Biology of the neonate最新文献

Introduction: An apparent re-emergence of kernicterus has been recently reported, with some cases occurring in otherwise healthy breastfed newborn.

Methods: We describe a case of kernicterus in a term Caucasian newborn.

Results: An exceptional polymorphism of UGT1A1 gene promoter co-existed with asymptomatic inherited spherocytosis, due to erythroid anion exchange (band-3) deficiency. Both concurred to the development of severe neonatal hyperbilirubinaemia.

Conclusion: As some cases of kernikterus remain unresolved, haemolytic diseases and bilirubin metabolism disorders should be carefully investigated in unexplained severe neonatal hyperbilirubinaemia.

Background: The lectin, phytohemagglutinin (PHA) has been shown to induce growth and functional maturation of the gastrointestinal (GI) tract in suckling rats.

Objectives: To investigate the effect of the administration route, and whether enteral exposure to PHA was necessary to induce functional maturation.

Methods: Fourteen-day-old rats were daily administered PHA via orogastric feeding (0.05 mg PHA/g BW) or via subcutaneous injection (0.05 or 0.005 mg PHA/g BW) for 3 days, while the controls received saline orogastrically. At 17 days of age, organ weight, intestinal and pancreatic function, and plasma corticosterone levels were analyzed. Moreover, 14-days old pups receiving a single dose of PHA, enterally or parenterally, were sacrificed after 12 h and examined for organ PHA binding using immunohistochemistry.

Results: Enteral PHA exposure resulted in PHA binding in the epithelial lining of the small intestine, increased gastrointestinal growth, reduced intestinal macromolecular absorption, altered the disaccharidase expression towards an adult-like pattern, and increased the pancreatic protein and trypsin contents. In contrast, parenteral PHA exposure (high dose) resulted in PHA-binding in extra-intestinal organs, increased liver and spleen weight, and decreased thymus weight. Moreover, the intestinal maltase activity increased moderately, and the transfer of BSA to blood plasma was partially reduced. Both PHA treatments led to elevated plasma corticosterone levels.

Conclusion: These results demonstrated that enteral exposure to PHA was necessary to induce the precocious maturation of the GI tract and the pancreas, while parenteral administration affects the extra-intestinal organs. Furthermore, the enteral effects were probably not mediated via a corticosteroid dependent pathway.

Background: Red blood cell (RBC) transfusions are associated with the development of retinopathy of prematurity (ROP). During the period of retinal neovascularization a rise of insulin-like growth factor 1 (IGF-1) may trigger rapid growth of new blood vessels.

Objectives: To study endocrine factors in RBC transfusions that might be of importance for ROP.

Methods: IGF-1, IGF-2 and their binding proteins 1-3 (IGFBP-1-3) were determined by radioimmunoassays in 7 very-low-birthweight (VLBW) infants with ROP >or= stage 2 receiving a RBC transfusion, in 10 controls (VLBW infants with ROP

Results: IGF-1 (mean +/- SD) in infants with ROP was 20.0 +/- 4.2 microg/l, in controls 35.9 +/- 15.2 microg/l (Mann-Whitney U test, p = 0.030). IGF-1 in RBC was 12.88 +/- 5.03 microg/l and in WRBC 0.45 +/- 0.74 microg/l (average of the three-course washing procedure). IGF-2 in infants with ROP was 485.67 +/- 158.73 microg/l, in controls 389.9 +/- 102.8 microg/l (not significant), in RBC 109.50 +/- 117.89 microg/l, in WRBC 61.07 +/- 30.0 microg/l. Except for IGFBP-3 other IGFBPs were barely or not detectable in RBC or WRBC.

Conclusions: Considering lower IGF-1 concentrations in preterm infants than in adults (factor 20), the IGF-1 in RBC transfusions is equivalent to a single dose of 1 microg/kg IGF-1 (5-10% of the adult dose with proved metabolic responses). Endocrinological relationships between the donor's load and the acceptor's individual features are a new aspect of potential side effects of RBC transfusions. Further research is necessary to clarify the share of the described IGF administration on the development of ROP.

Background: Neonatal jaundice is commonly encountered and rarely associated with morbidity and mortality. Nonetheless, infants with glucose-6-phosphate dehydrogenase deficiency often have hemolysis (a heme load) caused by an environmental oxidant trigger, thus increasing their risk for serious morbidity. The use of tin mesoporphyrin (SnMP) has been proposed for interdicting the development of severe hyperbilirubinemia in a variety of conditions.

