The Natural History of Inflammatory Bowel Disease and Pregnancy

4. The Natural History of Inflammatory Bowel Disease and Pregnancy

5. IBD and Pregnancy • Most women with IBD who desire to become pregnant can do so • Conceive successfully, carry to term, and deliver a healthy infant • However, management of IBD during pregnancy is challenging • Misconceptions • Unknowns • Some women with CD or UC will have difficulty becoming pregnant or have increased disease symptoms while pregnant • Control of disease activity before conception and during pregnancy is critical to optimize both maternal and fetal health

6. IBD and Pregnancy • Peak age ranges for pregnancy and IBD coincide • Many women develop CD/UC during reproductive years • Many of the ‘classic’ studies conducted in 1950s: Multiple shortcomings - • Before ‘modern era’ of drug therapy • Patients treated with steroids were not always clearly separated from those who were not • Drug therapy was inconsistent • No distinctions made on the different anatomical parts affected • Types of complications • Early studies on fertility and CD concluded that fertility is not impaired by CD • [Crohn et al, Gastroenterology, 1956] • However, multiple studies since that time refute this • Fertility has since been shown to be decreased in CD • [De Dombal et al, BMJ 1972]

7. Fertility and Pregnancy: CD • Patients with IBD have fewer children than expected for the population • Fertility has been shown to be decreased in CD • [De Dombal et al, BMJ 1972] • 40/86 women followed became pregnant (subfertility rate 54% vs. ~8-10% infertility in healthy couples) • After surgery, these women became pregnant at same rate as women in general population • Some suggest that women with inactive CD have normal fertility  Control of disease activity appears to restore normal fertility • Fertility is decreased in CD • Due to voluntary childlessness?

8. Fertility and Pregnancy: CD Question: Is this reduced gravidity voluntary or disease-related? • Large European study [Mayberry et al, Gut 1986] showed the reduced fertility rate is not voluntary b/c contraception was used less in CD patients • Possible etiologies: Medical… • Ovary and tube disruption by inflammatory process [R/L] • Perirectal, perineal, and rectovaginal abscesses and fistulas  dyspareunia and ⇩libido • Overall toxicity from CD (abdominal pain, malnutrition) • Men: reduced fertility taking sulfasalazine • Decreased sperm counts in ~60 - 80% men Others… • Relationship difficulties • Body image problems • Fear of pregnancy • Inappropriate medical advice

9. Fertility and Pregnancy: UC • Several studies [1982 – 1988] showed that infertility rate among women is same as in general population • However, female fertility is impaired by surgery • Rectal excision or if pelvic sepsis complicates post-op • Caveat: Studies 1980s – different surgical techniques nowadays

10. Effect of CD or UC on Pregnancy Pregnancy Outcome is Debatable… • Neither CD nor UC has any unfavorable effect on the outcome of pregnancy • Confirmed in several studies over past 3 decades • Incidence of premature births, spontaneous abortions, stillbirths and congenital abnormalities are similar to the general population • In review of 748 patients in 1970s, 1980s • <1% congenital abnormalities • 12% spontaneous abortions or stillbirth • However, others [Alstead and Nelson-Percy, Gut 2003] believe there’s a significant risk of preterm delivery (<37 wks) and low birth weight (<2500g) in mothers with IBD

11. Effect of CD or UC on Pregnancy Disease Activity • However, in CD there may be a higher rate of fetal abnormalities with active disease at time of conception: • Small babies 7% • Premature labor 6% • Respiratory distress 1% • [Woolfson K et al DCR 1990] • Higher preterm delivery rates in patients with IBD, especially with exacerbation of disease • [Fedorkow et al Am J Ob Gyn, 1989]

12. Conception and Disease Activity • In both CD and UC, increased inflammatory activity at the time of conception unfavorably affects the pregnancy and is associated with a significantly higher rate of complications • Unknown mechanism(s)

13. IBD Drug Therapy and Its Effect on Pregnancy • Conflict b/w obstetricians, who often recommend stopping all drugs during pregnancy, and gastroenterologists • Sulfasalazine and its 5-ASA derivative cross the placenta barrier and secreted in milk – but very low levels due to poor absorption from small bowel • No increases in prematurity or spontaneous abortion • Men: reduced fertility taking sulfasalazine • Decreased sperm counts in ~60 - 80% men • Returns after ~ 2 months of discontinuation • Corticosteroids cross the placenta; suppression of HPA axis is rare • No evidence of fetal damage but some isolated reports of fetal distress and stillbirth • Concentration in breast milk is low

14. Conclusions • In general, ~85% of women with IBD (CD, UC) experience normal, uncomplicated pregnancies • Congenital malformations in infants born to women with CD or UC occur ~1% • Risk of miscarriage also does not, in general, appear to be increased • All these rates correspond to those observed in healthy women

15. Effect of Pregnancy on IBD • Most changes in state of colitis occur in the first trimester • Mainly exacerbation • May be partially due to stopping maintenance meds • Improvement • It’s not possible to predict the course of IBD during subsequent pregnancies • Colitis can behave differently from one pregnancy to another

16. Effect of Pregnancy on IBD “Quiescence of disease before conception is likely to be followed by quiescence during pregnancy” • The course of IBD during pregnancy is directly affected by disease activity before conception [Mogadam DM et al Am J Gastro, 1981] • Series of 324 patient • 75% with quiescent to mild disease remained so • 51% active IBD continued with moderate to severe disease

17. Effect of Pregnancy on IBD “Quiescence of disease before conception is likely to be followed by quiescence during pregnancy” • Possibly, a rise in serum cortisol during late pregnancy and a rapid fall postpartum may account for the fall and rise in the relapse rate in UC • For active disease at conception, most will continue to have active disease during pregnancy: 25% - 100% • For chronic disease in remission, different studies show varying relapse rates during pregnancy: 10% - 54%

18. Effect of Pregnancy on IBD • Pregnancy in women who have had restorative proctocolectomy is usually uncomplicated • However, there’s a higher rate of C-sections • Due to fear of compromising continence • Uncertainty of how these patients would fare with vaginal deliveries • Pelvic location of the pouch protects it from effect of abdominal wall distention • But, makes it more susceptible to pressure exerted on the pelvic floor during pregnancy and delivery

19. Effect of Pregnancy on IBD • Many believe that indication for C-section should only be obstetric • No good data • Small, retrospective studies • In some of these, <50% C-sections were performed for obstetric reasons • Higher complication rates in patients with stoma may be due to abdominal wall distention • Patients with CD do not face any major additional GI risk during pregnancy • Episiotomy and CD?

20. Effect of Pregnancy on IBD • First IBD Attack During Pregnancy • Very few data: Usually thought that the prognosis is generally poor

21. Surgery for IBD During Pregnancy • Operate when need for surgery is obvious • Fulminant colitis • Toxic megacolon • Perforation • More typical and difficult situation is patient with severe disease flare who has incomplete response to medical therapy • Unfortunately, little literature to guide • Pushing medical therapy may not help; may increase the risk to mother and fetus • In the ill, pregnant IBD mother not responding to medical therapy, greater risk to the fetus is continued maternal illness (rather than surgery)