What are the guidelines for using Infliximab (chimeric monoclonal antibody against tumor necrosis factor alpha) during pregnancy?

Infliximab Use During Pregnancy

Infliximab should generally be continued throughout pregnancy in women with inflammatory bowel disease to maintain disease remission, as the benefits of disease control outweigh potential fetal risks. 1

Primary Recommendation: Continue Treatment

The Toronto Consensus (2016) provides the strongest guidance, making a strong recommendation for continuation of anti-TNF therapy including infliximab throughout pregnancy in women with IBD. 1 This recommendation is based on:

• No increased risk of major congenital abnormalities compared to unexposed IBD patients 1
• No increased risk of spontaneous abortions in systematic reviews of over 50 studies 1
• No increased risk of infections in offspring according to systematic reviews 1
• Maintaining remission is critical - discontinuation risks disease flare during pregnancy and postpartum (32% relapse rate in first 3 weeks postpartum when stopped) 1

Key Safety Data

Placental Transfer and Fetal Exposure

• Infliximab is an IgG1 monoclonal antibody that does not cross the placenta during the first trimester 2, 3
• Active placental transfer begins around week 13 and increases progressively through the second and third trimesters 1, 4
• Cord blood levels can be up to 4-fold higher than maternal blood levels at delivery 1
• Infliximab remains detectable in infant serum for up to 6-7 months after birth 1, 4, 2

Pregnancy Outcomes

• Registry studies (TREAT, Infliximab Safety Database, PIANO) show no increased risk of adverse pregnancy outcomes 1
• No increased rate of congenital malformations (OR 1.10; 95% CI 0.58-2.09) 1
• No increased risk of preterm birth or low birth weight when adjusted for disease severity 1

Alternative Strategy: Selective Discontinuation (Conditional)

If a patient is at very low risk for relapse and has compelling reasons to minimize fetal exposure, the last infliximab dose may be given at 22-24 weeks gestation. 1 This is a conditional recommendation with very low-quality evidence and should only be considered when ALL of the following criteria are met:

• Sustained symptomatic remission for 12 months before conception 1
• No active disease on endoscopy or imaging during preconception period 1
• No prior secondary loss of response to infliximab or dose escalation 1
• Demonstrated therapeutic drug levels 1
• No prior intestinal resections 1
• No hospitalizations in past 36 months 1

Critical Caveat on Timing

The older British Association of Dermatologists guideline (2009) suggests avoiding infliximab after 30 weeks if possible 1, but this conflicts with the more recent and robust Toronto Consensus, which found no evidence that continuing therapy throughout pregnancy causes harm and emphasizes that discontinuation risks maternal disease flare. 1

Postpartum Considerations

Infant Vaccination

• Live vaccines (BCG, rotavirus) must be delayed for at least 6 months after birth in infants exposed to infliximab in utero 1, 4, 2
• One fatal case of disseminated mycobacterial infection occurred in an infant who received BCG vaccine at 3 months after in utero infliximab exposure 2
• Non-live vaccines can be administered normally 2

Infant Monitoring

• Consider checking complete blood count in newborns, as case reports describe transient anemia and rare agranulocytosis 1, 4
• Monitor for infections, though systematic reviews show no increased infection risk in the first year of life 1, 5

Breastfeeding

Infliximab is compatible with breastfeeding - it is present in breast milk in only miniscule amounts with unlikely toxicity. 1, 4

Maternal Risks

One large French database study found that continuing anti-TNF therapy was associated with increased maternal complications (aOR 1.49) and infections (aOR 1.31), but discontinuation before week 24 increased disease relapse risk. 5 However, this must be balanced against the well-established risks of uncontrolled IBD during pregnancy.

Practical Algorithm

1. At conception/early pregnancy: Continue infliximab - no placental transfer occurs in first trimester 2, 3

2. Second trimester: Continue infliximab - maintaining remission is paramount 1

3. Third trimester decision point:

   • Default approach: Continue through delivery 1
   • Alternative (only if all low-risk criteria met): Last dose at 22-24 weeks 1

4. At delivery: Counsel on live vaccine delay for infant 1, 4, 2

5. Postpartum: Resume or continue therapy; breastfeeding is safe 1, 4