Bente Mertz Nørgård

Risk of cancer in a large cohort of nonaspirin NSAID users: a population-based study

There is increasing evidence of an inverse association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of colorectal cancer. However, data regarding other cancer sites are limited. Using data from the population-based North Jutland Prescription Database and the Danish Cancer Registry, we compared cancer incidence among 172 057 individuals prescribed nonaspirin NSAIDs with expected incidence (based on county-specific cancer rates) during a 9-year study period. A total of 6081 incident cancer cases were diagnosed among NSAID users vs 5722 expected (standardised incidence ratio (SIR) 1.1, 95% confidence interval (CI)1.0–1.1). The SIRs for colon and rectal cancer among persons who obtained 10 or more prescriptions were 0.7 (95% CI 0.6–0.9) and 0.6 (95% CI 0.4–0.9), respectively. Similarly, reduced risk estimates were found for stomach (SIR 0.7, 95% CI 0.4–1.1) and ovarian cancer (SIR 0.7, 95% CI 0.4–1.0). Standardised incidence ratios for other cancers among those with 10 or more prescriptions tended to be close to 1.0, except for lung, kidney, and prostate cancers with SIRs of 1.3 (95% CI 1.1–1.6), 1.4 (95% CI 0.9–2.1), and 1.6 (95% CI 1.3–2.0), respectively. We found protective associations of NSAIDs against colon, rectal, stomach, and ovarian cancer. Reasons for the increased risk for some cancer sites are not clear.

Therapeutic Drug Use in Women With Crohn's Disease and Birth Outcomes: A Danish Nationwide Cohort Study

BACKGROUND:Crohns disease (CD) is associated with increased risk of adverse birth outcomes. However, existing studies have not taken into account the impact of drug treatment. We examined the impact of drug treatment on birth outcomes—low birth weight (LBW), preterm birth, LBW at term, and congenital abnormalities (CAs)—among CD women.METHODS:A nationwide Danish cohort study of 900 children born to CD women between 1996 and 2004, based on the National Registry of Patients, the Birth Registry, and the nationwide prescription database. Pregnancies were classified according to receipt of prescriptions for CD medication: no drugs (reference group), 5-aminosalicylic acid (5-ASA)/sulfasalazine, steroids, and azathioprine (AZA)/6-mercaptopurine (6-MP). We used logistic regression analyses to estimate the relative risk of birth outcomes with 95% confidence intervals. We used a proxy measure for disease activity.RESULTS:Preterm births were more prevalent among steroid- and AZA/6-MP-exposed women (12.3% and 25%, respectively) compared with the reference group (6.5%). CAs were more prevalent among AZA/6-MP-exposed compared with reference group (15.4% vs 5.7%). Among steroid exposed, the risk of preterm birth was 1.4 (95% CI 0.6–3.3). Among AZA/6-MP exposed, the risk of preterm birth and CAs was 4.2 (95% CI 1.4–12.5) and 2.9 (95% CI 0.9–8.9), respectively.CONCLUSIONS:The relative risk of adverse birth outcomes among CD women varied by type of drugs prescribed during pregnancy. The risk of preterm birth and CAs was greater when AZA/6-MP was prescribed, even after adjusting for confounders. However, further information is needed to determine whether the associations are causal.

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.

Population-based case control study of the safety of sulfasalazine use during pregnancy

We studied the human teratogenic risk of sulfasalazine because this drug interferes with folate metabolism.

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.

Risk of specific congenital abnormalities in offspring of women with diabetes

Aims  To assess the extent to which the increased risk of congenital abnormalities seen in women with pre‐gestational insulin‐treated diabetes mellitus is unspecific or related to the embryology of specific organs.

Birth outcome in women treated with azathioprine or mercaptopurine during pregnancy: A Danish nationwide cohort study.

Data on birth outcome after exposure to azathioprine or mercaptopurine during pregnancy is sparse.

Psychological stress and inflammatory bowel disease: a follow-up study in parents who lost a child in Denmark.

OBJECTIVES:Little is known about the association between psychological stress and the risk of inflammatory bowel disease (IBD). This study aimed to examine whether the death of a child is related to the development and exacerbation of IBD in bereaved parents.METHODS:We undertook a follow-up study based on national registers. All 21,062 parents who lost a child (younger than 18 yr) from 1980 to 1996 in Denmark were included in the exposed cohort, and 293,745 parents matched on family structure were selected randomly from the general population to the unexposed cohort. Coxs proportional-hazards regression models were used to evaluate the relative risks (RRs) of first IBD hospitalization in the exposed parents, compared to the unexposed. Poisson regression models were fitted to estimate the frequency of IBD readmission between the exposed and the unexposed IBD parents. We used Wilcoxon tests to compare the mean duration of hospitalizations in the two groups of patients.RESULTS:There were 32 prevalent IBD patients at the study entry in the exposed cohort and 451 prevalent cases in the unexposed cases. We observed 301 incident cases of Crohns disease (20 in the exposed, 281 in the unexposed) and 766 incident cases of ulcerative colitis (51 in the exposed, 715 in the unexposed). The RRs of first hospitalization for Crohns disease and ulcerative colitis were 0.97 (95% CI = 0.62–1.53) and 1.01 (95% CI = 0.76–1.34), respectively. For incident or prevalent IBD patients, we did not observe any differences in the frequency or duration of hospitalization in the exposed and unexposed patients.CONCLUSIONS:Our findings do not support an association between psychological stress and the development of IBD in young-to-middle-aged adults.