An 8 days old exclusively breastfed female infant was referred to our hospital because of an infection of the umbilicus without fever. She was the second child of nonconsanguineous parents, both of Arab-Berber descent, born after 39 weeks of pregnancy, complicated by intrauterine growth restriction. Birth weight 2.570 kg (SD -1.6), length 48 cm (SD -0.8), and head circumference 32 cm (SD -1.7). The mother was known to have Crohn's disease, treated with oral methylprednisolone, in a gradually reducing dose with a maximum of 32 mg daily, and adalimumab, 40 mg subcutaneously every 2 weeks for up to 3 months before delivery. Additional investigations revealed a latent tuberculosis (positive interferon gamma release assay), for which she used INH 300 mg once a day, in combination with pyridoxine 125 mg, which both were started immediately after delivery. Family history is negative for hematologic diseases, syndromes, or early unexplained death. 
Physical examination of the neonate was, besides a local infection of the umbilicus, normal for her age. No (skeletal) malformations, cutaneous, or nail abnormalities; hepato-splenomegaly; or hypotonia were noted. However, complete blood count showed a picture of severe isolated neutropenia (hemoglobin 18.2 g/dL, mean corpuscular volume 97, plate-lets 254x109/L, leukocytes 7.56x109/L, and absolute neutrophil count [ANC] 0.04x109/L; C-reactive protein 73.1 mg/L). The child was admitted and broad-spectrum intravenous antibiotic treatment (ampicillin and cefotaxime) was started. Cultures of the umbilicus revealed the growth of Staphylococcus aureus. Urine and blood cultures remained negative.
The infection improved; however, the isolated neutropenia persisted. No viral etiology (TORCH, which includes Toxoplasmosis, Other [syphilis, varicella-zoster, parvovirus B19], Rubella, cytomegalovirus, and herpes infections, [para] influenza, respiratory syncytial virus, adenovirus) could be demonstrated. Testing for antineutrophil antibodies was not done, as the tests often show false-positive and false-negative results. Bone marrow aspiration revealed a severe dysgranulopoiesis, characterized by a maturation stop after meta-/myelocyte stage (Figure 1), indicating severe congenital neutropenia. Maternal usage of adalimumab during pregnancy can cause neutropenia because it can cross the placenta from the maternal circulation into the fetal circula tion. Also, agranulocytosis due to INH, used by the mother while breast-feeding, could not be excluded. Tuberculosis was excluded in the child, and the complete blood count of the mother did not show neutropenia. As a probability scale, we use the Naranjo algorithm, and this case was scored for both medications separately. INH was scored "3," while adalimumab was scored "4," both as a "possible" likelihood to be responsible for the neutropenia (Naranjo scores: 9 or 10 indicate "definitely"; 5-8 rate the likelihood as "probable"; 1-4 "possible"; <1 "doubtful").
Breast-feeding was terminated, and filgrastim (Neupogen , Amgen Inc., Thousand Oaks, CA, USA) 5 microg/kg subcutaneously was started. A very slow increase of ANC was seen, and so filgrastim dose was increased to 10 microg/kg subcutaneously, with good improvement. ANC increased to a maximum of 35.85x109/L. Two months after birth, filgrastim was terminated which, initially, led to a decrease of ANC, before it stabilized in the normal range (Figure 2). Two weeks after terminating, the filgrastim a new bone marrow aspiration (Figure 1) and a complete blood count was repeated. Both were normal, which excluded severe congenital neutropenia.