Darlene A. Calhoun

Immune-mediated neutropenia in the neonate

Alloimmune neonatal neutropenia, neonatal autoimmune neutropenia and autoimmune neutropenia of infancy have remained nebulous entities with difficulties in both clinical and laboratory identification. These disorders are reviewed in this article.

Effect of beginning recombinant erythropoietin treatment within the first week of life, among very-low-birth-weight neonates, on "early" and "late" erythrocyte transfusions: a meta-analysis

OBJECTIVES: Erythrocyte transfusions to neonates can be categorized as “early” if given during the first 3 weeks of life and “late” if given thereafter. We used a meta-analysis to determine whether recombinant erythropoietin (rEpo) administration to very-low-birth-weight (VLBW, <1500 g) neonates, beginning in the first week of life, reduces either “early” or “late” transfusions.STUDY DESIGN AND METHODS: Studies that used a randomized, placebo-controlled, double-masked design were deemed acceptable. We identified 12 acceptable, relevant, clinical trials. Additional data not provided in the publications were obtained from two of the authors.RESULTS: The acceptable studies involved an aggregate of 561 rEpo and 529 placebo recipients. If rEpo was begun in the first week of life, the summary odds ratio (OR) for receiving any transfusion (“early” or “late”) was 0.52, 95% confidence interval (CI): 0.34 to 0.79 (p=0.001). The OR for receiving an “early” transfusion was 0.54 (95% CI: 0.25 to 1.15; p=0.055), and the OR for receiving a “late” transfusion was 0.56 (95% CI: 0.37 to 0.83; p=0.036). Heterogeneity among studies was too great to estimate the effect of rEpo on the number of transfusions received or the volume of blood transfused (p<0.001 for the Q-test statistic). Subgroup analysis suggested that when rEpo is begun in the first week of life, neonates 1000 to 1500 g and >29 weeks are more likely to completely avoid transfusion than are extremely low-birth-weight (ELBW, <1000 g) neonates. No dose–response relationship was apparent between rEpo dose or iron dose and transfusion. No difference was apparent depending on whether the rEpo was given subcutaneously vs intravenously.CONCLUSION: If rEpo is begun in the first week of life, a moderate reduction can be expected (p=0.001) in the proportion of VLBW neonates transfused. Reduction is less significant in “early” transfusion (p=0.055) than in “late” transfusion (p=0.036). Such treatment is not likely to eliminate transfusions among ELBW neonates completely.

Enteral Administration of a Simulated Amniotic Fluid to Very Low Birth Weight Neonates

OBJECTIVE:To reduce feeding intolerance among very low birth weight neonates.STUDY DESIGN:A total of 10 neonates with birth weights of 750 to 1250 g were given oral-gastric boluses (2.5 ml/kg every 3 hours) of a solution patterned after amniotic fluid. When milk feedings were begun the milk was mixed with the test solution. The solution was given at a constant daily dose of 20 ml/kg/day while the volumes of milk feedings were gradually increased. When milk feedings reached 80 ml/kg/day the test solution was discontinued. A comparison group consisted of neonates who met study criteria but were cared for during the period immediately preceding the study. The outcome was the number of calories taken enterally over the first 21 days of life.RESULTS:The test solution was begun an average of 27 hours after birth (range, 4 to 45). In the test group the first milk feedings were introduced 74 hours after birth (range, 18 to 144), which was similar to the time milk was introduced in the comparison subjects (79 hours; range, 18 to 168). After milk feedings were started, the test patients had a total of four NPO days (0.4 NPO days per patient) during their first 21 days, while the comparison group had 34 NPO days (3.4 NPO days per patient). During the first 14 days of life the test solution recipients had a median of 26.5 enteral cal/kg/day (range, 4.3 to 68.9), while the comparison neonates had 8.5 (range, 0.2 to 25; p<0.05). During the first 21 days of life the test solution recipients had a median of 56.9 enteral cal/kg/day (range, 11.5 to 89.4), while the comparison neonates had 19.2 (range, 0.9 to 52.8; p<0.05).CONCLUSION:In all, 10 VLBW infants tolerated the test solution for periods up to 14 days with no significant adverse effects. A randomized trial to determine whether this solution reduces feeding intolerance among VLBW neonates should be conducted.

