Newborn Human Infants Research Articles

Transamination of Leucine and Nitrogen Accretion in Human Pregnancy and the Newborn Infant1–3

Kinetics of leucine and its oxidation were determined in human pregnancy and in the newborn infant, using stable isotopic tracers, to quantify the dynamic aspects of protein metabolism. These data show that in human pregnancy there is a decrease in whole-body rate of leucine turnover compared with nonpregnant women. In addition, data in newborn infants show that leucine turnover expressed as per kg body weight is higher compared with adults. The administering of nutrients resulted in a suppression of the whole-body rate of proteolysis. Because nonessential amino nitrogen is an important component of nutritional nitrogen and can be limiting for growth under certain circumstances, and because BCAA are an important source of nonessential amino nitrogen, we have examined the relations among the transamination of leucine, leucine N kinetics, and urea synthesis and glutamine kinetics in human pregnancy and newborn infants. In human pregnancy, early in gestation, there is a significant decrease in urea synthesis in association with a decrease in the rate of transamination of leucine. A linear correlation was evident between the rate of leucine reamination and urea synthesis during fasting in pregnant and nonpregnant women. In healthy-term newborn and growing infants, although the reamination of leucine was positively related to glutamine flux, leucine reamination was negatively related to urea synthesis, suggesting a redirection of amino N toward protein accretion. The regulatory mechanism involved in this redirection of nitrogen from irreversible loss to accretion remains under investigation.

Blood pressure responses to feeding in infancy: Spin‐offs of serendipity

This article summarizes results from a program of research that has focused on understanding the characteristics of, and factors that shape, acute cardiovascular responses to feeding in infants. The work developed from behavioral observations in rats suggesting a linkage between variations in maternal behavior and adult blood pressure. However, the hypothesis that specific types of interactions, in particular those associated with feeding, might alter cardiovascular function was greatly influenced by a serendipitous observation made by Myron Hofer several years earlier. Myron discovered that nutrient availability is a key regulator of cardiovascular function in newborn rats. Our spin-off studies established that, in newborn rats and human infants, ingestion of nutrient is associated with robust increases in heart rate and blood pressure.

Complement component 9 activation, consumption, and neuronal deposition in the post-hypoxic–ischemic central nervous system of human newborn infants

The role of complement in neonatal hypoxic–ischemic brain injury is not known. Therefore, cerebral spinal fluid (CSF) and post-mortem cerebral tissue were analyzed to determine whether complement is activated and complement component 9 (C9) is deposited on neurons in the central nervous systems (CNS) of newborn infants who developed moderate to severe hypoxic–ischemic encephalopathy (HIE). Control CSF samples were obtained during routine evaluation for possible sepsis from infants who were not depressed at birth. In ELISA assays of CSF obtained from 16 infants with HIE, compared to CSF from 7 control infants, the mean concentration of terminal complement complexes was elevated and the mean C9 concentration was diminished. Immunofluorescence microscopy of post-mortem frozen brain tissue obtained from two infants who expired at 4–5 days of life after severe HIE revealed that activated C9 was deposited on cells in all lobes. Double label immunofluorescence microscopy demonstrated that nearly all of the C9-positive cells were neurons and essentially all of the neurons were C9-positive. Immunoperoxidase immunohistochemistry of formalin-fixed tissue also confirmed the presence of many C9-positive cells, particularly in the hippocampus. The C9-positive cells usually manifested morphology consistent with neurons, most of which contained fragmented nuclei. In summary, complement was activated in the CNS of newborn infants who developed moderate to severe HIE. C9 was deposited on neurons, including morphologically apoptotic neurons. Further investigations into a possible role of complement in the pathogenesis of neonatal hypoxic–ischemic cerebral injury are warranted.

Extracellular virulence factors of group B Streptococci

Group B Streptococcus (GBS) is the leading cause of severe bacterial infections in human newborn infants. Advances in streptococcal molecular genetics and refinement of in vitro and in vivo model systems of GBS disease have led to the discovery and characterization of several extracellular virulence factors elaborated by this pathogen. This review summarizes our current understanding of GBS extracellular virulence factors including the beta-hemolysin/cytolysin, C5a-peptidase, hyaluronate lyase, CAMP factor, oligopeptidase, and carbohydrate exotoxin CM101. The molecular basis and potential pathogenic role(s) of each factor are considered in the context of neonatal infection.

