Chronic inflammatory bowel disease and pregnancy. Case control study

OBJECTIVES: To evaluate the influence of inflammatory bowel disease on pregnancy and fetal outcome. PATIENTS AND METHODS: One hundred and fifty pregnancies in 72 women (28 with ulcerative colitis and 44 with Crohn's disease) were compared with those of 150 control subjects. RESULTS: Among 150 pregnancies, 108 (group I) began before and 42 (group II) at the same time or after the diagnosis of inflammatory bowel disease. In ulcerative colitis patients, age at first pregnancy, mean birth weight and preterm birth rates were not different between groups I and II; rate of underweight offsprings was significantly higher (P < 0.05) in group II than in group I and controls. In Crohn's disease, compared to group I, mean age of first pregnancy was higher (P < 0.0001), mean birth weight was lower (P < 0.005) and preterm birth rate was higher (P = 0.001) than in group II. CONCLUSION: These results suggest that both ulcerative colitis and Crohn's disease induce deleterious effects on pregnancy and fetal outcome.     

Pregnancy in ulcerative colitis

The course of pregnancy in 97 women with ulcerative colitis was studied over a 12-year period. During this period they had 173 pregnancies and delivered 136 children. There were two gemellary deliveries. Nine women had a spontaneous and 16 an induced abortion, of which 4 were performed on therapeutic indication. For a woman with ulcerative colitis the risk of an exacerbation of the bowel disease was 32% per year in her fertile years, whereas it was 34% per year during pregnancy. This difference is not statistically significant. As compared with women with an inactive bowel disease, women in whom the disease was active at the start of pregnancy had a small but significantly greater risk of spontaneous abortion and premature delivery. The frequency of malformations, prematurity, and neonatal hyperbilirubinaemia was not higher in the children of ulcerative colitis mothers than in those of healthy mothers. Treatment with sulphasalazine, salazosulphadimidine, and corticosteroids had no influence on the course and outcome of pregnancy. Birth length and weight of the children of mothers with ulcerative colitis equalled those for children of healthy mothers. In conclusion, pregnancy does not necessitate any change in the usual medical treatment of ulcerative colitis. Women with ulcerative colitis should be advised preferably to conceive at a time when their bowel disease is inactive. Generally, ulcerative colitis constitutes no indication for induced abortion.     

Increased risk of preterm birth for women with inflammatory bowel disease

The reproductive histories of 177 women with Crohn's disease and 84 women with ulcerative colitis were compared with those of healthy control subjects. Inflammatory bowel disease was associated with reduced fertility as measured by number of pregnancies, but measures of childlessness, infertility, fecundability, and methods of birth control suggested that this reduced fertility was the patients' choice rather than a consequence of disease-mediated biological impairments. There was no evidence of increased risk of pregnancy loss, but the risk of preterm birth was significantly elevated for patients with Crohn's disease (odds ratio, 3.1; 95% confidence interval, 1.8-5.4) and for those with ulcerative colitis (odds ratio, 2.7; 95% confidence interval, 1.8-5.4). Several plausible biological mechanisms that could explain the link between preterm birth and inflammatory bowel disease are suggested. These results may be useful when counseling patients who desire pregnancy. Physicians can reassure patients about potential fertility problems but should also encourage close obstetrical monitoring during the third trimester of pregnancy.     

Circulating antibodies against human colonic extract enriched with a 40 kDa protein in patients with ulcerative colitis.

We have previously described a 40 kDa colonic protein(s) which is specifically recognised by tissue-bound immunoglobulin G obtained from the colon of patients with ulcerative colitis. We now report the presence of circulating antibodies against this antigen using an enzyme-linked immunosorbent assay with a highly enriched preparation of the 40 kDa protein from normal colon extracts. Serum was collected from 79 patients with ulcerative colitis, 36 with Crohn's disease, 16 with specific diarrhoeal syndromes, and from 19 normal subjects. Twenty nine of 79 patients with ulcerative colitis, 21 of 36 with Crohn's disease, and all patients with diarrhoea were symptomatic during the collection of sera. The difference in optical density values between patients with symptomatic ulcerative colitis and each of the other groups, including patients with ulcerative colitis in remission, was highly significant (p less than 0.01). Seventy nine per cent of patients with symptomatic ulcerative colitis had optical density values above the means for all other groups. Fifty five per cent of sera from patients with symptomatic ulcerative colitis had optical densities beyond two SDs of the values for all other groups and only two of 71 sera from non-ulcerative colitis patients (one Crohn's disease and one normal subject) had values in this range. These results show the presence of anti-colon antibodies against the 40 kDa protein(s) in the sera of many patients with symptomatic ulcerative colitis.     

