Kirsten Fonager

Pregnancy outcome for women with Crohn's disease: a follow-up study based on linkage between national registries

Objective:Crohns disease, characterized by chronic intestinal inflammation, is sometimes followed by malabsorption, which may interfere with embryogenesis and fetal growth. Therefore we examined birthweight, the frequency of preterm birth, and other reproductive outcomes in the offspring of women with Crohns disease.Methods:We used a historical registry-based study, with linkage between the Danish National Registry of Patients and the Danish Medical Birth Registry. Included were 510 newborns to mothers with Crohns disease and 3018 controls in the study period from 1982 to 1992.Results:The average birthweight of newborns to mothers with Crohns disease was 185 g, 134 g less than expected for primiparas and multiparas. After adjusting for potential confounders the differences were 142 g (95% confidence interval [CI95%] = 76, 208) and 105 g (CI95%= 37, 173), respectively. The risk of low birthweight was increased in Crohn patients (odds ratio [OR] = 2.4; CI95%= 1.6–3.7), as was the risk of preterm birth (OR = 1.6; CI95%= 1.1–2.3).Conclusions:We found a lower birthweight in newborns of patients with Crohns disease, indicating that Crohns disease or its treatment may influence fetal growth.

Assessment of the Diagnoses of Crohn's Disease and Ulcerative Colitis in a Danish Hospital Information System

BACKGROUND Our aim was to estimate the completeness-that is, whether all patients were included in the system-and the validity-that is, whether the diagnostic criteria were fulfilled for the patients registered-of the diagnoses of Crohns disease and ulcerative colitis in a Danish hospital system. METHODS Information in a regional hospital system, in the County of North Jutland, Denmark, was compared with hospital records and information in a pathology system. RESULTS The analysis of the completeness included 143 patients with Crohns disease and 285 patients with ulcerative colitis. The completeness of the regional hospital system using the pathology system as a reference standard was 94% for both diseases. The analysis of the validity included 281 patients registered as having Crohns disease and 506 patients registered as having ulcerative colitis. The validity of the two diagnoses was 97% and 90%, respectively. CONCLUSIONS The regional hospital system showed few misclassifications of the diagnoses of Crohns disease and ulcerative colitis. Thus the nationwide hospital system (based on the regional hospital systems) may provide a unique study base for future research.

Disease Activity in Pregnant Women With Crohn's Disease and Birth Outcomes: A Regional Danish Cohort Study

OBJECTIVES: CD is associated with increased risk of adverse birth outcomes, but existing studies have not assessed the impact of disease activity during pregnancy. We examined the impact of disease activity on birth outcomes: LBW, preterm birth, LBW at term, and CAs.METHODS: All births by CD women in North Jutland County, Denmark, from January 1, 1977 to December 31, 2005, were evaluated in a cohort study based on linkage between the Danish National Registry of Patients and the Medical Birth Registry. After identification of all births by CD women, review of medical records allowed collection of clinical details (including disease activity and drug therapy during pregnancy). The exposed cohort (N = 71) constituted pregnancies with low/moderate-high disease activity during pregnancy, and the unexposed cohort (N = 86) those with inactive disease. Logistic regression analyses were used to estimate the adjusted relative risks (with 95% confidence intervals) for adverse birth outcomes associated with disease activity in CD pregnancies. In subanalysis, we examined the impact of moderate-high activity.RESULTS: In women with disease activity, the adjusted risks of LBW, LBW at term, preterm birth, and CAs were 0.2 (0.0–2.6), 0.4 (0.0–3.7), 2.4 (0.6–9.5), and 0.8 (0.2–3.8), respectively. The crude risk of preterm birth was 3.4 (1.1–10.6) in those with moderate-high disease activity.CONCLUSIONS: Disease activity during pregnancy only increased the risk of preterm birth (especially in those with high disease activity). Further research is needed to assess the critical impact of disease activity in larger cohorts of CD women.

Azathioprine, mercaptopurine and birth outcome: a population‐based cohort study

Background : Data on the safety of azathioprine and mercaptopurine during pregnancy are very sparse.

Birth outcomes of women with celiac disease: A nationwide historical cohort study

OBJECTIVE:We aimed to examine birthweight, low birthweight (<2500 g), and intrauterine growth retardation in offspring of women with celiac disease in relation to their first hospitalization for the disease.METHODS:This was a historical cohort study based on The Danish Medical Birth Registry data of celiac women discharged from Danish hospitals from 1977–1992. The study included 211 newborns to 127 mothers with celiac disease, and 1260 control deliveries.RESULTS:Before celiac women were first hospitalized the mean birthweight of their newborns was 238 g (95% confidence interval [95% CI] = 150, 325 g) lower than that of the control women, after adjustment for potential confounders. After the first hospitalization the mean birthweight for newborns of diseased women was higher than that of controls, by 67 g (95% CI =−88, 223 g) after adjustment for potential confounders. Before celiac women were first hospitalized we found an increased risk of low birthweight (odds ratio [OR] = 2.6, 95% CI = 1.3–5.5) and intrauterine growth retardation (OR = 3.4, 95% CI = 1.6–7.2). After celiac women were first hospitalized we found no increased risk of low birthweight and no babies with intrauterine growth retardation.CONCLUSIONS:Offspring of mothers with celiac disease had lower birthweight than expected and more than a threefold higher risk of intrauterine growth retardation when birth occurred before the first hospitalization for the disease. After the mothers first hospitalization the birthweight was similar to controls and no increased risk of low birthweight was seen. Our study indicates that treatment of celiac women is important in the prevention of fetal growth retardation.

