“I have IBD and want to get pregnant” · 2020. 4. 6. · Sunhee Park, MD. Assistant Clinical Professor Gastroenterology. February 29, 2020 “I have IBD and want to get pregnant”

Sunhee Park, MDAssistant Clinical Professor GastroenterologyFebruary 29, 2020

“I have IBD and want to get pregnant”

Disclosures

Outline• Background• Pre-conception and family planning• Pregnancy

• Drug safety and risk of adverse outcomes

• Post-partum care

• Surgical considerations in IBD Pregnancy• Dorna Jafari, MD – Colorectal Surgery

Cases

Background

Kappelman et al 2013; Loftus et al 2014; CCFA; AGA

Risks of IBD to Pregnancy

Mahadevan et al 2019

The role of the GI


Pregnancy & Preconception

Planning

Disease & Medication

Management

Fertility Concerns Interdisciplinary Consultations

Healthcare Maintenance


Preconception & Family Planning

Preconception


Family Planning

3-month steroid-free remission prior to conception


Genetic Risk

Kappelman et al 2013; Loftus et al 2014; CCFA; AGA

Fertility Concerns• Women with IBD in remission who have never had surgery have fertility

rates equal to those in the general population • Women who have had IPAA, proctectomies, permanent ostomies have

decreased fertility due to inflammation and scarring of fallopian tubes• IBD patients who have not been able to conceive successfully x 6 months

should be referred for infertility evaluation• IBD meds have no effect on egg freezing or assisted reproductive

technology (ART) efficacy, and hormones used in ART have no adverse effect on IBD disease activity

• ART in IBD women not as effective as in infertile women in the general population, but once pregnant, women with IBD have equal chances of achieving a live birth compared to women in general population who underwent ART

Preconception: Medication• Avoid corticosteroids if possible

• Risk of gestational diabetes, preterm birth, low birth weight • Not good as maintenance therapy

• Methotrexate (teratogen) should be stopped at least 3 months prior to conception

• Stability of new medication for at least 3 months recommended• Biologics and thiopurines are low risk during pregnancy

• Serum drug levels of biologics should be measured and escalated/de-escalated as necessary before conception

• Subtherapeutic levels may lead to flares and supratherapeutic levels may lead to increased placental transfer (?altered levels of biologics during pregnancy)

• Limited data on Tofacitinib, but should be avoided during first trimester• Risk of malformation at supratherapeutic doses in animal studies• t1/2 = 3.2 hours; washout period of 1 week recommended before conception

Plan during Pregnancy

Higher risk of flare during pregnancy in patients with IBD who became pregnant with active disease

Caprilli et al, 2006; Bortoli et al, 2011; Abhyankar et al 2013

Recommendations on Medication Use during Pregnancy

Medical Therapy RecommendationsMedication Recommendations

Loperamide (Imodium) Limited human data; ?CV defects

Diphenoxylate (Lomotil) Limited human data; avoid use

Antibiotics• Metronidazole• Ciprofloxacin• Amoxicillin-Clavulanic Acid• Rifaximin

• Controversial; avoid first trimester (risk of cleft lip)• Low risk• Favorable profile; preferred choice• Avoid; teratogenic in animals

Corticosteroids• Budesonide• Prednisone

• Low risk• Moderate risk; orofacial cleft first-trimester exposure; adrenal

insufficiency, gestational diabetes, preterm birth, infant infectionsUse as adjunctive therapy for flares, but avoid as maintenance regimen


Medication Recommendations

Aminosalicylates• Balsalazide• Mesalamine• Sulfasalazine

• Low risk; maintain prepregnancy dose• Low risk; Asacol HD DBP (dibutyl phthalate) coating teratogenic in animals• Low risk; increase folic acid to 2mg daily

Immunomodulators• Cyclosporine• Methotrexate• Thiopurines

• Limited data; possible risk of preterm birth, low birth weight• Avoid; teratogenic; stop 3-6 months prior to conception• Low risk; delayed infant infections with combination therapy; avoid initiation

during pregnant

Biologics Maintain prepregnancy dosing; low risk

Tofacitinib Limited data; avoid during first trimester


Medical Therapy Recommendations

Biologics in Pregnancy• Infliximab and adalimumab

exposure to anti-TNF (alpha) drugs in utero does not increase short or long-term risk of severe infections in children born to mothers with IBD

