In a pregnant patient with an inflammatory disease, is it safe to continue TNF‑α inhibitors, what is the infection risk to mother and fetus, and how should the therapy be timed and monitored?

TNF Inhibitors in Pregnancy: Infection Risk Assessment

Primary Recommendation

Continue TNF-α inhibitors throughout pregnancy, as the infection risk to mother and fetus is not increased compared to unexposed IBD patients, and the benefits of maintaining disease remission substantially outweigh theoretical risks. 1

Infection Risk Evidence

Maternal Infection Risk

• Anti-TNF therapy during pregnancy is associated with a modest increase in maternal infections (adjusted OR 1.31,95% CI 1.16-1.47), though this may be confounded by disease severity rather than medication exposure alone 2
• Maternal complications overall are increased with anti-TNF use (adjusted OR 1.49,95% CI 1.31-1.67), but discontinuing therapy significantly increases disease relapse risk (adjusted OR 1.98,95% CI 1.25-3.15), which itself poses greater harm 3, 2
• Active, uncontrolled disease poses substantially greater risks than medication exposure, including increased perinatal bacterial infections even without biologic therapy 1

Fetal and Neonatal Infection Risk

• Systematic reviews of over 50 studies demonstrate no increased risk of infections in offspring exposed to TNF inhibitors in utero 1, 3
• One French national database study of 11,275 pregnancies found no increased infection risk in children during the first year of life (adjusted OR 0.89,95% CI 0.76-1.05) 2
• Meta-analysis of 5 IBD studies showed no significant differences in any adverse pregnancy outcomes, including infections (OR 1.00,95% CI 0.72-1.41) 1

Important Caveats

• Case reports document rare severe neonatal neutropenia with anti-TNF exposure 1
• One fatal disseminated BCG infection occurred in an infant vaccinated at 3 months whose mother received anti-TNF throughout pregnancy, highlighting the critical importance of delaying live vaccines 4
• Neonates should be considered immunosuppressed for 6-12 months postpartum depending on the specific TNF inhibitor used 3, 5

Timing and Monitoring Strategy

Standard Approach (Preferred)

• Continue TNF inhibitors through all three trimesters for women with active disease or high relapse risk 1, 3
• This approach maintains maternal remission and does not increase neonatal infection risk based on current evidence 1, 2

Alternative Discontinuation Strategy (Conditional, Highly Selective)

Only consider discontinuation at 22-24 weeks gestation if ALL of the following criteria are met: 1, 4

• Sustained symptomatic remission for ≥12 months before conception
• No active disease on pre-conception endoscopy or imaging
• No prior secondary loss of response or dose escalation
• Documented therapeutic drug levels
• No prior intestinal resections
• No hospitalizations in preceding 36 months

Critical warning: Discontinuation increases relapse risk by 32% in the first 3 weeks postpartum, and there is no evidence that stopping at 22-24 weeks meaningfully reduces placental transfer 1, 4

Neonatal Management Protocol

Live Vaccine Restrictions

• Delay all live or live-attenuated vaccines for 6-12 months after birth in infants exposed to TNF inhibitors during the third trimester 3, 4, 6, 5
• Non-live vaccines can be administered on the standard schedule 6
• The specific delay period depends on the agent used:
  • Infliximab: 6-7 months (detectable in infant serum this long) 6
  • Adalimumab: 6-12 months 4
  • Golimumab: 6 months 5
  • Certolizumab: Minimal placental transfer, but still exercise caution 7

Monitoring Recommendations

• Consider checking complete blood count in newborns to screen for transient anemia or rare agranulocytosis 6
• Monitor for signs of infection, though systematic surveillance has not shown increased infection rates 6

Agent-Specific Considerations

Certolizumab Pegol (Unique Profile)

• Certolizumab demonstrates negligible placental transfer in most infants due to its pegylated Fab' fragment structure lacking an Fc region 7
• Concentrations were unmeasurable in 13 of 15 infants at birth; when detectable, levels were <0.5 mcg/mL compared to maternal levels of 5-50 mcg/mL 7
• This may represent the safest option when initiating therapy during pregnancy, though continuation of any established TNF inhibitor is still preferred over switching 7

Standard Monoclonal Antibodies

• Infliximab, adalimumab, and golimumab are IgG1 antibodies with active placental transfer beginning around week 13, increasing progressively through the third trimester 4, 6, 5
• Cord blood levels can reach 4-fold higher than maternal levels at delivery 6

Lactation Safety

• All TNF inhibitors are safe during breastfeeding 3, 6, 5
• Large monoclonal antibodies transfer minimally into breast milk and have poor oral bioavailability 3
• Golimumab concentrations in breast milk are approximately 400-fold lower than maternal serum 5

Common Pitfalls to Avoid

1. Do not routinely discontinue TNF inhibitors solely because of pregnancy – the greatest risk comes from uncontrolled disease, not medication exposure 3, 4
2. Do not assume that modifying third-trimester dosing timing reduces placental transfer – current evidence does not support this practice 1, 4
3. Do not allow live vaccines in exposed infants before 6 months minimum – fatal infections have been documented 4
4. Do not underestimate disease flare risk with discontinuation – 32% relapse rate occurs within 3 weeks postpartum when therapy is stopped 1