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PubMed2001

High IL-13 production by human neonatal T cells: neonate immune system regulator?

Neonates are highly susceptible to diseases and display biased type 2 immune responses, although no skewing to type 2 cytokines has been reported. In view of the emerging importance of IL-13 in type 2 inflammatory responses and clinical allergy, we analyzed IL-13 production by neonatal T cells. We found that, mainly CD8 T cells produced high levels of IL-13, while producing low levels of IL-4, IL-10 and IFN-gamma, upon primary and secondary stimulation. Our results point towards a possible immunoregulatory role of CD8 T cells in neonate responses. Moreover, they suggest that the abundance of IL-13 in the neonate immune system might account for the type 2 bias in neonates, providing a basis for the high disease susceptibility of newborns, for instance to allergic diseases.

CD8-Positive T-Lymphocytes↗
PubMed2004

Neonatal tolerance revisited again: specific CTL priming in mouse neonates exposed to small numbers of semi- or fully allogeneic spleen cells.

Neonatal and adult mice mount distinct responses to allogeneic cells. Injection of neonates with fully allogeneic cells results in lethal graft-vs.-host disease (GVHD), whereas injection of semi-allogeneic (F1) cells leads to lifelong tolerance to the alloantigens, often marked by specific CTL non-responsiveness. In contrast, adults injected with the same number of either cell type become primed and develop vigorous anti-donor CTL activity. One possibility for this differential responsiveness may be developmental immaturity in the CTL arm of the immune system. Recent studies have shown that neonates are capable of mounting mature CTL responses, but only in the presence of strong Th1-promoting agents. Here, we demonstrate that neonates are competent to develop vigorous MHC class I-restricted CTL activity in vivo upon exposure to either fully or semi-allogeneic spleen cells. Specific CTL activity was generated using doses of cells approximately tenfold lower than levels used for the induction of GVHD or tolerance. Thus, the present studies demonstrate that mouse neonates are fully mature in their capacity to develop alloreactive CTL activity, as long as the dose of donor cells is low enough. These results have important implications for the known exposure of human fetuses and infants to small numbers of maternal cells.

Animals↗
PubMed1983

Maternal diabetes and neonatal macrosomia. II. Neonatal anthropometric measurements.

Anthropometric measurements were obtained within 12 h of birth in 52 infants of non-diabetic mothers and 61 infants of diabetic mothers. Most of the diabetic patients were under good control, only ten of 61 having postpartum hemoglobin A1c levels in excess of normal. Neonates were grouped as normally-grown or macrosomic. Birthweight, crown-heel length, head circumference and skinfold thickness were measured. In each diabetes class, macrosomic neonates had larger mean length, head circumference and skinfold thickness than their normally-grown peers. At equal birthweight, neonates of gestational diabetic mothers and of non-diabetic mothers were similar in length, head circumference and skinfold thickness. Neonates of permanently insulin-requiring diabetics were similar to their non-diabetic peers in length and head circumference but had thicker skinfold thicknesses. Anthropometric measurements do not permit differentiation of the origin of neonatal macrosomia.

Anthropometry↗
PubMed1993

Production of IL-3 by non-transformed primary neonatal murine keratinocytes: evidence for constitutive IL-3 gene expression in neonatal epidermis.

Interleukin 3 (IL-3) is a cytokine produced by activated T lymphocytes that is best understood as a hematopoietic growth and differentiation factor. Production of IL-3 by other cell types is controversial; while certain transformed non-lymphocyte cell lines can produce IL-3, it is generally assumed that their non-transformed counterparts do not. It has been previously reported that Pam 212, a transformed murine keratinocyte cell line, produces IL-3. In this study we report that IL-3 can also be secreted by normal murine keratinocytes. Using a cell line (FL5.12) which is responsive to IL-3 and not to other keratinocyte derived cytokines, (e.g. GM-CSF, IL-1 and IL-6), we tested conditioned media from cultures of normal neonatal keratinocytes for biologically active IL-3. These media stimulated the proliferation of FL5.12, and the effect could be neutralized by specific antibodies to IL-3. The presence of IL-3 mRNA was demonstrated by polymerase chain reaction (PCR) amplification of reverse transcribed IL-3 mRNA from cultured normal neonatal keratinocytes and confirmed by Southern blot analysis. By similar techniques, IL-3 mRNA could be identified in freshly isolated neonatal epidermis but not dermis. These data indicated that IL-3 is produced by keratinocytes in the skin of normal neonatal mice, raising the likelihood that the neonatal epidermal microenvironment may have hematopoietic or lymphopoietic properties.