Effect of dexamethasone on pulmonary and renal angiotensin-converting enzyme concentration in fetal sheep during late gestation

Objectives The effect of dexamethasone on tissue angiotensin-converting enzyme (ACE) was investigated in fetal sheep. Study design Pulmonary and renal ACE concentrations were measured in 16 sheep fetuses at between 127 and 131 days of gestation (term 145±2 days): 6 were untreated, whereas 10 were chronically catheterized and infused intravenously with either saline solution (0.9%, n = 4) or dexamethasone (45-60 μg · kg −1 · d −1, n = 6) for the previous 2 days. The dexamethasone dose increased plasma dexamethasone to around one fifth of that measured in newborn human infants delivered after maternal dexamethasone treatment. Results Over the period of infusion, arterial blood pressure increased significantly in the dexamethasone (+6.8±1.5 mm Hg, P<.05) but not saline-treated fetuses (+1.6±0.6 mm Hg). At delivery, pulmonary ACE in the dexamethasone-infused fetuses (1.24±0.26 nmoles hippurate · min −1 · mg protein −1) was significantly greater than in the control fetuses (0.50±0.07 nmoles · min −1 · mg protein −1, P<.005); renal ACE was unchanged by dexamethasone treatment. Overall, pulmonary ACE and blood pressure were correlated on the last day of infusion ( r = 0.70, P<.05). Conclusion The rise in pulmonary ACE seen in dexamethasone-treated sheep fetuses may contribute, in part, to the glucocorticoid-induced increase in blood pressure.

What imitation tells us about social cognition: a rapprochement between developmental psychology and cognitive neuroscience

Both developmental and neurophysiological research suggest a common coding between perceived and generated actions. This shared representational network is innately wired in humans. We review psychological evidence concerning the imitative behaviour of newborn human infants. We suggest that the mechanisms involved in infant imitation provide the foundation for understanding that others are 'like me' and underlie the development of theory of mind and empathy for others. We also analyse functional neuroimaging studies that explore the neurophysiological substrate of imitation in adults. We marshal evidence that imitation recruits not only shared neural representations between the self and the other but also cortical regions in the parietal cortex that are crucial for distinguishing between the perspective of self and other. Imitation is doubly revealing: it is used by infants to learn about adults, and by scientists to understand the organization and functioning of the brain.

SCD31/sPECAM-1 levels in breast milk and sera of mother-infant pairs in the early postpartum period.

Immunomediators seem to have a central role in the immune system of both human milk and newborn infants. CD31/PECAM-1 is an adhesion molecule, member of Ig gene superfamily, mediating cell-cell adhesion in both homophilic and heterophilic ways. Levels of the soluble form of PECAM-1 (sPECAM-1) were evaluated on the 2nd and 5th day postpartum in breast milk and serum paired samples from 20 lactating women as well as in time-matched serum from their single, term, healthy neonates. Concentrations of sPECAM-1 in breast milk (median, range) on both the 2nd (2.05 ng/ml, 0.0-7.2) and 5th day postpartum (0.89 ng/ml, 0.0-3.6) were about 10 and 20 times lower than those (mean +/- SD) in controls (healthy adults) (19.83 +/- 5.17, p<7 x 10(-8)), showing a significant fall from the 2nd to the 5th day postpartum (p<0.0005). Maternal serum sPECAM-1 values (mean +/- SD) were significantly lower on the 2nd day postpartum (14.21 +/- 5.15 ng/ml) than those in controls (p<0.002), but reached control values on the 5th day postpartum after a significant rise (p<0.0075). Neonatal serum sPECAM-1 values with no significant difference between the 2nd (14.4 +/- 4.11 ng/ml) and 5th day of life (14.54 +/- 4.99 ng/ml) were significantly lower than those in controls (p<0.002). Values of sPECAM-1 in milk and sera of lactating mothers and their neonates on the 2nd day postpartum depended on the mode of delivery, being significantly lower after caesarean section (p<0.034, p<0.0075 and p<0.035, respectively). In conclusion, our findings in the early postpartum period demonstrate that: (a) sPECAM-1 is present in human milk in low and decreasing concentrations; (b) the shedding of sPECAM-1 is an established component of the neonatal immune system from birth, though in lower concentrations than in adults, possibly reflecting its immaturity; and (c) the mode of delivery has a significant effect on sPECAM-1 values in milk and sera of lactating mothers and their neonates; the lower values after caesarean section may reveal a deranged endothelial homeostasis.