Prophylactic effects of olsalazine v sulphasalazine during 12 months maintenance treatment of ulcerative colitis. The Danish Olsalazine Study Group.

In a Danish multicentre trial we compared the relapse preventing effects of olsalazine and sulphasalazine in patients with ulcerative colitis over a 12 month treatment period. Two hundred and twenty seven patients (118 men) with at least two previous attacks of ulcerative colitis were randomly allocated according to a prearranged treatment schedule to olsalazine 500 mg bd or sulphasalazine 1 g bd in a double blind, double dummy fashion. One hundred and ninety seven patients completed the trial. The relapse rate after 12 month in the olsalazine group was 46.9% v 42.4% in the sulphasalazine group with a 95% confidence interval for the difference in proportions of -9% to 18%. Seven per cent of the patients were withdrawn from the trial because of adverse drug reactions and these were equally distributed between the two groups.     

Ectopic colonic mucosa in ulcerative colitis and in Crohn's disease of the colon

Colectomy specimens from 62 patients (22 with ulcerative colitis, 20 with Crohn's disease of the colon, and 20 with invasive adenocarcinoma [without inflammatory bowel disease]) were reviewed for the presence of ectopic colonic mucosa. One or more foci of ectopic colonic mucosa were found in 16 of the 22 specimens (72 per cent) with ulcerative colitis and in 11 of the 20 specimens (55 per cent) with Crohn's disease of the colon. None of the 20 specimens having adenocarcinoma (without chronic inflammatory bowel disease) had ectopic colonic epithelium. The presence of ectopic colonic mucosa was found to be dependent on the age of the patients (more frequent among younger patients) and on the number of sections per specimen. One adenocarcinoma in a case of long-standing ulcerative colitis had apparently originated in ectopic colonic mucosa. This study was supported by grants from the Karolinska Institute.     

Male infertility in inflammatory bowel disease

We examined fertility in men with inflammatory bowel disease (IBD) to determine whether the reported deficit in pregnancies in their spouses was due to reduced reproductive capacity. The cases were 106 men with Crohn's disease and 62 with ulcerative colitis drawn from the rosters of North Carolina chapters of the National Foundation for Ileitis and Colitis. The 140 normal controls were neighbors identified by the cases. There were 186 pregnancies among the spouses of men with Crohn's disease, 110 among the ulcerative colitis group, and 300 among the controls. The mean number of pregnancies among the Crohn's disease patients (1.75 +/- 0.12) was significantly lower than the number for controls (2.14 +/- 0.11), p less than 0.02. The reduction in the mean number of pregnancies among patients with ulcerative colitis (1.77 +/- 0.18) was not significantly different from controls (p less than 0.07). Analysis of waiting time to conception showed that fecundability (the probability of pregnancy in a menstrual cycle) was not different in spouses of IBD patients and controls. We conclude that the overall reproductive capacity of men with IBD is not markedly diminished.     

Compared azathioprine efficacy in ulcerative colitis and in Crohn's disease

AIM: To compare the 6-month efficacy and tolerance of azathioprine in 68 patients with steroid-resistant or steroid-dependent chronic ulcerative colitis (n=30) or Crohn's disease (n=38).METHODS: Clinical remission was defined as a Crohn's Disease Activity Index<150 for Crohn's disease and number of non-bloody stools<=3/day for ulcerative colitis, associated with prednisone requirement<=10 mg/day.RESULTS: Seventy-three per cent of patients with ulcerative colitis had distal or left-sided colitis and 84% of patients with Crohn's disease had pancolitis. Azathioprine was discontinued early for side-effect in 8 (26.7%) patients with ulcerative colitis and in 8 (21.1%) patients with Crohn's disease (NS). In patients treated at least 6 months by azathioprine, clinical remission rates were 77.3% and 70% for chronic ulcerative colitis and Crohn's disease (NS). Complete corticosteroids weaning was obtained significantly more often in ulcerative colitis patients than in Crohn's disease patients (59.1% vs 30%; P<0.05).CONCLUSION: Azathioprine seems to be at least as effective and equally tolerated in steroid-resistant or steroid-dependent chronic ulcerative colitis or Crohn's disease patients.     

