August 2019 Interactive Case: Uncomplicated Pregnancy

1. August 2019 Interactive Case: Uncomplicated Pregnancy Author: Elena fisher, FNP-BC, MS, RN Gastroenterology Nurse Practitioner Department of Veterans Affairs New Mexico VA Healthcare System reviewed by the Crohn’s & Colitis Foundation’s Nurse & Advanced Practice Committee

2. Instructions • To begin, please enter into “Presentation mode” to enable full interactivity of case and questions. (Click “slide show” tab)When you see words or phrases that are underlined click on the underlined word and this will take you to the next screen. To continue the presentation make sure you click back in the bottom left corner.

3. Objectives • 1.The reader will be able to discuss preconception planning with an IBD patient • 2. The reader will be able to feel confident on providing safety information to the pregnant patient regarding IBD treatments • 3. The reader feel more confident in helping manage and IBD patient with a normal pregnancy

4. Introduction/Background • Sarah 23 y/o woman • Diagnosed left sided ulcerative colitis 4 years ago • Initial presentation moderate to severe • Required 2 courses of steroids • 3 years ago started on infliximab 5mg/kg every 8 weeks • Last colonoscopy 1 yr. ago revealed mild inflammation in the rectum otherwise normal

5. Initial Visit • “Feels well” • Reports 2-3 soft stools a day, no pain or blood for a year • Weight is stable BMI 20 • Labs – mild anemia Hgb 11, MCV 75 • Works fulltime as a teacher, getting married in 6 months • Medications -infliximab 5mg/kg q 8 weeks, azathioprine 50 mg q day • MVI she takes occasionally

6. Initial Visit Continued • PE – no concerns • Labs – repeat CBC, iron panel, CMP, ESR, Hepatitis panel, TB quant • Imaging - DEXA if not done previously • Colonoscopy – mild changes in rectum a year ago, repeat? • Vaccinations - no records reports history of flu vaccination yearly • Psychosocial issues – Depression scale?

7. Preconception Planning • Goal optimization of IBD health and treatment during preconception and pregnancy to produce the best pregnancy outcomes • Up to 50% of patients have poor knowledge of IBD and IBD related treatments during pregnancy. This often leads to non-adherence in therapy. Wierstra, K., Sutton, R., Bal, J., Ismond, K., Dieleman, L., Halloran, B., ... & Huang, V. (2018). Innovative Online Educational Portal Improves Disease-Specific Reproductive Knowledge Among Patients With Inflammatory Bowel Disease. Inflammatory bowel diseases.

8. Preconception Planning Continued • Multidisciplinary team including: primary care provider, gastroenterologist, obstetrician, and maternal-fetal medicine specialist • Patient should be up-to-date on her healthcare maintenance, vaccinations, and surveillance colonoscopy • Disease activity should be assessed either byendoscopy, fecal calprotectin, or imaging as appropriate • Disease control should be optimized and medications adjusted to achieve a steroid free remission • Teratogenic medications should be discontinued

9. Sarah Pregnancy Case Discussion • Initiate discussion – wedding in 6 months • Birth control method? • Family planning discussed with fiancé? • Medications – risks versus benefits of infliximab and azathioprine during pregnancy and breastfeeding

10. Sarah’s Concerns • Not planning on pregnancy for at least 2 years • Was hoping to stop all medications prior to conception-Concerns? • Wants to breastfeed-Which medications are safe for breastfeeding?

11. 4 Month Follow-Up • Sarah reports she continues to do well but has some looser stools and cramping 1-2 weeks prior to infusions. • Labs Hgb 9, MCV 76, Calprotectin 560 (baseline when well <100) • Weight stable • Next steps: • Check Infliximab level at trough • Colonoscopy?

12. Follow-Up after labs reviewed • Infliximab level was 2, no Antibodies • You decide to increase to 10mg/kg every 8 weeks, continue azathioprine 50mg q day and monitor • Patient was started on iron 325mg po daily with Vitamin C 500mg a day and recommend daily chewable MVI

13. Sarah Returns 4 month later • Recently married, feels well. No further cramps or loose stools • Afraid she might be pregnant • Stopped azathioprine herself 2 weeks ago • Last Infliximab was 1 month ago 10mg/kg • Colonoscopy was not completed as previously recommended

14. What Do You Want To Do Now? • Colonoscopy ? • Imaging ? • Labs ? • Referrals?

15. Follow-Up • Sarah returns is doing well, no complaints • Found to be 14 week pregnant EDD • Labs Hgb 11, MCV 80, Calprotectin 200 • Remains on Infliximab 10mg/kg q 8 weeks – levels rechecked IFX 8, No antibodies

16. Monitoring • Sarah is seen every 2-3 months until delivery • Weight and labs are stable • Infliximab is scheduled through week 32 and 2 days after delivery • Patient is provided information regarding vaccinations for newborn • Patient will be scheduled for colonoscopy in the future either after breastfeeding or if any symptoms • Discussion regarding adding back azathioprine can wait until after colonoscopy

17. Normal pregnancy • Sarah is seen for infusion 2 days after delivery • Reports normal vaginal delivery, no complications • Infant and mother are doing well, breastfeeding is going well • No bowel changes at this time • Weight and labs are stable