Animals↗
PubMed2005

[Neonatal mortality in France: usefulness of a neonatal death certificate].

UNLABELLED: A neonatal death certificate was introduced in France in 1997. It provides detailed data on the causes of death and the characteristics of newborn, birth and parents. Our aim was to describe the new results of this certificate. METHOD: All deaths in 1999 in the first 27 days of life were included (N=2036). Certificates were analysed using the usual process, especially following the International Classification of Diseases. RESULTS: The neonatal death certificate was used for 87% of deaths. The proportion of documented items was 96% for gestational age and birthweight, 87% for maternal age and parity and 70% for maternal occupation. Almost three quarters of the deaths occurred in the first 6 days (36.9% in the first 24 hours and 35.1% between one and six days). 30.5% of the died infants were born before 27 weeks of gestation and 36.5% between 27 and 36 weeks. A shift in medical care was observed at 26 weeks, with an increase in caesarean sections before labour and newborn referrals. In all, 63.3% of neonatal deaths were due to perinatal conditions, and 27.9% to congenital anomalies. The proportion of deaths explained by congenital anomalies was higher for longer gestational age: 14% of deaths between 25 and 28 weeks of gestation vs 38 to 43% between 33 and 42 weeks. CONCLUSION: The neonatal death certificate was well accepted; however the data on detailed causes of death and parent's characteristics were insufficient. Analysis of the circumstances and the causes of death is facilitated with the neonatal death certificate and it will be developped in the future.

Cause of Death↗
PubMed2003

Ultrastructural characterization of effector-target interactions for human neonatal and adult NK cells reveals reduced intercellular surface contacts of neonatal cells.

Limitations in neonatal natural killer (NK) cell responses may be associated with the less efficient newborn capacity to solve viral infections. Although these limitations have been extensively reported they are poorly characterized. Making use of the major histocompatibility complex (MHC) class I negative cell line K562, the parameters required for the initial events involved in neonatal NK/target cell interactions were determined and compared with adult blood NK cell/target cell interactions. Ultrastructural characterization of effector-target cell interactions revealed that neonatal NK cells are more strongly activated upon contact with K562 cells than adult blood NK cells. Furthermore, the neonatal capacity to establish contacts, in particular extensive contacts, is significantly reduced when compared with adult blood NK cells. However, no significant differences were found either in the cell surface expression levels or activation state of LFA-1, which could account for the reduced intercellular contacts. Because extensive contacts are crucial for effective immunologic synapse formation, these data suggest that a limited or nonsustained positive signaling may occur on neonatal NK cells, restricting their NK cell-mediated lysis capacity.

Adult↗
PubMed1997

Neonatal injection of an ovarian peptide induces autoimmune ovarian disease in female mice: requirement of endogenous neonatal ovaries.

Neonatal female mice injected with the self ZP3 peptide are not tolerant to the peptide; they develop autoimmune ovarian disease (AOD) and autoantibody response 5 weeks later. ZP3 challenge leads to severe AOD and ZP3-specific T cell and antibody responses. In contrast, neonatal tolerance to foreign ZP3 peptide is established in male mice: ZP3 peptide-specific T cell proliferative response is reduced and AOD is absent in ovarian grafts. Tolerance is associated with a Th2-dominant T cell cytokine and antibody isotype profiles. As controls, neonatal tolerance to foreign peptides, with Th2 deviation, was induced in both male and female mice. Endogenous ZP3 is important for the gender difference. Ablation of ovaries in female mice on days 2 and 5, but not on day 7 or 14, switches the ZP3 autoimmune response to a tolerogenic response with a concomitant change in cytokine profile. Thus, neonatal self ZP3 peptide, supported by endogenous ovaries within a neonatal time window, evokes a pathogenic autoimmune response.

