Women s Health Issues in Inflammatory Bowel Disease IBD

1. Women�s Health Issues in Inflammatory Bowel Disease (IBD) Raymond Cross, MD, MS Chief, GI Section BVAMHCS Assistant Professor of Medicine Director, IBD Program University of Maryland School of Medicine University of Maryland and Maryland/Delaware Chapter of CCFA Patient Education Symposium 4/1/09

2. Problems encountered in clinical practice Many patients develop IBD during child bearing years Patients may flare during pregnancy Patients may have chronic active disease that may make pregnancy difficult Patients and providers have fears of drug therapy during pregnancy Perianal CD can effect mode of delivery Surgical therapy can impact future fertility

3. Overview Fertility Outcomes in Pregnancy Maternal Fetal Drug Therapy During Pregnancy Risk of Cervical Dysplasia

4. Fertility Infertility: the inability to conceive after 1 year of properly timed unprotected intercourse Affects 13-14% of reproductive-aged couples Approximately 50% of couples should become pregnant after 3 months

5. Infertility: ulcerative colitis

6. ILEAL POUCH-ANAL ANASTOMOSIS 222. ILEAL POUCH-ANAL ANASTOMOSIS The ileal pouch-anal anastomosis (IPAA) has become the conventional operation for ulcerative colitis with 90% of procedures for ulcerative colitis in many series involving IPAA. The operation can be done as a primary two stage procedure, a total procto-colectomy, and IPAA with temporary loop ileostomy, multistage with subtotal colectomy, oversow of rectal stump, and ileostomy followed by completion proctectomy and loop ileostomy closure or as a one stage procedure without loop ileostomy. The procedure can be done by a total mucosal proctectomy with hand suturing of the pouch to the anal canal or by leaving the anal transitional zone with stapling of the pouch to the anal canal. Long-term follow-up of pouch function and quality of life have indicated a high degree of success with an acceptable rate of complications. The standard Brooke ileostomy and in limited situations a straight ileal-rectal anastomosis continue to be important alternative to IPAA for some patients with ulcerative colitis. � Remzi FH, Fazio VW. Ileal anal pouch anastomosis. In: Bayless TM, Hanauer SB. eds. Advanced Therapy of Inflammatory Bowel Disease. London, BC Decker Inc., 2001;197-202. � Fazio VW, O�Riordon MG, Lavery IC et al. Long-term functional outcome and quality of life after stapled restorative procto-colectomy. Ann Surg 1999;230:578-86. � McIntyre PB, Pemberton JH, Wolff BG et al. Comparing functional results one year and 10 years after ileal pouch anal anastomosis for chronic ulcerative colitis. Dis Colon Rectum 1994;37:303-7.222. ILEAL POUCH-ANAL ANASTOMOSIS The ileal pouch-anal anastomosis (IPAA) has become the conventional operation for ulcerative colitis with 90% of procedures for ulcerative colitis in many series involving IPAA. The operation can be done as a primary two stage procedure, a total procto-colectomy, and IPAA with temporary loop ileostomy, multistage with subtotal colectomy, oversow of rectal stump, and ileostomy followed by completion proctectomy and loop ileostomy closure or as a one stage procedure without loop ileostomy. The procedure can be done by a total mucosal proctectomy with hand suturing of the pouch to the anal canal or by leaving the anal transitional zone with stapling of the pouch to the anal canal. Long-term follow-up of pouch function and quality of life have indicated a high degree of success with an acceptable rate of complications. The standard Brooke ileostomy and in limited situations a straight ileal-rectal anastomosis continue to be important alternative to IPAA for some patients with ulcerative colitis. � Remzi FH, Fazio VW. Ileal anal pouch anastomosis. In: Bayless TM, Hanauer SB. eds. Advanced Therapy of Inflammatory Bowel Disease. London, BC Decker Inc., 2001;197-202. � Fazio VW, O�Riordon MG, Lavery IC et al. Long-term functional outcome and quality of life after stapled restorative procto-colectomy. Ann Surg 1999;230:578-86. � McIntyre PB, Pemberton JH, Wolff BG et al. Comparing functional results one year and 10 years after ileal pouch anal anastomosis for chronic ulcerative colitis. Dis Colon Rectum 1994;37:303-7.

