Anti–TNF-α Therapy May Cause Neonatal Neutropenia

Abstract

Although anti-tumor necrosis factor (anti-TNF) antibodies are associated with a clear risk of agranulocytosis in adults and are known to cross the placenta, monitoring of the absolute neutrophil count (ANC) in neonates born to mothers receiving these biological agents is not currently recommended. Here, we report on the first case series of 4 newborn patients with severe neutropenia born to mothers treated for ulcerative colitis with infliximab during pregnancy (including the third trimester). The newborns presented with severe neutropenia at birth, which was subsequently complicated by skin infections. The newborns' ANCs returned to the normal range within 8 to 14 weeks, at which time infliximab could not be detected in the blood. Anti-TNF agents probably exert a direct, toxic effect on the bone marrow. Furthermore, the detection of a CD16 autoantibody in 1 mother-newborn pair suggests that infliximab can induce autoimmune neutropenia. Abnormally high levels of the CD16 autoantibody in newborn serum or immaturity of the fetal bone marrow might explain why neutropenia was observed in the child but not in the mother. We recommend the systematic measurement of ANC on cord blood at birth and (in the event of an infection) in the weeks thereafter.

Targeting of Tumor Necrosis Factor Alpha Receptors as a Therapeutic Strategy for Neurodegenerative Disorders

“…It has been mentioned that two patients with rheumatoid arthritis treated with an anti-TNF-α strategy developed neurological symptoms, including demyelination lesions [251]. Furthermore, it was shown that newborns presented severe neutropenia after their mothers were treated with infliximab for ulcerative colitis during pregnancy [252].…”

Pregnancy and rheumatoid arthritis

“…In contrast to these reassuring data, a small case series describes the presence of transient severe neutropenia, subsequently complicated by skin infections, in four newborns after intrauterine exposure to infliximab (including the third trimester) [102]. Furthermore, in view of the death of a 4.5-month-old female infant who developed disseminated Bacillus CalmetteeGu erin (BCG) following BCG vaccination at 3 months of age, live vaccines should be considered with caution.…”

Tailored anti-TNF therapy during pregnancy in patients with IBD: maternal and fetal safety

“…Although a few small follow-up studies4 9 suggest no serious adverse events in these children, one case report described a fatal case of disseminated bacille Calmette-Guérin infection in an infant exposed to IFX in utero, which showed that live attenuated vaccinations in children exposed to anti-TNF in utero may be associated with adverse outcome. In addition, a recent case series reported four infants exposed to IFX in utero with severe neutropenia at birth 10. Adverse outcomes in the newborn may be avoided by lowering perinatal anti-TNF serum levels in the infants by stopping anti-TNF treatment in the second trimester of pregnancy in women with IBD in remission 6.…”