What is the recommended management of Crohn’s disease in pregnancy?

Management of Crohn's Disease in Pregnancy

The cornerstone of managing Crohn's disease during pregnancy is maintaining disease remission through continuation of most maintenance medications, as active disease poses far greater risks to both mother and fetus than the medications themselves. 1

Preconception Planning

• Achieve clinical remission before conception to optimize pregnancy outcomes and reduce risks of preterm birth, low birth weight, and other complications 1
• Stop methotrexate at least 3-6 months before attempting conception due to teratogenic risk 1
• Stop thalidomide and ozanimod at least 6 months before conception 1
• If taking sulfasalazine, supplement with 2 mg/day of folic acid (higher than standard prenatal dose) starting 3 months before conception to prevent neural tube defects 1
• Counsel patients that conception during remission results in similar outcomes to non-pregnant patients with IBD 1

Multidisciplinary Care Structure

• All pregnant patients with Crohn's disease should be managed by a gastroenterologist throughout pregnancy 1
• Consult with a high-risk obstetrician (maternal-fetal medicine specialist) for all pregnant patients with active or complicated disease 1
• Transfer to a tertiary center if hospitalization is required, ensuring access to both gastroenterology and high-risk obstetrics 1

Maintenance Medication Management

Continue These Medications Throughout Pregnancy:

5-Aminosalicylates (5-ASA):

• Continue oral and/or rectal 5-ASA maintenance therapy throughout pregnancy 1
• The risks of active disease far outweigh the minimal risks associated with 5-ASA 1
• Higher doses (≥3 g/day) may slightly increase preterm delivery risk, but maintaining remission takes priority 1
• If using sulfasalazine, ensure 2 mg/day folic acid supplementation 1

Thiopurines (Azathioprine/6-Mercaptopurine):

• Continue thiopurine maintenance therapy throughout pregnancy 1
• Consider monitoring 6-thioguanine nucleotide and 6-methylmercaptopurine levels during pregnancy in women with active disease, as maternal metabolism changes 1
• Consider checking complete blood counts in newborns, as mild anemia has been reported 1

Anti-TNF Therapy (Infliximab, Adalimumab, Certolizumab):

• Continue anti-TNF maintenance therapy throughout pregnancy 1
• This is a strong recommendation as discontinuation risks disease flare, which carries higher maternal and fetal risks 1
• In select low-risk patients with compelling reasons to minimize fetal exposure, consider administering the last dose at 22-24 weeks' gestation 1
• Note that infliximab and adalimumab cross the placenta significantly in the second and third trimesters, resulting in cord blood levels up to 4-fold higher than maternal levels 1
• Certolizumab has minimal placental transfer due to lack of Fc portion, making it theoretically the safest biologic for the infant 2

Corticosteroids:

• Systemic corticosteroids and budesonide are safe during pregnancy 1, 3
• Continue if needed for maintenance, though not ideal for long-term use 1

Combination Therapy Considerations:

• For patients on combination anti-TNF and thiopurine therapy, individualize the decision to switch to monotherapy 1
• For thiopurine-naïve patients starting anti-TNF during pregnancy, use anti-TNF monotherapy rather than combination therapy 1

Managing Disease Flares During Pregnancy

Mild to Moderate Flares:

• Optimize combination oral and rectal 5-ASA therapy first 1
• The approach to managing flares during pregnancy is similar to non-pregnant patients 1

Flares Despite Optimal 5-ASA or Thiopurine Therapy:

• Treat with systemic corticosteroids or anti-TNF therapy to induce remission 1
• Do not delay appropriate treatment, as active disease poses greater risks than medications 1

Corticosteroid-Resistant Flares:

• Start anti-TNF therapy to induce remission 1

Perianal Disease with Sepsis:

• Use metronidazole and/or ciprofloxacin for perianal sepsis requiring antibiotics 1
• While fluoroquinolones are generally avoided in pregnancy, they may be used when benefits outweigh risks in this specific scenario 4

Monitoring Disease Activity

• Check fecal calprotectin at preconception, during each trimester, and after delivery to screen for active disease 1
• A cutoff of 200 mg/mg has 67-74% positive predictive value for disease activity 1
• Use flexible sigmoidoscopy or colonoscopy if results will affect management decisions 1
• Unsedated flexible sigmoidoscopy is preferred over colonoscopy 1

Imaging Considerations

• Limit radiologic investigations to ultrasound and MRI without gadolinium 1
• Avoid gadolinium during pregnancy 1, 4, 5
• Intestinal ultrasound is safe and can distinguish active from quiescent disease with 84% sensitivity and 98% specificity 1

Hospitalization Management

• Provide anticoagulant thromboprophylaxis during hospitalization for all pregnant patients with Crohn's disease 1
• This applies to both medical and surgical admissions 1
• Pregnant women with IBD have increased thrombotic risk 1

Surgical Considerations

• Do not delay urgent surgery to manage complications solely due to pregnancy 1, 4, 5
• Continued illness represents greater risk to the fetus than surgery 1

Delivery Planning

Mode of Delivery:

• Base cesarean delivery decisions on obstetric indications, not Crohn's disease diagnosis alone 1
• For patients with active perianal disease, recommend cesarean delivery to reduce risk of perianal injury 1
• For patients with ileal pouch-anal anastomosis (IPAA), consider cesarean delivery in consultation with obstetrician and surgeon to reduce anal sphincter injury risk 1

Thromboprophylaxis:

• Provide anticoagulant thromboprophylaxis during hospitalization after cesarean delivery 1

Breastfeeding

• Use of 5-ASA, systemic corticosteroids, thiopurines, or anti-TNF therapy should not influence the decision to breastfeed 1
• These medications are considered safe during lactation 1
• Avoid methotrexate during breastfeeding 1

Critical Pitfalls to Avoid

• Never discontinue maintenance medications due to pregnancy alone – active disease poses far greater risks than medications 1
• Do not use methotrexate during pregnancy – it is absolutely contraindicated due to teratogenicity 1, 6
• Do not delay treatment of active disease – flares during pregnancy carry high risk of adverse maternal and fetal outcomes 1
• Do not assume fertility is impaired – patients with Crohn's disease without prior pelvic surgery have normal fertility rates 1
• Do not forget higher-dose folic acid supplementation (2 mg/day) for patients on sulfasalazine 1
• Remember that disease activity at conception or during pregnancy is associated with preterm birth and low birth weight – maintaining remission is paramount 1