Abnormal Intestinal Histology in Neonates with Congenital Anomalies of the Gastrointestinal Tract

In animal models, when swallowing is experimentally prevented in utero, bowel length and weight are reduced, and villus height, crypt depth, and villus function are retarded. Little is known about the intestinal histology in infants with gastrointestinal (GI) tract anomalies. We examined the histological architecture of the intestine in neonates with GI anomalies in comparison to that of normal fetuses. Villus height, area, and length and crypt depth of normal fetuses were quantified in the proximal small bowel (n = 11) and measurements compared to those of surgical specimens of neonates with congenital anomalies of the GI tract (n = 16). Villus height and area and lamina propria height and area increased linearly from 8 to 24 weeks of gestation. In infants with anomalies of the GI tract, the villi were blunted and lacked normal histological architecture, the crypts were disorganized, and the crypt depth was significantly decreased (p = 0.004). Enterocyte height and area were significantly greater in neonates with congenital anomalies of the GI tract. The intestinal histology in neonates with congenital anomalies of the GI tract differs significantly from that of normal fetuses.

A neonate with severe thrombocytopenia and radio-ulnar synostosis.

Bone marrow failure syndromes can be associated with abnormalities of the forearms. We observed a neonate with congenital thrombocytopenia who had bilateral radio-ulnar synostosis and fifth finger clinodactly. We performed an evaluation of the mechanism causing the thrombocytopenia using a combination of direct and indirect measures of thrombopoiesis. These tests indicated decreased platelet production. This entity of congenital hyporegenerative thrombocytopenia with bilateral radio-ulnar synostosis and fifth-finger clinodactly is an uncommon but easily recognizable form of congenital amegakaryocytic thrombocytopenia (CAMT). This entity can be distinguished from the TAR syndrome (thrombocytopenia and absent radii) by the distinctive orthopedic issues, different underlying genetic mutations, and a more worrisome prognosis for CAMT than for TAR.

Effect of administering recombinant erythropoietin to women with postpartum anemia: a meta-analysis.

OBJECTIVES: Recombinant erythropoietin (rEpo) has been administered to women with postpartum anemia in an attempt to accelerate their increase in hemoglobin concentration and reduce postpartum transfusions. However, it is not clear whether such an approach can be supported by evidence and should be generally recommended.STUDY DESIGN AND METHODS: Medical and scientific literature from January 1990 to December 2002 was searched and studies that reported the administration of rEpo to women with postpartum anemia were evaluated.RESULTS: Eight evaluated studies reported an aggregate of 480 women; 300 rEpo recipients and 180 controls. Significant diversity in design was observed in rEpo dose, route of rEpo administration, iron supplementation, and baseline hemoglobin. No significant safety concerns were reported. In all five studies where it was reported, 4 to 7 days after beginning treatment, greater increases in hemoglobin concentration were observed among the rEpo recipients than among the controls. However, heterogeneity of results (Q-test statistic, p<0.01) indicated that it was not appropriate to apply summary statistics. The effect of rEpo on postpartum transfusion rate was not measurable by summary statistics because of the limited number of transfusions given (no transfusions among the 300 rEpo recipients vs two transfusions among the 180 controls).CONCLUSION: Administration of rEpo to women with postpartum anemia appears to be safe, and is associated with a trend toward a faster increase in hemoglobin concentration. However, its efficacy in terms of diminishing postpartum transfusions is unproven.

Benign B-Cell Precursors (Hematogones) Are the Predominant Lymphoid Population in the Bone Marrow of Preterm Infants

Bone marrow (BM) findings in 3rd-trimester stillborns and full-term living neonates have been previously described. However, there is no information regarding BM composition in living preterm infants. Specifically, it is unknown whether the BM lymphocytosis seen in full-term infants at 1–4 weeks of age also occurs in preterm infants. Furthermore, the lineage of these cells has never been investigated. We used a panel of immunohistochemical stains to characterize the BM composition in 11 neonates (8 living and 3 deceased). Unlike in the other age groups, immature B cells (hematogones) were the most common lymphoid population, accounting for 10–60% (mean 34%) of all cells. In two additional cases (both living patients), flow cytometry revealed a level of 3.8% of immature B cells in a <1-week-old neonate and 25.7% in a 19-week-old infant. Immature B cells were not identified in 6 peripheral blood samples from preterm neonates. These findings are pertinent for the interpretation of BM and peripheral blood samples in this age group as survival improves and diagnostic samples become more common.