18. Crohn’s & Colitis Foundation Resources • Patients • Fact sheets: (https://www.crohnscolitisfoundation.org/) • Pregnancy • Women and IBD • Support groups: • Online: www.crohnscolitiscommunity.org • In-person: Locate at www.crohnscolitisfoundation.org • IBD Help Center: available by email (info@crohnscolitisfoundation.org), phone (888-694-8872), or online chat • Providers • Inflammatory Bowel Disease in Pregnancy Clinical Care Pathway: A Report From the American Gastroenterological Association IBD Parenthood Project Working Group (https://doi.org/10.1093/ibd/izz037) • Other educational videos on pregnancy: (https://www.crohnscolitisfoundation.org/prescribers)

19. End of Presentation

20. Stopping Medications • Woman who has active disease at the time of conception is more likely to have active disease throughout pregnancy than a woman in remission at conception • RECOMMEDATION: Women to be in remission at the time of conception Back

21. IBD Medications During Pregnancy and Breastfeeding • Most experts consider use during breast feeding to be acceptable. Women studied show low or unmeasurable amounts in breastmilk. • Infliximab is usually not detectable in breastmilk, probably destroyed in infants GI tract. • References • Mothertobaby.org Azathioprine has not been proven to cause birth defects. The majority of pregnancies (1300) studies had no birth defects. Birth defects were similar to mothers with similar health conditions. • Mothertobaby.org 2017 Multiple small studies have not shown an increased risk in birth defects with Infliximab. • LactMed App- search all medications and risks for lactation Back

22. Medication Use During Lactation Mahadevan, U., McConnell, R. A., & Chambers, C. D. (2017). Drug safety and risk of adverse outcomes for pregnant patients with inflammatory bowel disease. Gastroenterology, 152(2), 451-462. Back

23. Infliximab Levels • Infliximab levels between 3-7 ug/ml in patients with CD was consistent with more patients in remission, lower CRP. • Gastrojournal.org Niels Vande Casteel et al published online Feb 24 2015 • Back

24. Colonoscopy During Pregnancy • Colonoscopy/sigmoidoscopy low risk for baby and mother • If possible should be avoided until 2nd trimester NCBI.NIM.NIH.GOV Back

25. Imaging During Pregnancy • American college of Obstetricians –Ultrasound/MRI no associated risks but should only completed when deemed necessary for treatment • Gadolinium should not be used in pregnancy • If CT deemed necessary should be low dose radiation ACOG.org Back

26. Monitoring Disease Activity in Pregnancy • Hemoglobin - altered by pregnancy as well as disease • Albumin – altered by pregnancy as well as disease • ESR - not accurate in pregnancy • CRP – not affected by pregnancy • Fecal Calprotectin – not enough data to suggest if useful in pregnancy Winter, R., Nørgård, B. M., & Friedman, S. (2015). Treatment of the pregnant patient with inflammatory bowel disease. Inflammatory bowel diseases, 22(3), 733-744. Back

27. Referral to High Risk Maternal Fetal OB • Maternal-fetal medicine plays a critical role in genetic counseling, stratifying risks and supporting the baby and patient while continuing on medical management for treatment of IBD. • Frequent office visits between specialties and fluid communication keeps the IBD patient confident in her care plan and providers. • Back Mahadevan, U. Matro, R. (2015). Care of the Pregnant Patient with Inflammatory Bowel Disease. Obstetrics and Gynecology, (2):401-12.

28. Vaccinations • Biologic therapy-medication level may be present in infants over 9 months after birth • Infant should receive all non-live vaccines on time • Live vaccines including rotavirus & oral polio should be held until 9 months of age • Back Beaulieu, D. B., Ananthakrishnan, A. N., Martin, C., Cohen, R. D., Kane, S. V., & Mahadevan, U. (2018). Use of biologic therapy by pregnant women with inflammatory bowel disease does not affect infant response to vaccines. Clinical Gastroenterology and Hepatology, 16(1), 99-105.

29. Thiopurines (Azathioprine/6MP) • Thiopurines – low risk in monotherapy • Delayed infant infections with combination therapy • Back Mahadevan, U., McConnell, R. A., & Chambers, C. D. (2017). Drug safety and risk of adverse outcomes for pregnant patients with inflammatory bowel disease. Gastroenterology, 152(2), 451-462.

30. Biologics • A systematic review including > 1500 pregnancies exposed to anti-TNF revealed no evidence of increased rate of adverse pregnancy outcomes or congenital anomalies1 • Infliximab is considered low risk in monotherapy2 • Timing of the medication during the third trimester should be adjusted if possible, to a dose at the end of second trimester/beginning of third trimester to limit placenta transfer of the medication to the baby 3 • Back 1 Nielsen OH, Loftus EV Jr, Jess T. Safety of TNF-alpha inhibitors during IBD pregnancy: a systematic review. BMC Med 2013;11:174. 2 Mahadevan, U., McConnell, R. A., & Chambers, C. D. (2017). Drug safety and risk of adverse outcomes for pregnant patients with inflammatory bowel disease. Gastroenterology, 152(2), 451-462. 3 Mahadevan, U., Wolf, D. C., Dubinsky, M., Cortot, A., Lee, S. D., Siegel, C. A., ... & Miller, J. (2013). Placental transfer of anti–tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clinical Gastroenterology and Hepatology, 11(3), 286-292.