"Idiopathic neutropenia" in very low birthweight infants

Abstract

We employed a standardized investigative approach to evaluate four cases of "idiopathic neutropenia" in very low birthweight infants. The evaluation included maternal anti-neutrophil antibodies, a marrow aspiration, and a three-day trial of recombinant granulocyte colony-stimulating factor (rG-CSF). All patients had neutropenia at or shortly following delivery, and remained neutropenic (generally <500/microl) for 1-9 weeks until rG-CSF was administered. Blood and bone marrow studies in all 4 indicated that the neutropenia was: (i) the kinetic result of diminished neutrophil production; (ii) not alloimmune; (iii) not cyclic; and (iv) not associated with recognized inborn errors, bacterial or viral infections, or medications. All responded to rG-CSF by transiently increasing their blood neutrophils to normal, and the neutropenia resolved in all cases with time. It is likely that "idiopathic neutropenia" in this population represents a common phenotype of several different causes, rather than a single entity. Some cases, perhaps the majority, will respond to a short course of rG-CSF administration.

Effect of Recombinant Granulocyte Colony-Stimulating Factor on Blood Neutrophil Concentrations among Patients with “Idiopathic Neonatal Neutropenia”: A Randomized, Placebo-controlled Trial

“…This interpretation is consistent with the reduced, but not depleted, marrow reserve we previously reported among four patients with this condition. 1 We observed that rG-CSF administration for 3 consecutive days effectuated a rapid and substantial increase in blood neutrophil counts that persisted for at least 5 days, but did not persist to 12 or to 15 days. We observed no clear benefit to rG-CSF administration among the five recipients, compared with the five placebo recipients, other than on blood neutrophil counts.…”

“…All responded to a 3-day course of recombinant granulocyte colonystimulating factor (rG-CSF) (10 mg/kg/day) with an increase in blood neutrophil counts. 1 Our investigations suggested that this variety was the result of reduced neutrophil production, which was not cyclic, not alloimmune, and not associated with recognized inborn errors, bacterial or viral infections, or medications.…”

“…8,9,15 The role of rG-CSF is less clear among neonates who have severe but self-limited varieties of neutropenia, such as those with alloimmune neutropenia, [16][17][18] autoimmune neutropenia, 19,20 the neutropenia of neonates born to women with severe pregnancyinduced hypertension, 21,22 and ''idiopathic neonatal neutropenia''. 1,2 Many different definitions for neutropenia in neonates have been proposed, including those by Xanthou 23 (1500 ml À1 ), 23 Manroe et al 24 (1800 ml À1 ), and Mozinho et al 25 (1100 ml À1 ). When defined as a circulating neutrophil concentration of less than 1500 ml À1 , neutropenia is a relatively common condition in the NICU, affecting between 6 and 58% of preterm infants.…”

“…As neutropenia in preterm infants can be a sign of incipient severe illness, particularly sepsis, this variety of neutropenia in the neonatal intensive care unit (NICU) often causes concern, and sometimes prompts evaluations for infection and repeated or prolonged courses of antibiotics. 1,2 We previously reported four patients with this variety of neutropenia, all with blood neutrophil counts less than 500 ml À1 . All responded to a 3-day course of recombinant granulocyte colonystimulating factor (rG-CSF) (10 mg/kg/day) with an increase in blood neutrophil counts.…”

“…1,2 Neonates with this condition have several features in common, including the fact that no specific variety of neutropenia is diagnosed, it often appears late in the clinical course, can be quite prolonged, and generally occurs in otherwise well infants. 1,2 It is not clear whether this condition is a single entity or represents multiple disorders with the common feature of severe but self-limited neutropenia. As neutropenia in preterm infants can be a sign of incipient severe illness, particularly sepsis, this variety of neutropenia in the neonatal intensive care unit (NICU) often causes concern, and sometimes prompts evaluations for infection and repeated or prolonged courses of antibiotics.…”