Multicenter,multiyear study of safety and efficacy of flexible sigmoidoscopy during pregnancy in 24 females with follow-up of fetal outcome

Our objectives were to analyze the risks versus benefits of flexible sigmoidoscopy to the pregnant female and fetus. We retrospectively studied 24 consecutive pregnant patients admitted to four university hospitals during seven years who underwent 26 flexible sigmoidoscopies. Sigmoidoscopy indications included hematochezia in 11, diarrhea in 12, abdominal pain in 7, constipation in 2, and occult rectal bleeding in 1. Seven patients were in the first trimester of pregnancy, nine were in the second trimester, and eight were in the third trimester. Sigmoidoscopy provided helpful clinical information in all patients. Twelve patients had a lesion diagnosed by sigmoidoscopy, including reactivation of Crohn's colitis, reactivation of ulcerative colitis, infectious colitis, nonspecific colitis, bleeding internal hemorrhoids, pseudomembranous colitis, anastomotic ulcer, and newly diagnosed Crohn's colitis. In particular, nine of 11 patients with rectal bleeding had a lesion identified by sigmoidoscopy. No endoscopic complications occurred to any pregnant female. Two pregnant patients underwent repeat sigmoidoscopy without complications. Fetal outcome was ascertained in all but one pregnancy. Eighteen pregnant females delivered healthy infants (16 at full term, two at 35 or 36 weeks). Their mean Apgar scores were 8.8±0.4sd at 1 min, and 9.0±0.4sd at 5 min. One diabetic and hypertensive female suffered an involuntary abortion nine weeks after sigmoidoscopy, which appeared unrelated to the sigmoidoscopy. Four pregnancies were voluntarily aborted. This study suggests that flexible sigmoidoscopy does not induce labor or result in congenital malformations, that sigmoidoscopy is not contraindicated during pregnancy, and that sigmoidoscopy should be considered in medically stable pregnant patients with significant gastrointestinal bleeding. Sigmoidoscopy should be performed with maternal monitoring by electrocardiography and pulse oximetry and possibly with fetal monitoring, after obstetrical consultation and after stabilization of vital signs. Medical stabilization may require transfusion of blood products and supplemental oxygen administration.     

Increased incidence of faecal coliforms with in vitro adhesive and invasive properties in patients with ulcerative colitis.

Faecal samples were collected from 23 patients with active ulcerative colitis, 15 patients with established ulcerative colitis in remission, 20 patients with active colitis of cause other than ulcerative colitis, and 20 normal control subjects. Ten coliform colonies were randomly selected from the faecal sample cultures and serotyped before the testing of each different serotype from each sample for adhesive or invasive properties on HeLa cell monolayers. In the patients with both active ulcerative colitis and ulcerative colitis in remission and those with other types of colitis one serotype tended to dominate the faecal coliform flora. In normal controls more variety was encountered. Thirty-five per cent of the patients with active ulcerative colitis and 27% of the patients with ulcerative colitis in remission had at least one adhesive or invasive faecal coliform as compared with 5% of the patients with other types of colitis and 5% of the normal controls. These findings are significant (P < 0.05) and may have aetiological and therapeutic significance.     

Hepatic Histological Changes in Ulcerative Colitis

Operative liver biopsy was performed on 58 consecutive patients coming to radical excisional surgery for ulcerative colitis.

The histological changes seen in the liver were: increased cellularity of the portal tracts (83 per cent); fatty infiltration (83 per cent); areas of focal necrosis (47 per cent); and early cirrhosis (2 per cent).

Severe liver damage was shown to he associated with severe active colitis, and with a poor subsequent post-operative prognosis. The mechanisms responsible for liver damage in patients with colitis are discussed.     

Inflammatory bowel disease during pregnancy

Opinion statement Physicians treating patients with Crohn’s disease and ulcerative colitis will often need to care for them throughout pregnancy and deal with the surrounding issues of fertility, childbirth, and sexuality. Patients often worry about continuing medications during pregnancy and feel particularly at risk for poor birth outcomes. However, because pregnancy outcomes are most closely tied to disease activity at the time of conception, patients who are in remission when they conceive will have the most successful pregnancies. The overriding principle in treating pregnant patients with inflammatory bowel disease (IBD) is continued and close surveillance of disease activity, with aggressive medical, and if indicated, surgical treatment. With few exceptions, medicines used to induce remission before pregnancy should be continued throughout pregnancy. Pregnant women with active IBD should be followed by a gastroenterologist with experience in the issues surrounding pregnancy, and by an obstetrician with access to a tertiary referral center. Properly treated and followed, patients with IBD can expect outcomes from their pregnancies that approximate those of patients without the disease.     

