{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T01:19:09Z","timestamp":1772759949834,"version":"3.50.1"},"reference-count":46,"publisher":"American Academy of Pediatrics (AAP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,7,1]]},"abstract":"<jats:p>Objectives.\u2003To determine whether adjunctive therapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF) could reverse sepsis-associated neonatal neutropenia and improve neonatal survival compared with conventional therapy in a phase I\/II-type trial.<\/jats:p><jats:p>Study Design.\u2003An intravenous infusion of rhG-CSF (10 \u03bcg\/kg\/d \u00d7 3 d) was administered to 14 septic neutropenic neonates. Neutrophilic responses and outcome of these neonates were compared with 11 concurrently treated, retrospectively selected, case-matched control septic patients identified by using a search of medical records coded for sepsis with neutropenia (\u226524 hours).<\/jats:p><jats:p>Results.\u2003Seven neonates with early-onset sepsis with neutropenia at birth and seven neonates with late-onset sepsis plus neutropenia (all with necrotizing enterocolitis) were entered in the rhG-CSF treatment group. Results were compared with a conventional therapy control group (five early onset, six late onset). No significant differences existed in the birth weight, gestational age, use of antibiotic therapy, magnitude of respiratory support, severity of metabolic acidosis, use of vasopressors, or other supportive therapy between the two groups. In the rhG-CSF-treated group and in the conventionally treated control group, the absolute neutrophil count (ANC) (mean \u00b1 SEM) was 585 \u00b1 138 and 438 \u00b1 152, respectively. The ANC increased to more than baseline in the rhG-CSF-treated group by 10-fold versus 2-fold at 24 hours, 18-fold versus 4-fold at 48 hours, 24-fold versus 5-fold at 72 hours (significant by one-way analysis of variance in the rhG-CSF group only), and 29-fold versus 16-fold at 7 to 10 days when compared with the conventional therapy group. There were no nonresponders in the rhG-CSF group by 24 hours after the first dose of study drug. Monocyte cell counts also increased significantly in both groups by 7 days after entry into this protocol but remained within normal range for age. No clinically significant effect on lymphocytes, erythrocytes, or platelet counts was noted. Thirteen patients in the rhG-CSF-treated group (92%; 13 out of 14) and five in the conventionally treated group (55%; 5 out of 11) survived to 28 days after the onset of the signs of sepsis. No adverse effects were noted in the rhG-CSF-treated group.<\/jats:p><jats:p>Conclusions.\u2003rhG-CSF can increase the neutrophil count in critically ill septic neutropenic neonates. This finding suggests that rhG-CSF may be effective in a therapeutically useful time frame to treat septic neonates with neonatal neutropenia attributable to bone marrow suppression or neutrophil consumption. Future randomized trials are needed to validate the beneficial effects of rhG-CSF and to determine whether any significant side effects of therapy exist.<\/jats:p>","DOI":"10.1542\/peds.100.1.e6","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T23:40:17Z","timestamp":1092440417000},"page":"e6-e6","source":"Crossref","is-referenced-by-count":49,"title":["Human Granulocyte Colony-stimulating Factor May Improve Outcome Attributable to Neonatal Sepsis Complicated by Neutropenia"],"prefix":"10.1542","volume":"100","author":[{"given":"Prabhakar","family":"Kocherlakota","sequence":"first","affiliation":[{"name":"From the Departments of Pediatrics and Neurobiology, State University of New York at Stony Brook, Stony Brook, New York."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edmund F. La","family":"Gamma","sequence":"additional","affiliation":[{"name":"From the Departments of Pediatrics and Neurobiology, State University of New York at Stony Brook, Stony Brook, New York."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"417","published-online":{"date-parts":[[1997,7,1]]},"reference":[{"key":"2021121015123755900_B1","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1056\/NEJM198103123041105","article-title":"Sepsis neonatorum.","volume":"304","author":"Siegel","year":"1981","journal-title":"N Engl J Med"},{"key":"2021121015123755900_B2","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1001\/archpedi.1983.02140350016005","article-title":"Neonatal infections. An important determinant of late NICU mortality in infants less than 1000 g at birth.","volume":"137","author":"La Gamma EF, Drusin LM, Mackles AW, Machalek S, Auld PAM","year":"1983","journal-title":"Am J Dis