CIRCULATING CXC-CHEMOKINE CONCENTRATIONS IN A MURINE INTESTINAL ISCHEMIA-REPERFUSION MODEL

Background: CXC-chemokines bearing the glutamic acid-leucine-arginine (ELR) motif (ELR+CXC chemokines) are potent neutrophil chemoattractants and hence may play a role in mucosal injury seen with intestinal ischemia-reperfusion (I/R). Methods: Serum concentrations of ELR+ CXC chemokines (keratinocyte-derived chemokine(KC)/CXC ligand (CXCL) 1, macrophage inflammatory protein (MIP)-2/CXCL 2/3, lipopolysaccharide-induced CXC chemokine (LIX)/CXCL5, and lungkine/CXCL15) were measured in a murine intestinal I/R model. Fifteen 4-week-old wild-type mice were studied in three subgroups: sham, ischemia (superior mesenteric artery [SMA] clamping for 60 min) and ischemia-reperfusion (SMA clamping for 60 min followed by reperfusion for 90 min). Results: Concentrations of KC/CXCL1 and MIP-2/CXCL2/3 in sham-treated animals (145 ± 123 and 107 ± 55 pg/mL, respectively) and the ischemia subgroup (646 ± 413 and 226 ± 129 pg/mL) were similar, but concentrations were significantly higher with reperfusion (6398 ± 2297, p < .001 and 874 ± 790 pg/mL, p = .04). LIX/CXCL5 and lungkine/CXCL15 concentrations did not change significantly with ischemia or following I/R. KC/CXCL1 and MIP-2/CXCL2/3 concentrations correlated positively with the severity of mucosal injury and with each other, whereas a negative relationship was observed between LIX/CXCL5 concentrations and microscopic injury scores. Conclusions: Development of mucosal injury in intestinal I/R is associated with increased serum concentrations of KC/CXCL1 and MIP-2/CXCL2/3, but not with those of LIX/CXCL5 and lungkine/CXCL15.

Persistent perianal abscess in early infancy as a presentation of autoimmune neutropenia

Autoimmune neutropenia of infancy is a primary, usually self-limiting, antineutrophil autoimmune phenomenon seen in infancy and early childhood. These infants are at a higher risk of infection, and early detection, particularly with the availability of newer therapeutic options such as hematopoietic growth factors, can allow close follow-up and, if needed, treatment. We report two infants with autoimmune neutropenia who presented with a persistent perianal abscess, which has not been documented previously in this population.

Tolerance of an Enterally Administered Simulated Amniotic Fluid-Like Solution by Neonates Recovering from Surgery for Congenital Bowel Abnormalities

OBJECTIVE: We report a single-centered, Phase I pilot trial, testing the enteral administration of an experimental amniotic fluid-like solution to 10 neonates who were otherwise “NPO” following surgery for congenital bowel abnormalities. The overall hypothesis was that the trophic effect of the solution on intestinal villi would facilitate advancement to full enteral feedings. The specific hypothesis tested in this pilot trial was that the solution would be tolerated.STUDY DESIGN: Ten neonates who were NPO following surgery for congenital bowel abnormalities, were studied before any “trophic” feedings were begun. Each received an experimental, sterile, isotonic, amniotic fluid-like solution at a dose of 20 ml/kg/day enterally. When milk feedings were begun they were mixed with the experimental solution. Increases in the volume of milk feedings occurred at the discretion of the neonatologist and surgeon, and the experimental solution was discontinued any time the neonatologist or surgeon felt it was not tolerated, or when 100 ml of milk feedings/kg/day was achieved. We quantified the amount and character of emesis, stools, and gastric residuals, measured abdominal girth and blood pressure, looked for skin rashes, and sought any signs of intolerance or adverse events. We recorded the days to achieve milk feedings of 20, 50, 100, and 120 ml/kg/day and length of hospital stay.RESULTS: The experimental solution was begun 4 to 32 days after surgery, invariably prior to the institution of “trophic” milk feedings. All subjects completed the doses with no evidence of intolerance. All achieved 100 ml/kg of milk feedings 14 days, or fewer, following institution of the experimental solution (mean 11.1 days, range, 3 to 14). All lived and were discharged home 20.2 days (range, 8 to 42) after the experimental solution was begun.CONCLUSIONS: In this pilot trial involving 10 neonates who had surgery for congenital bowel abnormalities, the enteral administration of a sterile, isotonic, amniotic fluid-like solution was tolerated.