Gaze-stabilizing deficits and latent nystagmus in monkeys with brief, early-onset visual deprivation: eye movement recordings.

The normal development and the capacity to calibrate gaze-stabilizing systems may depend on normal vision during infancy. At the end of 1 yr of dark rearing, cats have gaze-stabilizing deficits similar to that of the newborn human infant including decreased monocular optokinetic nystagmus (OKN) in the nasal to temporal (N-T) direction and decreased velocity storage in the vestibuloocular reflex (VOR). The purpose of this study is to determine to what extent restricted vision during the first 2 mo of life in monkeys affects the development of gaze-stabilizing systems. The eyelids of both eyes were sutured closed in three rhesus monkeys (Macaca mulatta) at birth. Eyelids were opened at 25 days in one monkey and 40 and 55 days in the other two animals. Eye movements were recorded from each eye using scleral search coils. The VOR, OKN, and fixation were examined at 6 and 12 mo of age. We also examined ocular alignment, refraction, and visual acuity in these animals. At 1 yr of age, visual acuity ranged from 0.3 to 0.6 LogMAR (20/40-20/80). All animals showed a defect in monocular OKN in the N-T direction. The velocity-storage component of OKN (i.e., OKAN) was the most impaired. All animals had a mild reduction in VOR gain but had a normal time constant. The animals deprived for 40 and 55 days had a persistent strabismus. All animals showed a nystagmus similar to latent nystagmus (LN) in human subjects. The amount of LN and OKN defect correlated positively with the duration of deprivation. In addition, the animal deprived for 55 days demonstrated a pattern of nystagmus similar to congenital nystagmus in human subjects. We found that restricted visual input during the first 2 mo of life impairs certain gaze-stabilizing systems and causes LN in primates.

Comparative expression of hedonic impact: affective reactions to taste by human infants and other primates

This study examines behavioral affective reactions elicited by tastes from eight newborn human infants, and from 27 other infant or adult primates. Non-human primates belonged to 11 species: three great apes (chimpanzee, orangutan, gorilla), three Old World monkeys (rhesus monkey, greater spot-nosed monkey, and red-capped mangabey), four New World monkeys (golden-handed tamarin, cotton-top tamarin, white tufted-ear marmoset, and Humboldt's night monkey), and one lemur (mongoose lemur). The taste of sucrose elicited homologous positive hedonic patterns of facial affective reactions from humans and other primates, whereas quinine elicited homologous aversive or negative affective patterns. The degree of similarity between human and other primate affective reaction patterns appeared to be strongly indicative of their phylogenetic relatedness. For example, affective reaction patterns of human infants and great apes were more similar to each other than either were to Old World monkeys or New World monkeys. Certain affective reaction components were found to be shared by humans and all primates, whereas other components were restricted to particular taxonomic groups. Finally, allometric timing parameters for the duration of components indicated that the ‘same’ affective reaction could have different durations in species of different size. These results show that both positive/negative valence and intensity of affective reaction may be quantitatively assessed in human and non-human primates, and indicate that taste-elicited affective reaction patterns of human infants are related systematically to those of other primate species.