7. IPAA: Cumulative Incidence of PregnancyWithin 5 Years This graph shows the cumulative incidence of pregnancy for the 4 groups of patients over a period of 5 years. The women in the �before-surgery� cohort track very closely to the reference group. Even after 5 years of trying, only about one third of women who had had proctocolectomies and IPAA succeeded in becoming pregnant.13 Another recent study had similar results. In that study, infertility rates were significantly higher for patients with IBD who underwent IPAA (38.6%) than for those whose IBD was treated nonsurgically (13.3%; P=.004). There was a 98% reduction in the odds of becoming pregnant after IPAA versus before surgery (P<.0001).14This graph shows the cumulative incidence of pregnancy for the 4 groups of patients over a period of 5 years. The women in the �before-surgery� cohort track very closely to the reference group. Even after 5 years of trying, only about one third of women who had had proctocolectomies and IPAA succeeded in becoming pregnant.13 Another recent study had similar results. In that study, infertility rates were significantly higher for patients with IBD who underwent IPAA (38.6%) than for those whose IBD was treated nonsurgically (13.3%; P=.004). There was a 98% reduction in the odds of becoming pregnant after IPAA versus before surgery (P<.0001).14

9. Summary: Female Fertility Ulcerative Colitis Similar to the general population prior to colectomy Significantly decreased after IPAA Crohn�s Disease Studies vary Infertility partly voluntary (painful intercourse, illness, MD advise) Surgery: decreased fertility

10. Overview Fertility Outcomes in Pregnancy Maternal Fetal Drug Therapy During Pregnancy Risk of Cervical Dysplasia

11. Fetal Outcomes in IBD Meta-analysis of 12 studies 3907 patients with IBD (2/3 CD) 320,531 controls Prematurity (< 37 week gestation) 1.87 RR (1.52-2.31) compared to controls Low birth weight (<2500 g)* 2.00 RR (1.38-3.19) compared to controls Congenital anomalies* 2.37 RR (1.47-3.82) compared to controls

12. Fetal Outcomes in IBD (cont.) LBW risk only increased in CD patients Congenital anomalies included all abnormalities, even if minor Only persisted for UC patients (one study) Studies did not account for disease activity and medication use

13. Maternal and Fetal Outcomes During Pregnancy in IBD Rule of thumb: Control symptoms prior to attempts at conception If in remission at time of conception: Normal baby 85% of UC patients Normal baby 84% of CD patients Comparable to general population

14. Effect of Pregnancy on UC: Disease Activity at Conception Remission at Conception 33% flare rate Similar to nonpregnant patients Active disease at conception 45% get worse 25% improve 25% remain unchanged Remission at Conception 33% flare rate Similar to nonpregnant patients Active disease at conception 45% get worse 25% improve 25% remain unchanged

15. Effect of Pregnancy on CD: Disease Activity at Conception Remission at conception 25% relapse Not different from nonpregnant patients Active disease at conception 1/3 improve 1/3 remain unchanged 1/3 worsen Remission at conception 25% relapse Not different from nonpregnant patients Active disease at conception 1/3 improve 1/3 remain unchanged 1/3 worsen

18. Pregnancy outcomes in women with IBD: population based cohort study Cohort study of Northern California Kaiser Permanente population 461 pregnant women with a pre-birth diagnosis of IBD and matched 493 non-pregnant women for age and hospital of pregnancy 300 UC and 154 CD IBD Duration: 5.7 years Immunosuppressant Use: 19 (4%) Aminosalicylate Use: 234 (51%) Corticosteroid Use: 96 (21%)

