84
longer detectable [ 23 ]. At the time of birth, the median ratio of cord blood to
maternal drug concentration for IFX was 160% (range 87–400%); for ADA, it was
179% (range 98–293%); and for CZP, it was 3.9% (range 1.5–24%). In this study,
the ADA levels remained detectable in the infant serum for up to 11 weeks from
birth, while the IFX was detectable for up to 7 months. More recently, a prospective
multicenter study of 80 pregnant women with IBD exposed to anti-TNF medica-
tions, including 44 on IFX and 36 on ADA with 39 on concomitant thiopurines,
measured maternal blood and cord blood drug levels at the time of birth as well as
infant blood levels every 3 months until the drug concentrations were no longer
detectable [ 26 ]. Similar to previous studies, the median cord blood drug concentra-
tion was more than the median maternal drug concentration at the time of birth for
both medications (for IFX: 5.9 μg/mL (range 0.12–28.7) vs. 2.0 μg/mL (range
0–22.2); for ADA: 2.0 μg/mL (range 0–12.1) vs. 1.5 μg/mL (range 0–10.0)). At
birth, the mean ratio of infant to mother drug concentration was 1.97 for IFX (95%
CI 1.50–2.43) and 1.21 for ADA (95% CI 0.94–1.49). Notably, this study found a
much longer time for drug clearance in the infants with the mean time for drug
clearance of ADA of 4 months (95% CI 2.9–5.0) and 7.3 months for IFX (95% CI
6.2–8.3; P < 0.0001); however, the drugs remained detectable in some infants until
12 months of age. In all of the studies, the presence of detectable anti-TNF drug
concentrations did not result in an increase in adverse pregnancy or fetal outcomes.
However, while these drug concentrations are detectable, the infants are essentially
immunosuppressed and should not be administered live vaccines until serum con-
centrations are no longer detectable. The previous recommendation was to avoid the
rotavirus, oral polio virus, and bacille Calmette-Guerin (BCG) vaccines for the first
6 months [ 29 , 30 ]; however, this time frame may need to be extended to the first
12 months of life, or the use of anti-TNF drug concentration testing may need to be
implemented prior to administration of a live vaccine to an infant with intrauterine
anti-TNF exposure.
Anti-TNFα Medications in Pregnancy
Infliximab
Few studies looking at pregnancy outcomes in women with IBD have limited their
study cohorts to those only exposed to IFX. A study using data from an infliximab
safety database included 96 pregnant women with autoimmune diseases (82 Crohn’s
disease, 1 UC, 8 rheumatoid arthritis (RA), 2 juvenile rheumatoid arthritis, 3
unknown) who were exposed to IFX (ranging from within 3 months prior to con-
ception to exposure during the first trimester) [ 31 ]. The 96 pregnancies resulted in
64 (67%) live births, 14 (15%) SAs, and 18 (19%) elective abortions, which were
reported to be similar to the expected rates for the general US population. Review
of the FDA-mandated infliximab safety registry (TREAT) revealed 142 pregnancies
in women exposed to IFX with 83.1% (118/142) live births, 92.4% (109/118) of
J.K.J. Gaidos and S.V. Kane