Prostaglandin endoperoxide H synthase type 1 and type 2 messenger ribonucleic acid in human fetal tissues throughout gestation and in the newborn infant

Objective: We determined the relative abundance of prostaglandin endoperoxide H synthase type 1 and type 2 messenger ribonucleic acid levels in the human fetus and newborn infant. Study Design: We used ribonuclease protection assays and normalized values to messenger ribonucleic acid of cyclophilin. Tissues were obtained from all 3 trimesters and in the first 9 days of the newborn period. Results: Prostaglandin endoperoxide H synthase type 1 and type 2 messenger ribonucleic acid is present in every fetal tissue examined (lung, kidney, intestine, heart, brain, and stomach). Kidney and lung demonstrated no changes in the expression of prostaglandin endoperoxide H synthase type 1 messenger ribonucleic acid with gestational age, whereas postnatal levels in lung were one third those in the first trimester (P <.05). A large increase (5-fold to 30-fold; P <.05) occurred throughout gestation for the expression of prostaglandin endoperoxide H synthase type 2 messenger ribonucleic acid in intestine, lung, and kidney, which extended into the newborn period for lung and kidney. Conclusions: These data imply that the expression of prostaglandin endoperoxide H synthase type 2 messenger ribonucleic acid may be responsible for prostaglandin-related effects and is coordinated in several human fetal tissues in late gestation. (Am J Obstet Gynecol 2001;184:169-74.)

Production and Excretion of Nitrate by Human Newborn Infants: Neonates Are Not Little Adults

Endothelium-derived relaxing factor, identified as nitric oxide or its adducts, is metabolized to nitrate and excreted in the urine. Since blood pressures are lower in newborn infants compared to adults, we hypothesized that newborn infants would have increased excretion of nitrate on the day of birth. Neonatal urine was collected before 24 h of age when exogenous intake of nitrate was low. Two different analytical methods showed that nitrate accounted for >99% of nitrogen oxides in urine of healthy neonates and adults. The absolute micromolar concentration of nitrate in urine from infants was significantly below that of adults. When nitrate content was standardized for the reduced renal function in the newborn infant (creatinine content) and body mass (kilogram weight), the concentration of nitrate in neonatal urine was significantly higher than that of adults. Nitrate concentrations in the urine of prematurely born infants were twice that of nitrate measured in urine from term infants. These findings suggested that nitric oxide is produced in larger intravascular quantities in newborn infants versus adults. Thus, we postulated that nitric oxide released from a nitrosothiol would be metabolized to nitrate more readily by neonatal erythrocytes compared to red blood cells obtained from adults. Neonatal erythrocytes, suspended at concentrations of 8, 12, or 16 g per deciliter of hemoglobin, produced 1.7- to 2.1-fold more nitrate than equivalent hemoglobin concentrations of adult erythrocytes that were each incubated with S-nitroso-N-acetylpenicillamine (100 μM) over a 2-h period. Taken together, the studies of urinary nitrate in newborn infants and the ability of neonatal erythrocytes to generate nitrate are consistent with a robust production of nitric oxide immediately after birth.

Progressive tissue injury in infantile hydrocephalus and prevention/reversal with shunt treatment

Infantile hydrocephalus, despite shunt treatment, can leave children with a variety of persistent neurological deficits. A rat strain (H-Tx) with inherited fetal-onset hydrocephalus, is a natural model for the study of progressive tissue changes resulting from hydrocephalus and the effects of shunt placement. The cerebral cortex of rat pups has been studied at post-natal day 4 (P4), early stage hydrocephalus and equivalent to a third trimester human fetus, at Pi 1, intermediate stage hydrocephalus and equivalent to a newborn human infant, and at P2I at advanced stage hydrocephalus. At P4, there is interstitial edema (increased water, sodium and chloride) and a non-reversible change in membrane lipids, particularly the phosphomonoesters. By PI I, there are additional, non-reversible, changes in intracellular potassium and energy metabolites (ATP and phosphocreatine). At P2I, the cells are severely damaged and further intracellular changes include a decrease in N-acetylaspartate (NAA) and loss of amino acids and many organic osmolytes. The interstitial edema is ~75% reversed after shunt treatment. The loss of energy metabolites, NAA and osmolytes can be prevented by early shunt treatment at P4, but the subsequent potassium loss is not prevented. Shunt at PI 1 does not prevent loss of NAA or aspartate, but osmolytes are normalized. It is concluded that persistent tissue damage is initiated by changes in cell membrane components leading to a decrease in energy metabolism and loss of cell homeostasis. A more complete understanding of the mechanisms involved could lead to new approaches for therapy. [Neurol Res 2000; 22: 89-96]

Induced brain hypothermia in asphyxiated human newborn infants: a retrospective chart analysis of physiological and adverse effects.