19. IBD Pregnancy Outcomes BACKGROUND & AIMS: The aim of this study was to determine whether pregnancy outcomes differ between women with and without inflammatory bowel disease (IBD) and to determine what risk factors adversely affect outcomes. METHODS: We conducted a cohort study of all pregnant women within the Northern California Kaiser Permanente membership between the years 1995 and 2002. We abstracted the records of all pregnancies in women with IBD (exposed cohort) and a random sample of pregnancies from age-matched women without IBD (unexposed cohort) and evaluated risk factors for spontaneous abortion, complications of pregnancy, and adverse newborn events. RESULTS: A total of 461 pregnant women with IBD were matched to 493 unexposed pregnant women. Women with IBD were more likely to have an adverse conception outcome (odds ratio, 1.65; 95% confidence interval, 1.09-2.48), an adverse pregnancy outcome (odds ratio, 1.54; 95% confidence interval, 1.00-2.38), or a pregnancy complication (odds ratio, 1.78; 95% confidence interval, 1.13-2.81); however, the difference between the 2 groups in adverse newborn outcomes was not statistically significant (odds ratio, 1.89; 95% confidence interval, 0.98-3.69). Independent predictors of an adverse outcome included a diagnosis of IBD, a history of surgery for IBD, and non-Caucasian ethnicity. Severity of disease and medical treatments were not associated with an adverse outcome. CONCLUSIONS: Women with IBD are more likely to have an adverse outcome related to pregnancy. Disease activity and medical treatment did not predict adverse outcomes in a large, nonreferral population. BACKGROUND & AIMS: The aim of this study was to determine whether pregnancy outcomes differ between women with and without inflammatory bowel disease (IBD) and to determine what risk factors adversely affect outcomes. METHODS: We conducted a cohort study of all pregnant women within the Northern California Kaiser Permanente membership between the years 1995 and 2002. We abstracted the records of all pregnancies in women with IBD (exposed cohort) and a random sample of pregnancies from age-matched women without IBD (unexposed cohort) and evaluated risk factors for spontaneous abortion, complications of pregnancy, and adverse newborn events. RESULTS: A total of 461 pregnant women with IBD were matched to 493 unexposed pregnant women. Women with IBD were more likely to have an adverse conception outcome (odds ratio, 1.65; 95% confidence interval, 1.09-2.48), an adverse pregnancy outcome (odds ratio, 1.54; 95% confidence interval, 1.00-2.38), or a pregnancy complication (odds ratio, 1.78; 95% confidence interval, 1.13-2.81); however, the difference between the 2 groups in adverse newborn outcomes was not statistically significant (odds ratio, 1.89; 95% confidence interval, 0.98-3.69). Independent predictors of an adverse outcome included a diagnosis of IBD, a history of surgery for IBD, and non-Caucasian ethnicity. Severity of disease and medical treatments were not associated with an adverse outcome. CONCLUSIONS: Women with IBD are more likely to have an adverse outcome related to pregnancy. Disease activity and medical treatment did not predict adverse outcomes in a large, nonreferral population.

20. Factors associated with adverse outcomes Independent predictors of an adverse outcome diagnosis of IBD non-Caucasian ethnicity IBD surgery (co, pc) Severity of disease and medical treatments were not associated with an adverse outcome No difference in CA and adverse newborn outcomes

21. Should IBD Impact the Mode of Delivery? Women with IBD 1.5 (1.26-1.79)times more likely to undergo C-section Risk of perianal complications after vaginal delivery with or without episiotomy is controversial

22. Mode of Delivery in IBD Recommend elective C section if: H/o perianal disease H/o RV fistula Even if inactive disease, 1/3 can reactivate during vaginal delivery

