related to differences in screening coverage, we further estimated relative risks of CIN3 within two years of screening among women who participated in the screening program using log-linear binomial regression. RESULTS: Coverage of the screening program was low during 1997-2011 with the highest level of 54% observed in 2011. Peaks in CIN3 incidence of around 300 per 100,000 person-years were observed in 1999 and between 2009 and 2011, while the incidence was lower of approximately 100 per 100,000 person-years between 2000 and 2008. During 2009-2011, the highest incidence was found among women aged 25-34 years. Similar patterns of CIN3 risk according to calendar period and age groups were observed among screened women. CONCLUSIONS: The great variations in CIN3 incidence and low screening coverage observed during 1997-2011 suggest that improvements in the Greenlandic screening program are warranted.

Hypertensive disorders of pregnancy and subsequent risk of solid cancer--A nationwide cohort study.

Women with hypertensive disorders of pregnancy (HDP) have higher levels of antiangiogenic growth factors during pregnancy than women with normotensive pregnancies. Since angiogenesis is necessary for solid cancer growth and spread, we hypothesized that women with a history of HDP might have a reduced risk of solid cancers (cancers other than lymphomas, hematologic cancers and nonmelanoma skin cancers) later in life. In a register-based cohort study of 1.08 million women giving birth at least once between 1978 and 2011, we used Cox regression to estimate hazard ratios (HRs) comparing solid cancer rates for women with and without a history of HDP. In this cohort, 68,236 women (6.3%) had ≥1 pregnancy complicated by HDP and 42,236 women (3.9%) developed solid tumors during follow-up. A history of HDP was not associated with a clinically meaningful reduction in the overall rate of solid cancer (HR 0.96, 95% confidence interval 0.92-1.00), regardless of HDP severity or time since HDP, nor was there a general tendency toward reduced solid cancer rates across organ sites. A history of HDP was only significantly associated with decreased rates of breast and lung cancers and with increased rates of endometrial and urinary tract cancers. Overall, our results do not support the hypothesis that women with a history of HDP have a reduced overall risk of solid cancer due to a persistent post-HDP antiangiogenic state or an innate tendency toward antiangiogenesis. Observed associations with specific cancers may instead be due to other pregnancy-related mechanisms or to residual/unmeasured confounding.

Maternal use of oral contraceptives and risk of birth defects in Denmark: prospective, nationwide cohort study.

STUDY QUESTION: Is oral contraceptive use around the time of pregnancy onset associated with an increased risk of major birth defects? METHODS: In a prospective observational cohort study, data on oral contraceptive use and major birth defects were collected among 880,694 live births from Danish registries between 1997 and 2011. We conservatively assumed that oral contraceptive exposure lasted up to the most recently filled prescription. The main outcome measure was the number of major birth defects throughout one year follow-up (defined according to the European Surveillance of Congenital Anomalies classification). Logistic regression estimated prevalence odds ratios of any major birth defect as well as categories of birth defect subgroups. STUDY ANSWER AND LIMITATIONS: Prevalence of major birth defects (per 1000 births) was consistent across each oral contraceptive exposure group (25.1, never users; 25.0, use >3 months before pregnancy onset (reference group); 24.9, use 0-3 months before pregnancy onset (that is, recent use); 24.8, use after pregnancy onset). No increase in prevalence of major birth defects was seen with oral contraceptive exposure among women with recent use before pregnancy (prevalence odds ratio 0.98 (95% confidence interval 0.93 to 1.03)) or use after pregnancy onset (0.95 (0.84 to 1.08)), compared with the reference group. There was also no increase in prevalence of any birth defect subgroup (for example, limb defects). It is unknown whether women took oral contraceptives up to the date of their most recently filled prescription. Also, the rarity of birth defects made disaggregation of the results difficult. Residual confounding was possible, and the analysis lacked information on folate, one of the proposed mechanisms. WHAT THIS STUDY ADDS: Oral contraceptive exposure just before or during pregnancy does not appear to be associated with an increased risk of major birth defects. FUNDING, COMPETING INTERESTS, DATA SHARING: BMC was funded by the Harvard T H Chan School of Public Health's Maternal Health Task Force and Department of Epidemiology Rose Traveling Fellowship; training grant T32HD060454 in reproductive, perinatal, and paediatric epidemiology and award F32HD084000 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development; and grant T32CA09001 from the National Cancer Institute. The authors have no competing interests or additional data to share.

Familial risk of inflammatory bowel disease: a population-based cohort study 1977-2011.

OBJECTIVES: Estimates of familial risk of inflammatory bowel diseases (IBDs), Crohn's disease (CD), and ulcerative colitis (UC) are needed for counseling of patients and could be used to target future prevention. We aimed to provide comprehensive population-based estimates of familial risk of IBD. METHODS: The study encompassed the entire Danish population during 1977-2011 (N=8,295,773; 200 million person-years). From national registries, we obtained information on diagnosis date of IBD (N=45,780) and family ties. Using Poisson regression, we estimated incidence rate ratios (IRRs) of IBD in relatives of IBD cases compared with individuals with relatives of the same type without IBD. RESULTS: The risk of CD was significantly increased in first-degree (IRR, 7.77; 95% confidence interval (CI), 7.05-8.56), second-degree (IRR, 2.44; 95% CI, 2.01-2.96), and third-degree relatives (IRR, 1.88; 95% CI, 1.30-2.71) to patients with CD, and was less pronounced in relatives to UC cases. Likewise, the risk of UC was increased in first-degree (IRR, 4.08; 95% CI, 3.81-4.38), second-degree (IRR, 1.85; 95% CI, 1.60-2.13), and third-degree relatives (IRR, 1.51; 95% CI, 1.07-2.12) of UC cases, and less pronounced in relatives of CD cases. IRRs increased with two or more IBD-affected relatives and were modified by age, with the highest family-related IRR observed in early life. CONCLUSIONS: The risk of IBD is significantly increased in first -, second-, and third-degree relatives of IBD-affected cases, with up to 12% of all IBD cases being family cases. The risk is particularly pronounced in young individuals.