Objectives: We studied the in vivo effects of prophylactic oral SnMP on heme oxygenase (HO) activity and bilirubin production, as indexed by the excretion rate of carbon monoxide (VeCO), following a subsequent oral heme load.

Methods: Adult mice were exposed serially to heme and assessed for in vivo bilirubin production rates, HO-1 transcription and protein, and HO activity. The effect of prophylaxis with a single oral dose of SnMP prior to an oral heme load was assessed by measuring VeCOand tissue HO activities.

Results: After serial heme exposures, VeCO, HO-1 transcription and protein, and liver and spleen HO activities increased incrementally. After pretreatment with oral SnMP, bilirubin production decreased in response to an oral heme load. Also, heme-mediated increases in liver, spleen, and intestine HO activities were significantly dampened.

Conclusions: A single oral dose of SnMP results in durable inhibition of bilirubin production and HO activity for at least 24 h in a mouse model of oral heme loading. Further studies are needed to fully elucidate the duration of this protection against hyperbilirubinemia due to a delayed heme load and any long-term consequences of prophylaxis with SnMP on HO-1 transcription and HO-1 protein.

Background: Previous studies indicate that there may be infant gender differences in cytokine expression associated with differences in neonatal morbidity.

Objective: We tested the hypothesis that umbilical cord interleukin-1 receptor antagonist (IL-1ra) correlates with infant gender and neonatal outcome in preterm infants.

Study design: IL-1ra was measured in cord blood taken from 58 preterm infants (33 males, 25 females) with gestational age less than 32 weeks. Receiver operating characteristics (ROC) curve were used for identifying IL-1ra values with high sensitivity and specificity for neonatal morbidity and adverse outcome, i.e., death or survival with severe intraventricular hemorrhage or periventricular leukomalacia.

Results: In the female infants, but not the male infants, cord IL-1ra values correlated with postnatal depression, expressed as Apgar scores at 1 min (correlation coefficient, r(s); p value: -0.542; 0.005), 5 min (-0.571; 0.018), and 10 min (-0.442; 0.035); and postnatal age at intubation (-0.799; 0.001). The ROC area under the curve (AUC) was 0.735 for adverse outcome (p=0.013), and 0.683 for bronchopulmonary dysplasia (p=0.021) when all infants were included. However, there was a significant gender difference in the ROC curve for adverse outcome (p=0.026), with AUC 0.640 (p=0.240) in males and AUC 0.929 (p=0.008) in females. Above a chosen cutoff at 13,500 ng/l for IL-1ra cord the sensitivity and specificity for predicting adverse outcome was 100 and 81%, respectively in females versus 50 and 84% in males.

Conclusion: Increased levels of cord IL-1ra levels are associated with neonatal morbidity and adverse outcome in preterm infants. Comparable levels of IL-1ra have different predictive value depending on infant gender.

Background and aim: Neonatal necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of premature infants. We recently demonstrated that the gut/liver axis plays an important role in the pathophysiology of NEC through the release of inflammatory mediators into the intestinal lumen. We have also shown that supplementation of formula with epidermal growth factor (EGF) dramatically decreases ileal pathology associated with experimental NEC. In this study, we examined the effects of EGF on the liver portion of the gut/liver axis in the neonatal rat model of NEC.

Methods: Newborn rats were divided into three experimental groups, NEC, hand-fed with growth-factor free formula; NEC + EGF, hand-fed with formula supplemented with 500 ng/ml rat EGF; or DF, dam fed. All animals were exposed to asphyxia and cold stress twice daily for 4 days to develop NEC.

Results: EGF receptor expression was significantly (p

Conclusion: The results of this study indicate that EGF normalizes cytokine overproduction in the liver of neonatal rats with NEC, which contributes to diminished intestinal damage during the development of experimental NEC. These data suggest that supplementation of formula with EGF can have beneficial effects on the gut/liver axis during NEC pathogenesis.