Risk of ulcerative colitis and Crohn’s disease among offspring of patients with chronic inflammatory bowel disease

Objective:The incidence of inflammatory bowel disease (IBD) varies among and within countries, but several studies have indicated that genetic factors may play an important role in the etiology of IBD. A Danish regional study has observed an almost 10-fold increased risk for ulcerative colitis (UC) and Crohns disease (CD) among first-degree relatives of patients with these diseases. To give more precise risk estimates we conducted a nationwide study using population-based data from the Danish National Registry of Patients (NRP).Methods:All patients from the entire Danish population (5.2 million), who were discharged between 1977 and 1992 with a diagnosis of either UC or CD were extracted from the NRP. The offspring of these patients born in 1958 or later were identified in the Civil Registration System and subsequently linked to the NRP by means of the civil registration number. All Danish citizens alive or born on April 1, 1968 or later are registered in the Civil Registration System by a unique registration number, which includes the data of birth and links the offspring to their parents. The prevalence proportion ratio (PPR) was estimated by dividing the observed number of offspring with UC or CD, respectively, with the expected number of cases from the general population.Results:The PPRs of CD and UC among offspring of patients with UC were 2.6 and 5.1, respectively, and the PPRs of CD and UC among offspring of patients with CD were 12.8 and 4.0, respectively. All ratios were significantly increased.Conclusion:The risk for UC and CD among offspring of patients with IBD is 2–13 times higher than the risk within the general population.

Risk of primary biliary liver cirrhosis in patients with coeliac disease : Danish and Swedish cohort data

BACKGROUND Several case reports, but only a few studies, have examined the coexistence of coeliac disease and primary biliary cirrhosis. AIM To estimate the risk of primary biliary cirrhosis in two national cohorts of patients with coeliac disease in Denmark and Sweden. METHODS Through record linkage all Danish patients hospitalised with coeliac disease were followed for possible occurrence of primary biliary cirrhosis from 1 January 1977 until 31 December 1992. All patients hospitalised with coeliac disease in Sweden from 1987 to 1996 were also followed in a separate analysis. RESULTS A total of 896 patients with coeliac disease were identified in Denmark with a median follow up period of 9.1 years for a total of 8040 person-years at risk. Two cases of primary biliary cirrhosis were observed where 0.07 were expected, giving a standardised incidence ratio of 27.6 (95% confidence interval 2.9 to 133.5). A total of 7735 patients with coeliac disease were identified in Sweden with a median follow up period of 5.1 years for a total of 39 284 person-years at risk. Twenty two people with primary biliary cirrhosis were identified compared with 0.88 expected, giving a standardised incidence ratio of 25.1 (95% confidence interval 15.7 to 37.9). CONCLUSION Patients with coeliac disease are at increased risk of having primary biliary cirrhosis.

Birth outcome in women exposed to 5-aminosalicylic acid during pregnancy: a Danish cohort study

Background: 5-Aminosalicylic acid (5-ASA) preparations are the firstline drugs in the treatment of inflammatory bowel disease. Data on the safety of these drugs in pregnancy are sparse. Aims: To examine the risk of adverse birth outcome in women who were prescribed 5-ASA drugs during pregnancy. Patients: Women were included in the study if they were prescribed 5-ASA drugs immediately before or during pregnancy. To examine the risk of malformations, we included 60 pregnancies exposed to 5-ASA drugs 30 days before pregnancy or in the first trimester. To examine stillbirths, preterm births, and low birth weight, we included 88 pregnancies exposed during the entire pregnancy. Outcomes were compared with those of 19 418 pregnancies in which no drugs were prescribed for mothers during the study period. Methods: We conducted a Danish cohort study based on data from a population based prescription registry, the Danish Birth Registry, and the Hospital Discharge Registry in North Jutland County. Results: Odds ratios for malformations, stillbirth, preterm birth, and low birth weight in women who received prescriptions for 5-ASA drugs were 1.9 (95% confidence interval 0.7–5.4), 6.4 (1.7–24.9), 1.9 (0.9–3.9), and 1.2 (0.4–3.3), respectively. The increased risk of stillbirth and preterm birth were found only in patients with ulcerative colitis. Conclusions: We found an increased risk of stillbirth and preterm birth in women who had been prescribed 5-ASA drugs during pregnancy but no substantial increased risk of malformations. It was difficult to distinguish the specific effects of disease activity and 5-ASA drugs.

Episodic heavy drinking in four Nordic countries: a comparative survey.

