Septic Episodes in a Premature Infant After In Utero Exposure to Rituximab

Pediatrics. 2017 Sep;140(3):e20162819. doi: 10.1542/peds.2016-2819. Epub 2017 Aug 2.

Abstract

Rituximab is an increasingly used immunotherapeutic agent for women of reproductive age for treatment of autoimmune diseases, leukemias, and lymphomas. Rituximab is a chimeric monoclonal antibody that targets B-cell surface antigen CD20 and can cross the placenta. Current evidence of the impact of this medication on the developing fetus is limited, but there is little to suggest that fetal exposure to this medication places an infant at increased risk of immunosuppression and subsequent infection. Here we report a case of in utero rituximab exposure that was associated with 2 severe septic episodes with Enterococcus faecalis, in a premature infant of 29 weeks' gestational age with a birth weight of 820 g. The patient had a critically depressed B-lymphocyte subset of 10% and undetectable immunoglobulin (Ig)G, IgM, and IgA levels at 37 weeks' postmenstrual age. Interestingly, both episodes of sepsis coincided with transition from donor human milk to formula feeds. She was treated with intravenous immunoglobulin, antibiotics, and donor human milk. We postulate that placental transfer of rituximab, prematurity, and the low levels of protective maternal antibodies increased the susceptibility of this patient to sepsis by E faecalis, a resident of the normal gut flora, whereas the secretory IgA in donor human milk may have played a protective role.

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Antibodies, Monoclonal / adverse effects*
  • Enterococcus faecalis / isolation & purification
  • Female
  • Gram-Positive Bacterial Infections / diagnosis*
  • Gram-Positive Bacterial Infections / drug therapy
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Infant, Newborn
  • Infant, Premature
  • Milk, Human
  • Rituximab / adverse effects*
  • Sepsis / chemically induced*
  • Sepsis / drug therapy

Substances

  • Anti-Bacterial Agents
  • Antibodies, Monoclonal
  • Immunoglobulins, Intravenous
  • Rituximab