23. Overview Fertility Outcomes in Pregnancy Maternal Fetal Drug Therapy During Pregnancy Risk of cervical dysplasia

24. Pharmaceutical TherapyAminosalicylates - I Aminosalicylates � Category B 165 pts. Exposed to mesalamine during pregnancy (Mean daily dose 2 gm) No teratogenicity 2.5 x increased risk of preterm delivery Slight decrease in mean birth weight BACKGROUND & AIMS: Mesalamine is a first-line drug in the treatment of inflammatory bowel disease. Information regarding human pregnancy experience with mesalamine has been scarce and uncontrolled despite its frequent use in women of childbearing age. The aim of this study was to examine the fetal safety of mesalamine. METHODS: The Motherisk Program prospectively enrolled and followed up 165 women exposed to mesalamine during pregnancy, 146 of whom had first trimester exposure. Pregnancy outcome was compared with that of a matched control group, who were counseled for nonteratogenic exposure. RESULTS: There was no increase in major malformations (1 of 127 [0.8%] for mesalamine vs. 5 of 131 [3.8%] for nonteratogenic controls; P = 0.23). There was an increase in the rate of preterm deliveries (13.0% for mesalamine vs. 4.7% for nonteratogenic controls; P = 0.02), a decrease in the mean maternal weight gain during pregnancy (13.1 +/- 6.3 kg for mesalamine vs. 15.6 +/- 6.0 kg for nonteratogenic controls; P = 0.0002), and a decrease in the mean birth weight (3253 +/- 546 g for mesalamine vs. 3461 +/- 542 g for nonteratogenic controls; P = 0.0005). There were no significant differences in the maternal obstetric history, rates of live births, miscarriages, pregnancy terminations, ectopic pregnancies, delivery method, or fetal distress between the groups. CONCLUSIONS: This study suggests that mesalamine does not represent a major teratogenic risk in humans when used in the recommended doses. BACKGROUND & AIMS: Mesalamine is a first-line drug in the treatment of inflammatory bowel disease. Information regarding human pregnancy experience with mesalamine has been scarce and uncontrolled despite its frequent use in women of childbearing age. The aim of this study was to examine the fetal safety of mesalamine. METHODS: The Motherisk Program prospectively enrolled and followed up 165 women exposed to mesalamine during pregnancy, 146 of whom had first trimester exposure. Pregnancy outcome was compared with that of a matched control group, who were counseled for nonteratogenic exposure. RESULTS: There was no increase in major malformations (1 of 127 [0.8%] for mesalamine vs. 5 of 131 [3.8%] for nonteratogenic controls; P = 0.23). There was an increase in the rate of preterm deliveries (13.0% for mesalamine vs. 4.7% for nonteratogenic controls; P = 0.02), a decrease in the mean maternal weight gain during pregnancy (13.1 +/- 6.3 kg for mesalamine vs. 15.6 +/- 6.0 kg for nonteratogenic controls; P = 0.0002), and a decrease in the mean birth weight (3253 +/- 546 g for mesalamine vs. 3461 +/- 542 g for nonteratogenic controls; P = 0.0005). There were no significant differences in the maternal obstetric history, rates of live births, miscarriages, pregnancy terminations, ectopic pregnancies, delivery method, or fetal distress between the groups. CONCLUSIONS: This study suggests that mesalamine does not represent a major teratogenic risk in humans when used in the recommended doses.

25. Pharmaceutical TherapyAminosalicylates - II Sulfasalazine should be given with folic acid 1 mg BID Folic acid: neural tube defects, CV, urinary tract, cleft palate Case reports of congenital malformation Placental and Breast Milk Transfer Occurs Potential of allergic reaction in newborn with watery diarrhea

26. Corticosteroids Minimal evidence of teratogenicity in humans Small increased risk of cleft palate if given in 1st trimester Poorer outcomes likely due to worse disease Theoretical concern of adrenal suppression in newborn Cross placenta 10-12% of maternal concentration Safe in breast feeding

27. Antibiotics Metronidazole/Ciprofloxacin Low risk of teratogenicity Metronidazole: case-control study and meta-analysis Ciprofloxacin: prospective controlled study Growing cartilage may be a target for Cipro toxicity Breast feeding is not advised Minimal benefit in Crohn�s and UC No data on long-term safety

28. Teratogenicity of 6MP/AZA Controversy - Class D label for pregnancy but commonly used in IBD, RA and transplant Teratogenic in animals (mice, rabbits, rats) Given IV/IP at supratherapeutic doses Increased cleft palate, ocular, skeletal, urogenital anomalies, hydrocephalus No consistent increase in human teratogenicity

29. Retrospective chart review from tertiary referral center All patients in remission at conception 155 patients 79 women 325 pregnancies Comparison groups No 6-MP exposure (n=165) Stopped 6-MP before conception (n=84) Conceived on 6-MP, then stopped (n=61) Conceived on 6-MP and continued thru pregnancy (n=15) Safety of 6-MP/AZA during pregnancy