Amino Acid Sequence↗
PubMed2002

Neonates with congenital diaphragmatic hernia have smaller neck veins than other neonates-An alternative route for ECMO cannulation.

BACKGROUND/PURPOSE: The aim of this study was to compare the size of the right internal jugular vein between neonates with congenital diaphragmatic hernia (CDH) who need extracorporeal membrane oxygenation (ECMO) and non-CDH neonates. The purpose also was to describe a method for cannulation of the right brachiocephalic vein if the internal jugular vein was too small for ECMO cannulation. METHODS: Birth weight and size of the right internal jugular vein were compared between CDH and non-CDH neonates subjected to ECMO treatment. A corrected venous size was calculated, estimating the venous size if the patient's birth weight was 3,000 g. RESULTS: The mean birth weight of the CDH patients (3,214 g) was lower than that of the non-CDH patients (3,497 g; P <.04). The mean venous size of the CDH patients (12.1 Charierre [Ch]) was significantly smaller (P <<.001) than that of non CDH patients (13.6 Ch). The corrected venous size also was significantly (P <.001) smaller among CDH patients. CONCLUSIONS: Severely affected neonates with CDH have significantly smaller right internal jugular veins than other neonates. If the patient needs ECMO and if the internal jugular vein is too small for cannulation, the right brachiocephalic vein can be successfully cannulated from the neck instead.

Birth Weight↗
PubMed1990

Early neonatal predictors of neonatal hypocalcemia in infants of diabetic mothers: an epidemiologic study.

Prematurity, neonatal asphyxia, hypomagnesemia, and advanced maternal diabetes are traditional risk factors for hypocalcemia in infants of diabetic mothers (IDMs). The aim of this study was to determine the relative contribution of these factors separately and combined in a cohort of diabetic pregnancies managed prospectively in the recent 9 years and to find accurate predictors of neonatal hypocalcemia in infants of diabetic mothers. We hypothesized that these factors plus low cord blood calcium (Ca) concentration allow prediction of IDMs who develop neonatal hypocalcemia. We studied 186 IDMs (White class B-RT); gestational age (GA, weeks) was by last menstrual period, confirmed +/- 2 weeks by Ballard score. The goals of glycemic control were: preprandial blood glucose less than 100 mg/dl and 90-minute postprandial blood glucose less than 140 mg/dl. Apgar scores, and cord, 24-, 48- and 72-hour serum calcium (Ca) (mg/dl) and magnesium (Mg; mg/dl) were determined. In univariate analysis, lowest serum Ca correlated with cord blood Ca (r = 0.48, p less than 0.001), GA (r = 0.37, p less than 0.001), and 1-minute Apgar score (r = 0.18, p = 0.09), but did not correlate with cord Mg or with advanced White class. In multiple regression, cord Ca and GA were dominant effects and other variables became insignificant. Lowest Ca (mg/dl) was predicted as follows: lowest Ca = 34.05 - 3.22 (Ca cord) - 0.84 (GA) + 0.10 (GA) (Ca cord). This equation predicts neonatal hypocalcemia (lowest Ca less than 8 mg/dl) with a sensitivity of 72% and a specificity of 75%. Thus, GA and cord Ca allow determination of IDMs at risk for neonatal hypocalcemia.

Asphyxia Neonatorum↗
PubMed1990

Circulating and breast-milk anti-rotaviral antibodies and neonatal rotavirus infections: a maternal-neonatal study.