Retinopathy of prematurity (ROP) is a multifactorial vasoproliferative retinal disorder that increases in incidence with decreasing gestational age. Recently, an association between hyperglycemia and severe ROP was found in extremely low birth weight infants (ELBWI). The purpose of this study was to evaluate the possible relation between hyperglycemia and ROP at any stage in very low birth weight infants (VLBWI). We analyzed the data of 201 VLBWI. The incidence of ROP and hyperglycemia was detected and the chi2 test was applied to investigate the association between the two variables. The Clinical Risk Index for Babies (CRIB) score was attributed as a marker of illness severity. The incidence of ROP and hyperglycemia in VLBWI was 35.3 and 19.4%, respectively. ROP developed more frequently in hyperglycemic infants (p < 0.001). The gestational age, birth weight, and Apgar scores were significantly lower, the CRIB score was higher in ROP patients. In hyperglycemic ROP patients the CRIB score was significantly higher compared to euglycemic ROP patients (mean (SD) 8.1 (4.2) vs. 5.5 (3.3); p < 0.01). A logistic regression model revealed that gestational age (OR 0.59; 95% CI 0.46-0.76; p < 0.001) and hyperglycemia (OR 3.15; 95% CI 1.12-8.84; p < 0.05) are independent risk factors in ROP development. When ELBWI were analyzed separately, gestational age (OR 0.38; 95% CI 0.20-0.72; p < 0.01) and CRIB score (OR 1.58; 95% CI 1.02-2.45; p < 0.05) were found as significant contributors. Further studies are needed to elucidate the pathophysiological role of hyperglycemia in the development of vasoproliferative retinal disorder.

Background: The rapid and reliable identification of biomarkers in the smallest possible amount of blood remains a challenge in biomarker epidemiological research involving preterm newborns.

Objective: We wanted to explore whether the proteomics approach of 'surface-enhanced laser desorption/ionization-time of flight mass spectrometry' (SELDI-TOF MS) is possible and feasible in whole cord blood previously dried on filter paper.

Methods: Umbilical cord blood from 7 healthy newborns was frozen as serum, whole blood (with or without additives), or dried on filter paper (with or without additives). We used the SELDI-TOF MS technique for protein detection on the ProteinChip arrays: weak cationic exchange array (CM10), hydrophobic array (H50), and strong anion exchange array (Q10). Profiles were compared in terms of peak intensity and number of resolved peaks.

Results: Dried neonatal blood, eluted from filter paper, revealed profiles similar to the profiles derived from serum at a protein range of 3-10 kDa. Among additives, heparin led to highest peak intensities for both blood and dried blood. Spectra from heparinized whole blood and heparinized dried blood from the umbilical cord of 8 different healthy newborns on three different types of ProteinChip arrays were very similar.

Conclusion: We conclude that it is possible and feasible to use SELDI-TOF MS for recovery and detection of whole proteins from dried blood collected on filter paper. The method is easy to perform in large groups of newborns, minimizing the amount of blood needed for biomarker studies. The validity and reproducibility of this method needs to be studied in detail.

Background: Allopregnanolone is a neurosteroid produced in the brain that can alter the excitability of the CNS. Neurosteroids have neuroprotective properties, and their elevation in response to stress may protect the newborn brain following infection or hypoxia. Infection, particularly of the respiratory tract, may lead to episodes of hypoxia. Infection and hypoxia have been identified as factors contributing to neonatal morbidity and mortality.

Objectives: To determine the effect of acute episodes of hypoxia alone or in combination with lipopolysaccharide (LPS) exposure on plasma and brain allopregnanolone concentrations in lambs 10-21 days old. Also, to examine plasma levels of cortisol and the cytokines, tumour necrosis factor-alpha and interleutkin-6 after these challenges.

Results: Allopregnanolone concentrations in the brain were markedly increased after hypoxia. Hypoxia following prior LPS treatment resulted in greater increases in brain allopregnanolone concentrations compared to either the LPS or hypoxia treatment alone. Importantly, brain regions unaffected by LPS or hypoxia alone (thalamus/hypothalamus, cerebellum) showed significant increases of allopregnanolone content following the combined LPS and hypoxia treatments. Plasma tumour necrosis factor-alpha and interleukin-6 concentrations were increased after LPS treatment with and without hypoxia, but not by hypoxia alone. In contrast, plasma cortisol concentrations were increased after both stressors.

Conclusions: These results show that the brain of young lambs readily responds to physiological stress by increased production of allopregnanolone. This response may protect the developing brain from the cytotoxicity following hypoxic and infectious episodes.