30. No difference in: Spontaneous abortion Abortion secondary to birth defect Major congenital malformations Neoplasia Infection rates Prematurity and LBW not analyzed Safety of 6-MP/AZA during pregnancy (cont)

31. Safety of drug therapy during pregnancy 113 women, 207 conceptions Outcomes: SAB, TAB, maternal or fetal illness, prematurity, multiple births, congenital defects, LBW 101 on IM No evidence after MV analysis for any difference in outcomes based on therapy OBJECTIVES: We reviewed data to investigate the effect of 5-ASA drugs, metronidazole, ciprofloxacin, prednisone, 6-mercaptopurine, azathioprine, and cyclosporine on pregnancy outcomes in patients with inflammatory bowel disease (IBD). METHODS: One hundred and thirteen female patients with a total of 207 documented conceptions were studied. Treatment information included: smoking history (patient and spouse), dates of conception and termination, and outcome of pregnancy (spontaneous abortion, therapeutic abortion, maternal or fetal illness resulting in abortion, premature birth, healthy full-term birth, multiple births, ectopic pregnancy, congenital defects), weight of baby, type of delivery (cesarian section, vaginal), medication history during each trimester (mean dose, maximum dose, frequency). We analyzed the effect on pregnancy outcome of medication use during the first trimester or at any time during the pregnancy. RESULTS: Thirty-nine patients (34.5%) had ulcerative colitis (UC), 73 (64.5%) had crohn's disease (CD), and 1 patient (1%) had indeterminate colitis. For 100 of the 207 conceptions, the patients were on 5-ASA drugs at some time during the pregnancy, 49 on prednisone, 101 on an immunomodulator (6-MP/azathioprine), 27 on metronidazole, 18 on ciprofloxacin, and 2 on cyclosporine. In 85 (31%) of the conceptions, patients were on none of these medications. No significant differences were found among the groups in each pregnancy with respect to outcome (p values 0.091 to 0.9). In multivariate analyses controlling for age of mother, there was no evidence that 5-ASA type drugs or any type of drug influenced pregnancy outcome. CONCLUSIONS: In 113 female patients with 207 conceptions none of the drugs used to treat IBD is associated with poor pregnancy outcomes. OBJECTIVES: We reviewed data to investigate the effect of 5-ASA drugs, metronidazole, ciprofloxacin, prednisone, 6-mercaptopurine, azathioprine, and cyclosporine on pregnancy outcomes in patients with inflammatory bowel disease (IBD). METHODS: One hundred and thirteen female patients with a total of 207 documented conceptions were studied. Treatment information included: smoking history (patient and spouse), dates of conception and termination, and outcome of pregnancy (spontaneous abortion, therapeutic abortion, maternal or fetal illness resulting in abortion, premature birth, healthy full-term birth, multiple births, ectopic pregnancy, congenital defects), weight of baby, type of delivery (cesarian section, vaginal), medication history during each trimester (mean dose, maximum dose, frequency). We analyzed the effect on pregnancy outcome of medication use during the first trimester or at any time during the pregnancy. RESULTS: Thirty-nine patients (34.5%) had ulcerative colitis (UC), 73 (64.5%) had crohn's disease (CD), and 1 patient (1%) had indeterminate colitis. For 100 of the 207 conceptions, the patients were on 5-ASA drugs at some time during the pregnancy, 49 on prednisone, 101 on an immunomodulator (6-MP/azathioprine), 27 on metronidazole, 18 on ciprofloxacin, and 2 on cyclosporine. In 85 (31%) of the conceptions, patients were on none of these medications. No significant differences were found among the groups in each pregnancy with respect to outcome (p values 0.091 to 0.9). In multivariate analyses controlling for age of mother, there was no evidence that 5-ASA type drugs or any type of drug influenced pregnancy outcome. CONCLUSIONS: In 113 female patients with 207 conceptions none of the drugs used to treat IBD is associated with poor pregnancy outcomes.