To assess the physiological effects and adverse side-effects of induced hypothermia in asphyxiated newborn infants as a base for future controlled, randomized trials. Retrospective chart analysis with historical controls. Tertiary neonatal intensive care unit of the University of Cape Town, South Africa. Twenty-one asphyxiated newborns treated with induced hypothermia between September 1997 and February 1998 were compared to 15 asphyxiated newborn infants admitted during March to August 1997. The two groups of infants did not differ in patient characteristics or severity of asphyxia (comparison group vs hypothermia group: Apgar at 5 min 5.3 +/- 3.1 vs 5.2 +/- 2.3; base deficit 15.6 +/- 6.3 vs 11.5 +/- 7.2 and Thompson neurological score 10.1 +/- 4.0 vs 9.1 +/- 3.6). Hypothermia was induced by placing a cap formed from coolpacks, at a temperature of about 10 degrees C, around the head of asphyxiated newborn infants to maintain the nasopharyngeal temperature between 34 and 35 degrees C. Hypothermia was maintained for 3 days. In the comparison group 4/15 infants died and in the hypothermia group 4/21 died. Hypothermia was induced at a median of 6.0 h (range 45 min to 53 h) post-partum, maintained for an average of 80 h (median 77.5 h, range 22 to 185 h) and resulted in an average nasopharyngeal temperature of 34.6 +/- 0.5 degrees C. Hypothermia reduced abdominal skin temperature from 36.3 +/- 0.5 degrees C to 35.1 +/- 0.35 degrees C (p = 0.0001), heart rate from 139 +/- 21 to 121 +/- 13 beats/min (p < 0.0001) and respiratory rate from 67 +/- 11 to 56 +/- 9 breaths/min (p = 0.005). Neither episodes of bradycardia nor dysrhythmias, apnea, clinical signs of bleeding diathesis in the hypothermia group nor differences in the frequency of hypoglycaemia and urinary output, blood in urine or tracheal secretion between the two groups were observed. In the survivors the neurological score, assessed at day 2 and day 5, fell from 10.9 +/- 3.5 to 8.1 +/- 4.5 in the hypothermia group and rose from 8.1 +/- 2. 5 to 9.0 +/- 3.1 in the comparison group (p = 0.003). Adverse effects of mild hypothermia induced for 3 days in asphyxiated newborns were significantly less than expected from previous reports on neonates with accidental hypothermia.

Insulin modulates intestinal response of suckling mice to the Escherichia coli heat-stable enterotoxin.

Effect of insulin on the response of suckling mice to the enterotoxigenic Escherichia coli heat-stable enterotoxin (STa) was studied. Four groups (8-10 in each group) of two day old Swiss Webster suckling mice were used. Five, 10, 25, and 50 micrograms of insulin were given orally to half the mice in each group respectively. The rest of the mice in each group were given normal saline as intra-litter controls. After 7 days, the suckling mouse assay for STa was performed on three mice from each insulin-treated and control groups. Enterocyte suspensions were prepared from mice in all groups. Intestinal tissue samples were taken for electron microscopy. Interaction of STa with its putative receptor on the enterocytes was evaluated using indirect immunofluorescence and flow cytometry. The suckling mouse assay revealed a significant increase in the gut weight to body weight ratio in all mice in the insulin treated groups compared to control mice (p < 0.05). Flow cytometry and indirect immunofluorescence analyses suggested that insulin had an upregulatory effect on the STa receptor level. Similarly, insulin was found to increase intestinal brush border membrane differentiation as indicated by the increase in the inward movement of milk particles through the intestinal mucosa. Insulin seems to modify the structure-function of the brush border membrane including the response of suckling mice to STa. This study may provide further insights into the mechanism of STa/receptor interaction in diarrhea in newborn animals and human infants.