• Follow-up mean of 4 years

Chaparro et al 2018; Mahadevan et al 2012

Biologic monotherapy preferred for maintenance therapy in pregnancy if disease well-controlled• Data not consistent; stopping thiopurine therapy is an individualized

decision based on severity of disease• Coelho et al did not find difference in outcome of pregnancy in patients with IBD

between those exposed to thiopurines during pregnancy and those exposure to other drugs or those exposed to no drugs at all

• Prospective study (Julsgaard et al): Anti-TNF drugs detectable until 12 months of age in infants born to mothers who received treatment during pregnancy

• Combination anti-TNF + thiopurine therapy during pregnancy increased the relative risk for infant infections ~3-fold compared with anti-TNF monotherapy

• Live vaccines should therefore be avoided for up to 1 year

Julsgaard et al 2016

Biologic Dosing Recommendations in PregnancyBiologic Recommendations*

Infliximab Low risk; continue until 8-10 weeks before delivery (30-32WG**)

Adalimumab Low risk; continue until 3-4 weeks before delivery (36-37WG)

Certolizumab Low risk; does not cross placenta; continue through pregnancy

Golimumab Low risk; continue until 4-6 weeks before delivery (34-36WG)

Natalizumab Low risk; continue until 4-6 weeks before delivery (34-36WG)

Vedolizumab Low risk; limited data; continue until 8-10 weeks before delivery (30-32WG)

Ustekinumab Low risk; limited data; continue until 8-10 weeks before delivery (30-32WG)


*Based on standard dosing**WG: weeks gestation

Thiopurine Therapy• Initiating thiopurine therapy for the first time during pregnancy not

recommended due to risk of pancreatitis, leukopenia, delayed time to effect

Coelho et al 2011

Anti-integrin Therapy

Delivery Plan


Post-partum Care

Post-Delivery Care

Post-Delivery Care for Baby

IBD Meds during LactationMedication Recommendations

Antibiotics• Metronidazole• Ciprofloxacin• Amoxicillin-Clavulanic Acid• Rifaximin

• Avoid; enters milk• Compatible; enters milk• Compatible; enters milk• Avoid; no human data

Corticosteroids• Budesonide• Prednisone

• Compatible; trace amounts in milk• Compatible; dose-dependent levels in milk

Aminosalicylates• Balsalazide• Mesalamine• Sulfasalazine

• Compatible; low levels in milk

• Diarrhea; sulfapyridine metabolite, excreted in milk at higher concentrations than parent drug

Mahadevan et al 2017 Table 2

IBD Meds during Lactation


Medication Recommendations

Immunomodulators• Cyclosporine

• Methotrexate• Thiopurines• Tacrolimus

• Probably compatible; infant receives <2% mother’s dose; monitor infant levels; limited data

• Lack of data: contraindicated; low doses in milk• Compatible; low levels in milk• Compatible; low levels in milk; limited data; monitor infant levels

Biologics• Infliximab• Adalimumab• Certolizumab• Golimumab• Natalizumab• Vedolizumab• Ustekinumab

• Compatible; low levels in milk• Peak excretion 1-4 days post infusion; ≤0.5% of mother’s plasma concentration• Peak excretion 1-6 days post injection; <1% of mother’s plasma concentration• Peak excretion 0.5-2 days post injection; undetectable• Undetectable• Undetectable• Unknown• Peak excretion in milk 1 day post-injection

Tofacitinib Limited data

Vaccine Recommendations for Newborn

Surgical Considerations in IBD Pregnancy

Dorna Jafari, MDColorectal Surgery

References

Thank [email protected]

Documents

“I have IBD and want to get pregnant” · 2020. 4. 6. · Sunhee Park, MD. Assistant Clinical Professor Gastroenterology. February 29, 2020 “I have IBD and want to get pregnant”