Child"},{"key":"2021121015123755900_B3","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/S0022-3476(96)70192-0","article-title":"Early-onset sepsis in very low birth weight neonates: A report from the National Institute of Child Health and Human Development Neonatal Research Network.","volume":"129","author":"Stoll","year":"1996","journal-title":"J Pediatr"},{"key":"2021121015123755900_B4","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0022-3476(96)70191-9","article-title":"Late-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network.","volume":"129","author":"Stoll","year":"1996","journal-title":"J Pediatr"},{"key":"2021121015123755900_B5","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/0002-9378(87)90294-8","article-title":"Congenital and nosocomial sepsis in infants born in a regional perinatal unit: cause, outcome, and white blood cell response.","volume":"156","author":"Ohlsson","year":"1987","journal-title":"Am J Obstet Gynecol"},{"key":"2021121015123755900_B6","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1097\/00006454-199412000-00008","article-title":"Bloodstream infections in neonatal intensive care unit patients: results of a multicenter study.","volume":"13","author":"Beck-Sague","year":"1994","journal-title":"Pediatr Infect Dis J"},{"key":"2021121015123755900_B7","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1093\/infdis\/162.3.672","article-title":"Population-based risk factors for neonatal group B streptococcal disease. 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(Review).","volume":"172","author":"Dale","year":"1995","journal-title":"J Infect Dis"},{"key":"2021121015123755900_B23","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1203\/00006450-199402000-00007","article-title":"Granulocyte and granulocyte-macrophage colony-stimulating factors in cord and maternal serum at delivery.","volume":"35","author":"Bailie","year":"1994","journal-title":"Pediatr Res"},{"key":"2021121015123755900_B24","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1203\/00006450-199206000-00007","article-title":"Decreased production of G-CSF and gene expression from mononuclear cells of newborn infants.","volume":"31","author":"Cairo","year":"1992","journal-title":"Pediatr Res"},{"key":"2021121015123755900_B25","first-page":"808","article-title":"Neutropenia in an extremely premature infant treated with recombinant human granulocyte colony-stimulating factor.","volume":"145","author":"Roberts","year":"1991","journal-title":"Am J Dis Child"},{"key":"2021121015123755900_B26","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1001\/archpedi.1994.02170070102021","article-title":"Using granulocyte colony-stimulating factor for neutropenia during neonatal sepsis.","volume":"148","author":"Murray","year":"1994","journal-title":"Arch Pediatr Adolesc Med"},{"key":"2021121015123755900_B27","doi-asserted-by":"crossref","first-page":"F53","DOI":"10.1136\/fn.72.1.F53","article-title":"Granulocyte colony stimulating factor treatment for neonatal neutropenia.","volume":"72","author":"Bedford-Russel","year":"1995","journal-title":"Arch Dis Child"},{"key":"2021121015123755900_B28","doi-asserted-by":"crossref","first-page":"291A","DOI":"10.1203\/00006450-199604001-01754","article-title":"G-CSF administration to neonates with early onset sepsis and neutropenia: a randomized, placebo-controlled trial.","volume":"39","author":"Schibler","year":"1996","journal-title":"Pediatr Res"},{"key":"2021121015123755900_B29","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0022-3476(95)70469-8","article-title":"Effect of granulocyte colony-stimulating factor on preeclampsia-associated neonatal neutropenia.","volume":"126","author":"La Gamma EF, Alpan O, Kocherlakota P","year":"1995","journal-title":"J Pediatr"},{"key":"2021121015123755900_B30","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/S0022-3476(95)70468-X","article-title":"Administration of granulocyte colony-stimulating factor to neutropenic low birth weight infants of mothers with preeclampsia.","volume":"126","author":"Makhlouf","year":"1995","journal-title":"J Pediatr"},{"key":"2021121015123755900_B31","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0022-3476(79)80096-7","article-title":"The neonatal blood count in health and disease. 