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

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 ~60 - 80% 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 PregnancyPregnancy 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 ~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

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)