Age-dependent variation in the density and affinity of Escherichia coli heat-stable enterotoxin receptors in mice.

Enterotoxigenic strains of Escherichia coli that produce heat-stable enterotoxin (STa), are a major cause of diarrheal disease worldwide. Resistance to diarrheal disease in human infants and newborn animals has been attributed to a gradual turnover in the intestinal brush border membrane receptors to bacterial pili. In this study, we demonstrated age-dependent variation in the density and affinity of the mouse enterocyte receptors specific for STa. Flow cytometry and radiolabeled-STa (125I-STa) assays were used as more reliable quantitative measures for the characterization of STa-enterocyte receptor interaction. These assays indicated a stronger interaction of STa with its putative receptor on the enterocytes of the 2-day-old suckling mice than with enterocytes from 1-week, 2-week and 2-month-old mice. Scatchard plot analysis of 125I-STa-receptor interaction suggested that STa-receptors exist at a higher number on enterocytes from the 2-day-old mice than enterocytes of the older mice. Additionally, receptors from the 2-day-old mice had a greater affinity for STa ligand than receptors from the older mice. Density of STa receptors on enterocytes and their affinity to STa may determine the extent of binding and severity of secretory response. This may further explain the increased susceptibility of newborn animals and human infants to STa-mediated diarrheal disease.

Effects of Reoxygenation (RO) Following Pneumothorax (PT) with 21% or 100% Oxygen (O) on Early Neurological Outcome (ENO) and on Cerebral Hystopathology(CH) of Newborn Piglets 1901

PT is far more frequent in the infants than any other period of life and associations exist between PT and central nervous system damage in human newborn infants. In the present study we tested the effect of RO following PT with 21% or 100% O on ENO and on CH of newborn piglets. Methods: 26 piglets were studied. Three experimental groups were formed: Shamoperated piglets (SHAM, n: 6), piglets with RO with 21% O after PT (RO21, n: 10) and animals with RO with 100% O after PT (RO100, n: 10). In RO21 and RO100 PT were induced under anesthesia with bilateral intrapleural air insufflation and critical phase with bradyarrythmia, arterial hypotension, hypoxemia and severe combined acidosis occurred 62 ± 6 (RO21) and 65 ± 7 min (RO100)(means ± SEM) after the start of the experiments. Ten min of RO period was started with ventilation with 21% O (RO21) or 100%O (RO100). Then the spontaneously breathing animals were followed on room air (21%O) during the next four hours and neurological examinations (M. H. LeBlanc et al. Stroke, 26:1908, 1995, neurological score of 20 normal, 5 brain dead) were performed by a blinded observer at the end of the experiments. The brains were perfusion fixed through the transcardiac route then stained with hematoxilin and eosin for CH (hyperchromatic and eosinophilic-staining neurons) in different brain regions (frontal and temporal cortex, cerebellum, hippocampus, basal ganglia, pons). Results: Neurological scores from SHAM were 18 ± 0, from RO21 12.5 ± 1.7 and from RO100 9.7 ± 1.6(significant differences - ANOVA p < 0.05 - between SHAM and RO21 and RO100, significant difference between RO21 and RO100). CH showed significant damages with similar severity in all regions studied in both PT groups (RO21 and RO100) compared to data observed in SHAM (quantitative values not given).Conclusion: RO following PT with 100% O might impair ENO but did not affect CH of newborn piglets.

Expression of Natural Killer (NK) Cells In Newborn Infants With Early Onset Sepsis 1461

Human newborn infants are believed to be more susceptible to sepsis due to immature host defense mechanisms. T-cells are essential for antigenic recognition. We previously have shown that there is a marked predominance of naive T-cells in newborns that is consistent with T-cell immune system immaturity. NK cells mediate cellular cytotoxicity independent of previous antigenic exposure. The role of NK cells in cytotoxicity against viral infection has been extensively studied. The role of these cells as a compensatory defense mechanism against neonatal sepsis is unclear. The purpose of the present study is to examine the expression of NK cells in newborn infants with and without early onset sepsis. We used flow cytometry to determine expression of cell surface markers on cord blood lymphocytes from 20 healthy newborn infants (GA 37±1 wks), peripheral blood lymphocytes from 15 newborn infants (GA 36±1 wks) with clinical or culture positive sepsis and 24 healthy adults. Comparisons among these 3 groups were made using ANOVA. Data presented are means and SE. The expression of NK cells was significantly higher in healthy newborn infants than adults (1160±144 vs 238±25 cells/μl, p<0.05). In septic newborn infants, NK cell expression was significantly lower at the time of diagnosis at 1.5±1 days of life than in healthy newborn infants (389±59 vs 1160±144 cells/μl, p<0.05).

