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

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.

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

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

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

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?

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.

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 by endoscopy, 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

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

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?

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?

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

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

What Do You Want To Do Now? Colonoscopy ? Imaging ? Labs ? Referrals?

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

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

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

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)

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Stopping Medications Back 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

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

Medication Use During Lactation Drug Breastfeeding Recommendations Mesalamine/sulfasalazine Compatible Corticosteroids Compatible, Dose >20mg (Delay feeding 3-4 hr. after dose) Thiopurines Compatible (Delay feeding 4 hr. if possible) Anti-TNF Methotrexate/thalidomide Contraindicated Metronidazole Ciprofloxacin Compatible (Delay feeding 3-4 hr. after dose) 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

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

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

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

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

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.

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.

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.

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.