1. PSC and IBD Women’s Health Issues
Alina Allen, MD
Laura Raffals, MD, MS

2. Gynecologic issues and family planning
Effect of pregnancy on IBD and PSC
Effect of IBD and PSC on pregnancy
Treatment in pregnancy
Delivery
Breastfeeding
Vaccines

3. Meet Heather. . .
17 yo female recently diagnosed with extensive ulcerative colitis and PSC
She is started on prednisone and mesalamine
Difficulty tapering off of prednisone so started on azathioprine and responds well
She is not sexually active
She has questions about birth control

4. Contraception is safe in IBD/PSC The choices for contraception are generally the same as those for the general population
Hormonal or non-hormonal intrauterine device or contraceptive implants are safest/most effective
Non-estrogen containing contraception is preferred due to increased risk of venous thromboembolism
Low-dose estrogen OCP is okay if no other risk factors for thromboembolism
Active small bowel disease or extensive small bowel resection can affect absorption and efficacy of oral contraceptives
Cirrhosis: no restriction, except in severe decompensated cirrhosis (lack of data)

5. Heather. . . 1 year later develops severe flare and hospitalized
Unresponsive to iv steroids and started on infliximab
Responds well and continues on azathioprine and mesalamine as well

6. Heather. . . 2 years later she is having recurrent symptoms
Planning on getting married next year to Steve
Wants to have children in the future
Worries about future surgery if symptoms persist as her sister underwent IPAA for medical refractory UC and had trouble conceiving after

7. Fertility in IBD and PSC
Fertility: achieving pregnancy within 1 year of intercourse without contraception
Background rate – 1 in 7 couples (14%)
Majority of women with IBD or PSC have normal fertility
Potential impact on infertility
Disease activity in IBD
Decompensated PSC cirrhosis (no menstrual cycles)
Medication (sulfasalazine in men)
Voluntary
Surgery
Patient choice
I have seen several pts who were told not to have kids..
General population infertility rate = 10%

8. Heather. . .
Medications adjusted and she has been in remission for 2 years
Actively trying to conceive
Wonders about the risk of her baby developing IBD

9. Heritability of IBD and PSC
Inheritance is major concern expressed by patients considering having children
IBD: family history is most important risk factor to predict lifetime risk
CD is more often familial than UC
Children of CD parent have 5-10% lifetime risk of IBD (2% with UC)
2 parents affected (1 with CD) have 35% lifetime risk
PSC: genetic risk variants identified, but familial disease is rare

10. Heather & Steve…
She is now 2 months pregnant and has an appointment with MFM
She wonders how her disease will affect her baby and likewise how being pregnant could affect her colitis and PSC

11. Gynecologic issues and family planning
Effect of pregnancy on IBD and PSC
Effect of IBD and PSC on pregnancy
Treatment in pregnancy
Delivery
Breastfeeding
Vaccines

12. Effect of pregnancy on IBD

13. Effect of Pregnancy on CD: Disease Activity at Conception
73%
33%
27%
32%
34%
Inactive
Active
No Relapse
Relapse
Worsened Activity
Continued
Activity
Decreased Activity
n=186
n=93
Effect of pg on ibd depends mainly on activity of the disease at conception.
Patients in remission are likely to stay in remission during pregnancy.
Active dz to start rule of thirds
Inactive dz 1/3 relapse most don’t similar rate of relapse for nonpg uc patients in a 9 month period******
Is some data to suggest higher rates of relapse post partum and with breastfeeding.
Also some thought that ibd should theoretically get better during pregnancy secondary to the somewhat immunosuppressed state of pregnancy.
Don’t want to harm baby so less immunogenicity all around.
Post-partum: some thought that ibd can flare at this time due to revived immune system.
ALSO every pg is different. No guarentee.
2nd square similar to uc, rule of 1/3rds
1st square if in remission at conception likely to stay in remission
What about perianal disease or fistulizing dz
Always been thought that vaginal delivery could worsen perianal cd
Some studies say it doesn’t but majority of patients with perianal dz have elective c-sections (for that matter most patients with ibd )
Could get fistulae at episiotomy site.
Miller JP. J R Soc Med. 1986;79:221-5.

