Birth outcomes of women with ulcerative colitis: a nationwide Danish cohort study

OBJECTIVE: Our study aimed to compare the birth outcomes in offspring of women with ulcerative colitis with controls without the disease. METHODS: A cohort study of 1531 newborns to mothers with ulcerative colitis, and 9092 controls, based on linkage between the Danish National Registry of Patients and the Danish Birth Registry from 1982 to 1992. RESULTS: Among the births to women with ulcerative colitis, 569 took place before and 962 after the first hospitalization for ulcerative colitis. We found no increased risk of either low birth weight or intrauterine growth retardation for newborns born before or after the mothers' first hospitalization. The risk of preterm birth was increased when birth occurred after the mothers' first hospitalization (odds ratio = 1.4, 95% confidence interval = 1.1-1.9), and particularly when the first hospitalization for ulcerative colitis took place during pregnancy (odds ratio = 3.4, 95% confidence interval = 1.8-6.4). CONCLUSIONS: In the offspring of women with ulcerative colitis, we found no increased risk of low birth weight or signs of intrauterine growth retardation. The risk of preterm birth was increased in the offspring of women with ulcerative colitis, particularly when the first hospitalization for ulcerative colitis occurred during pregnancy.     

Cobalamin status during normal pregnancy and postpartum: a longitudinal study comprising 406 Danish women

OBJECTIVES: To assess cobalamin (vitamin B(12)) status during normal pregnancy and postpartum in a longitudinal setting. METHODS: This study was performed in 1995-1996. It comprised 406 healthy, pregnant Danish Caucasian women, living in Copenhagen County. Cobalamin status, i.e. plasma (P-) cobalamin, P-methylmalonic acid and P-homocysteine was measured at 18, 32 and 39 wk gestation and 8 wk postpartum during lactation. RESULTS: P-cobalamin showed a gradual, significant decline during pregnancy (P < 0.0001) followed by a significant increase postpartum (P < 0.0001); at 18, 32, 39 wk gestation and 8 wk postpartum median values were 225, 172, 161 and 319 pmol/L, respectively. P-methylmalonic displayed a gradual, significant increase during pregnancy as well as postpartum (P < 0.001) with median values of 0.11, 0.13, 0.14, and 0.16 micromol/L, respectively. P-homocysteine demonstrated a significant increase during pregnancy and postpartum (P < 0.001). The frequency of P-cobalamin values <150 pmol/L increased during pregnancy from 15% at 18 wk to 43% at 39 wk gestation and subsequently declined to 3% postpartum. CONCLUSION: Low cobalamin status may occur among pregnant women, especially in late pregnancy. The recommendations for periconceptional vitamin B(12) supplementation should be reconsidered.     

Acute pancreatitis during oral 5-aminosalicylic acid therapy

Summary Therapy with oral 5-aminosalicylic acid for inflammatory bowel disease has been reported as effective and safe. We report two cases of biochemically proven mild acute pancreatitis occurring 2 and 14 days, respectively, after oral 5-aminosalicylic acid therapy was instituted for inflammatory bowel disease. A hypersensitivity mechanism might be involved, owing to possible erratic systemic absorption of the drug. We suggest clinical and biochemical monitoring for patients undergoing oral 5-aminosalicylic acid therapy in order to confirm its possible association with acute pancreatitis and to assess the actual incidence of such an adverse reaction.     

