The Natural History of Inflammatory Bowel Disease 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 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]

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?

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 ~ % men Others…  Relationship difficulties  Body image problems  Fear of pregnancy  Inappropriate medical advice Fertility and Pregnancy: CD

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

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

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] Effect of CD or UC on Pregnancy

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)

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 ~ % 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

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

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

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

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%

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

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?

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

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)