In view of the high prevalence of rotavirus (RV) diarrhoea in Indian (Asian) infants in South Africa, a hospital-based study of 124 mothers and their neonates was carried out to establish the prevalence of maternal and neonatal circulating anti-RV antibodies, RV antibodies in breast-milk, and neonatal RV infections in this population. Thirty-four per cent of the mothers and 38% of the neonates had complement-fixing (CF) serum antibodies. There was a significant correlation between maternal and cord blood antibody levels (p less than 0.001; chi-square test). Fifteen per cent of hospital-born newborns showed asymptomatic RV excretion while still in hospital, mostly at 2-6 days of age, but some even earlier, with two shedding the virus before the age of 24 h. This excretion occurred in both seronegative and seropositive babies. The breast-milk of only 3.2% of the mothers was positive for CF-anti-RV antibodies, implying that either these were not present in the breast-milk or that the CF-test employed was not sufficiently sensitive for detecting these antibodies in milk specimens. Eighteen (18.2%) of 99 infants followed up showed evidence of RV infection 1-7 months after birth; none was symptomatic; 12 excreted RV in the stools while 6 others seroconverted. Asymptomatic reinfection was documented in 4 of 14 babies who had been infected initially as neonates.

Adolescent↗
PubMed1989

Neonatal antibody-dependent cellular cytotoxic antibody levels are associated with the clinical presentation of neonatal herpes simplex virus infection.

The role of antiviral antibodies in protection against neonatal herpes simplex virus (HSV) infection remains controversial. The relationship between neonatal and maternal anti-HSV antibodies and disease presentation was analyzed in 47 babies. Of the neonates, 77% had localized and 23% had disseminated HSV infection. Antibody-dependent cellular cytotoxic (ADCC) antibodies were evaluated in comparison with HSV neutralizing antibodies. High maternal (greater than 1:10(4)) or neonatal (greater than 1:10(3)) anti-HSV ADCC antibody levels or high neonatal antiviral neutralizing levels (greater than 1:20) were independently associated with an absence of disseminated HSV infection. Cochran-Mantel-Haenszel analysis demonstrated that ADCC levels were associated with disease status (P less than .02) while controlling for the level of neutralizing antibody.

Antibodies, Viral↗
PubMed1991

Neonatal tolerance to MIs-1a determinants: deletion or anergy of V beta 6+ T lymphocytes depending upon MHC compatibility of neonatally injected cells.

Recent investigations in mice revealed that natural immunological tolerance to endogenous minor lymphocyte-stimulating locus 1a (MIs-1a) antigen correlates primarily with deletion of MIs-1a-specific V beta 6+ T lymphocytes in the thymus. Similar mechanisms account for acquired tolerance in some instances since the neonatal injection of MIs-1a-expressing MHC compatible cells in neonatal mice within the first 24 h of life causes clonal deletion of V beta 6+ T cells. Here we demonstrate that V beta 6+ T cells are not deleted in mice neonatally treated with MIs-1a spleen cells expressing allogeneic H-2 molecules. However, when such non-deleted V beta 6+ T cells were tested in vitro, no interleukin 2 (IL-2) secretion or proliferation was observed after MIs-1a stimulation. This non-responsive state could be overcome by addition of exogenous IL-2, consistent with the fact that V beta 6+ cells enlarged and expressed IL-2 receptors upon MIs-1a stimulation. Furthermore, the same neonatally treated mice showed in vitro functional unresponsiveness of cytotoxic T cells but not of IL-2-secreting cells specific for the tolerated allogeneic MHC antigens. Taken together, our data indicate that neonatal tolerance to MIs-1a can be accomplished by either clonal deletion or clonal anergy, and that it does not necessarily correlate with tolerance to MHC determinants.

Animals↗
PubMed1996

Behavioral sleep states in very low birth weight preterm neonates: relation to neonatal health and vagal maturation.