Disposition of 5-aminosalicylic acid from 5-aminosalicylic acid-delivering drugs during accelerated intestinal transit in healthy volunteers

In eight healthy volunteers accelerated intestinal transit time was induced with bisacodyl, and urinary and faecal excretion of sulphasalazine, olsalazine, 5-aminosalicylic acid (5-ASA), and acetyl-5-ASA was studied after a single oral dose of 3.3 mmol sulphasalazine, olsalazine, Pentasa, and Salofalk and 2.6 mmol of Asacol. The faecal and urinary excretion of acetyl-5-ASA was lowest after intake of sulphasalazine and olsalazine and highest after intake of Pentasa and Salofalk. The figures for Asacol were intermediate. This indicates insufficient release of 5-ASA from sulphasalazine and olsalazine. When the results of this study are compared with those of a previous study without accelerated transit time, the disposition of 5-ASA from all the 5-ASA-delivering drugs is influenced unfavourably by an accelerated gut transit but most pronounced in the case of sulphasalazine, olsalazine, and Asacol. The impaired release from the azo compounds sulphasalazine and olsalazine is a result of far less complete splitting of the diazo bond.     

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 three-fold higher risk of intrauterine growth retardation when birth occurred before the first hospitalization for the disease. After the mother's 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.     

Acute pancreatitis due to 5-aminosalicylic acid

We report a case of a 5-aminosalicylate-induced pancreatitis in a patient with Crohn's disease. These findings suggest that some side effects, traditionally thought to be related to sulphafapyridine, are really due to 5-aminosalicylate. The good prognosis of this rare complication depends on the early withdrawal of the drug. Therefore the degree of the clinical suspicion plays a essential role in the appropriate diagnosis, but a challenge with mesalazine must be carried out in those patients in which other causes of pancreatitis could not be excluded.     

Birth outcomes in women who have taken leflunomide during pregnancy

Objective

In preclinical reproductive studies, leflunomide was found to be embryotoxic and teratogenic. Women treated with leflunomide are advised to avoid pregnancy; those who become pregnant are advised to reduce fetal exposure through a cholestyramine drug elimination procedure. The present study was undertaken to investigate pregnancy outcomes in women who received leflunomide and were treated with cholestyramine during pregnancy.

Methods

Sixty‐four pregnant women with rheumatoid arthritis (RA) who were treated with leflunomide during pregnancy (95.3% of whom received cholestyramine), 108 pregnant women with RA not treated with leflunomide, and 78 healthy pregnant women were enrolled in a prospective cohort study between 1999 and 2009. Information was collected via interview of the mothers, review of medical records, and specialized physical examination of infants.

Results

There were no significant differences in the overall rate of major structural defects in the exposed group (3 of 56 live births [5.4%]) relative to either comparison group (each 4.2%)(P = 0.13). The rate was similar to the 3–4% expected in the general population. There was no specific pattern of major or minor anomalies. Infants in both the leflunomide‐exposed and non–leflunomide‐exposed RA groups were born smaller and earlier relative to infants of healthy mothers; however, after adjustment for confounding factors, there were no significant differences between the leflunomide‐exposed and non–leflunomide‐exposed RA groups.

Conclusion

Although the sample size is small, these data do not support the notion that there is a substantial increased risk of adverse pregnancy outcomes due to leflunomide exposure among women who undergo cholestyramine elimination procedure early in pregnancy. These findings can provide some reassurance to women who inadvertently become pregnant while taking leflunomide and undergo the washout procedure.

     