Development of Glutathione Synthesis and γ-Glutamyltranspeptidase Activities in Tissues from Newborn Infants

Following the observation that the level of glutathione in leukocytes from human newborn infants was lower in preterm and in male infants, a study was designed to document the level of activities of glutathione synthesis and γ-glutamyltranspeptidase during the development of preterm and term newborn infants. Measurements were performed in leukocytes from tracheal aspirates of oxygen dependent infants, and in leukocytes from cord blood. Contrary to the common belief concerning the development of antioxidant activity, the biosynthesis of glutathione was active in leukocytes from preterm infants; and by two days of life the activity of γ-glutamyltranspeptidase reached 3 times the level of that seen in cord blood. Our results suggest that the maturity of these enzymes was not the limiting step in maintaining cellular glutathione levels. This represents new information concerning the maturation of a central antioxidant in tissue derived from preterm and term human newborn infants at risk of oxidant stress. This implies that sources of cysteine crossing freely the cellular membrane could be used by tissues of term and preterm infants to produce glutathione.

T cell receptor repertoire diversity and clonal expansion in human neonates.

Newborn human infants, particularly those born prematurely, are susceptible to infection with a variety of microorganisms. We questioned whether limitations in the T cell repertoire contribute to the neonatal immunocompromised state. To describe developmental changes of the T cell repertoire, cDNA segments corresponding to third complementarity regions (CDR3) of human umbilical cord blood T cell receptors (TCR) from 24-41-wk gestational age were amplified with TCR family-specific probes. The resulting amplified CDRs were visualized by fingerprinting and single strand conformation polymorphism (SSCP) analysis. At 24-wk gestation there were no limitations in TCRBV family usage, and the degree of CDR3 size heterogeneity was not different from the adult. However, earlier in gestation, CDR3s were shorter for all families and gradually increased in size until term. The extent of oligoclonal expansion observed in cord blood was greater than in adult peripheral blood (p = 0.03). T cell oligoclonal expansion was greatest at 29-33-wk gestation and declined toward term. Expansions were detectable in both CD4+ and CD8+ subpopulations. Our findings indicate that the genetic mechanisms of repertoire diversification appear intact as early as 24 wk of gestation, but repertoire diversity is limited as a result of smaller CDR3 sizes. In addition, there was a developmentally regulated progression of oligoclonally expanded T cells. These differences in the TCRBV repertoire add to the body of evidence demonstrating immaturity of the neonatal immune system. However, the role that these subtle differences are likely to play in the relative immunodeficiency of the neonate remains to be determined.

Neural noise limitations on infant visual sensitivity.

Visual contrast sensitivity is poor in newborn human infants, but improves rapidly to approach adult levels by 8 months of age. During this period, infant sensitivity can be limited by physical factors affecting photon capture, such as eye size and photoreceptor density. Here we show that infant visual sensitivity is also limited by high levels of noise in the neural transduction process. Using a non-invasive electrophysiological measurement and a visual noise titration technique, we have found that intrinsic neural noise in neonates is approximately nine times higher than in adults. As intrinsic neural noise decreases during infancy, contrast sensitivity improves proportionally, suggesting that neural noise places critical limits on contrast sensitivity throughout development. Moreover, contrast gain control, an inhibitory process that adjusts visual responses to changing stimulation, is in place and operating in infants as young as 6 weeks of age, in spite of high levels of neural noise and significant immaturities in contrast sensitivity. The contrast gain control that we observed in human neonates may serve as a building block for more complex forms of visual inhibition, which develop later in infancy.