Lymphocyte subpopulations in healthy 1-3-day-old infants.

The primary objective of this study was to establish reference ranges for the major (B, T, and natural killer; NK) and clinically relevant minor lymphocyte subsets in the peripheral blood of healthy 1-3-day-old infants and then to compare the results with those obtained in a group of healthy adults analyzed simultaneously. Forty-three infants aged 1-3 days and 38 healthy adults were recruited to the study to establish the median, 10th, and 90th percentiles of the proportions and absolute numbers of relevant lymphocyte subsets. The samples obtained from the healthy adults served as a flow cytometry process control in addition to providing a group comparator. The peripheral blood of the newborns (vs. adults) contained elevated proportions of total T cells (83% vs. 77%) and T helper cells (63% vs. 46%), with decreased proportions of T suppressor/cytotoxic cells (23% vs. 28%) and NK cells (4% vs. 10.5%). The newborns had a higher proportion (P < 0.0001) of immature B lymphocytes compared with those of adults (CD10+CD19+, 1.5% vs. 0% and CD20+CD5+, 13% vs. 6%), and the proportion of activated T cells was significantly lower (P < 0.0001; CD3+CD25+, 7.0% vs. 15%;CD3+HLA-DR+, 2.0% vs. 6% and CD8 and CD57, 0.0% vs. 8.0%). In contrast, the proportions of neonatal CD8 cells expressing CD28 (90.2% vs. 67.7%) and CD38 (96.6% vs. 70.9%) were significantly higher (P < 0.0001). The reference ranges for 1-3-day-old healthy newborns generated in this study provides a valuable tool for the assessment of immune abnormalities in very young infants.

Purpuric phototherapy-induced eruption in transfused neonates: relation to transient porphyrinemia.

OBJECTIVE: Blue light phototherapy is commonly administered to neonates as treatment of indirect hyperbilirubinemia, often in conjunction with blood transfusions to treat hemolytic anemia. We observed a distinctive cutaneous complication of phototherapy in six neonates with hyperbilirubinemia. METHODOLOGY: We studied the clinical and histologic characteristics of the eruption, as well as the porphyrin levels in affected neonates. Five of the patients had erythroblastosis fetalis; the other had profound anemia from twin-twin transfusion. All of the neonates developed purpuric patches at sites of maximal exposure to the phototherapy lights, with dramatic sparing at shielded sites within 24 hours after initiation of the phototherapy. On discontinuation of phototherapy, all eruptions cleared within 1 week. Examination of skin biopsy sections showed purpura without significant inflammation or keratinocyte necrosis. Plasma porphyrins (copro- and proto-) were elevated in the two patients in which they were assessed. CONCLUSIONS: The distribution of the eruption in areas exposed to light and presence of circulating porphyrins suggest that porphyrinemia may underlie the light-induced purpuric eruption. Additional studies will be required to determine definitively the mechanisms of both the purpuric phototherapy-induced eruption and the development of increased blood porphyrin levels in these transfused neonates.

Toxicology testing in neonates. Is it ethical, and what does it mean?

A positive toxicology screen in a newborn may provide some explanation for signs and symptoms affecting the newborn's problems in the NICU. But, simply stated, it does not prove cause; it does not prove child neglect; it does not prove inadequate parenting capabilities. The evidence of maternal illicit substance use may provide us with information that a variety of risk factors associated with drug use may be interacting that could interfere with the infant's long-term well-being. The objective of screening must be focused on medical and health care issues, not on political or legal issues, and never intended for punitive actions toward the mother. Resources should be available to provide the mother with educational information, treatment programs, psychosocial counseling, and household support systems to assist her in her role as principal caregiver to her infant. Follow-up care for the baby should be provided by physicians and clinics familiar with high-risk infants and include ongoing neurodevelopmental surveillance in specialized programs if available.

Recombinant human erythropoietin stimulates erythropoiesis and reduces erythrocyte transfusions in very low birth weight preterm infants.

