Late-onset neutropenia in very low birth weight infants

Background. Neutropenia, defined as absolute neutrophil count (ANC) <1500/mm(3), affects 6% to 58% of premature infants in the first week of life. This early-onset neutropenia in premature infants has previously been correlated with sepsis, maternal hypertension, severe asphyxia, and periventricular hemorrhage. Late-onset neutropenia, defined as ANC <1500/mm(3) at a postnatal age of greater than or equal to 3 weeks, has not been previously reported. Objectives. The purposes of this study were to determine the prevalence of late-onset neutropenia in very low birth weight (VLBW) infants and to examine the factors that may be associated with this phenomenon. Methods. A weekly complete blood cell count (CBC) was performed routinely in all premature infants with birth weight less than or equal to 1500 g (n = 225) admitted to the neonatal intensive care in a 3-year period who survived until discharge. CBC and differentials were recorded at day 1, day 3, and then weekly until discharge. The clinical data of the study infants were collected by reviewing the medical records retrospectively. Results. Late-onset neutropenia was detected in 51 infants (22%). In both neutropenic (n = 51) and nonneutropenic infants (n = 174), ANC increased postnatally, remained above 5000/mm(3) for the first 3 weeks of life, and had a marked decrease at similar to 4 weeks of age. Thereafter, ANC decreased to a level of similar to 1400/mm(3) in the neutropenic infants and 4000/mm(3) in the nonneutropenic infants. The neutropenic infants had a significantly lower nadir ANC, lower hemoglobin, and higher reticulocyte count than did the nonneutropenic infants with similar platelet counts. None of the study infants received erythropoietin during their hospitalization. This late-onset neutropenia occurred at postnatal age of 6 +/- 2 weeks (range: 3-10 weeks). The duration of neutropenia was 1.7 +/- .7 weeks (range: 1-3 weeks). All of the neutropenic infants had anemia of prematurity with high reticulocyte count and normal platelet count. The neutropenic infants were stable, growing on full oral feedings, and had no signs or symptoms of sepsis. No adverse effects of late-onset neutropenia were apparent in these infants. Conclusion. Late-onset neutropenia is a common incidental finding in stable, growing VLBW infants that has not been previously reported. Late-onset neutropenia is a phenomenon that occurs in anemic premature infants who have marked reticulocytosis. Normal regulation of hematopoiesis is accompanied by a balance between colony-stimulating factors, such as erythropoietin and granulocyte colony-stimulating factor, which regulate erythropoiesis and granulopoiesis. We speculate that imbalance of these factors with increased reticulocytopoiesis in response to anemia of prematurity may explain this phenomenon. We recommend avoiding institution of aggressive, potentially harmful therapy for this phenomenon in healthy, growing VLBW infants.