Healing of the perineal wound after proctectomy for nonmalignant conditions

A series of 62 patients was studied as regards healing of the perineal wound after proctectomy; 23 patients suffered from ulcerative colitis, 25 from Crohn's colitis, and 14 from polyposis coli. The overall results were in keeping with data from the literature: 73.9 per cent of wounds in patients with ulcerative colitis and 60 per cent of wounds in patients with Crohn's colitis were healed at six months. The worst results were obtained with packing of the perineal wound, especially in inflammatory bowel disease: 61 per cent of those wounds were not healed at six months. Superior results were obtained with conservative surgery, consisting of perirectal excision and intersphincteric resection. With this technique perineal wounds were not healed at six months in 13.6 per cent of patients with inflammatory bowel disease. In the treatment of persistent sinuses after proctectomy, curettage proved disappointing. Better results were obtained with excision of the sinus tract and primary closure of the resulting wound.     

Inflammatory colorectal disease and pregnancy: Report of a case

A retrospective study of women in the child-bearing age with inflammatory disease of the bowel seems to suggest that these women become pregnant as often as other women in the general population. In this small study it was 100 per cent. The incidence of subjective difficulty with conception is likewise small. Patients with Crohn's disease appear to feel better in pregnancy with regard to their intestinal problems, while more than 60 per cent of the patients with ulcerative colitis appear to do poorly. The live-birth rates for both conditions in our series were approximately 80 per cent. An unusual complication in two of our patients with Crohn's disease was a postpartum, postepisiotomy rectovaginal fistula. This may indicate a possible danger of episiotomy in patients who have Crohn's disease.     

Pregnancy,Delivery, and Pouch Function After Ileal Pouch-Anal Anastomosis for Ulcerative Colitis

PURPOSE: This study was designed to evaluate the pregnancies, method of delivery, and functional results of females with chronic ulcerative colitis who have an ileal pouch-anal anastomosis. METHODS: A mailed questionnaire was sent to all females with an ileal pouch-anal anastomosis for chronic ulcerative colitis. Information on the pregnancy, method of delivery, and outcome was collected. Those females who had a successful pregnancy and delivery were contacted by telephone to clarify results and determine pouch functional results. Other clinical information was obtained from the Mount Sinai Hospital Inflammatory Bowel Disease database. RESULTS: Thirty-eight subjects had 67 pregnancies. Of these, 29 subjects had 49 deliveries. There were 25 vaginal deliveries and 24 cesarean sections. There were two pouch-related complications during the pregnancies and four pouch-related complications postpartum. All were treated nonoperatively. Stool frequency and day and night incontinence were increased during pregnancy in most subjects, but after delivery, prepregnancy function was restored in 24 (83 percent) of them. Five subjects (17 percent) had some degree of permanent deterioration in pouch function. Of these, three had vaginal deliveries, and two had cesarean sections. Multiple births and birth weight were not found to adversely affect subsequent pouch function. CONCLUSION: Pregnancy is safe in females with ileal pouch-anal anastomosis. Functional results are altered almost exclusively during the third trimester, but pouch function promptly returns to prepregnancy status in most females. A small proportion of females have long-term disturbances in function, but these are not related to the method of delivery. Thus, the method of delivery should be dictated by obstetric considerations.     

Pregnancy and Delivery Before and After Ileal Pouch-Anal Anastomosis for Inflammatory Bowel Disease: Immediate and Long-Term Consequences and Outcomes