DESIGN AND METHODS: We hypothesized that treatment with recombinant human erythropoietin (r-HuEPO) would stimulate erythropoiesis and would thereby reduce the need for erythrocyte transfusions in preterm infants. We treated 157 preterm infants born at 26.9 +/- 1.6 weeks of gestation who weighed 924 +/- 183 g at birth with either subcutaneous r-HuEPO (100 U/kg/d, 5 days per week) or placebo for 6 weeks in a randomized, double-blind, controlled clinical trial. All patients received oral iron and were managed according to uniform conservative transfusion guidelines. RESULTS: Treatment with r-HuEPO was associated with fewer erythrocyte transfusions (1.1 +/- 1.5 per infant in the r-HuEPO group versus 1.6 +/- 1.7 per infant in the placebo group; P = .046) and with a reduction in the volume of packed erythrocytes transfused (16.5 +/- 23.0 mL versus 23.9 +/- 25.7 mL per infant; P = .023). Overall, 43% of the infants in the r-HuEPO group and 31% of placebo-treated infants were transfusion-free during the study (P = .18). The volume of blood removed for laboratory tests and the need for respiratory support at the start of treatment had major effects on transfusion requirements independent of r-HuEPO. Reticulocyte counts were higher during treatment in the r-HuEPO group (P = .0001), and r-HuEPO-treated infants had higher hematocrit values at the end of the study (32% versus 27.3% in the placebo group; P = .0001). We found no differences in the incidence of major complications of prematurity between the treatment groups. CONCLUSION: We conclude that treatment with r-HuEPO at a weekly dose of 500 U/kg stimulates erythropoiesis, moderates the course of anemia, is associated with a reduction in erythrocyte transfusions, and appears safe in very low birth weight preterm infants who are receiving iron supplements. Conservative transfusion criteria, minimization of phlebotomy losses, and treatment with r-HuEPO are complementary strategies to reduce erythrocyte transfusions in these infants.

Absence of hyperinsulinemia in isoimmunized fetuses treated with intravascular transfusion.

We serially sampled blood from fetuses of five severely isoimmunized pregnancies at the time of each intrauterine intravascular transfusion and at birth. We were unable to demonstrate either an elevation in the plasma insulin/glucose ratio or a relationship between the insulin/glucose ratio and hemoglobin concentration at any time period. Plasma total glutathione concentration, however, decreased dramatically from the initial to the second transfusion (323 +/- 114 to 43 +/- 9 ng/ml; t = -5.06, p less than 0.01). We speculate that intrauterine transfusion may modify or prevent the previously reported fetal pancreatic beta-cell hyperplasia and hyperinsulinemia associated with isoimmunization by decreasing red blood cell hemolysis and thereby circulating glutathione.

Perinatal outcome following intravascular transfusion in severely isoimmunized fetuses.

Twenty-six severely isoimmunized pregnancies managed exclusively with ultrasonographically guided intravascular fetal transfusions are reported. The mean gestational age plus and minus one standard deviation (+/- SD) was 26.3 +/- 3.6 weeks and the mean hematocrit (+/- SD) prior to initial transfusion was 20.6 +/- 6.7%. Four of seven hydropic fetuses and 9 of 19 without hydrops were less than or equal to 26 weeks gestation at the first transfusion. Overall survival was 85% (22/26). Survival was similar whether or not fetal hydrops was present (6/7 vs. 16/19) and whether or not the first transfusion was administered at less than or equal to 26 weeks gestation (10/13 vs. 12/13).

Is intrauterine transfusion associated with diminished fetal growth?

Studies in animal models and human pregnancies suggest that severe fetal anemia and/or replacement of fetal with adult blood result in decreased pH, increased base deficit, and hyperlactacidemia. Similar changes have been noted in growth-retarded, nonanemic fetuses, and we therefore hypothesized that isoimmunized fetuses requiring intrauterine transfusions might have diminished growth. We longitudinally studied growth patterns in 17 isoimmunized fetuses by noting biparietal diameter and head and abdominal circumference measurements at each transfusion. The distributions of these measurements above and below the 25th, 50th, and 75th percentiles derived from our general obstetric population were compared at the initial transfusion and the last ultrasonogram performed before delivery. Birth weights also were noted and their distribution around the 25th, 50th, and 75th percentiles was compared to the expected distribution. For each ultrasonographic parameter, the distribution of measurements at the last ultrasonogram before delivery was not significantly different from the distribution at the initial ultrasonogram. The birth weight distribution also was not significantly different than the expected distribution. Thus we were unable to demonstrate slowing of fetal growth in our severely isoimmunized pregnancies.