14. Effect of Pregnancy on UC: Disease Activity at Conception
66%
45%
34%
24%
27%
Inactive
Active
No Relapse
Relapse
Worsened Activity
Continued
Activity
Decreased Activity
n=227
n=528
Effect of pg on ibd depends mainly on activity of the disease at conception.
Patients in remission are likely to stay in remission during pregnancy.
Active dz to start rule of thirds
Inactive dz 1/3 relapse most don’t similar rate of relapse for nonpg uc patients in a 9 month period******
Is some data to suggest higher rates of relapse post partum and with breastfeeding.
Also some thought that ibd should theoretically get better during pregnancy secondary to the somewhat immunosuppressed state of pregnancy.
Don’t want to harm baby so less immunogenicity all around.
Post-partum: some thought that ibd can flare at this time due to revived immune system.
ALSO every pg is different. No guarentee.
Miller JP. J R Soc Med. 1986;79:221-5.

15. Effect of pregnancy on PSC

16. Pregnancy does not worsen PSC progression, but can complicate cirrhosis
NO CIRRHOSIS
Portal hypertension
No portal hypertension
EGD to screen for esophageal varices prior to conception and 2nd trimester
Treat varices to prevent bleeding
Ultrasound to screen for splenic artery aneurysm
Risk of complications: ascites (10%), variceal bleeding (7%), encephalopathy (1%)
Itching may occur
-consider UDCA
Complications in 30-50% of patients
Pregnancy can be completed safely under close medical supervision

17. Gynecologic issues and family planning
Effect of pregnancy on IBD and PSC
Effect of IBD and PSC on pregnancy
Treatment in pregnancy
Delivery
Breastfeeding
Vaccines

18. Guiding Principle in Pregnant Patients With Active IBD
“The greatest risk to pregnancy is active disease—not active medicine.”
Goals
Establish remission before conception
Maintain remission during pregnancy
Basic science studies suggest that active inflammation bad for any pregnancy, not just in IBD
Sachar D. Gut. 1998;43:316.

19. Effect of IBD on Pregnancy Outcomes
Case-controlled studies and population based studies suggest:
Increased risk of adverse pregnancy outcomes
Spontaneous abortion
Low birth weight
Preterm delivery
Complications of L&D (pre-eclampsia, liver, and platelet disorders)
C-section rate
No major impact congenital abnormalities
Likely influenced by disease activity
Many different studies, mostly retrospective
Population based from Sweden Norwegian study May2010
Conflicting data sometimes, congenital abnormalities
Population based study of 756 females with ibd.
Are the results due to disease activity? Yes may be more in crohns
Definitions:
LBW <2500g (5.5#)
Very LBW g (1-3.3#)
Very PT <32 weeks
PT <37 weeks
Data may be confounded by frequent and inappropriate discontinuation of maintenance medications, increasing risk of flare

20. Impact of PSC cirrhosis on pregnancy
Maternal risk:
- correlates with liver disease severity. MELD ≥10 has worse outcomes
Fetal risk:
higher rate of prematurity and early fetal loss (20% vs 3-6% in general population)
Lower live birth rate (58%)

21. Gynecologic issues and family planning
Effect of pregnancy on IBD
Effect of IBD on pregnancy
Treatment in pregnancy
Delivery
Breastfeeding
Vaccines

22. Safety of IBD Medications During Pregnancy
Safe to Use Limited Data When Indicated Available Contraindicated
Oral mesalamine Cyclosporine Methotrexate
Topical mesalamine Natalizumab Thalidomide
Sulfasalazine Vedolizumab Rifaximin
Metronidazole/Cipro? Ustekinumab
Anti-TNF agents Tofacitinib (likely contraindicated)
Azathioprine/6-MP
Corticosteroids
Likely safe and we use them steroids, AZA/6mp, Remicaide ?humira
I wouldn’t use cipro

23. Placental transfer of biologics
Infliximab and adalimumab do not cross the placenta in the 1st TM
1st TM important for organ/neural development
Cross efficiently in the 3rd TM
Infliximab is detected in infant blood up to 6 months from birth
Certolizumab is pegylated Fab portion of Ab
Minimal placental transfer by passive diffusion
Humira doesn’t have commercially avail levels
Can check infliximab level in the newborns and if neg can vaccinate
Rotavirus only live vaccine given at early age
MMR and varicella which are live are not given until 12+months, should be ok
May need to check titres to killed vaccines in baby

24. Newer biologics Vedolizumab Ustekinumab Tofacitinib
Low risk; limited data
Ustekinumab
Tofacitinib
Limited data, teratogenic in animal studies
Not recommended in pregnancy
Mahadevan et al. Gastroenterology 2017
Moens et al. J Crohns Colitis 2019

25. Heather. . . 28 weeks pregnant, on bedrest for pre-term labor
No colitis symptoms
Wonders about infliximab dosing
She is due for dose in 2 weeks
Ob feels she will likely deliver early 36wks?
When should she get her last infliximab dose?