32. Infliximab in Pregnancy: Outcomes of Women Exposed to Infliximab During Pregnancy

33. Summary of drug safety during pregnancy in patients with IBD Stopping drug therapy is associated with a significant risk of flare 5-ASA and steroids probably safe MTX should not be used Antibiotics have a limited role in IBD 6-MP and IFX?

34. Overview Introduction to IBD Fertility Outcomes in Pregnancy Maternal Fetal Drug Therapy During Pregnancy Risk of cervical dysplasia

35. Risk of cervical dysplasia in IBD IBD typically affects women in the 2nd and 3rd decade of life Women at risk for human papilloma virus acquisition in adolescence and early adulthood Reports from transplant and HIV literature of high rates of cervical dysplasia/cancer Immune suppressants are being used increasingly in treatment of IBD Potential for higher risk of cervical dysplasia in women with IBD on IM

36. Risk of cervical dysplasia in women with IBD on IM Retrospective study from tertiary referral center for IBD Rates of cervical dyplasia in 40 IBD patients compared to historical controls Rate of abnormal PAP smears IBD 43% More likely to have higher grade lesions Controls 7% More likely to have abnormal pap if exposed to immune suppressants BACKGROUND AND AIMS: Immunosuppression results in a higher incidence of cervical dysplasia compared with healthy controls. We examined the relationship between immunomodulator use and the presence of abnormal cervical histology in women with inflammatory bowel disease (IBD). METHODS: Women with IBD and serial Pap smears were recruited. Patients were compared to age-, race-, and parity-matched controls. Pap smears were recorded in relation to exposure to immunomodulators. Variables included diagnosis, type and duration of immunosuppressant, and smoking. RESULTS: Forty patients (8 UC, 32 CD) with 134 Pap smears were included. The incidence of any abnormal Pap in a woman with IBD was 42.5%versus 7% of controls (P < 0.001). Women with IBD were more likely to have higher-grade lesions than controls (P < 0.001). Those women with a history of exposure to immunosuppression were more likely to have an abnormal Pap smear (P < 0.001) than controls. Pap smears done with >6 months exposure to an immunosuppressant resulted in increased risk (OR 1.5, 1.2-4.1, P= 0.021). Cytopathology of abnormal lesions revealed either HPV serotype 16 or 18 in all specimens. Multivariate analysis did not reveal any differences between the groups when controlled for other variables. CONCLUSIONS: Women with IBD have a higher risk of an abnormal Pap smear compared with healthy controls. Patients with immunomodulator use have a higher risk of an abnormal Pap smear associated with HPV infection. Women with IBD should be included in the American College of Obstetrics and Gynecology screening guidelines for immunocompromised individuals.BACKGROUND AND AIMS: Immunosuppression results in a higher incidence of cervical dysplasia compared with healthy controls. We examined the relationship between immunomodulator use and the presence of abnormal cervical histology in women with inflammatory bowel disease (IBD). METHODS: Women with IBD and serial Pap smears were recruited. Patients were compared to age-, race-, and parity-matched controls. Pap smears were recorded in relation to exposure to immunomodulators. Variables included diagnosis, type and duration of immunosuppressant, and smoking. RESULTS: Forty patients (8 UC, 32 CD) with 134 Pap smears were included. The incidence of any abnormal Pap in a woman with IBD was 42.5%versus 7% of controls (P < 0.001). Women with IBD were more likely to have higher-grade lesions than controls (P < 0.001). Those women with a history of exposure to immunosuppression were more likely to have an abnormal Pap smear (P < 0.001) than controls. Pap smears done with >6 months exposure to an immunosuppressant resulted in increased risk (OR 1.5, 1.2-4.1, P= 0.021). Cytopathology of abnormal lesions revealed either HPV serotype 16 or 18 in all specimens. Multivariate analysis did not reveal any differences between the groups when controlled for other variables. CONCLUSIONS: Women with IBD have a higher risk of an abnormal Pap smear compared with healthy controls. Patients with immunomodulator use have a higher risk of an abnormal Pap smear associated with HPV infection. Women with IBD should be included in the American College of Obstetrics and Gynecology screening guidelines for immunocompromised individuals.