Effects of intravascular, intrauterine transfusion on prenatal and postnatal hemolysis and erythropoiesis in severe fetal isoimmunization.

In an investigation of the effects of intrauterine, intravascular transfusions (IUT) on fetal and neonatal hemolysis and erythropoiesis, 12 fetuses who received IUT for treatment of severe isoimmunization had serial measurements of hemoglobin concentration, Kleihauer-Betke stains to detect fetal hemoglobin-containing erythrocytes, and determination of plasma erythropoietin (EPO) concentration before each IUT, at birth, and postnatally. Reticulocyte counts and sensitizing antibody titers were measured in five fetuses. Mean values before the first IUT, before the final IUT, and at birth were as follows: hemoglobin level, 6.1, 9.1, and 11.3 gm/dl; reticulocyte count, 22.7%, 0.5%, and 0.9%; fetal hemoglobin-containing erythrocytes, 100%, 1.6%, and 1.5%; and EPO level, 12, 56, and 756 mU/ml, respectively. Only one neonate required exchange transfusion. In the first month postnatally, all infants had a profound anemia. All but one infant required simple blood transfusions postnatally. Before the first postnatal transfusion, mean hemoglobin concentration was 6.2 gm/dl, mean reticulocyte count was 0.8%, mean erythropoietin concentration was 23 mU/ml, and the sensitizing antibody titer remained markedly elevated. Except for the surge of EPO at birth, EPO levels did not rise prenatally or postnatally unless marked anemia (hemoglobin level less than 5 gm/dl) occurred. These observations suggest that the intrauterine and postnatal anemia in fetuses who receive IUTs may be explained both by hemolysis of newly formed erythrocytes by circulating antibody, which typically persisted for more than a month after birth, and by suppressed erythropoiesis.

The changing spectrum of neonatal endocarditis.

This article reviews both infective and noninfective endocarditis in neonates, contrasting historical observations with recent descriptions of this disease. Pathogenesis, etiologic agents, diagnostic tests, and treatment all are discussed in addition to complications and prognosis of endocarditis in newborns, which appears to be increasing in frequency.

Rifampin and penicillin for the elimination of group B streptococci in nasally colonized infant rats.

Although multiple antibiotic strategies to eradicate group B streptococci (GBS) from colonized infants and women have been utilized, no regimen has been successful in eliminating GBS carriage reliably. Because rifampin has been successful in terminating nasopharyngeal colonization with other bacteria, we tested both the in vitro sensitivity of GBS to rifampin and the in vivo efficacy of rifampin in eliminating GBS from a new animal model of nasally colonized infant rats. The minimal inhibitory concentration of rifampin for 18 clinically derived strains of type III GBS ranged from 0.1 to 0.4 micrograms/ml. Atraumatic nasal inoculation of infant rats with 10(6)-10(7) colony forming units of GBS twice daily for 4 days resulted in heavy asymptomatic carriage for at least 10 days. Colonized animals were divided into four treatment groups: saline, oral rifampin, intraperitoneal penicillin, or oral rifampin plus intraperitoneal penicillin. Treatment was administered every 12 h for 4 days. All 78 saline-treated controls and 47 of 52 (90.4%) penicillin-treated animals had continued GBS carriage 36 h after completion of therapy. In contrast, only 18 of 52 (34.6%) rifampin-treated animals and seven of 54 (13.0%) rifampin plus penicillin-treated animals remained GBS-positive. No rifampin-resistant GBS were detected. Combination rifampin plus penicillin therapy was significantly more effective in terminating GBS carriage compared to saline or penicillin alone (p less than 0.0001) or to rifampin (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)