26. Minimizing Placental Transfer
Adjustment of dosing schedule
Resume biologic:
24 hours after vaginal delivery
48 hours after c-section
Biologic
Timing of Last Dose
Infliximab
Week 30-32
Adalimumab
Week 36-37
Certolizumab pegol
No adjustment
Golimumab
Week 34-36
Natalizumab
Vedolizumab
Ustekinumab

27. Pregnancy after liver transplant (LT)
Impact of LT on fetus
Early conception within 12 months after LT is a risk factor for stillbirth  WAIT 1 year after LT.
Live birth: 69-77% of pregnancies.
Higher rate of complications: preeclampsia (22%), cesarean section (45-50%), and premature delivery (31- 39%).
Antirejection medications can lead to congenital malformations and miscarriage  DISCONTINUE:
mycophenolate mofetil
sirolimus

28. Pregnancy after liver transplant (LT)
Impact of pregnancy on the liver allograft
Pregnancy increases the risk of rejection
The risk is higher with early pregnancy vs 1 year after LT: 46% compared with 11%
Avoid unplanned pregnancy in the first year after LT!

29. Gynecologic issues and family planning
Effect of pregnancy on IBD
Effect of IBD on pregnancy
Treatment in pregnancy
Delivery
Breastfeeding
Vaccines

30. Mode of Delivery
Women with IBD or cirrhosis have fold greater risk of C- section
Women with UC and perianal CD have increased risk of C- section
Delivery method should be at discretion of the OB/Mom
Most women with IBD can have vaginal delivery
Exceptions: those who need C-section:
Active (or quite recent) perianal disease
History of rectovaginal fistula
UC patients with J pouch (?)
Women with large esophageal varices
Burke (and Cheifetz) did a 10-year retrospective cohort study on nulliparous women who delivered a singleton infant. Overall incidence of c section in women with CD was similar to that among women without IBD. Women with active and inactive perianal disease did have increased risk. Women with UC had a 1.8 fold increased risk of c section, with highest incidence in women with IPAA
Burke KE et al. Inflamm Bowel Dis 2017
Manosa et al. Scand J Gastroenterol 2013

31. Gynecologic issues and family planning
Effect of pregnancy on IBD
Effect of IBD on pregnancy
Treatment in pregnancy
Delivery
Breastfeeding
Vaccines

32. Breastfeeding: IBD Medications
LactMed
US National Library of Medicine free online database
Most IBD medications are safe for breastfeeding

33. Summary: IBD Meds & Breastfeeding
Medication
Recommendation
Potential concerns
Aminosalicylates
Compatible
Rare diarrhea in infant
Metronidazole
Contraindicated
Ciprofloxacin
Probably compatible
Delay feeding 4 hours
Amoxicillin-clavulanic acid
Rifaximin
Avoid
No human data
Corticosteroids
Methotrexate
Thiopurines
Biologics
Low or undetectable levels (Vedo unknown)
Tofacitinib
Unknown
Ustekinumab – low or undetectable levels –
Vedo – unknown
Tofacitinib - unknown

34. Post-liver transplant meds & Breastfeeding
Compatible: tacrolimus, cyclosporine, prednisone, UDCA.
Limited data: sirolimus, MMF.

35. Take Home Points
Majority of women with IBD and non-cirrhotic PSC have normal fertility
Contraception is safe in IBD/PSC
The greatest risk to pregnancy is active disease— not active medicine
Pregnancy is contraindicated in cirrhosis with MELD>10 or portal hypertension (varices, ascites)
Pregnancy after transplant has good outcomes if conception occurs >1 year after LT
Most medications can be continued during pregnancy and lactation
Interdisciplinary approach is essential

36. Questions & Discussion