5-氨基水杨酸在结肠炎癌变模型小鼠中的初步研究

目的 应用5-氨基水杨酸(5-ASA) 干预偶氮氧甲烷(AOM)联合葡聚糖硫酸钠(DSS)诱导小鼠结肠炎癌变的模型,观察结肠过氧化物酶体增殖物激活受体γ(PPAR-γ)、β-catenin的表达水平.方法 36只BALB/c小鼠均分为对照组、模型组和干预组.模型组和干预组均于实验前1d予AOM 10 mg/kg腹腔注射,继以自由饮用4％DSS 1周,再普通饮水2周,饮用DSS及普通饮水共重复3个循环.干预组于实验前3d予5-ASA 150 mg/kg饲喂至实验结束.对照组于实验前1d予0.9％ NaCl溶液腹腔注射,普通饮水9周.监测小鼠疾病症状,评价实验1周末及9周末结肠组织学病理变化,检测9周末结肠PPAR-γ、β-catenin蛋白及结肠PPAR-γ mRNA表达水平.统计学处理采用t检验.结果 干预组饮用DSS 1周后结肠炎疾病活动指数(DAD为1.81+0.59,9周末平均肿瘤数为4.11±1.05,均较模型组(DAI为2.47±0.53,肿瘤数为9.71±2.29)明显降低(t=2.88和6.55,P均＜0.01).干预组结肠PPAR-γ蛋白(2.11±1.36)及mRNA(1.45±0.10)平均表达水平均较模型组(分别为0.43±0.53,0.57±0.08)明显增加(t=3.07和18.99,P均＜0.01).各组间β-catenin表达差异无统计学意义(P＞0.05).结论 5-ASA有效减轻AOM和DSS诱导的小鼠结肠炎癌变模型的炎性反应及肿瘤负荷,同时促进PPAR-γ在结肠中的表达,而对结肠中β-catenin的表达无明显影响.     

Association between ulcer site and outcome in complicated peptic ulcer disease: a Danish nationwide cohort study

Objective: Mortality rates in complicated peptic ulcer disease are high. This study aimed to examine the prognostic importance of ulcer site in patients with peptic ulcer bleeding (PUB) and perforated peptic ulcer (PPU).

Materials and methods: Design: a nationwide cohort study with prospective and consecutive data collection. Population: all patients treated for PUB and PPU at Danish hospitals between 2003 and 2014. Data: demographic and clinical data reported to the Danish Clinical Registry of Emergency Surgery. Outcome measures: 90- and 30-d mortality and re-intervention. Statistics: the crude and adjusted association between ulcer site (gastric and duodenal) and the outcome measures of interest were assessed by binary logistic regression analysis.

Results: Some 20,059 patients with PUB and 4273 patients with PPU were included; 90-d mortality was 15.3% for PUB and 29.8% for PPU; 30-d mortality was 10.2% and 24.7%, respectively. Duodenal bleeding ulcer, as compared to gastric ulcer (GU), was associated with a significantly increased risk of all-cause mortality within 90 and 30 d, and with re-intervention: adjusted odds ratio (OR) 1.47 (95% confidence interval 1.30–1.67); p?p?p?p?=?0.698, OR 0.93 (0.78 to 1.10); p?=?0.409, and OR 0.97 (0.80–1.19); p?=?0.799, respectively.

Conclusions: DU site is a significant predictor of death and re-intervention in patients with PUB, as compared to GU site. This does not seem to be the case for patients with PPU.     

Bioavailability of 5-aminosalicylic acid from slow release 5-aminosalicylic acid drug and sulfasalazine in normal children

The bioavailability of a controlled release 5-aminosalicylic acid preparation (Pentasa) was investigated in nine healthy children after a medication period of six days (1000 mg/day) and compared with sulfasalazine (Salazopyrin) (2000 mg/day). The local bioavailability in the distal gut lumen, reflected by the 5-aminosalicylic acid concentration in the fecal water, showed comparable values after Pentasa (4.44 mmol/liter) and Salazopyrin (6.25 mmol/liter). The concentration ofN-acetyl-5-ASA was significantly higher after Pentasa, reflecting the more proximal release of 5-aminosalicylic acid compared with Salazopyrin. No relation was found between the 5-aminosalicylic acid fecal water concentration and the 5-aminosalicylic acid dose per kilogram of body weight. The urinary excretion of 5-aminosalicylic acid andN-acetyl-5-aminosalicylic acid was higher after Pentasa than after Salazopyrin (32% vs 25%). Dose interval plasma concentration curves showed low values after both preparations. Based on the concept that the fecal water concentration is decisive for the efficacy of 5-aminosalicylic acid in distal inflammatory bowel disease, Pentasa treatment offers a relevant alternative in cases of Salazopyrin intolerance or allergy in children. The higher systemic bioavailability from Pentasa warrants monitoring of the renal function.