90
no other complications. Cellular immunity was noted to be normal in all infants, and
response to vaccination, which was evaluated in 15 of the children, was adequate.
One of the most recent updates from the PIANO registry includes an assessment of
developmental milestones using the Denver Developmental Score completed by the
mother at 4, 9, and 12 months as well as by using the Ages and Stages Questionnaire
at 1, 2, 3, and 4 years of age which showed that, in all areas of development, the
infants exposed to thiopurines, anti-TNF agents, or combination therapy had similar
or better achievement of milestones compared to the unexposed infants [ 66 ].
Duration of Anti-TNFα Medication Use in Pregnancy
Disease remission in the pregnant IBD patient is the driving factor regarding when
to discontinue anti-TNF therapy during pregnancy. The current recommendations
are to give the last IFX infusion at around 20 weeks of gestation or the last ADA
injection around 24 weeks of gestation in those in disease remission; CZP may be
safely continued throughout pregnancy [ 30 ]. The purpose of tailoring the dosing
schedule is to maintain remission in the mother while minimizing exposure to the
fetus. In one case-control study, 51 women in remission discontinued anti-TNF
therapy before GW 25 which did not result in an increased rate of disease flare
(5/51, 9.8%) compared to the rate of flare in the cohort who continued anti-TNF
therapy beyond week 30 (5/32, 15.6%; P = 0.14) [ 25 ]. In another study of 31 preg-
nancies in 28 women, all with quiescent disease, 12/18 (71%) discontinued IFX
before GW 30, and all women remained in remission, while all of the women on
ADA discontinued treatment before GW 30 which resulted in a disease flare in 2/13
(15.3%) [ 24 ]. Both of these studies concluded that anti-TNF medications can be
safely discontinued in the second trimester in women with quiescent disease.
The goal of discontinuing anti-TNF therapy in the second trimester is to limit
drug exposure during the time of highest transmission of immunoglobulins from the
mother to the fetus. Several studies have shown that timing of the last anti-TNF
administration correlates with maternal serum and cord blood levels, however, not
in a linear fashion. In a study looking at cord blood levels of IFX, ADA, and CZP,
Mahadevan et al. noted that a longer duration of time from the last dose to delivery
did not always correlate with lower cord blood drug concentrations [ 23 ]. For exam-
ple, there were two infants with intrauterine ADA exposure, one last exposed 7 days
prior to birth and the other 56 days prior to birth, yet they had similar cord blood
drug concentrations at birth (6.17 and 6.01 μg/mL). Similarly, in two infants with
intrauterine IFX exposure, cord blood drug levels at birth were 23.6 and 28.2 μg/mL
despite the last dose in the first at 14 days prior to delivery and at 55 days prior to
birth in the second. This variability is likely due to differences in maternal dose and
interval, individual pharmacokinetics, as well as immaturity of the newborn reticu-
loendothelial systems. A similar variability in cord blood drug concentrations was
also noted by Julsgaard et al. to which they concluded that it is “not possible to
identify a gestational week to stop maternal anti-TNF treatment that would reliably
J.K.J. Gaidos and S.V. Kane