37. Risk of cervical dysplasia in women with IBD on IM (cont) Study from Manitoba, Canada Large study 19,000+ women with abnormal Paps 57,000+ controls IBD itself not associated with abnormal Paps Women with CD that received more than 10 rx�s for OCP�s had a higher risk Exposure to immune suppressants and steroids associated with an increased risk BACKGROUND & AIMS: We evaluated the risk of cervical abnormalities in women with inflammatory bowel disease (IBD) in a population-based, nested, case-control study. METHODS: The Manitoba Cervical Cancer Screening Program database was used to identify women with abnormal Papanicolaou's (Pap) smears or cervical biopsies. Cases were matched with up to 3 controls (normal Pap smears) by year of birth, year of first health care coverage, and number of Pap smears in the preceding 5 years. A diagnosis of IBD before the index date was identified from the University of Manitoba IBD Epidemiology Database. Exposures to immunosuppressant drugs and corticosteroids were determined from the provincial drug prescription database. Analyses were adjusted for socioeconomic status and exposure to oral contraceptives and nonsteroidal anti-inflammatory drugs. RESULTS: A total of 19,692 women with cervical cytologic and/or histologic abnormalities were matched with 57,898 controls with normal Pap smears. There was no association between cervical abnormalities and ulcerative colitis (odds ratio [OR], 1.03; 95% confidence interval [CI], 0.77-1.38). The increase in risk in women with Crohn's disease was limited to those exposed to 10 or more prescriptions of oral contraceptives (OR, 1.66; 95% CI, 1.08-2.54). The combined exposure to corticosteroids and immunosuppressants was associated with increased risk of cervical abnormalities (OR, 1.41; 95% CI, 1.09-1.81). There was no interaction between the effect of IBD and corticosteroids and/or immunosuppressants. CONCLUSIONS: These findings do not support an association between IBD itself and the risk of developing cervical abnormalities. An increased risk in patients given a combination of corticosteroids and immunosuppressants should be considered in managing women with IBD. BACKGROUND & AIMS: We evaluated the risk of cervical abnormalities in women with inflammatory bowel disease (IBD) in a population-based, nested, case-control study. METHODS: The Manitoba Cervical Cancer Screening Program database was used to identify women with abnormal Papanicolaou's (Pap) smears or cervical biopsies. Cases were matched with up to 3 controls (normal Pap smears) by year of birth, year of first health care coverage, and number of Pap smears in the preceding 5 years. A diagnosis of IBD before the index date was identified from the University of Manitoba IBD Epidemiology Database. Exposures to immunosuppressant drugs and corticosteroids were determined from the provincial drug prescription database. Analyses were adjusted for socioeconomic status and exposure to oral contraceptives and nonsteroidal anti-inflammatory drugs. RESULTS: A total of 19,692 women with cervical cytologic and/or histologic abnormalities were matched with 57,898 controls with normal Pap smears. There was no association between cervical abnormalities and ulcerative colitis (odds ratio [OR], 1.03; 95% confidence interval [CI], 0.77-1.38). The increase in risk in women with Crohn's disease was limited to those exposed to 10 or more prescriptions of oral contraceptives (OR, 1.66; 95% CI, 1.08-2.54). The combined exposure to corticosteroids and immunosuppressants was associated with increased risk of cervical abnormalities (OR, 1.41; 95% CI, 1.09-1.81). There was no interaction between the effect of IBD and corticosteroids and/or immunosuppressants. CONCLUSIONS: These findings do not support an association between IBD itself and the risk of developing cervical abnormalities. An increased risk in patients given a combination of corticosteroids and immunosuppressants should be considered in managing women with IBD.

38. Risk of cervical dysplasia in women with IBD Evidence of higher risk of dysplasia in women with IBD on IM Recommendations: Annual PAP and pelvic in women on immune suppressants Consider HPV vaccine in eligible patients on immune suppressants

39. Summary Most women with IBD conceive without difficulty Surgery may decrease fertility Pregnancy outcomes in women with IBD is good Attempt to conceive while well Stopping drug therapy increases risk of flare C-section is not required in all women with IBD Women with IBD on immune suppressants have higher rates of abnormal Pap smears

40. Questions?