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P467. Infliximab levels in newborns exposed to anti-TNFa during pregnancy for maternal inflammatory bowel disease correlate with gestational age at last drug application

D. Duricova1, N. Machkova1, M. Bortlik1, K. Malickova2, L. Hrdlicka1, M. Lukas1, 1Charles University, IBD Clinical and Research Centre, Iscare, Prague, Czech Republic, 2Charles University, Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Medical Faculty, Prague, Czech Republic

Background

IgG1 antibodies, including anti-TNFa antibodies infliximab and adalimumab, are actively transported through placental barrier already since second trimester resulting in high levels of the drug in cord blood of newborns. Our aim was to assess anti-TNFa levels in cord blood of newborns and to evaluate whether cord drug levels correlate with gestational age or time to delivery from last drug application.

Methods

Children born to women with inflammatory bowel disease (IBD) treated with anti-TNFa preparations during pregnancy were included. Anti-TNFa levels were measured at the time of delivery from cord blood and from mother. Correlation between time interval from the last application to delivery, gestational week of last application and drug levels in cord blood was analyzed by Spearman's correlation. Anti-TNFa serum levels were measured by ELISA.

Results

A total of 27 healthy children were born to women with IBD (19 with Crohn's disease and 8 with ulcerative colitis) treated at our centre with anti-TNFs. Of them 22 were exposed to infliximab and 5 to adalimumab. Four babies were born preterm (gestational week 34 to 36) and 23 at term with a median birth weight of 3146g (2400–4450). Infliximab levels were measured in 10 children exposed to last infusion at a median gestational week 29.5 (24–31). Infliximab levels in cord blood ranged from 0.5 to 25mcg/ml with a median 7.95mcg/ml. The corresponding levels in 7 mothers measured at delivery were 0.6mcg/ml (range 0–18). Statistically significant positive correlation was found between gestational week of last application and infliximab cord levels in newborns (rho = 0.674, p = 0.033) while a negative, not significant correlation was seen with the time since last infusion to delivery (rho = −0.553, p = 0.097). Regarding adalimumab, 4 babies had measurement of drug levels with only one having undetectable serum concentrations. In remaining 3 newborns adalimumab levels ranged from 0.7 to 3.3mcg/ml while all but 1 mother had undetectable drug concentrations at the time of delivery. Gestational week of last application ranged from 24th to 35th week.

Conclusion

Discontinuation of anti-TNFa at the end of second or beginning of third trimester does not prevent newborns from exposure to the drug. Infliximab levels in cord blood positively correlated with foetal gestational age at the time of last application.