PURPOSE: This study was designed to evaluate pregnancy, delivery, and functional outcome in females before and after ileal pouch-anal anastomosis for chronic ulcerative colitis.METHODS: From a prospective database of 1,454 patients who underwent ileal pouch-anal anastomosis for chronic ulcerative colitis between 1981 and 1995, a standardized questionnaire was sent to all female patients aged 40 years or younger at the time of ileal pouch-anal anastomosis (n = 544).RESULTS: The response rate was 83 percent (450/544) with a mean follow-up after ileal pouch-anal anastomosis of 13 years. A total of 141 females were pregnant after the chronic ulcerative colitis diagnosis, but before ileal pouch-anal anastomosis (236 pregnancies; mean, 1.7) and 87 percent delivered vaginally. A mean of five (range, 1–16) years after ileal pouch-anal anastomosis, 135 females were pregnant (232 pregnancies; mean, 1.7). Comparison of pregnancy and delivery before and after ileal pouch-anal anastomosis in the same females (n = 37) showed no difference in birth weight, duration of labor, pregnancy/delivery complications, vaginal delivery rates (59 percent before vs. 54 percent after ileal pouch-anal anastomosis), and unplanned cesarean section (19 vs.14 percent). Planned cesareans occurred only after ileal pouch-anal anastomosis and were prompted by obstetrical concerns in only one of eight. Pouch function at first follow-up after delivery (mean, 7 months) was similar to pregravida function. After ileal pouch-anal anastomosis, daytime stool frequency was the same after delivery as pregravida (5.4 vs. 5.4, not significant) but was increased at the time of last follow-up (68 months after delivery; 5.4 vs. 6.4; P < 0.001). The rate of occasional fecal incontinence also was higher (20 percent after ileal pouch-anal anastomosis and 21 percent pregravida vs. 36 percent at last follow-up; P = 0.01). No difference in functional outcome was noted compared with females who were never pregnant after ileal pouch-anal anastomosis (n = 307). Age and becoming pregnant did not affect the probability of pouch-related complications, such as stricture, pouchitis, and obstruction.CONCLUSIONS: Successful pregnancy and vaginal delivery occur routinely in females with chronic ulcerative colitis before and after ileal pouch-anal anastomosis. The method of delivery should be dictated by obstetrical considerations. Pouch function and the incidence of complications in females with pregnancies seem largely unaffected long-term.Read at the meeting of The American Society of Colon and Rectal Surgeons, New Orleans, Louisiana, June 23 to 27, 2003.     

The epidemiology of inflammatory bowel disease: a large, population-based study in Sweden

Previous population-based incidence studies of inflammatory bowel disease are limited by small numbers, short duration, or inadequate case-finding. To address these problems, we identified all persons with confirmed ulcerative colitis (n = 2509) or Crohn's disease (n = 1469) in the Uppsala Health Care Region from 1965 to 1983. Age-specific incidence rates by sex were slightly greater for males with ulcerative colitis and females with Crohn's disease. Incidence rates for ulcerative colitis and Crohn's disease were higher in urban than rural areas. The annual incidence rate of ulcerative colitis increased from less than 7 per 100,000 to more than 12 per 100,000 during the study period, while the rate for Crohn's disease remained between 5 and 7 per 100,000. The increase in the incidence of ulcerative colitis was the result of a marked increase in the number of patients with ulcerative proctitis. Analyses by 5-year birth cohorts suggest that those born from 1945 through 1954 were at higher risk for ulcerative colitis and Crohn's disease, and that this effect was accounted for by those born in the first half of the year. The seasonality in the cohort effect, combined with the urban preponderance of disease, suggests that environmental causes may be involved in ulcerative colitis and Crohn's disease.     

Failure of colonoscopic surveillance in ulcerative colitis.

A prospective surveillance programme for patients with longstanding (> = 8 years), extensive (> = splenic flexure) ulcerative colitis was undertaken between 1978 and 1990. It comprised annual colonoscopy with pancolonic biopsy. One hundred and sixty patients were entered into the programme and had 739 colonoscopies (4.6 colonoscopies per patient; 709 patient years follow up). Eight eight per cent of examinations reached the right colon. There was no procedure related death. One Dukes's A cancer was detected. Forty one patients (25%) defaulted. Of these 25 remain well; 13 are unaccounted for, and one died from colonic cancer. One patient had colectomy for medical reasons, and another died of carcinoma of the pancreas. Retrospectively an additional 16 eligible patients were identified who had not been recruited. Of these, 14 remain well, two are unaccounted for. None developed colonic cancer. Four patients refused colonoscopy. All remain well. Over the same period seven other cases of colonic cancer were found in association with ulcerative colitis, two in patients who had erroneously been diagnosed as having only proctitis and were therefore not entered into the programme, but were found at operation to have total colitis, one in a patient with colitis of seven years duration, and four patients who had previously attended the clinic but had been lost to follow up before 1978 and then had represented with new symptoms during the surveillance period. Thus, of the nine colitis related cancers diagnosed in this centre during the study period only one was detected by the surveillance programme. The results of this large study, a a review of published works, cast doubts on the effectiveness of colonoscopic surveillance programmes in detecting colorectal cancer in patients with ulcerative colitis.     

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.