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Reference values for neutrophilic cells.","volume":"95","author":"Manroe","year":"1979","journal-title":"J Pediatr"},{"key":"2021121015123755900_B32"},{"key":"2021121015123755900_B33","first-page":"33","article-title":"Change in the pattern of neonatal septicemia and meningitis.","volume":"122","author":"McCracken","year":"1966","journal-title":"Am J Dis Child"},{"key":"2021121015123755900_B34","first-page":"470","article-title":"Determinants of blood pressure in infants admitted to neonatal intensive care units: a prospective multicenter study.","volume":"15","author":"Zubrow","year":"1995","journal-title":"J Perinatol"},{"key":"2021121015123755900_B35","first-page":"271","article-title":"Feeding practices for infants weighing less than 1500 g at birth and pathogenesis of necrotizing enterocolitis.","volume":"21","author":"La Gamma EF, Brown LE","year":"1995","journal-title":"Clin Perinatol"},{"key":"2021121015123755900_B36","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/S0022-3476(85)80681-8","article-title":"Neonatal blood cell counts in health and disease. 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Values for lymphocytes, monocytes and eosinophils.","volume":"106","author":"Weinberg","year":"1985","journal-title":"J Pediatr"},{"key":"2021121015123755900_B37","first-page":"A535","article-title":"Filgrastim in the treatment of hospitalized patients with community acquired pneumonia (CAP).","volume":"153","author":"Nelson","year":"1996","journal-title":"Am J Respir Crit Care Med"},{"key":"2021121015123755900_B38","first-page":"A123","article-title":"Clinical response to filgarism in pneumonia with severe sepsis.","volume":"153","author":"Wunderink","year":"1996","journal-title":"Am J Respir Crit Care Med"},{"key":"2021121015123755900_B39","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1182\/blood.V84.5.1427.1427","article-title":"A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia.","volume":"84","author":"Gillan","year":"1994","journal-title":"Blood"},{"key":"2021121015123755900_B40","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/S0749-0704(18)30063-0","article-title":"Nutritional management and multisystem organ failure\/systemic inflammatory response in critically ill preterm neonates.","volume":"11(3)","author":"Adan","year":"1995","journal-title":"Crit Care Clin"},{"key":"2021121015123755900_B41","first-page":"F1","article-title":"Effect of increased red cell mass on subclinical tissue acidosis in hyaline membrane disease.","volume":"75","author":"La Gamma EF, Krauss A, Auld PAM","year":"1996","journal-title":"Arch Dis Child"},{"key":"2021121015123755900_B42","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1203\/00006450-199006000-00016","article-title":"Prophylactic or simultaneous administration of recombinant human granulocyte colony stimulating factor in the treatment of group B streptococcal sepsis in neonatal rats.","volume":"27","author":"Cairo","year":"1990","journal-title":"Pediatr Res"},{"key":"2021121015123755900_B43","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1182\/blood.V86.4.1301.bloodjournal8641301","article-title":"Granulocyte colony-stimulating factor versus placebo in addition to penicillin G in a randomized blinded study of gram-negative pneumonia sepsis. Analysis of survival and multisystem organ failure.","volume":"86","author":"Smith","year":"1995","journal-title":"Blood"},{"key":"2021121015123755900_B44","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1002\/bjs.1800780607","article-title":"Pathophysiology of ischaemia reperfusion injury: central role of the neutrophil.","volume":"78","author":"Welbourn","year":"1991","journal-title":"Br J Surg"},{"key":"2021121015123755900_B45","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0022-3476(96)70443-2","article-title":"A two year follow up of neonates with presumed sepsis treated with recombinant human granulocyte colony stimulating factor during the first week of life.","volume":"128","author":"Rosenthal","year":"1996","journal-title":"J Pediatr"},{"key":"2021121015123755900_B46","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1097\/00007890-199506000-00009","article-title":"The use of granulocyte colony stimulating factor after liver transplantation.","volume":"59","author":"Foster","year":"1995","journal-title":"Transplantation"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/100\/1\/e6\/890168\/e6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/100\/1\/e6\/890168\/e6.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T07:33:03Z","timestamp":1734507183000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/100\/1\/e6\/38818\/Human-Granulocyte-Colony-stimulating-Factor-May"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,7,1]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[1997,7,1]]},"published-print":{"date-parts":[[1997,7,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.100.1.e6","relation":{},"ISSN":["1098-4275","0031-4005"],"issn-type":[{"value":"1098-4275","type":"electronic"},{"value":"0031-4005","type":"print"}],"subject":[],"published":{"date-parts":[[1997,7,1]]}}}