title: 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.
authors.affiliation: Service de Pédiatrie, and.
authors.forename: Tamazoust
authors.initials: T
authors.lastname: Guiddir
authors.affiliation: Service de Pédiatrie, and.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Frémond
authors.affiliation: Laboratoire d'Hématologie, Université Paris 13, Sorbonne Paris Cité, Hôpital Jean Verdier, Assistance Publique des Hôpitaux de Paris, Bondy Cedex, France;
authors.forename: Tewfik Bibi
authors.initials: TB
authors.lastname: Triki
authors.affiliation: Laboratoire d'Immunologie, Université Paris Descartes, Sorbonne Paris Cité, Hôpital Necker, Paris, France;
authors.forename: Sophie
authors.initials: S
authors.lastname: Candon
authors.affiliation: Etablissement Français du Sang, Créteil, France; and.
authors.forename: Laure
authors.initials: L
authors.lastname: Croisille
authors.affiliation: Service d'Hématologie Pédiatrique, Hôpital Robert Debré, AP-HP, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Leblanc
authors.affiliation: Service de Pédiatrie, and loic.de-pontual@jvr.aphp.fr.
authors.forename: Loïc
authors.initials: L
authors.lastname: de Pontual
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D000069285:Infliximab; D008297:Male; D009503:Neutropenia / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000097:blood; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
keywords: agranulocytosis; infliximab; neonatal neutropenia