1. Pregnancy and Pregnancy Outcomes in Women With IBD

2. Effects of IBD on Pregnancy Outcomes Preterm birth Preterm birth – risk in both UC and CD 1,2,5 4 of 5 studies: no major impact on risk of congenital abnormalities 1-5 4 of 5 studies: no major impact on risk of congenital abnormalities 1-5 Significant in risk of low birth weight 2-5 Significant in risk of low birth weight 2-5 risk of maternal/delivery complications 5 risk of maternal/delivery complications 5 1 Baird DD, et al. Gastroenterology. 1990;99:987-994. 2 Dominitz JA, et al. Am J Gastroenterol. 2002;97:641-648. 3 Porter RJ, Stirrat GM. Br J Obstet Gynaecol. 1986;93:1124-1131. 4 Fonager K, et al. Am J Gastroenterol. 1998;93:2426-2430. 4 1 Baird DD, et al. Gastroenterology. 1990;99:987-994. 2 Dominitz JA, et al. Am J Gastroenterol. 2002;97:641-648. 3 Porter RJ, Stirrat GM. Br J Obstet Gynaecol. 1986;93:1124-1131. 4 Fonager K, et al. Am J Gastroenterol. 1998;93:2426-2430. 4 Mahadevan U, et al. Gastroenterol. 2007;133:1106-1112

3. Meta-analysis 12 studies 12 studies –N= 3907 (CD 1952, UC 1113) vs. 320, 531 Prematurity OR = 1.87 (1.52-2.31) p<0.001 Prematurity OR = 1.87 (1.52-2.31) p<0.001 LBW OR = 2.10 (1.38-3.19), p<0.001 LBW OR = 2.10 (1.38-3.19), p<0.001 C-section OR = 1.50 (1.26-1.79) p <0.001 C-section OR = 1.50 (1.26-1.79) p <0.001 Congen Abnorm. = 2.37 (1.47-3.82) p <0.001 Congen Abnorm. = 2.37 (1.47-3.82) p <0.001 –4 studies reported on the incidence IBD vs. controls, no difference –UC vs. controls in two studies (Larzilliere 1998, Dominitz) Cornish Gut 2006;0:1-8.

4. Effect of Pregnancy on UC: Disease Activity at Conception Miller JP. J R Soc Med. 1986;79:221-225. Inactive Active No Relapse Relapse Worsened Activity ContinuedActivity Decreased Activity 0 n=528 n=227 66 34 45 24 27 80 70 60 50 40 30 20 10 Percent

5. 32 Effect of Pregnancy on CD: Disease Activity at Conception Miller JP. J R Soc Med. 1986;79:221-225. Inactive Active No Relapse Relapse Worsened Activity ContinuedActivity Decreased Activity 0 n=186 n=93 73 27 33 34 80 70 60 50 40 30 20 10 Percent

6. Disease activity during pregnancy in women with IBD Majority of patients have inactive to mild disease during pregnancy Majority of patients have inactive to mild disease during pregnancy Mahadevan U, et al. Gastroenterol. 2007;133:1106-1112 Trimester Percentage of patients Disease activity in Crohns disease Disease activity in ulcerative colitis

7. Effect of Pregnancy on IBD: Maternal-Fetal HLA Disparity Prepartum disease activity significantly predicts disease activity during pregnancy (P=.008) Prepartum disease activity significantly predicts disease activity during pregnancy (P=.008) In single-locus disparity, no significant difference between DR and DQ prepartum, during trimesters 1-3, or postpartum In single-locus disparity, no significant difference between DR and DQ prepartum, during trimesters 1-3, or postpartum Disparity at both DR and DQ loci significantly predicts disease activity during pregnancy (P=.001) Disparity at both DR and DQ loci significantly predicts disease activity during pregnancy (P=.001) Maternal immune response to paternal HLA antigens may play role in pregnancy-induced remission of IBD Maternal immune response to paternal HLA antigens may play role in pregnancy-induced remission of IBD Kane S, et al. Gastroenterology. 1998;114:A1006. Abstract G4121.

8. Concerns Regarding Pregnancy and Delivery What is the effect of pregnancy on pouch function before and after delivery? What is the effect of pregnancy on pouch function before and after delivery? Should the woman deliver vaginally or have cesarean section? Should the woman deliver vaginally or have cesarean section? Are there unique concerns if cesarean section is performed? Are there unique concerns if cesarean section is performed?

9. Delivery Mode and Perineal Injury Study indicates that more women with IBD have cesarean sections 1 Study indicates that more women with IBD have cesarean sections 1 Vaginal delivery is usually safe for women with inactive perianal symptoms 1 Vaginal delivery is usually safe for women with inactive perianal symptoms 1 1 Ilnyckyji A, et al. Am J Gastroenterol. 1999;94:3274-3278.

10. Pouch Function During and After Pregnancy 10 vaginal deliveries, 6 cesarean sections 10 vaginal deliveries, 6 cesarean sections –No pouch complications 8.1 bowel movements/day during pregnancy vs 6.5/day postpartum 8.1 bowel movements/day during pregnancy vs 6.5/day postpartum 3 women had incontinence during pregnancy, 1 frequent and 2 mild 3 women had incontinence during pregnancy, 1 frequent and 2 mild 1 woman had nighttime incontinence postpartum 1 woman had nighttime incontinence postpartum Scott HJ, et al. Int J Colorectal Dis. 1996;11:84-87.

11. Pregnancy, Delivery, and Pouch Function After IPAA in UC Questionnaires sent to women with IPAA for UC Questionnaires sent to women with IPAA for UC Results Results –49 deliveries for 29 women (25 vaginal, 24 c-sections) –6 pouch-related complications (2 during pregnancy; 4 postpartum) – stool frequency and incontinence during pregnancy –83% regained prepregnancy function; 17% had some permanent pouch function deterioration not related to delivery method –Delivery method did not affect incontinence, stool frequency Conclusion: Pregnancy is safe for women with IPAA Conclusion: Pregnancy is safe for women with IPAA Ravid A, et al. Dis Colon Rectum. 2002;45:1283-1288.

12. IBD in Pregnancy: Summary Pregnancy outcomes best if patient in remission at time of conception, though even patients in remission can have higher rates of adverse outcomes compared to the general population Pregnancy outcomes best if patient in remission at time of conception, though even patients in remission can have higher rates of adverse outcomes compared to the general population IBD increases the risk of preterm birth and low birth weight and maternal complications IBD increases the risk of preterm birth and low birth weight and maternal complications No significant increase in risk of congenital abnormalities No significant increase in risk of congenital abnormalities Women with IBD have a higher rate of cesarean sections Women with IBD have a higher rate of cesarean sections Pregnancy may not increase the risk of relapse or significantly increase disease activit Pregnancy may not increase the risk of relapse or significantly increase disease activit