Assessed the relation of behavioral codes of quiet versus active sleep state to neonatal health status in 62 very low birth weight preterm neonates. Sleep sessions (12 min) were coded for percentage time in active versus quiet sleep at 33, 34, and 35 weeks conceptional age. ECG was monitored during each sleep session to derive measures of heart rate, heart rate variability, and an index of cardiac vagal tone derived from respiratory sinus arrhythmia. Higher risk neonates spent more sleep session time in active sleep than healthier preterm neonates. Cardiac vagal tone showed a maturational change during the study weeks, whereas percentage of sampled sleep time in active sleep did not. Vagal maturation measured by age-related increases in the amplitude of respiratory sinus arrhythmia was associated with less active sleep overall, although weekly measures of respiratory sinus arrhythmia and sleep state were not related. Follow-up data on 30 of the neonates indicated that heart rate variability and cardiac vagal tone, but not sleep state measures, were related to better outcomes in mental processing, social skills, and motor skills, and to fewer behavior problems. Results are discussed in terms of the lack of coupling between behavioral and physiological components of preterm sleep states at this age as compared with that seen in full-term sleep states.

Female↗
PubMed2000

Comparison of work of breathing between two neonatal ventilators utilizing a neonatal pig model.

OBJECTIVE: The purpose of this study was to determine whether variations in the delivery systems of continuous positive airway pressure between two ventilators would lead to differences in patient work of breathing (WOBp). DESIGN: Comparison of two neonatal ventilators with a neonatal pig model. SETTING: Animal laboratory. SUBJECTS: Thirty healthy, intubated, sedated, spontaneously breathing neonatal piglets weighing 1.0-2.0 kg. INTERVENTIONS: Patient work of breathing (WOBp) (gm cm/kg) was measured by using measurements based on an esophageal balloon and a flow transducer. Each breath was analyzed for ventilator response times (in msecs) and negative deflection of pressure. Each animal was studied with the Siemens SV300 and Drager Babylog 8000, on continuous positive airway pressure settings of 0, 3, and 5 cm H2O. Data were analyzed by using Wilcoxon's Signed Rank Test with significance of p 1 cm H2O negative pressure before flow was available with the Babylog. CONCLUSIONS: In intubated patients, maximum energy expenditure occurs at the initiation of ventilator breaths. WOBp in neonatal pigs was significantly increased. The response time of the ventilators may explain the differences in initiation of flow times and patient work. These differences may have important implications for energy kinetics, weight gain, and duration of mechanical ventilation in preterm neonates.

Journal Article↗
PubMed1997

Neonatal lupus erythematosus: HLA-DR and -DQ distributions are different among the groups of anti-Ro/SSA-positive mothers with different neonatal outcomes.

Neonatal lupus erythematosus (NLE) is an antibody-mediated disorder of infants characterized by two major clinical manifestations; cutaneous lupus lesions and congenital heart block (CHB). The disease is associated with placentally transferred maternal anti-Ro/SSA and/or La/SSB antibodies. There is a tendency for the same disease expression to occur within a sibship. To reveal a possible association of class II MHC genes with maternal anti-Ro/SSA autoimmune responses and neonatal outcomes in NLE with a relatively homogeneous ethnic background, haplotype, and allele distributions were analyzed based on the PCR-RFLP results in 26 Japanese anti-Ro/SSA-positive mothers from three groups defined by neonatal outcomes. The results were as follows: (i) maternal HLA-DR5 haplotype DRB1*1101-DQA1*0501-DQB1*0301 and individual class II alleles making up this haplotype were significantly associated with neonatal cutaneous lupus but not CHB. Conversely, maternal HLA-DQB1*0602 carried on HLA-DR2 haplotypes was associated with CHB but not cutaneous NLE; (ii) HLA-DQA1 alleles with glutamine at position 34 of the first domain, which have reportedly been associated with the autoimmune responses to Ro/SSA antigens in other ethnic groups, were increased in the mothers of infants with cutaneous involvement; and (iii) there was no particular class II HLA profile that distinguished the disease manifestations in infants. These findings suggest that specific maternal MHC class II genes might correlate with specific neonatal outcomes in NLE.