AIMS The purpose of this study was to compare the phenomenon of episodic heavy drinking (binge drinking) and its different indicators in the Nordic countries. DESIGN A comparative survey of four Nordic countries. SETTING Telephone interviews in Denmark, 1997; Finland, 1996; Norway, 1996; and Sweden 1996-97. PARTICIPANTS Random samples of men and women aged 19-71 years. MEASUREMENTS Episodic heavy drinking was measured by the frequency of subjective intoxication, of drinking six or more drinks at a time (6+), and of negative consequences (mainly hangover symptoms). Additionally, annual consumption and measures of intake per occasion were used. FINDINGS Annual consumption, overall frequency of drinking and frequency of drinking 6+ were highest in Denmark and lowest in Norway. Frequency of subjectively defined intoxication was highest in Finland. There it was clearly higher than the frequency of drinking 6+, whereas in Denmark the contrary was observed. Finnish and Norwegian men and Danish women reported the largest quantities drunk per occasion. Results on 6+ frequency and the prevalence of negative consequences, with annual consumption held constant, suggest that Danes have the least concentrated drinking pattern. With annual consumption held constant, Norwegians report as high a frequency of intoxication, as do Finns. CONCLUSIONS The relations between subjective and more objective measures of episodic heavy drinking vary considerably between the Nordic countries. The results suggest that the definition, acceptability and experience of intoxication vary even when a set of relatively homogeneous countries are compared.

Return to Work in Out-of-Hospital Cardiac Arrest Survivors: A Nationwide Register-Based Follow-Up Study

Background— Data on long-term function of out-of-hospital cardiac arrest survivors are sparse. We examined return to work as a proxy of preserved function without major neurologic deficits in survivors. Methods and Results— In Denmark, out-of-hospital cardiac arrests have been systematically reported to the Danish Cardiac Arrest Register since 2001. During 2001–2011, we identified 4354 patients employed before arrest among 12 332 working-age patients (18–65 years), of whom 796 survived to day 30. Among 796 survivors (median age, 53 years [quartile 1–3, 46–59 years]; 81.5% men), 610 (76.6%) returned to work in a median time of 4 months [quartile 1–3, 1–19 months], with a median time of 3 years spent back at work. A total of 74.6% (N=455) remained employed without using sick leave during the first 6 months after returning to work. This latter proportion of survivors returning to work increased over time (66.1% in 2001–2005 versus 78.1% in 2006–2011; P=0.002). In multivariable Cox regression analysis, factors associated with return to work with ≥6 months of sustainable employment were as follows: (1) arrest during 2006–2011 versus 2001–2005, hazard ratio (HR), 1.38 (95% CI, 1.05–1.82); (2) male sex, HR, 1.48 (95% CI, 1.06–2.07); (3) age of 18 to 49 versus 50 to 65 years, HR, 1.32 (95% CI, 1.02–1.68); (4) bystander-witnessed arrest, HR, 1.79 (95% CI, 1.17–2.76); and (5) bystander cardiopulmonary resuscitation, HR, 1.38 (95% CI, 1.02–1.87). Conclusions— Of 30-day survivors employed before arrest, 76.6% returned to work. The percentage of survivors returning to work increased significantly, along with improved survival during 2001–2011, suggesting an increase in the proportion of survivors with preserved function over time.Background— Data on long-term function of out-of-hospital cardiac arrest survivors are sparse. We examined return to work as a proxy of preserved function without major neurologic deficits in survivors. Methods and Results— In Denmark, out-of-hospital cardiac arrests have been systematically reported to the Danish Cardiac Arrest Register since 2001. During 2001–2011, we identified 4354 patients employed before arrest among 12 332 working-age patients (18–65 years), of whom 796 survived to day 30. Among 796 survivors (median age, 53 years [quartile 1–3, 46–59 years]; 81.5% men), 610 (76.6%) returned to work in a median time of 4 months [quartile 1–3, 1–19 months], with a median time of 3 years spent back at work. A total of 74.6% (N=455) remained employed without using sick leave during the first 6 months after returning to work. This latter proportion of survivors returning to work increased over time (66.1% in 2001–2005 versus 78.1% in 2006–2011; P =0.002). In multivariable Cox regression analysis, factors associated with return to work with ≥6 months of sustainable employment were as follows: (1) arrest during 2006–2011 versus 2001–2005, hazard ratio (HR), 1.38 (95% CI, 1.05–1.82); (2) male sex, HR, 1.48 (95% CI, 1.06–2.07); (3) age of 18 to 49 versus 50 to 65 years, HR, 1.32 (95% CI, 1.02–1.68); (4) bystander-witnessed arrest, HR, 1.79 (95% CI, 1.17–2.76); and (5) bystander cardiopulmonary resuscitation, HR, 1.38 (95% CI, 1.02–1.87). Conclusions— Of 30-day survivors employed before arrest, 76.6% returned to work. The percentage of survivors returning to work increased significantly, along with improved survival during 2001–2011, suggesting an increase in the proportion of survivors with preserved function over time. # CLINICAL PERSPECTIVE {#article-title-36}