Adult↗
PubMed2006

Maternal and neonatal influences on, and reproducibility of, neonatal aortic pulse wave velocity.

Aortic pulse wave velocity (aPWV), a noninvasive measure of vascular stiffness, is an independent predictor of cardiovascular disease both before and in overt vascular disease. Its characteristics in early life and its relationship to maternal factors have hardly been studied. To test the hypothesis that infant aPWV was positively related to maternal anthropometry and blood pressure (BP) at 28 weeks gestation, after adjusting for neonatal anthropometry and BP, 148 babies born in Manchester were measured 1 to 3 days after birth. A high reproducibility of aPWV, assessed in 30 babies within 3 days of birth, was found with a mean difference between occasions of -0.04 m/s (95% CI: -0.08 to 0.16 m/s). Contrary to our hypothesis, a significant inverse relation was found between neonatal aPWV (mean: 4.6 m/s) and maternal systolic BP (mean: 108.9 mm Hg; r=-0.57; 95% CI: -0.67 to -0.45) but not maternal height nor weight. Neonatal aPWV was positively correlated with birth length, birth weight, and systolic BP. In multiple regression, neonatal aPWV remained significantly inversely associated with maternal systolic BP (adjusted beta coefficient: -0.032; 95% CI: -0.040 to -0.024; P<0.001), after adjustment for maternal age, birth weight, length, and neonatal BP (all independently and positively related to aPWV) and for gestational age, maternal weight, and height (unrelated). These results suggest that infant aPWV may be a useful index of infant vascular status, is less disturbing to measure than infant BP, and is sensitive to the gestational environment marked by maternal BP.

Adult↗
PubMed2005

Neonatal sepsis in Jamaican neonates.

AIM: To determine the incidence and causative organisms of bacterial sepsis in neonates at The University Hospital of the West Indies. METHODS: A retrospective review of all neonates with culture-proven sepsis admitted to the hospital between January 1995 and December 2000 was conducted. Incidence rates and antimicrobial susceptibility patterns were determined. RESULTS: There were 4702 admissions to the neonatal unit during the study period. Of these, 135 had culture-proven sepsis and 115 were inborn, giving an incidence of 6.7/1000 live births. There were 89 positive blood cultures, 51 positive urine cultures and two positive CSF cultures. The single most common organism was Klebsiella spp (28%). Other organisms included Escherichia coli (16%), group B Streptococcus (11%) and Enterobacter spp (10%). The aminoglycoside resistance rate of Klebsiella spp was 46% and seven isolates had multiple resistance to antibiotics. There was a case fatality rate of 6.7%. CONCLUSION: Physicians involved in newborn care at The University Hospital of the West Indies need to recognise the important role Klebsiella now plays in neonatal sepsis and its contribution to neonatal mortality. Empirical antibiotic regimens for gram-negative sepsis must take into consideration the high rates of aminoglycoside resistance that are now prevalent.

Anti-Bacterial Agents↗
PubMed1979

Intensive care for sick neonates, the earlier the better: improved survival rate of IRDS children, referred by means of a mobile neonatal intensive care unit.

A mobile intensive care unit has been used since september 1976 in the region referring sick neonates to the two University Hospital NICU's of Amsterdam. The present study compares two groups of neonates (suffering from the I.R.D.S.) i.e. a group that had been referred by non specialized transport teams (N S T-group) and a group admitted after institution of the neonatal-transport service (S. T.-group). Significant difference is found in the temperature on admission (S T group greater than N S T group). In the N S T-and the S T-group the need for ventilatory assistance was not significantly different but in the S T-group it was started significantly earlier. Survival after institution of ventilatory assistance and overall-survival are significantly better in the S T-group. These conclusions point to the fact that administering intensive care to sick neonates as early as possible and transportation of this group by means of special "neonatal"-transport services increases their survival rates.

Humans↗